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Sample records for chronic liver impairment

  1. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove;

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  2. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

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    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  3. Chronic Liver Disease Impairs Bacterial Clearance in a Human Model of Induced Bacteremia

    OpenAIRE

    Ashare, Alix; Stanford, Clark; Hancock, Patricia; Stark, Donna; Lilli, Kathleen; Birrer, Emily; Nymon, Amanda; Doerschug, Kevin C.; Hunninghake, Gary W.

    2009-01-01

    Sepsis often causes impaired hepatic function. Patients with liver disease have an increased risk of bacteremia. This is thought to be secondary to impaired reticuloendothelial system function. However, this has not been demonstrated clinically. Since transient bacteremia occurs following toothbrushing, we hypothesized that subjects with cirrhosis would have impaired bacterial clearance following toothbrushing compared with subjects with pulmonary disease and healthy controls. After baseline ...

  4. Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

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    Stephanie C Burke Schinkel

    Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

  5. Trace elements and chronic liver diseases

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    Loguercio, C.; De Girolamo, V.; Federico A., A.; Del Vecchio Blanco, C. [Seconda Universita di Napoli, Naples (Italy). Cattedra di Gastroenterologia; Feng, S.L.; Gialanella, G. [Naples Univ. (Italy). Dipt. di Scienze Fisiche; Cataldi, V. [Naples Univ. (Italy). Prima Medicina Ospedale Ascalesi

    1997-12-31

    The relationships between chronic liver diseases and trace element (TE) contents are debated. Particularly, no defined data are available about the TE levels in viral liver disease patients with or without malnutrition. In this study we evaluated blood and plasma levels of various trace elements in patients with HCV-related chronic liver disease, at different stages of liver damage (8 patients with chronic hepatitis and 32 with liver cirrhosis) with or without malnutrition. We also studied 10 healthy volunteers as control group. We found that cirrhotic subjects had a significant decrease of blood levels of Zn and Se, independently on the nutritional status, whereas plasma levels of Fe were significantly reduced only in malnourished cirrhotic patients. Our data indicate that liver impairment is the main cause of the blood decrease of Se and Zn levels in patients with non alcoholic liver disease, whereas the malnutrition affects Fe levels only. (orig.)

  6. Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: how well do they predict clinical outcomes?

    DEFF Research Database (Denmark)

    Peters, L.; Rockstroh, J.K.

    2010-01-01

    patients at risk of liver-related complications. Findings from studies investigating the validity of the Model for End-Stage Liver Disease (MELD) score in HIV-infected liver transplant candidates are conflicting. Two large studies of HIV/hepatitis C virus (HCV) coinfected patients have shown that plasma...... levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models...

  7. Nutrition in Chronic Liver Disease

    OpenAIRE

    Marco Silva; Sara Gomes; Armando Peixoto; Paulo Torres-Ramalho; Hélder Cardoso; Rosa Azevedo; Carla Cunha; Guilherme Macedo

    2015-01-01

    Protein-calorie malnutrition is a transversal condition to all stages of chronic liver disease. Early recognition of micro or macronutrient deficiencies is essential, because the use of nutritional supplements reduces the risk of complications. The diet of patients with chronic liver disease is based on a standard diet with supplements addition as necessary. Restrictions may be harmful and should be individualized. Treatment management should aim to maintain an adequate protein and caloric...

  8. Autonomic dysfunction in chronic liver disease

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    Frith J

    2011-08-01

    Full Text Available James Frith, Julia L NewtonNIHR Biomedical Research Centre in Ageing, Institute for Ageing and Health, Newcastle University, Newcastle, UKAbstract: It is becoming increasingly clear that quality of life (QOL is impaired in those with chronic liver disease (CLD. One of the most important contributors to impaired QOL is the symptomatic burden which can range from slight to debilitating. Autonomic dysfunction accounts for a significant proportion of these symptoms, which can be common, non-specific and challenging to treat. Investigating the autonomic nervous system can be straight forward and can assist the clinician to diagnose and treat specific symptoms. Evidence-based treatment options for autonomic symptoms, specifically in CLD, can be lacking and must be extrapolated from other studies and expert opinion. For those with severely impaired quality of life, liver transplantation may offer an improvement; however, more research is needed to confirm this.Keywords: quality of life, treatment, fatigue, angiotensin II

  9. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1998-01-01

    Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid...... regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric...... and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral...

  10. Telomeres, NAFLD and Chronic Liver Disease.

    Science.gov (United States)

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  11. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    1996-01-01

    This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension....... In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive...

  12. Kidneys in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marek Hartleb; Krzysztof Gutkowski

    2012-01-01

    Acute kidney injury (AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomeruIonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

  13. Anemia of Chronic Liver Diseases

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    Shin, Hyun Chung; Lee, Jhung Sang; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1971-09-15

    The pathogenetic mechanisms of anemia in patients with chronic liver disease were observed. Seventeen patients with moderate to advanced hepatic diseases were studied by various methods. Only patients without previous blood loss were included : 14 had cirrhosis, 2 had active chronic hepatitis, and one had inferior vena cava obstruction with associated liver cirrhosis. The followings were the results: 1. The anemia based on red blood cell count, Hb., and Ht. was found in 76.5-78.6% of the patients. 2. Red cell indices indicated that normo-macrocytic and normochromic anemia was present is the majority of the patients. 3. No evidence of megaloblastic anemia was found on the basis of the morphological examinations. 4. Serum iron, TIBC, % saturation and iron content in the bone marrow indicated that iron deficiency anemia was present in about half of the patients. 5. In the view of the erythrocyte dynamics, primary increase in the red cell destruction was ascribed to the cause of the anemia. 6. Decrease in the red cell survival time was not correlated with MCV, % saturation and S.L. ratio. Also, hemoglobin level was not correlated with MCV, % saturation and T{sub 50} Cr. Therefore, multiple causes may be involved in the pathogenesis of the anemia. 7. Anemia as determined by the red cell volume was found in only 60% of the patients. It may be possible that hemodilutional anemia is present.

  14. Metformin promotes isolated rat liver mitochondria impairment

    OpenAIRE

    Carvalho, Cristina; Correia, Sónia; Santos, Maria,; Seiça, Raquel; Oliveira, Catarina; Moreira, Paula

    2008-01-01

    Abstract Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated rat liver mitochondria status. We observed that metformin concentrations =8 mM induce an impairment of the respiratory chain characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations =10 ...

  15. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Xin-juan Yu; Quan-jiang Dong

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  16. Lactate metabolism in chronic liver disease

    DEFF Research Database (Denmark)

    Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming;

    2013-01-01

    Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

  17. Role of cannabinoids in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Anna Parfieniuk; Robert Flisiak

    2008-01-01

    Cannabinoids are a group of compounds acting primarily via CB1 and CB2 receptors. The expression of cannabinoid receptors in normal liver is low or absent. However, many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells, as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases. It has been shown that CB1 receptor signalling exerts profibrogenic and proinflammatory effects in liver tissue, primarily due to the stimulation of hepatic stellate cells, whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis. Similarly, CB1 receptor stimulation contributes to progression of liver steatosis. In end-stage liver disease, the endocannabi-noid system has been shown to contribute to hepatic encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation, relative pe-ripheral hypotension and probably cirrhotic cardiomy-opathy. So far, available evidence is based on cellular cultures or animal models. Clinical data on the effects of cannabinoids in chronic liver diseases are limited. However, recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis. Moreover, controlling CB1 or CB2 signal-ling appears to be an attractive target in managing liver diseases.

  18. Insulin-like growth factor 1 and growth hormone in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Becker, Povl Ulrik

    1992-01-01

    mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary......, and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver...

  19. Management of Pruritus in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Angeline Bhalerao

    2015-01-01

    Full Text Available Background. There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease. Methodology. A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms “pruritus,” “chronic liver disease,” “cholestatic liver disease,” and “treatment.” Results. The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion. The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.

  20. Transcending chronic liver disease: a qualitative study.

    Science.gov (United States)

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  1. Etiologies of chronic liver disease in children

    Directory of Open Access Journals (Sweden)

    Farahmand F

    2001-11-01

    Full Text Available Chronic Liver diseases in children is the result of many different diseases including: metabolic, genetic, infectious, toxic and idiopathic causes. This was a case series study on 133 infants and children with age range 6 month to 12 years old, who presented clinically with manifestation of chronic liver disease and were admitted to Children Hospital Medical Center from year 1999 to 2000. In this study, 32 (24.5 percent patients had autoimmune chronic hepatitis, 15 (11.3 percent Glycogen storage diseases, 12 (9 percent extrahepatic biliary atresia, 11 (8.2 percent willson disease, 10 (7.5 percent cryptogenic cirrhosis, 6 (4.5 percent chronic hepatitis C, 5 (3.8 percen chronic hepatitic B, 5 (3.8 percent galactosemia 3 (2.25 percent congenital hepatic fibrosis, 3 (3.8 percent histiocytosis X, 3 (2.25 percent sclerosing cholangitis, 2 (1.5 percent byler’s disease 2 (1.5 percent primary tuberculosis, 1 (0.75 percent choledocalcyst, 1 (0.75 percent Alagyle syndrome. According to our data, chronic liver disease should be considered in infants and children. In our study, the most common causes are found to be: metabolic and genetic diseases (37.5 percent, chronic autoimmune hepatitis (24 percent and biliary disorders (14 percent, that encompass 86 percent of the patients.

  2. Interleukin-10 and chronic liver disease

    OpenAIRE

    ZHANG, LI-JUAN; Wang, Xiao-Zhong

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a ...

  3. Interleukin-10 and chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Zhang; Xiao-Zhong Wang

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.

  4. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1996-01-01

    renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension...

  5. Chronic Liver Disease and American Indians/Alaska Natives

    Science.gov (United States)

    ... Native > Chronic Liver Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, ... 54. 1 At a glance – Cancer Rates for American Indian/Alaska Natives (2008-2012) Cancer Incidence Rates per ...

  6. Metabolic Disturbances in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    A Rezaeian

    2014-04-01

    Full Text Available Introduction: Liver disease results in complex pathophysiologic disturbances affecting nutrient digestion, absorption, distribution, storage, and use. This article aimed to present a classification of metabolic disturbances in chronic liver disease in children?   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"  ” metabolic disorder””children” between 1999 to 2014. Finally, 8 related articles have been found.   Results: Metabolic disorder in this population could be categorized in four set: 1carbohydrates, 2proteins,3 fats and 4vitamins. 1 Carbohydrates: Children with CLD are at increased risk for fasting hypoglycemia, because the capacity for glycogen storage and gluconeogenesis is reduced as a result of abnormal hepatocyte function and loss of hepatocyte mass. 2 Proteins: The liver’s capacity for plasma protein synthesis is impaired by reduced substrate availability, impaired hepatocyte function, and increased catabolism. This results in hypoalbuminemia, leading to peripheral edema and contributing to ascites. Reduced synthesis of insulin-like growth factor (IGF-1 and its binding protein IGF-BP3 by the chronically diseased liver results in growth hormone resistance and may contribute to the poor growth observed in these children. 3 Fats: There is increased fat oxidation in children with end-stage liver disease in the fed and fasting states compared with controls, which is probably related to reduced carbohydrate availability. The increased lipolysis results in a decrease in fat stores, which may not be easily replenished in the setting of the fat malabsorption that accompanies cholestasis. Reduced bile delivery to the gut results in impaired fat emulsification, and hence digestion. The products of fat digestion are also poorly absorbed, because bile is also required for micelle formation

  7. Chronic liver disease in Aboriginal North Americans

    Institute of Scientific and Technical Information of China (English)

    John D Scott; Naomi Garland

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death.Alcoholic liver disease is the leading etiology of CLD,but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD.Future research should monitor the incidence and etiology of CLD and should be geographically inclusive.In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholicfatty liver disease (NAFLD) in this population.

  8. Vascular cognitive impairments in chronic kidney disease

    OpenAIRE

    I. V. Rogova; Fomin, V. V.; I. V. Damulin; E. G. Minakova; O. Yu. Selivanova; Yu. A. Petleva

    2015-01-01

    Objective: to study the specific features of development of cognitive impairments (CIs), the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD) and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR) of...

  9. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial...

  10. Vitamin D deficiency in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Paula; Iruzubieta; lvaro; Terán; Javier; Crespo; Emilio; Fábrega

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

  11. the Pathogenesis of acute on Chronic Hepatitis B liver Failure

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  12. Mineral Requirements in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    A Rezaeian

    2014-04-01

    Full Text Available Introduction: Decreased oral intake or impaired function / structure in the gut, such as hypertension port associated with atrophic changes in the protein nutrition - calories can lead to micronutrient deficiencies.This paper examines the status of micronutrients in chronic liver disease in children.   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"” minerals””children” between 1999 to 2014. Finally, 3 related articles have been found.   Results: In chronic liver disease changes in micronutrient metabolism lead to changes in the daily requirements, such that in certain circumstances intake increasing or decreasing  is needed. Low serum calcium and phosphate concentrations are often the reflection of malabsorption-induced bone disease that is unresponsive to vitamin D store normalization. Iron is usually deficient in children with CLD and supplementation frequently needed. The origin of iron deficiency is multifactorial and includes ongoing losses, inadequate intakes, serial blood draws and malabsorption secondary to hypertensive enteropathy. Zinc plays an important role in cognitive function, appetite and taste, immune function, wound healing, and protein metabolism. Low plasma zinc levels are frequent in children with chronic cholestasis, but unfortunately plasma concentrations are not reflective of total body zinc status. Copper and manganese, unlike other minerals, are increased in CLD, because they are normally excreted through bile. Parenteral nutrition in cholestatic patients can induce manganese intoxication and accumulation in basal ganglia.   Conclusion:  In fants with CLD are prone to multiple nutritional deficiencies. Mineral state should be evaluated, treated and reevaluated, until sufficient daily requirement achieved. Poster  Presentation, N 33  

  13. Is liver biopsy mandatory in children with chronic hepatitis C?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Liver biopsy is considered the most accurate means to estimate the necroinflammatory activity and the extent of fibrosis. However, histology evaluation is an invasive procedure associated with risk to the patient, risk of sampling error and diagnostic inconsistencies due to inter- and intra-observer error. On the basis of histological studies performed so far, chronic hepatitis C in children appears morphologically benign in the majority of cases.At the Pediatric Liver Unit of our university, a total of 67 children with chronic hep, atitis C underwent liver biopsy.Liver biopsy was repeated 5.5 years after the initial histological evaluation in 21 children. On a total number of 88 liver biopsies, micronodular cirrhosis was detected only in one genotype 1b-infected obese child. Since liver histology investigation of a child with chronic hepatitis C has few chances to highlight severe lesions, we question how liver biopsy helps in the management of children with chronic hepatitis C.

  14. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  15. Ovarian carcinoma in two patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mehlika Isildak; Gulay Sain Guven; Murat Kekilli; Yavuz Beyazit; Mustafa Erman

    2005-01-01

    Ascites is a common and debilitating complication of cirrhosis. However, patients with chronic liver disease are not spared from other causes of ascites and physicians should be careful not to miss an underlying malignancy.Ovarian cancer is an insidious disease, which is difficult to diagnose and it ranks first in mortality among all gynecological cancers. Here, we present two cases of patients with chronic liver disease that developed ascites not simply because of cirrhosis but as a manifestation of ovarian cancer. We would like to emphasize that the causes of ascites, other than the liver itself, should not be overlooked in patients with chronic liver disease.

  16. [Noncirrhotic liver fibrosis after chronic arsenic poisoning].

    Science.gov (United States)

    Piontek, M; Hengels, K J; Borchard, F; Strohmeyer, G

    1989-10-27

    A 67-year-old woman with portal hypertension, splenomegaly without portal vein thrombosis, leucopenia and thrombocytopenia of splenic origin had repeated episodes of life-threatening haemorrhage from esophageal varices. Since childhood she had suffered from psoriasis and had been treated over a period of 15 years with Fowler's solution (in all about 25 g of arsenic trioxide). She had the characteristic skin lesions of arsenical poisoning-palmar hyperkeratoses and two basal cell carcinomas on the trunk. Histological examination of a wedge biopsy from the liver showed definite structural changes with fibrosis around the central veins and in the portal tracts. There was no evidence of cirrhotic alteration. The hepatocytes were normal by light microscopy and electron microscopy. This case of noncirrhotic hepatic fibrosis is considered to have been caused by chronic arsenical poisoning.

  17. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Gao; Shu-Sen Zheng

    2004-01-01

    Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain.This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.

  18. Gut microbiota and probiotics in chronic liver diseases.

    Science.gov (United States)

    Cesaro, Claudia; Tiso, Angelo; Del Prete, Anna; Cariello, Rita; Tuccillo, Concetta; Cotticelli, Gaetano; Del Vecchio Blanco, Camillo; Loguercio, Carmelina

    2011-06-01

    There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage. PMID:21163715

  19. Cognitive impairment in patients with chronic fatigue: a preliminary study.

    OpenAIRE

    McDonald, E; Cope, H; David, A

    1993-01-01

    Subjective impairment of memory and concentration is a frequent complaint in sufferers from chronic fatigue. To study this, 65 general practice attenders identified as having chronic fatigue were administered a structured psychiatric interview and a brief screening battery of cognitive tests. Subjective cognitive impairment was strongly related to psychiatric disorder, especially depressed mood, but not fatigue, anxiety, or objective performance. Simple tests of attention and concentration sh...

  20. Mechanisms of impaired gallbladder contractile response in chronic acalculous cholecystitis.

    Science.gov (United States)

    Merg, Anders R; Kalinowski, Scott E; Hinkhouse, Marilyn M; Mitros, Frank A; Ephgrave, Kimberly S; Cullen, Joseph J

    2002-01-01

    The mechanisms involved in the impaired gallbladder contractile response in chronic acalculous cholecystitis are unknown. To determine the mechanisms that may lead to impaired gallbladder emptying in chronic acalculous cholecystitis, gallbladder specimens removed during hepatic resection (controls) and after cholecystectomy for chronic acalculous cholecystitis were attached to force transducers and placed in tissue baths with oxygenated Krebs solution. Electrical field stimulation (EFS) (1 to 10 Hz, 0.1 msec, 70 V) or the contractile agonists, CCK-8 (10(-9) to 10(-5)) or K(+) (80 mmol/L), were placed separately in the tissue baths and changes in tension were determined. Patients with chronic acalculous cholecystitis had a mean gallbladder ejection fraction of 12% +/- 4%. Pathologic examination of all gallbladders removed for chronic acalculous cholecystitis revealed chronic cholecystitis. Spontaneous contractile activity was present in gallbladder strips in 83% of control specimens but only 29% of gallbladder strips from patients with chronic acalculous cholecystitis (P < 0.05 vs. controls). CCK-8 contractions were decreased by 54% and EFS-stimulated contractions were decreased by 50% in the presence of chronic acalculous cholecystitis (P < 0.05 vs. controls). K(+)-induced contractions were similar between control and chronic acalculous cholecystitis gallbladder strips. The impaired gallbladder emptying in chronic acalculous cholecystitis appears to be due to diminished spontaneous contractile activity and decreased contractile responsiveness to both CCK and EFS.

  1. Vascular cognitive impairments in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    I. V. Rogova

    2015-01-01

    Full Text Available Objective: to study the specific features of development of cognitive impairments (CIs, the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR of і60 ml/min/1.73 m2, signs of renal lesion; 20 with Stages III CKD: a GFR of <60–30 ml/min/1.73 m2, and 11 with Stages VI CKD: a GFR of <30–15 ml/min/1.73 m2. Results and discussion. CIs were more common in the patients with Stages III–IV than in those with Stages I–II, as shown by the scores of the mini-mental state examination (p<0.001, the frontal assessment battery (p=0.001, and the regulatory function test (p<0.001. These tests showed that the magnitude of CIs increased with the higher stage of CKD. Stages III–IV CKD is an independent predictor of CIs in persons with predialysis-stage kidney lesion. CIs were found to be related to hyperhomocysteinemia, anemia, abdominal obesity, left ventricular hypertrophy, and patient age. The signs of atherosclerotic lesion of the common carotid arteries and the indicators of arterial stiffness were also associated with the incidence and magnitude of CIs in CKD. The detection of CIs in patients with early CKD allows one to timely initiate adequate therapy aimed particularly at improving cerebral circulation, eliminating the impact of risk factors, and slowing down the vascular remodeling. The management tactics for patients with CKD must involve the identification and correction of cardiovascular risk factors, and duplex scanning of the wall of the common carotid arteries may be used as a noninvasive method to assess the risk of the development and progression of CIs in predialysis CKD. 

  2. Conseqüências nutricionais das alterações metabólicas dos macronutrientes na doença hepática crônica Nutritional consequences of macronutrients metabolism impairment in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Regiane MAIO

    2000-01-01

    Full Text Available A doença hepática crônica cursa, freqüentemente, com anormalidades metabólicas de macronutrientes que propiciam o desenvolvimento ou agravamento da desnutrição protéico-energética. O papel central do fígado no metabolismo dos substratos energéticos e de proteínas e aminoácidos é revisto, de modo relacionado à desnutrição protéico-energética, em pacientes com hepatopatia crônica. Aceita-se que a redução da ingestão dietética seja um dos principais componentes etiológicos da desnutrição, particularmente em pacientes alcoolistas. Acresce-se a iatrogenia pela indicação de dietas restritas e jejum prolongado aos pacientes hospitalizados. Como fatores agravantes, há má absorção intestinal de gorduras e o hipermetabolismo associado ao alcoolismo agudo. Hipoglicemia, resistência insulínica, esteatose e hipertrigliceridemia constituem achados comuns, assim como níveis elevados de alguns aminoácidos com conseqüências neurológicas. O entendimento desses mecanismos fisiopatológicos permite a intervenção nutricional apropriada reduzindo a morbidade e mortalidade desses pacientes.Liver chronic pathologies often courses with metabolic abnormalities of macronutrients leading to or aggravating a protein-energy malnutrition status. This review raised the major pathophysiologycal mechanisms related to the protein-energy malnutrition in chronic liver patients. By large the reduced dietary intake is the most accepted cause particularly among alcoholic patients. Moreover during the treatment prevails the iatrogenic anorexia by unpalatable (restricted diets interpolated with long-lasting fastings of hospitalyzed patients. Intestinal fat malabsorption is a common finding whereas hypermetabolism can be found associated with an acute alcoholism. Hipoglycemia or insulin resistance, hypertriglyceridemia and liver steatosis are common findings as well as lower plasma proteins along with higher levels of ammonia, aromatic and sulfer

  3. Chronic liver injury induced by drugs: a systematic review.

    Science.gov (United States)

    Stine, Jonathan G; Chalasani, Naga

    2015-11-01

    To examine the available literature and summarize what is known about chronic drug-induced liver injury. We reviewed PubMed/MEDLINE through March 2015. We developed a MEDLINE search strategy using PubMed medical subject heading terms chronic liver injury, hepatotoxicity, drug-induced liver injury, cirrhosis and chronic liver disease. We reviewed the reference list of included articles to identify articles missed in the database search. Chronic liver injury from drugs is more common than once thought with prevalence as high as 18% based on large national registries. Patients with cholestatic injury, age ≤65 years, and a long latency period (>365 days) are at increased risk. Of the most common drugs associated with drug-induced liver injury, antibiotics (amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin) are most likely to cause chronic injury. The presence of autoantibodies is common with chronic DILI, however, it is not diagnostic nor is it specific to autoimmune-like drug-induced liver injury. Immunosuppressive therapy may be necessary for individual cases of autoimmune-like drug-induced liver injury where cessation of the drug alone does not result in resolution of injury, however, the lowest dose should be used for the shortest duration with careful attention to the development of side effects. The effectiveness of treament of cholestatic liver injury with corticosteroids or ursodiol remains unclear. Cases of drug-induced fatty liver, nodular regenerative hyperplasia and peliosis hepatitis are less common subtypes of chronic drug-induced liver injury that deserve special consideration. A high degree of clinical suspicion is required for the diagnosis of chronic drug-induced liver injury and should be suspected in any patient with liver associated enzyme abnormalities that persist out past 6 months of initial presentation. Treatment with drug removal and/or immunosuppressive therapy appears to be effective for the majority of cases

  4. Hepatic lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Henry; C; Bodenheimer; David; J; Clain; Albert; D; Min; Neil; D; Theise

    2010-01-01

    AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 pati...

  5. Chronic liver disease questionnaire:Translation and validation in Thais

    Institute of Scientific and Technical Information of China (English)

    Abhasnee Sobhonslidsuk; Chatchawan Silpakit; Ronnachai Kongsakon; Patchareeya Satitpornkul; Chaleaw Sripetch

    2004-01-01

    AIM: Quality of life (QOL) is a concept that incorporates many aspects of life beyond "health". The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL. The objectives of this study were to translate and validate a liver specific questionnaire, the CLDQ.METHODS: The CLDQ was formally translated from the original version to Thai language with permission. The translation process included forward translation, back translation, cross-cultural adaptation and a pretest. Reliability and validity of the translated version was examined in CLD patients. Enrolled subjects included CLD and normal subjects with age- and sex-matched. Collected data were demography,physical findings and biochemical tests. All subjects were asked to complete the translated versions of CLDQ and SF-36, which was previously validated. Cronbach's alpha and test-retest were performed for reliability analysis. One-way Anova or non-parametric method was used to determine discriminant validity. Spearman's rank correlation was used to assess convergent validity. P-value <0.05 was considered statistically significant.RESULTS: A total of 200 subjects were recruited into the study, with 150 CLD and 50 normal subjects. Mean ages (SD) were 47.3(11.7) and 49.1(8.5) years, respectively. The number of chronic hepatitis: cirrhosis was 76:74, and the ratio of cirrhotic patients classified as Child A:B:C was 37(50%): 26(35%): 11(15%). Cronbach's alpha of the overall CLDQ scores was 0.96 and of all domains were higher than0.93. Item-total correlation was >0.45. Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores. The CLDQ was found to have discriminant validity. The highest scores of CLDQ domains were in the normal group, scores were lower in the compensated group and lowest in the decompensated group. The significant correlation between domains of the CLDQ and SF-36 was found

  6. Ovarian carcinoma in two patients with chronic liver disease

    OpenAIRE

    Isildak, Mehlika; Guven, Gulay Sain; Kekilli, Murat; Beyazit, Yavuz; Erman, Mustafa

    2005-01-01

    Ascites is a common and debilitating complication of cirrhosis. However, patients with chronic liver disease are not spared from other causes of ascites and physicians should be careful not to miss an underlying malignancy. Ovarian cancer is an insidious disease, which is difficult to diagnose and it ranks first in mortality among all gynecological cancers. Here, we present two cases of patients with chronic liver disease that developed ascites not simply because of cirrhosis but as a manifes...

  7. Telomere and telomerase in chronic liver disease and hepatocarcinoma

    OpenAIRE

    Carulli, Lucia; Anzivino, Claudia

    2014-01-01

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (...

  8. Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Bellanti, Francesco; Mitarotonda, Domenica; Tamborra, Rosanna; Blonda, Maria; Iannelli, Giuseppina; Petrella, Antonio; Sanginario, Vittorio; Iuliano, Luigi; Vendemiale, Gianluigi; Serviddio, Gaetano

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disorder affecting up to 25% of the general population. Several intracellular events leading to NAFLD and progression to non-alcoholic steatohepatitis (NASH) have been identified, including lipid accumulation, mitochondrial dysfunction and oxidative stress. Emerging evidence links both hepatic free fatty acids (FFAs) and cholesterol (FC) accumulation in NAFLD development; in particular oxysterols, the oxidative products of cholesterol, may contribute to liver injury. We performed a targeted lipidomic analysis of oxysterols in the liver of male Wistar rats fed a high-fat (HF), high-cholesterol (HC) or high-fat/high-cholesterol (HF/HC) diet. Both HF and HC diets caused liver steatosis, but the HF/HC diet resulted in steatohepatitis with associated mitochondrial dysfunction. Above all, the oxysterol cholestane-3beta,5alpha,6beta-triol (triol) was particularly increased in the liver of rats fed diets rich in cholesterol. To verify the molecular mechanism involved in mitochondrial dysfunction and hepatocellular toxicity, Huh7 and primary rat hepatocytes were exposed to palmitic acid (PA) and/or oleic acid (OA), with or without triol. This compound induced apoptosis in cells co-exposed to both PA and OA, and this was associated with impaired mitochondrial respiration as well as down-regulation of PGC1-alpha, mTFA and NRF1.In conclusion, our data show that hepatic free fatty acid or oxysterols accumulation per se induce low hepatocellular toxicity. On the contrary, hepatic accumulation of both fatty acids and toxic oxysterols such as triol are determinant in the impairment of mitochondrial function and biogenesis, contributing to liver pathology in NAFLD. PMID:26461297

  9. Review article: hepatitis vaccination in patients with chronic liver disease.

    Science.gov (United States)

    Reiss, G; Keeffe, E B

    2004-04-01

    Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

  10. Chronic liver disease related mortality pattern in northern Pakistan

    International Nuclear Information System (INIS)

    Objective: To describe the mortality pattern pertaining to chronic liver disease (CLD) in Northern Pakistan. Results: There were a total of 8529 admissions in twelve months period from August 2001 to July 2002. There were 283 (3.31%) total deaths. Out of these, 160 deaths were pertaining to medical causes. Out of these medical cases, 33 (20.6%) patients had died of chronic liver disease. Other major causes of death were cerebro-vascular accident (18.7%), malignancy (18.1%) and acute myocardial infarction (10.6%). Out of 33 patients of CLD, 12 (36%) presented with acute gastrointestinal (Gl) bleeding, 9(27%) presented with Ascites and 6(18%) presented with altered mental status due to hepatic encephalopathy. Rest of them had jaundice and fever as their initial presentation. Out of these 33 patients with CLD, 23 (70%) had hepatitis C virus (HCV) as cause of their liver disease, 4 (12%) had hepatitis B virus (HBV) infection, 3(9%) had both hepatitis B and hepatitis C virus infections and 3 (9%) had no known cause of their chronic liver disease. Conclusion: Chronic liver disease is a major cause of mortality in this part of Pakistan at a tertiary care hospital. HCV infection is the main cause of chronic liver disease followed by either HBV or a combination of these viruses. Major manifestations of CLD have been gastrointestinal bleeding, hepatic failure and portal hypertension.(author)

  11. [Pathogenetic correction of metabolic disturbances in chronic liver affections].

    Science.gov (United States)

    Romantsov, M G; Petrov, A Iu; Aleksandrova, L N; Sukhanov, D S; Kovalenko, A L

    2012-01-01

    The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual. PMID:23700935

  12. Impaired conversion of prednisone to prednisolone in patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Madsbad, S; Bjerregaard, B; Henriksen, Jens Henrik Sahl;

    1980-01-01

    Fourteen patients with liver cirrhosis received oral prednisone or prednisolone (0.3 mg per kg) randomised on two consecutive days. Serum prednisone and prednisolone were measured over the following four hours. Mean serum prednisolone concentration after oral prednisone decreased with impaired...... liver function estimated by galactose elimination capacity (r = 0.64, P less than 0.03). Mean serum prednisolone concentration after oral prednisone in the seven patients with severely impaired liver function was only 53% (P less than 0.05) of that observed in the seven patients with slightly impaired...... liver function. Conversely, mean serum prednisone concentration after oral prednisone in the patients with severely impaired liver function was 74% higher (P = 0.05) than in patients with slightly impaired liver function. Mean serum prednisolone after oral prednisolone was independent of liver function...

  13. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B;

    2004-01-01

    BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease...... and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...

  14. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Pengtao [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 (China); Huang, Zhen [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Wei, Taotao, E-mail: weitt@moon.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China)

    2013-04-19

    Highlights: •Free fatty acids exposure induces elevated autophagy. •H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-α, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  15. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

    OpenAIRE

    Lu Zhao; Jianhua Xu; Fang Liang; Ao Li; Yong Zhang; Jue Sun

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also assoc...

  16. Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

    Directory of Open Access Journals (Sweden)

    Davide Degli Esposti

    2012-01-01

    Full Text Available The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.

  17. Chronic liver disease in Kuala Lumpur, Malaysia: a clinical study.

    Science.gov (United States)

    Kudva, M V; Zawawi, M M

    1990-08-01

    This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively.

  18. Utility of Modeling End-Stage Liver Disease in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Kianifar

    2014-01-01

    Full Text Available Introduction: Chronic liver diseases consist of wide spectrum disorders that may be complicated by cirrhosis and therefore need to transplantation. The pediatric end-stage liver disease (PELD score and model of end-stage liver disease (MELD score has been used as predictors of mortality chronic liver diseases listed for liver transplantation. The aim of this study is evaluation of relation between PELDMELD score and evidence of cirrhosis in children with choronic liver disease.   Materials and Method: This cross-sectional study conducted on 106 patients of chronic liver disease referred to Ghaem Haspital, Mashhad University of Medical Science, Iran during 24 months period (2010-2013. PELD and MELD score were calculated for all patients. Clincal and patholoogical findings of cirrhosis were recorded.   Results: Mean age of patients was 68/3 ± 41.8 months. Mean PELDMELD score was -1/59± 9/64. There was significant correlation between PELDMELD score and clinical icter, spelenomegaly, evidence of hepatopulminary syndrome, esophageal varices, evidence of cirrhosis in tissue specimences.   Conclusion: PELDMELD score appear to be benefit for detection of cirrhotic children among paients with choronic liver disease.

  19. Impaired function of bone marrow-derived endothelial progenitor cells in murine liver fibrosis.

    Science.gov (United States)

    Shirakura, Katsuya; Masuda, Haruchika; Kwon, Sang-Mo; Obi, Syotaro; Ito, Rie; Shizuno, Tomoko; Kurihara, Yusuke; Mine, Tetsuya; Asahara, Takayuki

    2011-01-01

    Liver fibrosis (LF) caused by chronic liver damage has been considered as an irreversible disease. As alternative therapy for liver transplantation, there are high expectations for regenerative medicine of the liver. Bone marrow (BM)- or peripheral blood-derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat liver cirrhosis. We investigated the biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were subcutaneously injected with carbon tetrachloride (CCl(4)) every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical examination. Assessments of EPC in the peripheral blood and BM were performed by flow cytometry and EPC colony-forming assay, respectively, using purified MNCs and BM c-KIT(+), Sca-1(+), and Lin(-) (KSL) cells. Liver tissues underwent histological analysis with hematoxylin/eosin/Azan staining, and spleens were excised and weighed. CCl(4)-treated mice exhibited histologically bridging fibrosis, pseudolobular formation, and splenomegaly, indicating successful induction of LF. The frequency of definitive EPC-colony-forming-units (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells decreased significantly (p changes in primitive EPC-CFU occurred in LF mice. The frequency of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF mice compared with control mice. Together, these findings indicated the existence of impaired EPC function and differentiation in BM-derived EPCs in LF mice and might be related to clinical LF.

  20. Per-rectal portal scintigraphy in chronic liver diseases

    International Nuclear Information System (INIS)

    Portal circulation has been evaluated by per-rectal portal scintigraphy in 21 controls and in 30 pts affected by chronic liver diseases. Tc99m-pertechnetate (10 mci) was given through a Nelaton's catheter in the upper rectum; a per-rectal portal shunt index (SI) was calculated. A relevant overlap is evident between controls and CHP pts; no overlap exists between controls and B or C graded cirrhosis. We conclude that the technique may be suggested to monitor the course of chronic liver diseases and different therapeutic regimens. (orig.)

  1. CdSe quantum dot (QD-induced morphological and functional impairments to liver in mice.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Quantum dots (QDs, as unique nanoparticle probes, have been used in in vivo fluorescence imaging such as cancers. Due to the novel characteristics in fluorescence, QDs represent a family of promising substances to be used in experimental and clinical imaging. Thus far, the toxicity and harmful health effects from exposure (including environmental exposure to QDs are not recognized, but are largely concerned by the public. To assess the biological effects of QDs, we established a mouse model of acute and chronic exposure to QDs. Results from the present study suggested that QD particles could readily spread into various organs, and liver was the major organ for QD accumulation in mice from both the acute and chronic exposure. QDs caused significant impairments to livers from mice with both acute and chronic QD exposure as reflected by morphological alternation to the hepatic lobules and increased oxidative stress. Moreover, QDs remarkably induced the production of intracellular reactive oxygen species (ROS along with cytotoxicity, as characterized by a significant increase of the malondialdehyde (MDA level within hepatocytes. However, the increase of the MDA level in response to QD treatment could be partially blunted by the pre-treatment of cells with beta-mercaptoethanol (β-ME. These data suggested ROS played a crucial role in causing oxidative stress-associated cellular damage from QD exposure; nevertheless other unidentified mediators might also be involved in QD-mediated cellular impairments. Importantly, we demonstrated that the hepatoxicity caused by QDs in vivo and in vitro was much greater than that induced by cadmium ions at a similar or even a higher dose. Taken together, the mechanism underlying QD-mediated biological influences might derive from the toxicity of QD particles themselves, and from free cadmium ions liberated from QDs as well.

  2. Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

    Science.gov (United States)

    García-Compeán, Diego; González-González, José Alberto; Lavalle-González, Fernando Javier; González-Moreno, Emmanuel Irineo; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

    2016-02-01

    Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

  3. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

  4. Liver fibrosis in chronic viral hepatitis: An ultrasonographic study

    Institute of Scientific and Technical Information of China (English)

    Rong-Qin Zheng; Qing-Hui Wang; Ming-De Lu; Shi-Bin Xie; Jie Ren; Zhong-Zhen Su; Yin-Ke Cai; Ji-Lu Yao

    2003-01-01

    AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology.METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed.RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P<0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P<0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis.However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P<0.05). False positive and false

  5. Role of spleen elastography in patients with chronic liver diseases.

    Science.gov (United States)

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-09-21

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

  6. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin;

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  7. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

    Science.gov (United States)

    Castro, María Cecilia

    2016-01-01

    We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation. PMID:27597864

  8. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction.

    Science.gov (United States)

    Villagarcía, Hernán Gonzalo; Sabugo, Vanesa; Castro, María Cecilia; Schinella, Guillermo; Castrogiovanni, Daniel; Spinedi, Eduardo; Massa, María Laura; Francini, Flavio

    2016-01-01

    We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation. PMID:27597864

  9. Hepatitis C virus infection in chronic liver disease in Somalia.

    Science.gov (United States)

    Aceti, A; Taliani, G; Bruni, R; Sharif, O S; Moallin, K A; Celestino, D; Quaranta, G; Sebastiani, A

    1993-04-01

    To assess the role of hepatitis C virus (HCV) in liver disease in Somalia, antibody to HCV (anti-HCV) was studied by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) in 110 patients with chronic liver diseases, in 309 healthy adults, in 179 institutionalized subjects with a high prevalence of intestinal parasites and Schistosoma haematobium, and in 287 children with diseases other than hepatitis. According to the RIBA test, anti-HCV was present in three healthy adults (0.97%), in four institutionalized individuals (2.2%), but in none of the children. The prevalence of anti-HCV was 4.8% in patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases and 20.6% in patients with HBsAg-negative chronic liver diseases. Thus, HCV infection appears to play a minor role in HBsAg-positive liver disease in Somalia but may be an important factor in HBsAg-negative chronic liver disease. The low anti-HCV prevalence in individuals with no hepatic disorders is consistent with the fact that HCV does not spread by nonpercutaneous transfer. We found also a large proportion of both patients with hepatic disease and institutionalized individuals who tested positive by ELISA but not confirmed by RIBA. However, the likelihood of a true positive result increases proportionally with the ELISA value; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true positive reaction. PMID:7683179

  10. Assessment of adult patients with chronic liver failure for liver transplantation in 2015: who and when?

    Science.gov (United States)

    McCaughan, G W; Crawford, M; Sandroussi, C; Koorey, D J; Bowen, D G; Shackel, N A; Strasser, S I

    2016-04-01

    In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease (MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future. PMID:27062203

  11. Liver dialysis in acute-on-chronic liver failure: current and future perspectives.

    Science.gov (United States)

    Maiwall, Rakhi; Maras, Jaswinder Singh; Nayak, Suman Lata; Sarin, Shiv Kumar

    2014-09-01

    Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients. PMID:26201332

  12. Telomere and telomerase in chronic liver disease and hepatocarcinoma.

    Science.gov (United States)

    Carulli, Lucia; Anzivino, Claudia

    2014-05-28

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma. PMID:24876749

  13. Cardiopulmonary complications in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Sφren Mφller; Jens H Henriksen

    2006-01-01

    Patients with cirrhosis and portal hypertension exhibit characteristic cardiovascular and pulmonary hemodynamic changes. A vasodilatatory state and a hyperdynamic circulation affecting the cardiac and pulmonary functions dominate the circulation.The recently defined cirrhotic cardiomyopathy may affect systolic and diastolic functions, and imply electromechanical abnormalities. In addition, the baroreceptor function and regulation of the circulatory homoeostasis is impaired. Pulmonary dysfunction involves diffusing abnormalities with the development of the hepatopulmonary syndrome and portopulmonary hypertension in some patients. Recent research has focused on the assertion that the hemodynamic and neurohumoral dysregulation are of major importance for the development of the cardiovascular and pulmonary complications in cirrhosis. This aspect is important to take into account in the management of these patients.

  14. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

    Directory of Open Access Journals (Sweden)

    Michele Barone

    2015-01-01

    Full Text Available Background. Hepatitis C virus (HCV infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan and aspartate aminotransferase to platelet ratio index (APRI, carotid intima-media thickness (c-IMT, and brachial artery flow-mediated vasodilatation (FMD were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa showed FMD values were significantly lower than second and first tertiles (4.7±1.7% versus 7.1±2.8%, p=0.03. FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p=0.02 was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

  15. Accuracy of ultrasound to identify chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Richard; Allan; Kerry; Thoirs; Maureen; Phillips

    2010-01-01

    AIM:To identify and assess studies reporting the diagnostic performance of ultrasound imaging for identifying chronic liver disease(CLD)in a high risk population. METHODS:A search was performed to identify studies investigating the diagnostic accuracy of ultrasound imaging for CLD.Two authors independently used the quality assessment of diagnostic accuracy studies(QUADAS)checklist to assess the methodological quality of the selected studies.Inter-observer reliability of the QUADAS tool was assessed by measu...

  16. Gastric emptying in patients with chronic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ishizu, Hirotaka; Shiomi, Susumu; Kawamura, Etsushi; Iwata, Yoshinori; Nishiguchi, Shuhei; Kawabe, Joji; Ochi, Hironobu [Osaka City Univ. (Japan). Graduate School of Medicine

    2002-05-01

    There have been a number of reports of gastric emptying in cirrhosis, all with unconfirmed results. Moreover, the mechanism for delayed emptying in cirrhotic patients in unclear. We evaluated gastric emptying in patients with chronic hepatitis and cirrhosis by means of gastric emptying scintigraphy. The subjects were 18 normal controls and 75 patients with chronic viral hepatitis (50 patients had chronic hepatitis and 25 patients had cirrhosis). Tc-99m diethyltriamine pentaacetic acid labeled solid meals were used to evaluate gastric emptying; the half-time (T 1/2) of which was calculated. Digestive symptom scores were determined at the time of gastric emptying tests. Fourteen (28%) of 50 patients with chronic hepatitis and 16 (64%) of 25 patients with cirrhosis had delayed gastric emptying. T 1/2 in patients with cirrhosis was significantly higher than that in normal controls and patients with chronic hepatitis (p=0.0001 and 0.0003, respectively). The difference between T 1/2 in patients with chronic hepatitis and that in normal controls was not significant. On regression analysis, two indices, the serum albumin level and platelet count, were found to be significantly related to delayed gastric emptying. Gastric emptying was more delayed in cirrhotic patients than in those with chronic hepatitis and normal controls. Delayed gastric emptying may be related to liver function and portal hypertension. (author)

  17. Hepatic encephalopathy in acute-on-chronic liver failure.

    Science.gov (United States)

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  18. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  19. Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.

    Science.gov (United States)

    Alzoubi, Karem H; Mayyas, Fadia A; Khabour, Omar F; Bani Salama, Fatima M; Alhashimi, Farah H; Mhaidat, Nizar M

    2016-07-01

    Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P sleep-deprived rats (P  0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD. PMID:26084441

  20. Acute-on-chronic liver failure: a review

    Directory of Open Access Journals (Sweden)

    Zamora Nava LE

    2014-04-01

    Full Text Available Luis Eduardo Zamora Nava,1 Jonathan Aguirre Valadez,2 Norberto C Chávez-Tapia,3 Aldo Torre21Department of Endoscopy, 2Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 3Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Mexico City, MexicoAbstract: There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population. This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.Keywords: acute-on-chronic liver failure, cirrhosis, organ failure, acute kidney injury, infection

  1. Apoptosis pathway of liver cells in chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Nai-Ling Chen; Zhen-Qiu Zhou; Ling Bai; Lin Li; Pei-Lan Chen; Chang Zhang; Chao-Ying Liu; Tao Deng; Hao Chen; Ke-Ming Jia

    2004-01-01

    AIM: To study the pathway of apoptosis in chronic liver disease and the role of mitochondria in programmed cell death.METHODS: Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied. The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2, Bcl-xL, Bcl-2α were studied immunohistochemically by SP method. Specimens from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for their ultramicrostructures with special attention to their mitochondrial changes. Specimens from 3 normal adults (demised in traffic accidents) were used as control.RESULTS: The expression of proapoptotic proteins (Fas,FasL, Bax) in hepatocytes was significantly higher in the chronic hepatitis group than in the cirrhosis group (P<0.001).In the study of ultramicrostructure 364 hepatocytes were examined, from 12 cases of chronic hepatitis (including 10mild cases, 1 moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes were found with various kinds of destruction in their mitochondria. Rupture of the outer membrane of mitochondria and the leakage of matrix from the intermembrane space were definitely demonstrated. The ultramicrostructural changes of mitochondria in the chronic hepatitis group were statistically higher than that in normal adults control group (χ2=4.32, P<0.05).CONCLUSION: The result of the study was in support of the current view that the apoptotic process in chronic hepatitis patients were largely along the intrinsic pathway (mitochondrial pathway), given that the intrinsic and extrinsic pathways could interlinked (converged) at some point on their progression, also it is impossible at present to exclude the possibility that the two pathways could be chosen by hepatocytes in parallel simultaneously.

  2. Peripheral blood lymphocytes DNA in patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Vasiliy I Reshetnyak; Tatyana I Sharafanova; Ludmila U Ilchenko; Elena V Golovanova; Gennadiy G Poroshenko

    2001-01-01

    BACKGROUND Viral replication in blood cells with nucleuses may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions.AIM Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL)DNA in the patients with chronic liver diseases.MATERIALS AND METHODS Sixteen-ninepatients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol + virus G),30 women with primary biliary cirrhosis-PBC)were examined. The condition of DNA structure of PBL-was measured by the fluorescenceanalysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (thepresence of DNA single-stranded breaks and alkalinelabile sights).RESULTS AND CONCLUSION . The quantity of DNA single-stranded breaks and alkalinelabile sightsin DNA in all patients with chronic viral hepatitis .didnt differ from the control group,excluding the patients with chronic hepatitis (CH) C + G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity.This fact may be connected with hypothesisabout the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednison was demonstrated. Probably, the tendency to increase the quantity of DNA singlestranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.

  3. Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease.

    Directory of Open Access Journals (Sweden)

    Jack X Q Pang

    Full Text Available BACKGROUND: Liver stiffness measurement (LSM by transient elastography (TE, FibroScan is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. METHODS: In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation. The performance of LSM to predict complications was determined using the c-statistic. RESULTS: Among 2,052 patients (median age 51 years, 65% with hepatitis B or C, 87 patients (4.2% died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months. Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005. The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005. After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06. The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85. A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%; however, the positive predictive value of higher results was sub-optimal (20%. CONCLUSIONS: Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.

  4. Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure

    OpenAIRE

    Hessel Franz P

    2006-01-01

    Abstract Background Acute-on-chronic liver failure (ACLF) is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods I...

  5. Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Melum, Espen; Friman, Styrbjörn; Bjøro, Kristian;

    2007-01-01

    BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries in a...... 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used. RESULTS: Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61...

  6. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  7. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl4, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  8. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies.

  9. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

  10. Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver

    OpenAIRE

    Shuai Zhang; Tao-Sheng Li; Akihiko Soyama; Takayuki Tanaka; Chen Yan; Yusuke Sakai; Masaaki Hidaka; Ayaka Kinoshita; Koji Natsuda; Mio Fujii; Tota Kugiyama; Zhassulan Baimakhanov; Tamotsu Kuroki; Weili Gu; Susumu Eguchi

    2016-01-01

    Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the ...

  11. Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation

    Directory of Open Access Journals (Sweden)

    Gerhardt T

    2009-05-01

    Full Text Available Abstract Objectives Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT and has impact on survival. Patients receiving calcineurin inhibitors (CNI are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF has been shown to improve renal function. Methods The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR. 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8 or to receive CNI at 25% of the initial dose (group 2; n = 13 each in combination with 1000 mg MMF b.i.d. Results At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031 and GFR improved (8.6 ± 13.1 mL/min/1.73 m2, p = 0.015 in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3% and infections (4.8%. Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP increased by 11 ± 22 mmHg (p = 0.03. Conclusions Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.

  12. Protective mechanisms of garlic and wolfberry derivatives on acute and chronic liver injury animal models

    OpenAIRE

    Xiao, Jia; 肖佳

    2012-01-01

    Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supple...

  13. Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

    Science.gov (United States)

    Li, Peng; Yin, Ya-Ling; Zhu, Mo-Li; Pan, Guo-Pin; Zhao, Fan-Rong; Lu, Jun-Xiu; Liu, Zhan; Wang, Shuang-Xi; Hu, Chang-Ping

    2016-04-01

    Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID:26818681

  14. Liver cirrhosis as a result of chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    A. A. Sukhoruk

    2014-01-01

    Full Text Available The incidence of chronic hepatitis C in St. Petersburg is 124.4 per 100 000 population. The number of patients with liver cirrhosis is significant.Aim of this study: to examine the demographic, clinical and epidemiological characteristics of patients with cirrhosis in the results of chronic hepatitis C.Materials and methods: 100 patients with cirrhosis due to chronic hepatitis C in age 31–70 years were included. Patients with infection hepatitis viruses A and B, HIV, alcohol abuse, drug addicts, previously received antiviral therapy were excluded. Liver cirrhosis was diagnosed on the basis clinical, laboratory and instrumental investigations.Results: most patients (86,2% male and 81,7% female are socially adapted. In 23,2% of patients antibodies to hepatitis C virus were first detected simultaneously with the diagnosis of cirrhosis. Medical procedures were the most common route of infection (25,6% male and 57,1% female. Genotype 1 was dominant (65.7%. Viral load over 800 000 IU/ml was detected in 36,7% of patients. ALT activity was normal or not more than 2 upper limit of normal in 59% of patients, AST – 47%. Normal levels of total bilirubin were recorded in 37% of cases.Conclusions: the first detection of antibodies to hepatitis C virus at the stage of cirrhosis, absence of jaundice, normal or low cytolytic activity once again confirms the need for screening for markers of hepatitis C virus. Dominance of genotype 1 is probably due on the one hand with features routes of transmission, and the other – with the speed of transformation chronic hepatitis to cirrhosis.

  15. Acute and chronic tramadol administration impair spatial memory in rat

    Science.gov (United States)

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  16. Why,who and how should perform liver biopsy in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Ioan Sporea; Alina Popescu; Roxana Sirli

    2008-01-01

    Chronic viral hepatitis is a common disease in the general population.During chronic hepatitis,the prognosis and clinical management are highly dependent on the extent of liver fibrosis.The fibrosis evaluation can be performed by FibroTest (using serological markers),by Elastography or FibroScan (a noninvasive percutaneous technique using the elastic properties of the hepatic tissue) and by liver biopsy (LB),considered to be the "gold standard".Currently,there are three techniques for performing LB: percutaneous,transjugular and laparoscopic.The percutaneous LB can be performed blind,ultrasound (US) guided or US assisted.There are two main categories of specialists who perform LB: gastroenterologists (hepatologists) and radiologists,and the specialty of the individual who performs the LB determines if the LB is performed under ultrasound guidance or not.There are two types of biopsy needles used for LB: cutting needles (Tru-Cut,Vim-Silverman) and suction needles (Menghini,Klatzkin,Jamshidi).The rate of major complications after percutaneous LB ranges from 0.09% to 2.3%,but the echoguided percutaneous liver biopsy is a safe method for the diagnosis of chronic diffuse hepatitis (costeffective as compared to blind biopsy) and the rate of complications seems to be related to the experience of the physician and the type of the needle used (Menghini type needle seems to be safer).Maybe,in a few years we will use non-invasive markers of fibrosis,but at this time,most authorities in the field consider that the LB is useful and necessary for the evaluation of chronic hepatopathies,despite the fact that it is not a perfect test.

  17. Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Anna Del Prete

    2012-01-01

    Full Text Available Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology. The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.

  18. Non-invasive assessment of liver fibrosis in chronic liver diseases: Implementation in clinical practice and decisional algorithms

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani

    2009-01-01

    Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications, including decompensation, bleeding and liver cancer. Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease. Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis, while cirrhosis requires a specific follow-up including screening for esophageal varices and hepatocellular carcinoma. Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive, costly and prone to sampling errors. Recently, blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis. However, there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available. This is due to an unsatisfactory accuracy for some of them, and to an incomplete validation for others. Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they re combined. Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement noninvasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

  19. Proteomic analysis of liver in rats chronically exposed to fluoride.

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

    Full Text Available Fluoride (F is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group. At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS. Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  20. EFFECT OF METHIONINE ENKEPHALIN ON MIGRATION OF MACROPHAGES FROM MICE WITH IMPAIRED LIVER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To observe the effects of methionine enkephalin (M-Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl4 and macrophage migration inhibitory factor (MMIF) was produced by Con A-stimulated spleen lympho- cytes. Inhibition of macrophage migration was measured in reaction system by adding M-Enk. Results Migration of macrophages in both liver-impaired and control group were suppressed by MMIF, but the suppression might be re- versed by adding 1 μmol/L M-Enk (P<0. 05). M-Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes (P<0. 01). Macrophages from liver-imparied group showed a higher sensitivity compared to the control group (P<0. 05). Conclusion The study suggests that opi- oid peptieds play an important role in the modulation of the immune response under stress as liver impairment.

  1. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    International Nuclear Information System (INIS)

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation

  2. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

    2013-07-19

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

  3. Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in intensive care unit patients with alcoholic cirrhosis.

    Directory of Open Access Journals (Sweden)

    Roland Amathieu

    Full Text Available INTRODUCTION: Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance ((1H-NMR spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. PATIENTS: Ninety-three patients with compensated or decompensated cirrhosis (CLF group but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group, were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at -80°C until (1H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. RESULTS: The predictability of the model was 0.73 (Q(2 Y and the explained variance was 0.63 (R(2 Y. The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. CONCLUSION: A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with (1H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function.

  4. Extracorporeal support for patients with acute and acute on chronic liver failure.

    Science.gov (United States)

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-01-01

    The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds.

  5. Is there a rationale for treatment of chronic liver disease with antithrombotic therapy?

    NARCIS (Netherlands)

    Hugenholtz, Greg C. G.; Northup, Patrick G.; Porte, Robert J.; Lisman, Ton

    2015-01-01

    Recent advances in the understanding of the coagulopathy in chronic liver disease have provided a strong support for anticoagulation as a new therapeutic paradigm for patients with cirrhosis. Laboratory studies indicate that the net effect of changes in hemostasis in many patients with chronic liver

  6. Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

    Science.gov (United States)

    Zhang, Shuai; Li, Tao-Sheng; Soyama, Akihiko; Tanaka, Takayuki; Yan, Chen; Sakai, Yusuke; Hidaka, Masaaki; Kinoshita, Ayaka; Natsuda, Koji; Fujii, Mio; Kugiyama, Tota; Baimakhanov, Zhassulan; Kuroki, Tamotsu; Gu, Weili; Eguchi, Susumu

    2016-01-01

    Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the PH and sham groups 14 days after operation. However, compared with those in the sham group, the livers in mice in the PH+BDL group had a smaller size, a lower cell proliferative activity, and more fibrotic tissue 14 days after the operation, suggesting the insufficient regeneration of the cholestatic liver. Pathway-focused array analysis showed that many genes were up- or down-regulated over 1.5-fold in both PH+BDL and PH groups at 1, 3, 7, and 14 days after treatment. Interestingly, more genes that were functionally related to the extracellular matrix and inflammatory chemokines were found in the PH+BDL group than in the PH group at 7 and 14 days after treatment. Our data suggest that up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

  7. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

    Science.gov (United States)

    Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

    2014-04-01

    Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

  8. Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Bin Liu

    2013-01-01

    Full Text Available Despite advances in immunosuppressive drugs, long-term success of liver transplantation is still limited by the development of chronic liver allograft dysfunction. Although the exact pathogenesis of chronic liver allograft dysfunction remains to be established, there is strong evidence that chemokines are involved in organ damage induced by inflammatory and immune responses after liver surgery. Chemokines are a group of low-molecular-weight molecules whose function includes angiogenesis, haematopoiesis, mitogenesis, organ fibrogenesis, tumour growth and metastasis, and participating in the development of the immune system and in inflammatory and immune responses. The purpose of this review is to collect all the research that has been done so far concerning chemokines and the pathogenesis of chronic liver allograft dysfunction and helpfully, to pave the way for designing therapeutic strategies and pharmaceutical agents to ameliorate chronic allograft dysfunction after liver transplantation.

  9. Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment

    NARCIS (Netherlands)

    Smolders, Elise J; de Kanter, Clara T M M; van Hoek, Bart; Arends, Joop E; Drenth, Joost P H; Burger, David M

    2016-01-01

    Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects d

  10. A Diagnostic Significance of Early Renal Impairment with Liver Cirrhosis through the Determination of Urinary Enzymes

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    @@ It is quite common for liver cirrhosis to be followed subsequently by kidney impairment,which,being recessive in state and showing no clinical symptoms,is trouble some in diagnosis.With the development of disease course,the injury gets worse,so an early diagnosis is necessary.

  11. Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

    DEFF Research Database (Denmark)

    Almdal, T; Schroeder, T; Ranek, L

    1989-01-01

    The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range...... any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease....

  12. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tudorache E

    2015-09-01

    Full Text Available Emanuela Tudorache,1 Cristian Oancea,1 Claudiu Avram,2 Ovidiu Fira-Mladinescu,1 Lucian Petrescu,3 Bogdan Timar4 1Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, 2Physical Education and Sport Faculty, West University of Timisoara, 3Department of Cardiology, University of Medicine and Pharmacy “Victor Babes”, 4Department of Biostatistics and Medical Informatics, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Background/purpose: Chronic obstructive pulmonary disease (COPD, especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD] phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.Methods: We enrolled 41 patients with COPD (22 stable and 19 in AECOPD and 20 healthy subjects (control group, having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I questionnaire, Berg Balance Scale (BBS, Timed Up and Go (TUG test, Single Leg Stance (SLS, 6-minute walking distance (6MWD, isometric knee extension (IKE between these groups, and also the correlation between these scores and inflammatory biomarkers.Results: The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001, 6MWD (P<0.001, SLS (P<0.001, and BBS (P<0.001, at the same time noting a significant increase in median TUG score across the studied groups (P<0.001. The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP levels (10.60 vs 4.01; P=0.003 and decrease in PaO2 (70.1 vs 59.1; P<0.001. We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes

  13. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    Science.gov (United States)

    Tudorache, Emanuela; Oancea, Cristian; Avram, Claudiu; Fira-Mladinescu, Ovidiu; Petrescu, Lucian; Timar, Bogdan

    2015-01-01

    Background/purpose Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation. Methods We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers. Results The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001). The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001). We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes. In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test. Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire. Conclusion According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity

  14. Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Nematizadeh Fariborz

    2004-11-01

    Full Text Available Abstract Background Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM and impaired glucose tolerance (IGT in Iranian patients with chronic liver disease (CLD, and explore the factors associated with DM in these patients. Methods One hundred and eighty-five patients with CLD were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to the latest American Diabetes Association criteria. Results The subjects included 42 inactive HBV carriers with a mean age of 42.2 ± 12.0 years, 102 patients with HBV or HCV chronic hepatitis with a mean age of 41.2 ± 10.9 years, and 41 cirrhotic patients with a mean age of 52.1 ± 11.4 years. DM and IGT were diagnosed in 40 (21.6% and 21 (11.4% patients, respectively. Univariate analysis showed that age (P = 0.000, CLD status (P = 0.000, history of hypertension (P = 0.007, family history of DM (P = 0.000, and body mass index (BMI (P = 0.009 were associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8–12.2, family history of DM (OR = 6.6, 95%CI: 2.6–17.6, chronic hepatitis (OR = 11.6, 95%CI: 2.9–45.4, and cirrhosis (OR = 6.5, 95%CI: 2.4–17.4 remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhotic patients (OR = 9.6, 95%CI: 1.0–88.4 and older age (OR = 7.2, 95%CI: 1.0–49.1, higher fibrosis score (OR = 59.5, 95%CI: 2.9–1211.3/ OR = 11.9, 95%CI: 1.0–132.2, and higher BMI (OR = 30.3, 95%CI: 3.0–306.7 in patients with chronic hepatitis were found to be associated with higher prevalence of DM. Conclusions Our findings indicate that patients with cirrhosis and chronic hepatitis are at the increased risk of DM occurrence. Older age, severe liver disease, and obesity were associated

  15. ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Juliana Ayres de Alencar Arrais GUERRA

    2015-09-01

    Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

  16. Colchicine reduces procollagen Ⅲ and increases pseudocholinesterase in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Sergio; Muntoni; Marcos; Rojkind; Sandro; Muntoni

    2010-01-01

    AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patient...

  17. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    OpenAIRE

    Ignacio Negrón-Oyarzo; Francisco Aboitiz; Pablo Fuentealba

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral response...

  18. Impact of hepatic function on serum procalcitonin for the diagnosis of bacterial infections in patients with chronic liver disease: A retrospective analysis of 324 cases.

    Science.gov (United States)

    Qu, Junyan; Feng, Ping; Luo, Yan; Lü, Xiaoju

    2016-07-01

    Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, it is unclear whether its accuracy in predicting bacterial infections is affected by impaired liver function. This study aimed to assess the impact of compromised liver function on the diagnostic value of PCT.This retrospective study was conducted between January 2013 and May 2015. A total of 324 patients with chronic liver disease were enrolled. Routine laboratory measurements and PCT were performed. Patients were divided into 3 groups according to clinical diagnosis: chronic hepatitis (group 1), decompensated cirrhosis (group 2), and acute-on-chronic liver failure/chronic liver failure (group 3). The correlation between PCT and liver function was analyzed. The area under the receiver operating characteristic (AUCROC) curve of PCT was analyzed according to infection status and liver function.PCT was more accurate than white blood cell count (P PCT had a moderate positive correlation with serum total bilirubin (TBIL) (r = 0.592), and a weak correlation with model for end-stage liver disease score (r = 0.483) and international normalized ratio (r = 0.389). The AUCROC and optimum thresholds of PCT and for predicting bacterial infections at different levels of TBIL were 0.907 (95% CI 0.828-0.958) and 0.38 ng/mL, respectively, for TBIL PCT was a valuable marker of bacterial infection in patients with chronic liver diseases. TBIL affected PCT threshold, so different cut-offs should be used according to different TBIL values. PMID:27472699

  19. The Role of Iron and Iron Overload in Chronic Liver Disease

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  20. The Role of Iron and Iron Overload in Chronic Liver Disease.

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  1. [The role of immune complexes in chronic liver diseases and their dynamics during treatment].

    Science.gov (United States)

    Iakhontova, O I; Dudanova, O P

    1992-01-01

    Chronic liver diseases are marked by a well-defined relationship between the intensity of the cytolytic syndrome and the level of circulating immune complexes (CIC). The highest damaging action on hepatocytes is produced by medium-sized CIC because of their penetrating and complement fixing effects. The level of thrombocytopenia and, to a less measure, of leukopenia also depends on the concentration and size of CIC in CAH and liver cirrhosis (LC), which may provide indirect evidence of the lytic action of CIC on hepatocytes, leading in turn to the impairment of microcirculation and aggravation of hepatocyte hypoxia. The data obtained attest to the role CIC of varying size play in the pathogenesis of CAH and LC. The changes in the properties of immune complexes induced by the derangement of cellular membranes also influence the course of immune responses, favouring an increase of antibody formation. As a result of an appreciable suppression of antibody and medium-sized CIC formation enhancing the cytolytic syndrome, the preference during glucocorticoid treatment should be given to the use of the medium doses of prednisolone which ensure less intensity and less duration of cytolysis as compared to the application of large drug doses. PMID:1509358

  2. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  3. Osseous and Nonosseous Bone Scan Findings in Liver Transplant Candidates with end-stage Chronic Liver Disease

    OpenAIRE

    Seval Erhamamcı; Ayşe Aktaş; Tatiana Bahçeci; Kevser Kavak

    2013-01-01

    Objective: End-stage chronic liver disease (CLD) adversely affects the function of multiple organ systems including the skeletal system. The aim of this study was to assess osseous and nonosseous bone scintigraphy (BS) findings in liver transplant (LT) candidates with end-stage CLD. Methods: We retrospectively evaluated BS findings in 50 consecutive patients with end-stage CLD who were undergoing preoperative assessment for LT from January 2006 to December 2011. All the patients were analyzed...

  4. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers

    OpenAIRE

    Lai, G.Y.; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; R. Sinha; Freedman, N D

    2013-01-01

    Background: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease...

  5. STUDY OF SERUM URIC ACID IN CHRONIC LIVER DISEASE AND ITS RELATION WITH OTHER PARAMETERS

    Directory of Open Access Journals (Sweden)

    Rudrajit Paul

    2013-07-01

    Full Text Available In chronic liver disease, high uric acid levels are independently associated with severe disease and poor prognosis. However, studies regarding the relation of uric acid levels with different parameters of liver dysfunction are rare from India. Our aim was to study uric acid (UA levels in chronic liver disease and find any association of UA with different blood parameters and prognosis. We selected patients of chronic liver disease of any etiology. We did the serum UA test along with full liver function tests. Child Turcot Pugh (CTP score was calculated for each patient. Then by suitable statistical tests, any association or correlation was studied. We had total of 52 patients with 31 % female. 19 (36.5 % of the cases had liver disease secondary to alcoholism followed by 15 cases of non alcoholic fatty liver disease. 69.2 % of the patients were in CTP class B or C. Serum UA levels were significantly higher in chronic viral hepatitis cases (p<0.001. UA levels showed significant correlation with serum bilirubin (r=0.567, SGOT (r=0.464 and mortality. The UA levels showed significant correlation with severe disease and mortality. However, whether UA can be included in risk stratification of chronic liver disease can only be determined by larger randomized trials.

  6. Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

    Science.gov (United States)

    Keeffe, Emmet B

    2006-01-01

    A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

  7. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas.

    Science.gov (United States)

    Paradis, V; Youssef, N; Dargère, D; Bâ, N; Bonvoust, F; Deschatrette, J; Bedossa, P

    2001-03-01

    There is growing evidence that senescent cells accumulate in vivo and are associated with the aging process in parallel with the progressive erosion of telomeres. Because recent data show that telomere shortening is involved in the pathogenesis of liver cirrhosis, we looked for replicative senescence cells in normal livers, chronic hepatitis C, and hepatocellular carcinoma (HCC). Replicative senescent cells were detected on liver tissue cryosections using expression of a specific marker, senescence-associated beta-galactosidase, a cytoplasmic enzyme detected at pH 6. A total of 57 frozen liver samples (15 normal liver, 32 chronic hepatitis C, and 10 HCCs) were studied. Replicative senescence was graded as absent in 56% of cases (32 of 57) and present in 44% (25 of 57). Replicative senescence was considered present in 3 of 15 normal livers (20%), 16 of 32 chronic hepatitis cases (50%), and 6 of 10 HCCs (60%). In the group of nontumoral livers, the presence of senescent cells in liver was associated with older age (P =.03). In the group with chronic hepatitis C, fibrosis stage, but not activity grade, was significantly correlated with the accumulation of replicative senescent cells (P HCC in the surrounding liver (P HCC development. Detection of replicative senescent cells may then serve as a predictive marker of a hepatocellular carcinoma in the surrounding tissue. HUM PATHOL 32:327-332. PMID:11274643

  8. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  9. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

    Institute of Scientific and Technical Information of China (English)

    Ioan; Sporea; Roxana; Sirli; Alexandra; Deleanu; Adriana; Tudora; Alina; Popescu; Manuela; Curescu; Simona; Bota

    2010-01-01

    AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...

  10. Recent trends in chronic disease, impairment and disability among older adults in the United States

    OpenAIRE

    Ross Joseph S; Hung William W; Boockvar Kenneth S; Siu Albert L

    2011-01-01

    Abstract Background To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults. Methods We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthr...

  11. Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case–control study

    OpenAIRE

    Wang, J-B; Abnet, C. C.; Chen, W.; Dawsey, S M; Fan, J-H; Yin, L-Y; Yin, J.; Major, J M; Taylor, P R; Qiao, Y-L; Freedman, N D

    2013-01-01

    Background: Although vitamin D deficiency has been noted in cross-sectional studies of chronic liver disease and laboratory studies suggest possible benefits of vitamin D in preventing liver cancer, little epidemiologic data are available. Methods: We performed a nested case–control study in the Linxian Nutrition Intervention Trials on participants developing incident liver cancer or dying from chronic liver disease over 22 years of follow-up. Baseline serum 25(OH) vitamin D was measured for ...

  12. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  13. Insulin-like growth factor 1 and growth hormone in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Becker, Povl Ulrik

    1992-01-01

    Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease...

  14. Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

    NARCIS (Netherlands)

    P. Tapia (Pablo); D. Soto (Dagoberto); A. Bruhn (Alejandro); L. Alegría (Leyla); N. Jarufe (Nicolás); C. Luengo (Cecilia); E. Kattan (Eduardo); T. Regueira (Tomas); A. Meissner (Arturo); R. Menchaca (Rodrigo); M.I. Vives (María Ignacia); N. Echeverría (Nicolas); G.A. Ospina-Tascon (Gustavo A); J. Bakker (Jan); G. Hernandez (Glenn)

    2015-01-01

    textabstractIntroduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver

  15. Hepatic encephalopathy as a complication of liver disease

    Institute of Scientific and Technical Information of China (English)

    Stephan vom Dahl; Gerald Kircheis; Dieter Haussinger

    2001-01-01

    @@INTRODUCTION Hepatic encephalopathy ( HE) is a frequent complication of chronic liver disease .It is defined as a characteristic functional and reversible alteration of the mental state ,due to impaired liver function and / or increased portosystemic shunting .

  16. Impaired vascular reactivity in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Tetzner, Fabian; Scholze, Alexandra; Wittstock, Antje;

    2008-01-01

    Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics.......Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics....

  17. Screening for significant chronic liver disease by using three simple ultrasound parameters

    Energy Technology Data Exchange (ETDEWEB)

    Lignon, Grégoire [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Boursier, Jérome [Department of Hepatology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Laboratory HIFIH, UPRES 3859, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Delumeau, Stéphanie [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Michalak-Provost, Sophie [Department of Pathology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Lebigot, Jérome [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Oberti, Frederic [Department of Hepatology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Laboratory HIFIH, UPRES 3859, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); and others

    2015-08-15

    Highlights: • Three US parameters have diagnosis accuracy for the diagnosis of severe fibrosis equal to 66%. • These three signs detect unidentified fibrosis with a predictive positive value of 32%. • It would be an easy way to detect patients with silent chronic liver diseases. - Abstract: Objectives: Chronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease. Methods: Three hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected. Results: In the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110 mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F ≥ 1), 5 had significant fibrosis (F ≥2) and two cirrhosis. Conclusion: The generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease.

  18. Screening for significant chronic liver disease by using three simple ultrasound parameters

    International Nuclear Information System (INIS)

    Highlights: • Three US parameters have diagnosis accuracy for the diagnosis of severe fibrosis equal to 66%. • These three signs detect unidentified fibrosis with a predictive positive value of 32%. • It would be an easy way to detect patients with silent chronic liver diseases. - Abstract: Objectives: Chronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease. Methods: Three hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected. Results: In the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110 mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F ≥ 1), 5 had significant fibrosis (F ≥2) and two cirrhosis. Conclusion: The generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease

  19. Molecular changes associated with chronic liver damage and neoplastic lesions in a murine model of hereditary tyrosinemia type 1.

    Science.gov (United States)

    Angileri, Francesca; Roy, Vincent; Morrow, Geneviève; Scoazec, Jean Yves; Gadot, Nicolas; Orejuela, Diana; Tanguay, Robert M

    2015-12-01

    Hereditary tyrosinemia type 1 (HT1) is the most severe inherited metabolic disease of the tyrosine catabolic pathway, with a progressive hepatic and renal injury and a fatal outcome if untreated. Toxic metabolites accumulating in HT1 have been shown to elicit endoplasmic reticulum (ER) stress response, and to induce chromosomal instability, cell cycle arrest and apoptosis perturbation. Although many studies have concentrated on elucidating these events, the molecular pathways responsible for development of hepatocellular carcinoma (HCC) still remain unclear. In this study the fah knockout murine model (fah(-/-)) was used to investigate the cellular signaling implicated in the pathogenesis of HT1. Fah(-/-) mice were subjected to drug therapy discontinuation (Nitisinone withdrawal), and livers were analyzed at different stages of the disease. Monitoring of mice revealed an increasing degeneration of the overall physiological conditions following drug withdrawal. Histological analysis unveiled diffuse hepatocellular damage, steatosis, oval-like cells proliferation and development of liver cell adenomas. Immunoblotting results revealed a progressive and chronic activation of stress pathways related to cell survival and proliferation, including several stress regulators such as Nrf2, eIF2α, CHOP, HO-1, and some members of the MAPK signaling cascade. Impairment of stress defensive mechanisms was also shown by microarray analysis in fah(-/-) mice following prolonged therapy interruption. These results suggest that a sustained activation of stress pathways in the chronic HT1 progression might play a central role in exacerbating liver degeneration. PMID:26360553

  20. Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

    OpenAIRE

    Kiat-Hon Lim; Jason Pik-Eu Chang; Chee-Kiat Tan; Lynette Lin-Ean Oon; Boon-Huan Tan; Hoe-Nam Leong; Hui-Hui Tan

    2011-01-01

    Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.

  1. Safety and pharmacology of paclitaxel in patients with impaired liver function : a population pharmacokinetic-pharmacodynamic study

    NARCIS (Netherlands)

    Joerger, M.; Huitema, A. D. R.; Huizing, M. T.; Willemse, P. H. B.; Rosing, H.; Schellens, J. H. M.; Beijnen, J. H.; Vermorken, J. B.

    2007-01-01

    Aims To assess quantitatively the safety and pharmacology of paclitaxel in patients with moderate to severe hepatic impairment. Methods Solid tumour patients were enrolled into five liver function cohorts as defined by liver transaminase and total bilirubin concentrations. Paclitaxel was administere

  2. Steatosis as a co-factor in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcello; Persico; Achille; Iolascon

    2010-01-01

    The finding of lipid accumulation in the liver, so-called hepatic steatosis or non-alcoholic fatty liver disease, is a common condition frequently found in healthy subjects. Its prevalence, in fact, has been estimated by magnetic resonance studies to be about 35% in the general population and 75% in obese persons. Nevertheless, its presence generates liver damage only in a small percentage of subjects not affected by other liver diseases. It should be defined as a "co-factor" capable of affecting severity a...

  3. Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver.

    Science.gov (United States)

    Fragou, Domniki; Zanos, Panos; Kouidou, Sofia; Njau, Samuel; Kitchen, Ian; Bailey, Alexis; Kovatsi, Leda

    2013-04-26

    Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment. PMID:23454526

  4. Relationship between clinical and pathologic findings in patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Lun-Gen Lu; Jun Ye; Xiong Cai; Cheng-Wei Chen; Ji-Yao Wang; Shan-Ming Wu; Jin-Shui Zhu; Xia-Qiu Zhou; Min-De Zeng; Yi-Min Mao; Ji-Qiang Li; De-Kai Qiu; Jing-Yuan Fang; Ai-Ping Cao; Mo-Bin Wan; Cheng-Zhong Li

    2003-01-01

    AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues.METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues.RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P<0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST),N-terminal procollagen Ⅲ (PⅢ NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time,GGT, apoprotein A1) index, PGAA (PGA+△2-macroglobublin)index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis.CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.

  5. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease.

    Science.gov (United States)

    Peres, W A F; Chaves, G V; Gonçalves, J C S; Ramalho, A; Coelho, H S M

    2011-12-01

    Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCV-related liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values ≤ 0·78 μmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study. PMID:21736776

  6. Platelet Dysfunction: Status of Thrombopoietin in Thrombocytopenia Associated with Chronic Liver Failure.

    Science.gov (United States)

    Giannini, Edoardo G; Peck-Radosavljevic, Markus

    2015-07-01

    Thrombocytopenia is a common hematological abnormality in patients with chronic liver disease, and its prevalence is higher in patients with liver failure. Although the presence of thrombocytopenia has historically been associated with portal hypertension, the characterization of thrombopoietin has improved our understanding of the determinants of platelet count in patients with liver disease. In particular, the association between thrombopoietin levels and residual liver function helped disclose the multifaceted pathophysiology of thrombocytopenia in patients with chronic liver failure. In this regard, important results were provided by studies performed in patients with chronic viral hepatitis that assessed the complex interplay between thrombocytopenia induced by the myelosuppressive effect of interferon-based treatment and thrombopoietin pathophysiology. These studies showed that successful antiviral therapy is accompanied by improved hepatic thrombopoietin production. Moreover, studies that evaluated thrombopoietin and platelet count dynamics before and after liver transplantation were instrumental in describing how restoration of liver function determines a normalization of the thrombopoietin-platelet count feedback that is deranged in patients with end-stage liver disease. PMID:26049067

  7. Interactions between Myc and Mediators of Inflammation in Chronic Liver Diseases

    OpenAIRE

    Ting Liu; Yu Zhou; Kwang Suk Ko; Heping Yang

    2015-01-01

    Most chronic liver diseases (CLDs) are characterized by inflammatory processes with aberrant expressions of various pro- and anti-inflammatory mediators in the liver. These mediators are the driving force of many inflammatory liver disorders, which often result in fibrosis, cirrhosis, and liver tumorigenesis. c-Myc is involved in many cellular events such as cell growth, proliferation, and differentiation. c-Myc upregulates IL-8, IL-10, TNF-α, and TGF-β, while IL-1, IL-2, IL-4, TNF-α, and TGF...

  8. Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Ming-Qing Xu; Lu-Nan Yan; Xiao-Bo Chen; Jiao Liu

    2012-01-01

    AIM:To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats.METHODS:Allogeneic liver transplantation from DA rats to Lewis rats was performed.Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5.Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer administered intravenously every 10 d starting from POD 10.The recipient rats were injected with physiological saline,rAdEasy-A20 (1 x 109 pfu/30 g weight) or rAdEasy (1 x 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10.Liver tissue samples were harvested on POD 30 and POD 60.RESULTS:Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis.A20 overexpression ameliorated the effects on liver function,attenuated liver allograft fibrosis and prolonged the survival of the recipient rats.Treatment with A20 suppressed hepatic protein production of tumor growth factor (TGF)-β1,interleukin1β,caspase-8,CD40,CD40L,intercellular adhesion molecule-1,vascular cell adhesion molecule-1 and E-selectin.A20 treatment suppressed liver cell apoptosis and inhibited nuclear factor-κB activation of Kupffer cells (KCs),liver sinusoidal endothelial cells (LSECs)and hepatic stellate cells (HSCs),and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs.CONCLUSION:A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs,LSECs and HSCs.

  9. Impaired homocysteine metabolism in patients with alcoholic liver disease in Taiwan.

    Science.gov (United States)

    Chien, Yi-Wen; Chen, Ya-Ling; Peng, Hsiang-Chi; Hu, Jui-Ting; Yang, Sien-Sing; Yang, Suh-Ching

    2016-08-01

    Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan. To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection. Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh Class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh Class A. These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury. PMID:27565754

  10. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection.

    Science.gov (United States)

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-08-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  11. Interleukins in chronic liver disease: lessons learned from experimental mouse models

    Directory of Open Access Journals (Sweden)

    Hammerich L

    2014-09-01

    Full Text Available Linda Hammerich, Frank Tacke Department of Medicine III, University Hospital Aachen, Aachen, Germany Abstract: Interleukins represent a class of immunomodulatory cytokines, small intercellular signaling proteins, that are critically involved in the regulation of immune responses. They are produced in large amounts by various cell types during inflammatory reactions, and the balance of cytokines determines the outcome of an immune response. Therefore, cytokines are regarded as interesting therapeutic targets for the treatment of patients with liver diseases. Mouse models provide a good tool for in vivo studies on cytokine function, as human and mouse cytokines share many homologies. Sophisticated mouse models either mimicking distinct pathological conditions or targeting cytokines and cytokine-signaling pathways in the liver or even in distinct cellular compartments have provided enormous insight into the different functions of interleukins during hepatic inflammation. Interleukins may have pro- as well as anti-inflammatory functions in chronic liver diseases, some interleukins even both, dependent on the inflammatory stimulus, the producing and the responding cell type. IL-17, for example, promotes hepatic fibrogenesis through activation of hepatic stellate cells and facilitates development of liver cancer through recruitment of myeloid-derived suppressor cells. IL-22, on the other hand, protects from development of fibrosis or steatohepatitis. IL-12 balances T-helper (Th-1 and Th2 cell responses in infectious disease models. IL-13 and IL-33, two cytokines related to Th2 cells and innate lymphoid cells, promote fibrotic responses in the liver. IL-10 is the prototypic anti-inflammatory interleukin with tissue-protective functions during chronic liver injury and fibrogenesis. Despite its critical role for inducing the acute-phase response in the liver, IL-6 signaling is protective during fibrosis progression, but promotes hepatocellular carcinoma

  12. Gender difference in motor impairments induced by chronic administration of vinblastine

    OpenAIRE

    Shahrnaz Parsania; Mohammad Shabani; Kasra Moazzami; Moazamehosadat Razavinasab; Mohammad Hassan Larizadeh; Masoud Nazeri; Majid Asadi-Shekaari; Moein Kermani

    2014-01-01

    Objective(s): Neurotoxicity of anticancer drugs complicates treatment of cancer patients. Vinblastine (VBL) is reported to induce motor and cognitive impairments in patients receiving chronic low-dose regimen. Materials and Methods: The effects of VBL treatment on motor, learning and memory functions of male and female Wistar rats were studied by behavioral related tests. Animals were given chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks) from postnatal day 23 to 52. Mot...

  13. Effect of Compound Glycyrrhizin Injection on Liver Function and Cellular Immunity of Children with Infectious Mononucleosis Complicated Liver Impairment

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. Methods: Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group.All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Results: Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 +/CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01 ). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). Conclusion: Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

  14. Spontaneous rupture of the liver in a patient with chronic hepatitis B and D

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Spontaneous rupture of the liver is a rare condition with serious consequences, if not recognized and treated in time. It has been reported as a complication of several disorders, including benign or malignant liver tumors,connective tissue disease, infiltrating liver disease,preeclampsia, and post anticoagulant therapy. We report a case of spontaneous rupture of liver in a noncirrhotic, chronic hepatitis B and D patient presenting with acute hemoperitoneum and shock. The subcapsular hematoma and rupture of liver were documented by image studies. The patients' condition gradually stabilized after fluid resuscitation. The reported case and literature review suggest that spontaneous rupture of liver must be considered in a differential diagnosis of acute hemoperitoneum. A high index of suspicion and early diagnosis with imaging are critically important.

  15. The role of lifestyle changes in the management of chronic liver disease

    Directory of Open Access Journals (Sweden)

    Feldstein Ariel E

    2011-06-01

    Full Text Available Abstract The prevalence of obesity worldwide has dramatically increased during the last three decades. With obesity comes a variety of adverse health outcomes which are grouped under the umbrella of metabolic syndrome. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several liver conditions which are directly affected by overweight and obese status, including non-alcoholic fatty liver disease, chronic infection with hepatitis C virus and post-liver transplant status. The deleterious effects of obesity on liver disease and overall health can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting non-pharmacological, lifestyle interventions that lead to weight reduction, improved physical activity and better nutrition as part of the management and treatment of these liver conditions.

  16. [The effect of chronic internal irradiation from incorporated radionuclides on liver function].

    Science.gov (United States)

    Dedenko, I K; Zakharash, M P; Ganich, O N; Siksaĭ, L T; Shnitser, R I; Sofienko, G I; Bytsaĭ, N N; Zemskov, V S; Trunov, V I; Bukanov, V N

    1990-01-01

    On chronic supply to the body of a mixture of nuclear division products lanthanum-140, barium-140, tellurium-132, neodymium-147, neptunium-239, zirconium-95, niobium-95, iodine-131, cerium-141, -144, cesium-134, -137, and ruthenium-103 are detectable in liver tissue within the first months. In the 2 to 4 years following the disaster, liver tissue primarily accumulates cerium-144, radium-226, thorium-228, -232, ruthenium-106, antimony-125, and europium-154. Within the first periods the liver radionuclide content was 19 to 31% higher than that in the blood, and in the following years it was 24 to 38% higher. The radionuclides indicated were actively excreted with the bile into the gastrointestinal lumen. Within the first months after the chronic internal radiation the functional liver disorders were detectable in 30 to 40% of the patients. Later on diverse acute and chronic diseases of the liver, gallbladder and pancreas were detectable in 20 to 30% of the patients. The radionuclide content in the body was found to be in parallel with functional liver disorders. Acceleration of radionuclide excretion from the body results in liver function improvement.

  17. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  18. Impairment induced by chronic occupational cadmium exposure during brazing process

    International Nuclear Information System (INIS)

    Cadmium (CD) is considered a metal of the 20th century to which all inhabitants of develop societies are exposed. Long-term occupational and environmental exposure to CD often results in renal dysfunction as the kidney is considered the critical target organ. The aim of this work was to evalutate both resporatory and renal manifestations induced by occupational exposure to CD compounds during brazing process, and suggesting a protocol for prevention and control for CD- induced health effects. This study was conducted on 20 males occupationally exposed workers. They are divided into two groups: Group-1 included (10) exposed smokers and group-2 included (10) exposed non-smokers. Results of both groups were compared with those of 10 healthy age and sex matched non-smokers. All subjects were subjected to detailed history taking and laboratory investigations including blood and urinary CD, liver profile (SGOT, SGPT and alkline phosphates), kindey function tests (blood urea, creatinine and urinary beta2- microglobulin). The level of Cd in the atmosphere of the work plase air was also assessed to detect the degree of exposure as it was about 6 times greater than thesave level (1 mu /m3).(1) This study demonstrated elevation levels of blood CD, urea, creatinine and urinary CD and beta2 -microglobulin for both exposed worker groups than the controls. In additions no appreciable were noted for liver function tests, although the levels fell within normal range

  19. Liver fibrosis is associated with cognitive impairment in HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Nicoletta Ciccarelli

    2014-11-01

    Full Text Available Introduction: The aim of our study was to investigate the potential relationship between liver fibrosis (LF and cognitive performance in HIV+ patients. Materials and Methods: We performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models. Results: A total of 413 patients [77% males, median age 46 (IQR 39–52, 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA 3.25 and 14/129 (3% had liver stiffness >14KPa. Forty-seven patients (11% were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02–4.72; p=0.044 after adjusting for education (OR 0.79, 95% CI 0.71–0.88; p14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42–33574.06; p=0.020 after adjusting for education (OR 0.54, 95% CI 0.31–0.92; p=0.024, age (for 10 years increase (OR 2.03, 95% CI 0.55–7.53; p=0.288, past IDU (OR 4.43, 95% CI 0.35–7.57; p=0.526, HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00–0.18; p=0.003, HIV history (for 1 year increase (OR 0.96, 95% CI 0.83–1.12; p=0.641, CD4 cells count at nadir (OR 1.10, 95% CI 0.56–2.16; p=0.779, and HCV co-infection (OR 0.06; 95% CI 0.00–1.93; p=0.113. Conclusions: In HIV-infected patients higher LF, estimated through non

  20. Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Seung Up Kim

    Full Text Available Liver stiffness measurement (LSM using transient elastography (FibroScan® can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs in chronic hepatitis B (CHB patients showing histologically advanced liver fibrosis.Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB before starting nucleot(side analogues and showed histologically advanced fibrosis (≥F3 with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome and hepatocellular carcinoma (HCC.The mean age of the patient (72 men, 56 women was 52.2 years. During the median follow-up period [median 27.8 (12.6-61.6 months], LREs developed in 19 (14.8% patients (five with hepatic decompensation, 13 with HCC, one with both. Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257-22.812; P = 0.001.LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis.

  1. Chronic bile duct hyperplasia is a chronic graft dysfunction following liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Jian-Wen Jiang; Zhi-Gang Ren; Guang-Ying Cui; Zhao Zhang; Hai-Yang Xie; Lin Zhou

    2012-01-01

    AIM:To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats.METHODS:The whole experiment was divided into three groups:(1) normal group (n =12):normal BN rats without any drug or operation; (2) syngeneic transplant group (SGT of BN-BN,n =12):both donors and recipients were BN rats; and (3) allogeneic transplant group (AGT of LEW-BN,n =12):Donors were Lewis and recipients were BN rats.In the AGT group,all recipients were subcutaneously injected by Cyclosporin A after LT.Survival time was observed for 1 year.All the dying rats were sampled,biliary tract tissues were performed bacterial culture and liver tissues for histological study.Twenty-one day after LT,8rats were selected randomly in each group for sampling.Blood samples from caudal veins were collected for measurements of plasma endotoxin,cytokines and metabonomic analysis,and faeces were analyzed for intestinal microflora.RESULTS:During the surgery of LT,no complications of blood vessels or bile duct happened,and all rats in each group were still alive in the next 2 wk.The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases,5 rats in which died of chronic bile duct hyperplasia.Compared to the SGT and normal groups,survival ratio of rats significantly decreased in the AGT group (P< 0.01).Moreover,liver necrosis,liver infection,and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain.On 21 d after LT,compared with the normal group (25.38 ± 7.09 ng/L)and SGT group (33.12 ± 10.26 ng/L),plasma endotoxin in the AGT group was remarkably increased (142.86± 30.85 ng/L) (both P < 0.01).Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL,323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07pg/mL,114.6 ± 36.67 pg/mL) and SGT groups (321.3± 88.47 pg/mL,205.2 ± 53.06 pg/mL) (P

  2. Correlation between ultrasound imaging and serum markers of liver fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jian-Xia Liu

    2016-01-01

    Objective:To investigate the clinical value of ultrasonic imaging in the assessment of liver fibrosis in patients with chronic hepatitis B. Methods:A total of 20 cases of liver biopsy in chronic hepatitis B, according to the degree of hepatic fibrosis were divided into mild hepatic fibrosis group, moderate fibrosis group, severe fibrosis group, the other selected healthy volunteers as control group, using color Doppler ultrasound, the use of imaging technology and automatic tracking. Strengthen the quantitative analysis, using the second generation microbubble contrast agent SonoVue contrast analysis, contrast agent reach the portal time (PVAT), hepatic artery time (HAAT), hepatic vein (HVVT), the calculation time of hepatic arteriovenous transit time (VAT) and hepatic portal vein transit time (VVT), using chemiluminescence detection of serum liver fiber hyaluronic acid (HA), laminin (LN) and collagen type IV (CIV) index. Results:there was no significant difference in HAAT, PVAT, VAT, VVT and HVAT in all groups, and there was no significant difference, mild, moderate and severe liver fibrosis group, and HA, LN and C levels were significantly higher than those in control group. Conclusion:serum liver fibrosis indexes can guide the degree of liver fibrosis. The ultrasound contrast can reflect the changes of liver blood flow dynamics, and it has a certain guiding significance to the assessment of the degree of liver fibrosis, the monitoring of the disease and the clinical treatment.

  3. A Dynamic Bronchial Airway Gene Expression Signature of Chronic Obstructive Pulmonary Disease and Lung Function Impairment

    NARCIS (Netherlands)

    Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Florido, Roberta; Campbell, Joshua; Liu, Gang; Xiao, Ji; Zhang, Xiaohui; Duclos, Grant; Drizik, Eduard; Si, Huiqing; Perdomo, Catalina; Dumont, Charles; Coxson, Harvey O.; Alekseyev, Yuriy O.; Sin, Don; Pare, Peter; Hogg, James C.; McWilliams, Annette; Hiemstra, Pieter S.; Sterk, Peter J.; Timens, Wim; Chang, Jeffrey T.; Sebastiani, Paola; O'Connor, George T.; Bild, Andrea H.; Postma, Dirkje S.; Lam, Stephen; Spira, Avrum; Lenburg, Marc E.

    2013-01-01

    Rationale Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. Objectives: We sought to determine whether COPD-associated processes are reflected in gene express

  4. Motor control impairment of the contralateral wrist in patients with unilateral chronic wrist pain

    NARCIS (Netherlands)

    Smeulders, MJC; Kreulen, M; Hage, JJ; Ritt, MJPF; Mulder, T

    2002-01-01

    Objective: Assessment of the quality of fine motor control in patients with unilateral chronic wrist pain seldom focuses on the possibility that control of movements is effector independent at the cerebral level. This mechanism may be involved in an impairment of motor function in the unaffected wri

  5. Cumulative life course impairment in other chronic or recurrent dermatologic diseases

    DEFF Research Database (Denmark)

    Ibler, Kristina S; Jemec, Gregor B E

    2013-01-01

    but massive psychosocial impairment in specific communities such as vitiligo, are all suitable for further studies. Life course studies are particularly suitable for skin diseases due to their often chronic recurrent course, low mortality and their psychosocial aspects. The development of a stronger empirical...

  6. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the presen

  7. Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Giuseppe Astarita

    Full Text Available Reduced brain levels of docosahexaenoic acid (C22:6n-3, a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P  =  0.007. Mini Mental State Examination (MMSE scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P =  0.005 and mid-frontal cortex (P  =  0.018, but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's disease patients than control subjects (P  =  0.011. Liver docosahexaenoic/α-linolenic ratios correlated positively with MMSE scores (r  =  0.78; P<0.0001, and negatively with global deterioration scale grades (P  =  0.013. Docosahexaenoic acid precursors, including tetracosahexaenoic acid (C24:6n-3, were elevated in liver of Alzheimer's disease patients (P  =  0.041, whereas expression of peroxisomal d-bifunctional protein, which catalyzes the conversion of tetracosahexaenoic acid into docosahexaenoic acid, was reduced (P  = 0.048. Other genes involved in docosahexaenoic acid metabolism were not affected. The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain.

  8. Detection of HBV, PCNA and GST-π in hepatocellular carcinoma and chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Shen; Hua-Xian Zhang; Zong-Ji Zhang; Jin-Yun Li; Ming-Qin Chen; Wei-Bo Yang; Run Huang

    2003-01-01

    AIM: To investigate the change of HBV DNA, PCNA and GST-π in chronic liver disease and hepatocellular carcinoma (HCC).METHODS: Hepatitis B surface antigen (HBsAg), proliferating cell nuclear antigen (PCNA) and glutathione S-transferases (GST-π) were detected by immunohistochemical staining and HBV DNA was detected by in situ hybridization (ISH) in formalin-fixed and paraffin-embedded sections with a total of 111 specimens of chronic hepatitis, liver cirrhosis,paratumorous tissue, HCC and normal liver tissue.RESULTS: The positive rates of HBsAg and HBVDNA were 62.5 %(15/24) and 75.0 %(12/16) in chronic hepatitis,64.0 %(16/25) and 83.3 %(15/18) in liver cirrhosis, 72.7 %(16/22) and 85.7 %(12/14) in the paratumorous tissu and 45.0 %(14/31) and 64.3 %(9/14) in HCC. The positive HBVDNA granules in chronic hepatitis, liver cirrhosis and the paratumorous tissue were more intense than that in HCC.The positive rates of PCNA and GST-π were 34.8 %(8/23)and 25.0 %(4/16) in chronic hepatitis, 73.7 %(14/19) and 17.6 %(3/17) in liver cirrhosis, 86.7 %(13/15) and 53.3 % (8/15) in the paratumorous tissue, 100 %(15/15) and 60.0 %(9/15) in HCC, respectively, and the positive rate of GST-πin the paratumorous tissue was significantly higher than that in the liver cirrhosis without tumor (P<0.05), but same as that in HCC(P>0.05).CONCLUSION: The HBV infection may increase expression of PCNA and GST-π. The paratumor cirrhosis may be a sequential lesion of precancerous cirrhosis around HCC.

  9. Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis.

    Science.gov (United States)

    Iwasaki, Ayumi; Sakai, Keiko; Moriya, Kei; Sasaki, Takako; Keene, Douglas R; Akhtar, Riaz; Miyazono, Takayoshi; Yasumura, Satoshi; Watanabe, Masatoshi; Morishita, Shin; Sakai, Takao

    2016-01-01

    Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-β activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-β1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-β1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-β bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.

  10. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Karvellas, Constantine J; Subramanian, Ram M

    2016-07-01

    Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit. PMID:27339682

  11. Cumulative life course impairment in other chronic or recurrent dermatologic diseases.

    Science.gov (United States)

    Ibler, Kristina S; Jemec, Gregor B E

    2013-01-01

    Skin diseases are visible, and identifying abnormal skin generally does not require specialist knowledge. Dermatology is therefore a ripe field for studies of cumulative life course impairment, because of the many diseases that affect not only the patients, but also their psychosocial interaction with others. Dermatological patients are visibly sick. The stigma associated with visible as well as hidden skin diseases is considerable and may have a major negative impact on the life course of patients. Stigma and psychosocial relations are however not the only sources of impairment for patients with dermatological diseases. Hand eczema is a prototypical example of a skin disease that causes life course impairment not only due to stigmatization, but also to a major loss of function. The impairment therefore occurs through several mechanisms increasing the potential impact of hand eczema on patients. The list of skin diseases where an assessment of cumulative life course impairment is relevant can be enlarged considerably. Diseases with functional impairment such as, e.g. scleroderma, diseases with prominent subjective symptoms such as acne or hidradenitis, and diseases with limited physical impairment but massive psychosocial impairment in specific communities such as vitiligo, are all suitable for further studies. Life course studies are particularly suitable for skin diseases due to their often chronic recurrent course, low mortality and their psychosocial aspects. The development of a stronger empirical framework is welcomed, and may lead to considerable benefits for patients.

  12. Impaired synthesis contributes to diabetes-induced decrease in liver glutathione.

    Science.gov (United States)

    Furfaro, Anna Lisa; Nitti, Mariapaola; Marengo, Barbara; Domenicotti, Cinzia; Cottalasso, Damiano; Marinari, Umberto Maria; Pronzato, Maria Adelaide; Traverso, Nicola

    2012-05-01

    Diabetes-induced glutathione (GSH) decrease is usually ascribed to GSH oxidation. Here we investigate, in streptozotocin-treated rats, if impairment of GSH synthesis contributes to GSH decrease in diabetic liver, and if antioxidant treatments can provide protection. Diabetic rats were divided into 3 groups: untreated diabetic rats (UD); N-acetyl-cysteine (NAC)-treated diabetic rats; taurine (TAU)-treated diabetic rats; a group of non-streptozotocin-treated rats was used as control (CTR). All rats were sacrificed at 40 weeks of age. Diabetes induced hepatic glutathione decrease, but oxidized glutathione (GSSG) did not increase significantly. Accumulations of cysteine and cysteinyl-glycine in UD suggest respectively decreased glutathione synthesis and increased loss through the plasma membrane with subsequent degradation. Decreased expression of γ-glutamyl-cysteine synthetase in UD is consistent with repressed GSH synthesis. Moreover, diabetes caused increase of GSSG/GSH ratio and induction of heme oxygenase-1, both signs of oxidative stress. Supplementation with NAC or TAU resulted in amelioration of glutathione levels, probably depending on antioxidant activity, more efficient glutathione synthesis and decreased GSH loss and degradation. In conclusion, impaired synthesis and increased loss and degradation of GSH appear to contribute to a decrease in GSH levels in diabetic liver. NAC and TAU are able to partially protect from oxidative stress and GSH decrease, while enhancing GSH synthesis and restricting GSH loss.

  13. Impaired transport of thyroid hormones into livers of obese (ob/ob) mice

    International Nuclear Information System (INIS)

    Obese (ob/ob) mice exhibit impaired hepatic thyroid hormone action that is mediated, at least in part, by a reduced nuclear 3,5,3'-triiodothyronine (T3) receptor occupancy. The possibility that lowered occupancy in obese mice may be caused by decreased transport of T3 across the hepatic plasma membrane was examined by measuring the unidirectional influx of [125I]T3 into livers of 8- to 10-wk-old obese and lean mice using a tissue-sampling portal vein-injection technique. Influx of [125I]thyroxine (T4), a substrate for T4 5'-deiodinase, was also measured. Unidirectional clearance of T3 and T4 was 64 and 80% lower, respectively, in obese mice than in lean mice. Hepatic T3 and T4 uptake was nonsaturable in both lean and obese mice, suggesting that transport occurs by lipid-mediated free diffusion. Clearance of another lipid-soluble hormone, hydrocortisone, was also lower in obese mice than in lean mice. Decreased membrane permeability to the above hormones in obese mice may result from reported changes in membrane lipid composition. In conclusion, decreased hepatic thyroid hormone uptake may contribute to impaired thyroid hormone action and T3 production in livers of obese mice

  14. Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

    Science.gov (United States)

    Maan, Raoel; de Knegt, Robert J; Veldt, Bart J

    2015-11-01

    Thrombocytopenia (platelet count management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

  15. Evidence that chronic hypoxia causes reversible impairment on male fertility

    Institute of Scientific and Technical Information of China (English)

    Vittore Verratti; Francesco Berardinelli; Camillo Di Giulio; Gerardo Bosco; Marisa Cacchio; Mario Pellicciotta; Michele Nicolai; Stefano Martinotti; Raffaele Tenaglia

    2008-01-01

    Aim: To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time. Methods: Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months. Results: Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature sperma- tozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P=0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values. Conclusion: Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility. (Asian J Androl 2008 Jul; 10: 602-606)

  16. Antioxidant enzyme activities in hepatic tissue from children with chronic cholestatic liver disease

    Directory of Open Access Journals (Sweden)

    Ismail Nagwa

    2010-01-01

    Full Text Available Background/Aim: To study the oxidative stress status in children with cholestatic chronic liver disease by determining activities of glutathione peroxidase (GPx, superoxide dismutase (SOD and catalase (CAT in liver tissue. Materials and Methods: A total of 34 children suffering from cholestatic chronic liver disease were studied. They were selected from the Hepatology Clinic, Cairo University, and compared with seven children who happened to have incidental normal liver biopsy. The patients were divided into three groups: extrahepatic biliary atresia (n=13, neonatal hepatitis (n=15 and paucity of intrahepatic bile ducts (n=6; GPx, SOD and CAT levels were measured in fresh liver tissue using ELISA . Results: In the cholestatic patients, a significant increase was found in mean levels of SOD, GPx and CAT in hepatic tissue compared to control children. The three enzymes significantly increased in the extrahepatic biliary atresia group, whereas in the groups of neonatal hepatitis and paucity of intrahepatic bile ducts, only GPx and CAT enzymes were significantly increased. Conclusion: Oxidative stress could play a role in the pathogenesis of cholestatic chronic liver diseases. These preliminary results are encouraging to conduct more extensive clinical studies using adjuvant antioxidant therapy.

  17. Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

    Science.gov (United States)

    Chang, Hye Kyung; Chang, Eun Young; Ryu, Seonae

    2016-01-01

    Purpose The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. Materials and Methods From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. Results Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. Conclusion COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia. PMID:27189282

  18. Severity Assessment of Chronic Liver Disease in Children

    Directory of Open Access Journals (Sweden)

    S Tehranian

    2014-04-01

    A total of 106 patients, 53% females and 47% males with the mean age of 68.3±41.8 months participated. The most common clinical finding was hepatomegaly (76%, followed by jaundice and splenomegaly. Jaundice, hepatopulmonary syndrome, cirrhosis and splenomegaly were clearly correlated with PELD score. The increasing of PELD/MELD (model for end-stage liver disease scores were in line with the high level of liver alkaline phosphatase enzyme and there was a significant relation between them (P

  19. Low-dose steroid pretreatment ameliorates the transient impairment of liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Toshihito Shibata; Toru Mizuguchi; Yukio Nakamura; Masaki Kawamoto; Makoto Meguro; Shigenori Ota; Koichi Hirata; Hidekazu Ooe; Toshihiro Mitaka

    2012-01-01

    AIM:To determine if liver regeneration (LR) could be disturbed following radiofrequency (RF) ablation and whether modification of LR by steroid administration occurs.METHOIDS:Sham operation,partial hepatectomy (PH),and partial hepatectomy with radiofrequency ablation (PHA) were performed on adult Fisher 344 rats.We investigated the recovery of liver volume,DNA synthetic activities,serum cytokine/chemokine levels and signal transducers and activators of transcription 3 DNA-binding activities in the nucleus after the operations.Additionally,the effects of steroid (dexamethasone) pretreatment in the PH group (S-PH) and the PHA group (S-PHA) were compared.RESULTS:The LR after PHA was impaired,with high serum cytokine/chemokine induction compared to PH,although the ratio of the residual liver weight to body weight was not significantly different.Steroid pretreatment disturbed LR in the S-PH group.On the other hand,low-dose steroid pretreatment improved LR and suppressed tumor necrosis factor (TNF)-α elevation in the S-PHA group,with recovery of STAT3 DNA-binding activity.On the other hand,low-dose steroid pretreatment improved LR and suppressed TNF-α elevation in the S-PHA group,with recovery of STAT3 DNA-binding activity.CONCLUSION:LR is disturbed after RF ablation,with high serum cytokine/chemokine induction.Low-dose steroid administration can improve LR after RF ablation with TNF-α suppression.

  20. Chronic Liver Failure after Treatment with Infliximab for Ankylosing Spondylitis in a Patient with Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Yun-ru Li; Feng-xin Chen; Xue-fei Duan; Xue-song Gao; Xiao-ling Fan

    2013-01-01

    A 50-year-old man with ankylosing spondylitis was treated successfully with inlfiximab, who was also a HBV carrier for about twenty-ifve years. After injection with inlfiximab for four times, he developed jaundice and HBV DNA was detectable in serum. Serum aminotransferase and total bilirubin levels were higher than normal. Then he was hospitalized and treated with entacavir and Chinese herb medicine. But his liver damage aggravated and was diagnosed as acute on chronic liver failure. Finally, liver transplantation was carried out and he was cured successfully.

  1. The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Piscaglia, Fabio, E-mail: fabio.piscaglia@unibo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Marinelli, Sara, E-mail: sara_marinelli@libero.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara (Romania); Serra, Carla, E-mail: carla.serra@aosp.bo.it [Division of Medical Liver Transplant Care, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Venerandi, Laura, E-mail: laura.venerandi@gmail.com [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Leoni, Simona, E-mail: leonisimona@yahoo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Salvatore, Veronica, E-mail: veronica.salvatore@unibo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy)

    2014-03-15

    This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation.

  2. The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

    International Nuclear Information System (INIS)

    This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation

  3. Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions

    Science.gov (United States)

    Tan, Cher Heng; Venkatesh, Sudhakar Kundapur

    2016-01-01

    Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including non-alcoholic fatty liver disease, will be elaborated. PMID:27563019

  4. Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kovač, Jelena Djokić, E-mail: jelenadjokic2003@yahoo.co.uk [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Daković, Marko [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Physical Chemistry, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Stanisavljević, Dejana [Institute for Statistics, Faculty of Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade (Serbia); Alempijević, Tamara; Ješić, Rada [Clinic for Gastroenterohepatology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Seferović, Petar [Institute for Cardiovascular Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade (Serbia)

    2012-10-15

    Purpose: To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. Materials and methods: Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b = 0, 50, 200, 400 and 800 s/mm{sup 2}. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. Results: The mean ADCs (×10{sup −3} mm{sup 2}/s; b = 0–800 s/mm{sup 2}) were significantly different at stage F1 versus F ≥ 2 (p < 0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV = 9.54 ± 6.3%). Conclusion: DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.

  5. Correlation between ultrasonographic and pathologic diagnosis of liver fibrosis due to chronic virus hepatitis

    Institute of Scientific and Technical Information of China (English)

    Lei Shen; Ji-Qiang Li; Min-De Zeng; Lun-Gen Lu; Si-Tao Fan; Han Bao

    2006-01-01

    AIM: To evaluate the validity of ultrasonographic and pathologic diagnosis of liver fibrosis in patients with chronic viral hepatitis.METHODS: The liver fibrosis status in 324 patients was evaluated by both needle biopsy and ultrasonography.Liver fibrosis was divided into S0 -S4 stages. S4 stage was designated as definite cirrhosis. The ultrasonographic examination included qualitative variables, description of liver surface and parenchyma, and quantitative parameters, such as diameter of vessels, blood flow velocity and spleen size.RESULTS: Ultrasonographic qualitative description of liver surface and parenchyma was related with the severity of fibrosis. Among the quantitative ultrasonographic parameters, cut-off value of spleen length (12.1 cm) had a sensitivity of 0.600 and a specificity of 0.753 for diagnosis of liver cirrhosis. The diameters of spleen (8 mm) and portal vein (12 mm) had a diagnostic sensitivity of 0.600and 0.767, and a diagnostic specificity of 0.781 and 0.446,respectively. The diagnostic accuracy for liver cirrhosis was moderately satisfactory, and the negative predictive values of these parameters reached near 0.95.CONCLUSION: Ultrasonography can predict the degree of liver fibrosis or cirrhosis. A single ultrasonographic parameter is limited in sensitivity and specificity for the diagnosis of early cirrhosis. The presence or absence of liver cirrhosis in patients with chronic virus hepatitis can be detected using 2 or 3 quantitative and qualitative parameters, especially the length of spleen, the diameter of spleen vein and echo pattern of liver surface.

  6. The Molecular Epidemiology of Chronic Aflatoxin Driven Impaired Child Growth

    Science.gov (United States)

    Turner, Paul Craig

    2013-01-01

    Aflatoxins are toxic secondary fungal metabolites that contaminate dietary staples in tropical regions; chronic high levels of exposure are common for many of the poorest populations. Observations in animals indicate that growth and/or food utilization are adversely affected by aflatoxins. This review highlights the development of validated exposure biomarkers and their use here to assess the role of aflatoxins in early life growth retardation. Aflatoxin exposure occurs in utero and continues in early infancy as weaning foods are introduced. Using aflatoxin-albumin exposure biomarkers, five major studies clearly demonstrate strong dose response relationships between exposure in utero and/or early infancy and growth retardation, identified by reduced birth weight and/or low HAZ and WAZ scores. The epidemiological studies include cross-sectional and longitudinal surveys, though aflatoxin reduction intervention studies are now required to further support these data and guide sustainable options to reduce the burden of exposure. The use of aflatoxin exposure biomarkers was essential in understanding the observational data reviewed and will likely be a critical monitor of the effectiveness of interventions to restrict aflatoxin exposure. Given that an estimated 4.5 billion individuals live in regions at risk of dietary contamination the public health concern cannot be over stated. PMID:24455429

  7. Chronic Kidney Disease Impairs Bone Defect Healing in Rats.

    Science.gov (United States)

    Liu, Weiqing; Kang, Ning; Seriwatanachai, Dutmanee; Dong, Yuliang; Zhou, Liyan; Lin, Yunfeng; Ye, Ling; Liang, Xing; Yuan, Quan

    2016-03-09

    Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

  8. Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia

    NARCIS (Netherlands)

    B.J. Olivier; A.M. Schoenmaker; R.E. Mebius; V. Everts; C.J. Mulder; K.M.J. van Nieuwkerk; T.J. de Vries; S.W. van der Merwe

    2008-01-01

    Osteoporosis is a common complication of chronic liver disease, and the underlying mechanisms are not understood. We aimed to determine if osteoclasts develop from osteoclast precursors in peripheral blood mononuclear cells (PBMCs) of chronic liver disease patients with osteopenia compared with cont

  9. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  10. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  11. Impaired postprandial lipemic response in chronic kidney disease.

    Science.gov (United States)

    Saland, Jeffrey M; Satlin, Lisa M; Zalsos-Johnson, Jeanna; Cremers, Serge; Ginsberg, Henry N

    2016-07-01

    Dyslipidemia in chronic kidney disease (CKD) is usually characterized by hypertriglyceridemia. Here we studied postprandial lipemia in children and young adults to determine whether an increasing degree of CKD results in a proportional increase in triglyceride and chylomicron concentration. Secondary goals were to determine whether subnephrotic proteinuria, apolipoprotein (apo)C-III and insulin resistance modify the CKD effect. Eighteen fasting participants (mean age of 15 years, mean glomerular filtration rate (GFR) of 50 ml/min/1.73 m(2)) underwent a postprandial challenge with a high fat milkshake. Triglycerides, apoB-48, insulin, and other markers were measured before and 2, 4, 6, and 8 hours afterward. Response was assessed by the incremental area under the curve of triglycerides and of apoB-48. The primary hypothesis was tested by correlation to estimated GFR. Significantly, for every 10 ml/min/1.73 m(2) lower estimated GFR, the incremental area under the curve of triglycerides was 17% greater while that of apoB-48 was 16% greater. Univariate analyses also showed that the incremental area under the curve of triglycerides and apoB-48 were significantly associated with subnephrotic proteinuria, apoC-III, and insulin resistance. In multivariate analysis, CKD and insulin resistance were independently associated with increased area under the curve and were each linked to increased levels of apoC-III. Thus, postprandial triglyceride and chylomicron plasma excursions are increased in direct proportion to the degree of CKD. Independent effects are associated with subclinical insulin resistance and increased apoC-III is linked to both CKD and insulin resistance. PMID:27162092

  12. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC), mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection, alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli, and these cells produce extracellular matrix components.Chronic hepatitis B appears to progress more rapidly in males than in females, and NAFLD, cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice, and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.

  13. Seroprevalence of anti-HAV among patients with chronic viral liver disease

    Institute of Scientific and Technical Information of China (English)

    Hyun Chin Cho; Seung Woon Paik; Yu Jin Kim; Moon Seok Choi; Joon Hyeok Lee; Kwang Cheol Koh; Byung Chul Yoo; Hee Jung Son; Seon Woo Kim

    2011-01-01

    AIM: To investigate the current seroprevalence of hepatitis A virus (HAV) antibodies in patients with chronic viral liver disease in Korea. We also tried to identify the factors affecting the prevalence of HAV antibodies.METHODS: We performed an analysis of the clinical records of 986 patients (mean age: 49 ± 9 years, 714males/272 females) with chronic hepatitis B virus (HBV)or hepatitis C virus (HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS: The overall prevalence of IgG anti-HAV was 86.61% (854/986) in patients with chronic liver disease and was 88.13% (869/986) in age- and gendermatched patients from the Center for Health Promotion.The anti-HAV prevalence was 80.04% (405/506)in patients with chronic hepatitis B, 86.96% (20/23)in patients with chronic hepatitis C, 93.78% (422/450)in patients with HBV related liver cirrhosis, and 100%(7/7) in patients with HCV related liver cirrhosis. The anti-HAV prevalence according to the decade of age was as follows: 20s (6.67%), 30s (50.86%), 40s (92.29%), 50s (97.77%), and 60s (100%). The anti-HAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age. Multivariable analysis showed that age ≥ 40 years, female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity.CONCLUSION: Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

  14. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  15. Liver Stiffness Measurement-Based Scoring System for Significant Inflammation Related to Chronic Hepatitis B

    Science.gov (United States)

    Hong, Mei-Zhu; Zhang, Ru-Mian; Chen, Guo-Liang; Huang, Wen-Qi; Min, Feng; Chen, Tian; Xu, Jin-Chao; Pan, Jin-Shui

    2014-01-01

    Objectives Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers. Methods The training set included chronic hepatitis B patients (n = 327), and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement. Results An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+) patients and 0.978, 85.0%, and 94.0% in the HBeAg(−) patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+) patients and 0.977, 95.2%, and 95.8% in the HBeAg(−) patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+) and HBeAg(−) patients for recognizing significant inflammation (G ≥3). Conclusions Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation. PMID:25360742

  16. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B;

    2004-01-01

    and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...

  17. Effects of liver inflammation on FibroScan diagnosis of hepatic fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    刘志权

    2013-01-01

    Objective To investigate the influence of liver inflammation on the ability of the FibroScan non-invasive elastrography scanner to diagnose hepatic fibrosis in patients with chronic hepatitis B (CHB) .Methods A total of 124 CHB patients who received liver biopsy and concomitant liver stiffness measurement (LSM) by FibroScan

  18. Gut flora and bacterial translocation in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    John Almeida; Sumedha Galhenage; Jennifer Yu; Jelica Kurtovic; Stephen M Riordan

    2006-01-01

    Increasing evidence suggests that derangement of gut flora is of substantial clinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection.Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.

  19. Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction.

    OpenAIRE

    Vos, R.; Desmet, V

    1992-01-01

    Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the pe...

  20. Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

    OpenAIRE

    Mario Pirisi; Carlo Fabris; Maria Piera Panozzo; Giorgio Soardo; Pierluigi Toniutto; Ettore Bartou

    1993-01-01

    Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P

  1. Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver.

    Directory of Open Access Journals (Sweden)

    Tetsuo Nakajima

    Full Text Available Sake is a traditional Japanese alcoholic beverage that is gaining popularity worldwide. Although sake is reported to have beneficial health effects, it is not known whether chronic sake consumption modulates health risks due to radiation exposure or other factors. Here, the effects of chronic administration of sake on radiation-induced metabolic alterations in the livers of mice were evaluated. Sake (junmai-shu was administered daily to female mice (C3H/He for one month, and the mice were exposed to fractionated doses of X-rays (0.75 Gy/day for the last four days of the sake administration period. For comparative analysis, a group of mice were administered 15% (v/v ethanol in water instead of sake. Metabolites in the liver were analyzed by capillary electrophoresis-time-of-flight mass spectrometry one day following the last exposure to radiation. The metabolite profiles of mice chronically administered sake in combination with radiation showed marked changes in purine, pyrimidine, and glutathione (GSH metabolism, which were only partially altered by radiation or sake administration alone. Notably, the changes in GSH metabolism were not observed in mice treated with radiation following chronic administration of 15% ethanol in water. Changes in several metabolites, including methionine and valine, were induced by radiation alone, but were not detected in the livers of mice who received chronic administration of sake. In addition, the chronic administration of sake increased the level of serum triglycerides, although radiation exposure suppressed this increase. Taken together, the present findings suggest that chronic sake consumption promotes GSH metabolism and anti-oxidative activities in the liver, and thereby may contribute to minimizing the adverse effects associated with radiation.

  2. Air Manganese Levels and Chronic Liver Disease Mortality in North Carolina Counties: An Ecological Study

    Directory of Open Access Journals (Sweden)

    John G. Spangler

    2012-09-01

    Full Text Available Manganese is an essential trace element which is toxic in high doses. Over the past several decades, manganese has replaced lead as the anti-knock agent in gasoline, raising concern about air and road-side contamination with this element. In addition, manganese is absorbed by the liver, making specific populations (e.g., pregnant women, infants and children, and patients with liver disease susceptible to its toxic effects. Using data from the US Census Bureau, the North Carolina State Center for Health Statistics, and the US Environmental Protection Agency, this ecological study evaluated chronic liver disease mortality rates in North Carolina’s 100 counties. It correlated these rates with county-level demographics as well as on-road and non-road air borne manganese concentrations. Median income by county was inversely associated with chronic liver disease mortality, while the logarithmically transformed airborne concentrations of on-road manganese were positively correlated with county-level chronic liver disease mortality. Because environmental manganese near roads is likely to increase over time, these pilot findings potentially have regulatory implications and argue for further research.

  3. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

    Institute of Scientific and Technical Information of China (English)

    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2008-01-01

    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  4. Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Liliana SC Mendes; Marcelo E Nita; Suzane K Ono-Nita; Evandro S Mello; Luiz Caetano da Silva; Ven(a)ncio AF Alves; Flair J Carrilho

    2008-01-01

    AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies.METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised.Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System.RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease.The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22+0.50 vs -0.15 ± 0.46, P = 0.0053).Immuno-expression of interferon receptor is not a relevant factor.CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis.Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.

  5. [The diagnostic value of immunologic findings in the differentiation of chronic liver diseases].

    Science.gov (United States)

    Manns, M; Meyer zum Büschenfelde, K H; Arnold, W

    1988-12-01

    Various types of virus induced and non-virus induced chronic active hepatitis (CAH) as well as chronic non-suppurative destructive cholangitis (PBC) and primary sclerosing cholangitis have to be distinguished. Classical autoimmune type "lupoid" CAH is characterized by antinuclear antibodies (ANA), liver membrane antibodies (LMA) and smooth muscle antibodies (SMA). A second subgroup of autoimmune type CAH is characterized by anti liver kidney-microsomal antibodies (LKM) which are directed against a specific cytochrome p-450 isoenzyme. A third subgroup of autoimmune type CAH is identified by auto-antibodies to a soluble cytoplasmic liver antigen (SLA). Autoimmune type CAH profits from immuno-suppressive therapy, i.e. corticosteroids alone or in combination with azathioprin. Chronic hepatitis B virus infection is nowadays treated with Interferon when HBV-DNA is detectable in serum, duration of liver disease is less than 5 years and superinfection with HDV and HIV can be excluded. PBC is diagnosed through the detection of antimitochondrial antibodies (AMA) and its PBC specific subtypes anti p 62 (M2) and anti p 48. Aetiology and pathogenesis of PBC are still unknown. Liver transplantation is an established therapy for endstage PBC. This is also true for primary sclerosing cholangitis (PSC).

  6. Factors influencing health-related quality of life in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Abhasnee Sobhonslidsuk; Chatchawan Silpakit; Ronnachai Kongsakon; Patchareeya Satitpornkul; Chaleaw Sripetch; Anya Khanthavit

    2006-01-01

    AIM: To investigate the factors contributing to healthrelated quality of life (HRQL) in chronic liver disease (CLD).METHODS: Patients with CLD and age- and sexmatched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD,socioeconomic factors, and self-rating health perception on HRQL.RESULTS: Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed,blue-collar career and poor health perception increased significantly from chronic hepatitis to Child's Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL.In overall, the positive impact of self-rating health perception on HRQL was consistently showed.CONCLUSION: Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease.

  7. Leptin is essential for the hepatic fibrogenic response to chronic liver injury

    NARCIS (Netherlands)

    Leclercq, IA; Farrell, GC; Schriemer, R; Robertson, GR

    2002-01-01

    Background/Aims: Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on th

  8. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze;

    2013-01-01

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...

  9. Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

    Science.gov (United States)

    Kappus, Matthew R; Mendoza, Mardeli Saire; Nguyen, Douglas; Medici, Valentina; McClave, Stephen A

    2016-08-01

    Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process. PMID:27372291

  10. Chronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report.

    Science.gov (United States)

    Kurihara, Takeshi; Yoshizumi, Tomoharu; Itoh, Shinji; Harimoto, Norifumi; Harada, Noboru; Ikegami, Toru; Inagaki, Yuki; Oshiro, Yukio; Ohkohchi, Nobuhiro; Okamoto, Hiroaki; Maehara, Yoshihiko

    2016-12-01

    Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy. PMID:27059470

  11. Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Abeer El-Sayed Abd El-Wahab

    2012-04-01

    Full Text Available Background: Chronic liver disease (CLD is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1.Objectives: This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.Patients and Methods: Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA, and erythrocyte-reduced glutathione (GSH were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis and 15 healthy controls.Results: HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.Conclusions: HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.

  12. BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality.

    Science.gov (United States)

    Ikawa-Yoshida, Ayae; Matsumoto, Takuya; Okano, Shinji; Aoyagi, Yukihiko; Matsubara, Yutaka; Furuyama, Tadashi; Nakatsu, Yoshimichi; Tsuzuki, Teruhisa; Onimaru, Mitsuho; Ohkusa, Tomoko; Nomura, Masatoshi; Maehara, Yoshihiko

    2016-01-01

    A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1(L/L)) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1(L/L) mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up-regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1(L/L), mice after PHx. In addition, knockdown of BubR1 expression caused down-regulation of DSC1 in a human keratinocyte cell line. BubR1 insufficiency results in the impaired liver regeneration through weakened microstructural adaptation against PHx, enhanced transient liver failure and delayed hepatocyte proliferation. Thus, our data suggest that a reduction in BubR1 levels causes failure of liver regeneration through the DSC1 abnormality. PMID:27561386

  13. Mental development and growth in children with chronic liver disease of early and late onset.

    Science.gov (United States)

    Stewart, S M; Uauy, R; Kennard, B D; Waller, D A; Benser, M; Andrews, W S

    1988-08-01

    Comparison was made of the mental function and physical growth of 21 children in whom liver disease occurred in the first year of life with 15 patients with late (17 months of age to 12 years of age) manifestation of liver disease. Ages (mean +/- SD) at testing for the two groups was 8 +/- 3 years for the early group and 11 +/- 5 years for the late group. Wechsler verbal, performance, and full-scale IQ scores were lower for the early group (range of mean scores: early, 85 to 86 v late, 96 to 103). Growth measures were significantly different in the two groups. Means +/- SD (percentage of standard) were: length for early group, 92 +/- 9; for late, 99 +/- 7; and head circumference for early, 98 +/- 4; for late, 101 +/- 2. The groups were similar in severity of liver disease and acute nutritional status, however. Patients with intellectual impairment had a longer duration of illness, poor nutritional status, and vitamin E deficiency; 82% of impaired patients were in the early group. The data suggest that liver disease during early life has pernicious effects on intellectual function and linear growth. Careful monitoring of nutritional status of children with early-onset liver disease and aggressive nutritional support beginning at the time of diagnosis may help reduce delays in growth and mental development. PMID:3399290

  14. Recent trends in chronic disease, impairment and disability among older adults in the United States

    Directory of Open Access Journals (Sweden)

    Ross Joseph S

    2011-08-01

    Full Text Available Abstract Background To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults. Methods We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthritis; prevalence of impairments, including impairments of cognition, vision, hearing, mobility, and urinary incontinence; prevalence of disability, including activities of daily living (ADLs and instrumental activities of daily living (IADLs. Results The proportion of older adults reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI], 12.4%-13.8% in 1998 to 7.8% (95% CI, 7.2%-8.4% in 2008, whereas the proportion reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6% in 1998 to 92.2% (95% CI, 91.6%-92.8% in 2008. In addition, the proportion reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4% in 1998 to 17.4% (95% CI, 16.6%-18.2% in 2008. The proportion of older adults reporting no impairments was 47.3% (95% CI, 46.3%-48.4% in 1998 and 44.4% (95% CI, 43.3%-45.5% in 2008, whereas the proportion of respondents reporting 3 or more was 7.2% (95% CI, 6.7%-7.7% in 1998 and 7.3% (95% CI, 6.8%-7.9% in 2008. The proportion of older adults reporting any ADL or IADL disability was 26.3% (95% CI, 25.4%-27.2% in 1998 and 25.4% (95% CI, 24.5%-26.3% in 2008. Conclusions Multiple chronic disease is increasingly prevalent among older U.S. adults, whereas the prevalence of impairment and disability, while substantial, remain stable.

  15. [A case of multiple liver abscesses associated with Streptococcus salivarius in a patient with chronic periodontitis].

    Science.gov (United States)

    Kamachi, Saori; Otsuka, Taiga; Tsuji, Chika; Nakashita, Shunya; Ide, Yasushi; Mizuta, Toshihiko

    2014-08-01

    Streptococcus salivarius is an oral commensal bacterium that rarely causes disease in humans. Here, we report a case of liver abscess associated with S. salivarius in a 41-year-old woman who presented with continuous abdominal discomfort, fatigue, and fever. She was diagnosed with multiple liver abscesses; she underwent percutaneous transhepatic abscess drainage. Thereafter, S. salivarius was isolated in all bacterial cultures of the drained abscesses, and it was sensitive to penicillins. She made a good recovery after treatment. In the absence of an infective source other than chronic periodontitis, the cause of liver abscesses was attributed to oral S. salivarius. S. salivarius is a normal oral commensal, and oral commensals must be considered if the infective origin of liver abscess cannot be determined. PMID:25100350

  16. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

    Science.gov (United States)

    Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

    2015-05-19

    Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas.

  17. Small hepatocellular carcinomas in chronic liver disease: Detection with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, M.; Hirasa, M.; Takakuwa, H.; Ibuki, Y.; Fujimi, K.; Miyamura, M.; Tomita, S.; Komori, H.; Todo, A.; Kitaura, Y.

    1986-06-01

    Single-photon emission computed tomography (SPECT) performed using a rotating gamma camera was compared with ..cap alpha../sub 1/-fetoprotein (AFP) assay, conventional liver scintigraphy, ultrasound (US) imaging, computed tomography (CT), and selective celiac angiography in 40 patients with a total of 50 small hepatocellular carcinomas (HCCs;<5 cm). The detection rates of US and CT were determined on an initial screening study and on a second, more precisely focused study. The detection rate of small HCCs by the various modalities was as follows: AFP, 13%; liver scintigraphy, 36%; SPECT, 72%; initial screening US, 80%; second, more precise US studies, 94%; initial screening CT, 64%; second, more precise CT study, 82%; angiography, 88%. Although SPECT was inferior to the initial screening US examination in detecting HCCs less than 2 cm in size, its sensitivity was identical to that of the initial screening US study for detecting HCCs of 2-5 cm. The combination of SPECT and US was an excellent method for the early detection of HCCs, yielding a detection rate of 94%.

  18. Complexity in caring for an ageing heart failure population: concomitant chronic conditions and age related impairments.

    Science.gov (United States)

    De Geest, Sabina; Steeman, Els; Leventhal, Marcia E; Mahrer-Imhof, Romy; Hengartner-Kopp, Beatrice; Conca, Antoinette; Bernasconi, Arlette T; Petry, Heidi; Brunner-La Rocca, Hanspeter

    2004-12-01

    The complexity of caring for the ageing heart failure (HF) population is further complicated by concomitant chronic conditions (i.e., polypharmacy, depression), age related impairments (i.e., hearing, visual and cognitive impairments, impairments in activities of daily living (ADL/IADL), and other issues (e.g., health illiteracy, lack of social support). This paper provides an overview of these risk factors, outlines how they individually and in interplay endanger favourable outcome by putting patients at risk for poor self-management. Moreover, suggestions are made on how these issues could be addressed and integrated in heart failure management by applying gerontological care principles in caring for the ageing heart failure population.

  19. Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

    Science.gov (United States)

    Behairy, Behairy El-Sayed; Sira, Mostafa Mohamed; Zalata, Khaled Refat; Salama, El-Sayed Ebrahem; Abd-Allah, Mohamed Ahmed

    2016-01-01

    AIM: To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases. METHODS: A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected. RESULTS: The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable

  20. Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Zhi-Xin Zhao; Qing-Xian Cai; Xiao-Mou Peng; Yu-Tian Chong; Zhi-Liang Gao

    2008-01-01

    AIM: To study the expression of suppressor of cytokine signaling-1 (SOCS-1) in the liver tissues of chronic hepatitis B (CHB) and the clinical significance of this expression.METHODS: The expression of SOCS-1 in liver tissues of 45 cases of CHB was investigated by immunohistochemical staining, and its correlations with inflammation grades and fibrosis stage were analyzed by SPSS statistics software.RESULTS: The result showed SOCS-1 expressing could be observed in the liver tissue of CHB. The expression of SOCS-1 was mainly distributed near the portal area in the liver tissue of mild inflammation CHB group, and was diffusely distributed in the liver tissue of moderate and severe inflammation groups. SOCS-1 positive stains mainly appear in the hepatocytes, only a few of liver interstitial cells were involved. Inside the hepatocyte, SOCS-1 positive stains are mainly distributed in the plasma. Some of the staining was observed on the membrane. The inclusion bodies in the plasma of hepatocytes were observed occasionally. There were both obvious correlations between the expression of SOCS-1 and the inflammatory grade, and that between the expression of SOCS-1 and the fibrosis stage.CONCLUSION: The distribution of SOCS-1 in the liver tissue of CHB is variable. This expression was correlated with the inflammation grade and fibrosis stage.

  1. Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease Proven by Transient Elastography

    Directory of Open Access Journals (Sweden)

    Ivana Mikolasevic

    2013-09-01

    Full Text Available Background/Aim: Preliminary data suggest an association between chronic kidney disease (CKD and non-alcoholic fatty liver disease (NAFLD. The aim of this study was to further investigate the association between NAFLD and decreased kidney function. Methods: A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter was used to detect and quantify liver steatosis (Fibroscan®. NAFLD was defined by CAP values ≥238 dB.m-1. Results: CKD stage III was present in 29 patients (46.8% and CKD stage IV in 33 patients (53.2%. Out of 62 CKD patients 53 (85.5% had NAFLD and of these 14/53 patients (26.4% had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;pConclusion: The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.

  2. Expression and function of the atypical cadherin FAT1 in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Valletta, Daniela; Czech, Barbara [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Thasler, Wolfgang E. [Grosshadern Tissue Bank and Center for Liver Cell Research, Department of Surgery, Ludwig-Maximilians-University Munich (Germany); Mueller, Martina [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Bosserhoff, Anja-Katrin [Institute of Pathology, University of Regensburg, Regensburg (Germany); Hellerbrand, Claus, E-mail: claus.hellerbrand@ukr.de [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer The expression of the atypical cadherin FAT1 is increased in chronic liver disease. Black-Right-Pointing-Pointer FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. Black-Right-Pointing-Pointer FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. Black-Right-Pointing-Pointer FAT1 is a new therapeutic target for prevention and treatment of hepatic fibrosis. -- Abstract: Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these

  3. Safety and efficacy of hepatitis A vaccine in children with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Hanaa Mostafa El-Karaksy; Manal Ismail El-Hawary; Nehal Mohammad El-Koofy; Rokaya El-Sayed; Mona Al-Saeed El-Raziky; Samah Asaad Mansour; Gamal Mohammad Taha; Fatma El-Mougy

    2006-01-01

    AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix:720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine,as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events,immediate or late, were reported by the mothers after each dose of the vaccine.CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

  4. Hyerferritinemia is a risk factor for steatosis in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Anna Licata; Maria Elena Nebbia; Giuseppe Cabibbo; Giovanna Lo Iacono; Francesco Barbaria; Virna Brucato; Nicola Alessi; Salvatore Porrovecchio; Vito Di Marco; Antonio Craxì; Calogero Cammà

    2009-01-01

    AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and g-glutamyltransferase were independent predictors of steatosis. Ferritin levels were significantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

  5. Analyses of prognostic indices of chronic liver failure caused by hepatitis virus

    Institute of Scientific and Technical Information of China (English)

    Xiao-Mao Li; Lin Ma; Yue-Bo Yang; Zhong-Jie Shi; Shui-Sheng Zhou

    2005-01-01

    AIM: To analyze the related indices about the prognosesof chronic liver failure caused by hepatitis virus.METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P = 1/(1+e-y)(y= 1.7262-0.0948X1+2.9846X2+0.6992X3+ 1.6019X4+2.0398X5). (Note: X1-Prothrombin activity; X2-digestive tract hemorrhage; X3-hepatic encephalopathy; X4-hepatorenal syndrome; X5-pulmonary infection.).CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

  6. Viral and host causes of fatty liver in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Emin Altlparmak; Seyfettin K(o)klü; Mesut Yallnkilic; Osman Yüksel; Bahattin Cicek; Ertugrul Kayacetin; Tülin Sahin

    2005-01-01

    AIM: To investigate the viral and host causes of fatty liver in chronic hepatitis B patients and the role of fat deposits in liver damage.METHODS: A total of 164 patients (113 males and 51 females, average age 35±11.3 years, and range 10-62 years) with previously untreated chronic hepatitis B were included in the study. The patients were divided into two groups depending on the result of liver biopsy: group without steatosis (100 patients with <5% hepatosteatosis) and group with steatosis (64 patients with >5% hepatosteatosis). The groups were compared in terms of gender, body mass index (BMI), liver enzymes (ALT, AST, ALP, GGT), cholesterol, triglyceride, HBeAg, viral load, and histological findings. In the group with steatosis, the patients were subdivided depending on the degree of steatosis into mild group (45 patients with 5-24% steatosis), and severe group (19 patients with >25% steatosis). RESULTS: In the group of chronic hepatitis B with steatosis, the mean age, BMI, cholesterol, and triglyceride levels were significantly higher than those in the group without steatosis (P<0.05). Steatosis was found in 53 (46.9%) of male patients and 11 (22%) of female patients (P<0.05). No significant difference was found in the positivity of ALT, AST, ALP, GGT, HBeAg, viral load, histological activity index (HAI) and stage between the two groups (P>0.05). In the group with severe steatosis, the BMI was significantly higher than that in the group with mild steatosis (P<0.05). No significant difference was found in the other parameters between the groups (P>0.05). CONCLUSION: Steatosis in chronic hepatitis B appears to be a result of metabolic factors of the host rather than the effect of viruses. Steatosis is unrelated to the HAI and degree of fibrosis, which are considered as the histological indicators of liver damage.

  7. Ductular proliferation in liver tissues with severe chronic hepatitis B: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Yao-Kai Chen; Xu-Xia Zhao; Jun-Gang Li; Song Lang; Yu-Ming Wang

    2006-01-01

    AIM: To clarify the pathogenesis of ductular proliferation and its possible association with oval cell activation and hepatocyte regeneration.METHODS: Immunohistochemical staining and image analysis of the ductular structures in the liver tissues from 11 patients with severe chronic hepatitis B and 2healthy individuals were performed. The liver specimens were sectioned serially, and then cytokeratin 8 (CK8),CK19, OV6, proliferating cell nuclear antigens (PCNA),glutathione-S-transferase (GST), o-fetal protein (AFP)and albumin were stained immunohistochemically.RESULTS: Typical and atypical types of ductular proliferation were observed in the portal tracts of the liver tissues in all 11 patients. The proliferating ductular cells were positive for CK8, CK19, OV6 and PCNA staining.Some atypical ductular cells displayed the morphological and immunohistochemical characteristics of hepatic oval cells. Some small hepatocyte-like cells were between hepatic oval cells and mature hepatocytes morphometrically and immunohistochemically.CONCLUSION: The proliferating ductules in the liver of patients with severe chronic liver disease may have different origins. Some atypical ductular cells are actually activated hepatic oval cells. Atypical ductular proliferation is related to hepatocyte regeneration and small hepatocyte-like cells may be intermediate transient cells between hepatic oval cells and mature hepatocytes.

  8. Validation of hepascore as a predictor of liver fibrosis in patients with chronic hepatitis C infection.

    Science.gov (United States)

    Kalantari, Hamid; Hoseini, Hannan; Babak, Anahita; Yaran, Majid

    2011-01-01

    Introduction. Liver biopsy is an invasive determinator for hepatic fibrosis. Serum biomarkers can probably be used as an alternative to liver biopsy in assessment of the degree of fibrosis in patients with chronic Hepatitis C. Method. Eighty patients with chronic Hepatitis C were included in the study using simple nonrandom sampeling metod. After fulfillment of liver biopsy, the patients were categorized according to the METAVIR Scoring system. The Hepascore algorithm is computed based on age, sex, and the serum levels of total bilirubin, δ-glutamyl transferase, α2-Macroglobulin, and hyaluronic acid. The spearman and ROC tests were used. Results. According to the liver biopsy results, 12, 25, 20, 7 and 16 patients had F0, F1, F2, F3, and F4, respectively. With regard to the 0.34 cut-off point Hepascore had 67%, 56%, 64%, and 56% sensitivity, specificity, respectively, positive prediction value (PPV), and negative prediction value (NPV), respectively, for diagnosis of significant fibrosis. For a Hepascore cut-off point 0.61, sensitivity, specificity, respectively, PPV and NPB 82%, 86%, 70%, and 92% in diagnosis of severe fibrosis. For a Hepascore cut-off point 0.84, sensitivity, specificity, PPV and NPB were respectively 100%, 97%, 89%, and 100% for diagnosis of cirrhosis. Conclusion. Hepascore has a high value in diagnosis of the level of fibrosis, particularly cirrhosis. Therefore, it can be used for primary screening of patients to determine the need for liver biopsy.

  9. Diagnostic Value of the 13C Methacetin Breath Test in Various Stages of Chronic Liver Disease

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    Hamizah Razlan

    2011-01-01

    Full Text Available The accuracy of the 13C-methacetin breath test (13C-MBT in differentiating between various stages of liver disease is not clear. A cross-sectional study of Asian patients was conducted to examine the predictive value of the 13C-MBT in various stages of chronic liver diseases. Diagnostic accuracy of the breath test was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve analysis. Seventy-seven patients (47 men/30 women, mean age 50±16 years were recruited. Forty-seven patients had liver cirrhosis (Child Pugh A = 11, Child Pugh B = 15, and Child Pugh C = 21, 21 had fibrosis, and 9 had chronic inflammation. The sensitivity and positive predictive value for liver fibrosis, cirrhosis (all stages, Child-Pugh A, Child-Pugh B, and Child-Pugh C were 65% and 56%, 89% and 89%, 67% and 42%, 40% and 40%, and 50% and 77%, respectively. Area under curve values for fibrosis was 0.62 (0.39–0.86, whilst that for cirrhosis (all stages was 0.95 (0.91–0.99. The 13C-methacetin breath test has a poor predictive value for liver fibrosis but accurately determines advanced cirrhosis.

  10. 1H MRS study of brain metabolic disorder in patients with chronic liver cirrhosis

    International Nuclear Information System (INIS)

    Objective: To study the metabolic alterations in the brain of patients with chronic liver cirrhosis with 1H magnetic resonance spectroscopy (1H MRS) for better understanding the pathophysiology of chronic hepatic encephalopathy (CHE), which will help us in the diagnosis and treatment of this disease. Methods: STEAM 1H MRS and MRI were performed in 30 patients with chronic liver cirrhosis is and 15 healthy volunteers. The height of resonance peaks of different metabolites was measured and the ratios of the other metabolites to Cr were calculated. The authors also studied the correlation between metabolites and the association between globus pallidum signal intensity and the spectroscopic alterations. Results: In patients with severe cirrhosis (in decompensatory period) or CHE, the mean values of mI/Cr and Cho/Cr ratio were significantly lower than those in healthy volunteers or patients with minor cirrhosis (in compensatory period) (P0.05). There was negative correlation between mI/Cr and Glx-α/Cr(r -0.51, n = 44, P1-weighted images, the globus pallidum signal intensity was significantly higher in patients with severe cirrhosis or CHE. mI/Cr, Cho/Cr and Glx-α/Cr correlated significantly with MRI signal changes respectively. Conclusions: Proton MRS can demonstrate brain metabolic changes in patients with chronic liver cirrhosis in vivo noninvasively, thereby helping interpret the pathophysiology of CHE

  11. Validity of Autotaxin as a Novel Diagnostic Marker for Liver Fibrosis in Egyptian Chronic HCV Patients

    OpenAIRE

    Ezzat, Wafaa M.; Halla M. Ragab; Nabila Abd El Maksoud; Nour A. Abdulla; Yasser A. Elhosary

    2013-01-01

    We aimed to detect the validity of serum ATX as a diagnostic marker for liver fibrosis. Forty-eight males and 16 females were enrolled in the current study. Their ages ranged from 29-57 years with mean of 45.09, all were chronically HCV infected. Laboratory assessment was done for all subjects in form of complete blood picture; liver function test; lipid profile and serum detection of ATX. Patients were grouped according to the stage of fibrosis into group 1: fibrosis score 0, 1, 2, 3; group ...

  12. YKL-40 expression in CD14+ liver cells in acute and chronic injury

    Institute of Scientific and Technical Information of China (English)

    Oscar Pizano-Martínez; Vidal Delgado-Rizo; Irinea Ya(n)ez-Sánchez; Pilar Alatorre-Carranza; Alejandra Miranda-Díaz; Pablo C Ortiz-Lazareno; Trinidad García-Iglesias; Adrian Daneri-Navarro; Mónica Vázquez-Del Mercado; Mary Fafutis-Morris

    2011-01-01

    AIM: To demonstrate that CD14+ cells are an important source of the growth factor YKL-40 in acute and chronic liver damage.METHODS: Rats were inoculated with one dose of CCl4 to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl4 was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot. RESULTS: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14+ cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14- cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls.CONCLUSION: Hepatic CD14+ cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated

  13. Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stress.

    Science.gov (United States)

    Baena, Miguel; Sangüesa, Gemma; Hutter, Natalia; Sánchez, Rosa M; Roglans, Núria; Laguna, Juan C; Alegret, Marta

    2015-02-01

    Supplementation with 10% liquid fructose to female rats for 2weeks caused hepatic steatosis through increased lipogenesis and reduced peroxisome proliferator activated receptor (PPAR) α activity and fatty acid catabolism, together with increased expression of the spliced form of X-binding protein-1 (Rebollo et al., 2014). In the present study, we show that some of these effects are preserved after sub-chronic (8weeks) fructose supplementation, specifically increased hepatic expression of lipid synthesis-related genes (stearoyl-CoA desaturase, ×6.7-fold; acetyl-CoA carboxylase, ×1.6-fold; glycerol-3-phosphate acyltransferase, ×1.65-fold), and reduced fatty acid β-oxidation (×0.77-fold), resulting in increased liver triglyceride content (×1.69-fold) and hepatic steatosis. However, hepatic expression of PPARα and its target genes was not modified and, further, livers of 8-week fructose-supplemented rats showed no sign of unfolded protein response activation, except for an increase in p-IRE1 levels. Hepatic mTOR phosphorylation was enhanced (×1.74-fold), causing an increase in the phosphorylation of UNC-51-like kinase 1 (ULK-1) (×2.8-fold), leading to a decrease in the ratio of LC3B-II/LC3B-I protein expression (×0.39-fold) and an increase in the amount of the autophagic substrate p62, indicative of decreased autophagy activity. A harmful cycle may be established in the liver of 8-week fructose-supplemented rats where lipid accumulation may cause defective autophagy, and reduced autophagy may result in decreased free fatty acid formation from triglyceride depots, thus reducing the substrates for β-oxidation and further increasing hepatic steatosis. In summary, the length of supplementation is a key factor in the metabolic disturbances induced by fructose: in short-term studies, PPARα inhibition and ER stress induction are critical events, whereas after sub-chronic supplementation, mTOR activation and autophagy inhibition are crucial.

  14. A cross-sectional study on occurrence of type 2 diabetes among patients admitted with chronic liver diseases in a medical college in Kolkata

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    Shuvankar Mukherjee

    2013-01-01

    Full Text Available Objectives: To study the magnitude of the problem of type 2 diabetes mellitus and impaired glucose intolerance among the patients with various types of chronic liver diseases and to find out the association of diabetes mellitus and impaired glucose tolerance with the demographic and clinical characteristics of the patients. Materials and Methods: This observational study, which was cross-sectional in design, was undertaken in the Department of General Medicine at a medical College in Kolkata during October 2010 to July 2011. Altogether 161 patients diagnosed with chronic liver disease (CLD were admitted in the General Medicine ward during the study period, out of which 9 patients got themselves discharged against medical advice. From the remaining 152 patients, a total of 136 patients aged 20 years and above were selected for the study according to the inclusion criteria. A detailed history was taken, and a thorough clinical examination was done followed by further investigations, all of which were recorded in a pre-designed, structured proforma. Results : Among the study subjects, 58.1% had impaired glucose tolerance (IGT, while 14.0% had overt diabetes mellitus. IGT and diabetes were significantly higher among the CLD patients aged 45 years or more (P < 0.05. However, similar association was not observed with regard to sex of the patients. No association was found between the occurrence of IGT and/or overt diabetes with either severity (as per Child-Pugh score or with the duration of CLD. More than half of the study subjects having alcoholic liver disease or chronic hepatitis B or C or autoimmune hepatitis and one third of those having Wilson's disease had IGT, while one third of those with either chronic hepatitis C or Wilson's disease and one fourth of those having autoimmune hepatitis had overt diabetes. Twenty-one percent of those with chronic hepatitis B also found to have overt diabetes, which was least in those with alcoholic liver

  15. Status quo of chronic liver diseases, including hepatocellular carcinoma, in Mongolia.

    Science.gov (United States)

    Jazag, Amarsanaa; Puntsagdulam, Natsagnyam; Chinburen, Jigjidsuren

    2012-06-01

    Because Mongolia has much higher liver disease burden than any other regions of the world, it is necessary to provide information on real-time situation of chronic liver disease in Mongolia. In this article, we reviewed studies performed in Mongolia from 2000 to 2011 on seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among healthy individuals and patients with chronic liver diseases, and on the practice patterns for the management of liver cirrhosis and hepatocellular carcinoma (HCC). According to previous reports, the seroprevalence of HBV and HCV in general population in Mongolia is very high (11.8% and 15% for HBV and HCV, respectively). Liver cirrhosis is also highly prevalent, and mortality from liver cirrhosis remained high for the past decade (about 30 deaths per 100,000 populations per year). Among patients with cirrhosis, 40% and 39% are positive for HBsAg and anti-HCV, respectively, and 20% are positive for both. The seroprevalence is similar for HCC and more than 90% of HCC patients are positive for either HBV or HCV. The incidence of HCC in Mongolia is currently among the highest in the world. The mortality from HCC is also very high (52.2 deaths per 100,000 persons per year in 2010). Partly due to the lack of established surveillance systems, most cases of HCC are diagnosed at an advanced stage. The mortality from liver cirrhosis and HCC in Mongolia may be reduced by implementation of antiviral therapy program and control of alcohol consumption.

  16. Routine blood tests to predict liver fibrosis in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yung-Yu Hsieh; Shui-Yi Tung; Kamfai Lee; Cheng-Shyong Wu; Kuo-Liang Wei; Chien-Heng Shen; Te-Sheng Chang; Yi-Hsiung Lin

    2012-01-01

    AIM:To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C,compared with other noninvasive tests.METHODS:This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment.FibroQ,aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR),AST to platelet ratio index,cirrhosis discriminant score,age-platelet index (API),Pohl score,FIB-4 index,and Lok's model were calculated and compared.RESULTS:FibroQ,FIB-4,AAR,API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test:P < 0.001).FibroQ trended to be superior in predicting significant fibrosis score in chronic hepatitis C compared with other noninvasive tests.CONCLUSION:FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.

  17. High neutrophil-lymphocyte ratio indicates poor prognosis for acute-on-chronic liver failure after liver transplantation

    Science.gov (United States)

    Lin, Bing-Yi; Zhou, Lin; Geng, Lei; Zheng, Zhi-Yun; Jia, Jun-Jun; Zhang, Jing; Yao, Jia; Zheng, Shu-Sen

    2015-01-01

    AIM: To investigate the significance of pre-transplant neutrophil-lymphocyte ratio (NLR) in determining the prognosis of liver transplant (LT) recipients with acute-on-chronic liver failure (ACLF). METHODS: Data were collected from the liver transplantation data bank. The NLR values and other conventional inflammatory markers were evaluated for their ability to predict the prognosis of 153 patients with ACLF after LT. The NLR cut-off value was based on a receiver operating characteristic curve analysis. A Kaplan-Meier curve analysis and univariate and multivariate Cox regression models were used to define the independent risk factors for poor outcomes. RESULTS: The optimal NLR cut-off value was 4.6. Out of 153 patients, 83 (54.2%) had an NLR ≥ 4.6. The 1-, 3-, and 5-year overall survival rates were 94.3%, 92.5% and 92.5%, respectively, in the normal NLR group and 74.7%, 71.8% and 69.8%, respectively, in patients with high NLRs (P < 0.001). Furthermore, there was a significant difference in infectious complications after LT between the high and normal NLR groups. There were no significant differences for other complications. In the multivariate Cox regression model, a high NLR was defined as a significant predictor of poor outcomes for LT. CONCLUSION: A high NLR is a convenient and available predictor for prognosis of LT patients and can potentially optimize the current criteria for LT in ACLF. PMID:25805939

  18. Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    Hessel Franz P

    2006-10-01

    Full Text Available Abstract Background Acute-on-chronic liver failure (ACLF is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods In a clinical cohort trial with a prospective follow-up of 3 years 33 ACLF-patients treated with MARS were compared to 46 controls. Survival, health-related quality of life as well as direct medical costs for in- and outpatient treatment from a health care system perspective were determined. Based on the differences in outcome and indirect costs the cost-effectiveness of MARS expressed as incremental costs per life year gained and incremental costs per QALY gained was estimated. Results The average initial intervention costs for MARS were 14600 EUR per patient treated. Direct medical costs over 3 years follow up were overall 40000 EUR per patient treated with MARS respectively 12700 EUR in controls. The 3 year survival rate after MARS was 52% compared to 17% in controls. Kaplan-Meier analysis of cumulated survival probability showed a highly significant difference in favour of MARS. Incremental costs per life-year gained were 31400 EUR; incremental costs per QALY gained were 47200 EUR. Conclusion The results after 3 years follow-up of the first economic evaluation study of MARS based on empirical patient data are presented. Although high initial treatment costs for MARS occur the significantly better survival seen in this study led to reasonable costs per live year gained. Further randomized controlled trials investigating the medical efficacy and the cost-effectiveness are recommended.

  19. Impairment and Coping in Children and Adolescents with Chronic Fatigue Syndrome: A Comparative Study with Other Paediatric Disorders

    Science.gov (United States)

    Garralda, M. Elena; Rangel, Luiza

    2004-01-01

    Background: Functional impairment is a key feature of chronic fatigue syndrome (CFS) of childhood. Aim: To compare impairment, illness attitudes and coping mechanisms in childhood CFS and in other paediatric disorders. Method: Participants were 28 children and adolescents with CFS, 30 with juvenile idiopathic arthritis (JIA) and 27 with emotional…

  20. Assessment of health-related quality of life and related factors in patients with chronic liver disease

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    Neila Paula de Souza

    2015-12-01

    Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Assessing health-related quality of life is an important aspect of clinical practice. Thus, the present study attempts to assess the health-related quality of life of patients with chronic liver disease. METHODS: A cross-sectional survey was conducted on 133 chronic liver disease patients, using three instruments: a demographic questionnaire, the Chronic Liver Disease Questionnaire, and Model for End-Stage Liver Disease index. Variables were expressed as frequencies, percentages, means, and standard deviations. The statistical analysis included Pearson's correlation, Student's t-test, and analysis of variance (p < 0.05 was considered significant. RESULTS: The mean age of included subjects was 50.5 ± 13.3 years. The majority were male (66.2%, Caucasian (70.7%, and had a family income of US$329-US$658.2. Over half of the patients (56.4% were infected by hepatitis C virus and 93.2% had low Model for End-Stage Liver Disease scores. Model for End-Stage Liver Disease score was related to age (r = 0.185;p = 0.033. Higher mean Chronic Liver Disease Questionnaire scores were obtained for emotional function (39.70/SD ± 12.98 and while lower scores were obtained for abdominal symptoms (16.00/SD ± 6.25. Fifty-two patients (39.1% presented overall low (<5 Chronic Liver Disease Questionnaire scores. Furthermore, Chronic Liver Disease Questionnaire score was related to family income (r = 0.187, p = 0.031. CONCLUSION: Most individuals presented high mean Chronic Liver Disease Questionnaire scores, indicating low health-related quality of life, especially individuals with low family income.

  1. Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

    Institute of Scientific and Technical Information of China (English)

    Nicola Dioguardi; Fabio Grizzi; Barbara Fiamengo; Carlo Russo

    2008-01-01

    AIM:To describe a quantitative analysis method for liver biopsy sections with a machine that we have named "Dioguardi Histological Metriser" which automatically measures the residual hepatocyte mass (including hepatocytes vacuolization),inflammation,fibrosis and the loss of liver tissue tectonics.METHODS:We analysed digitised images of liver biopsy sections taken from 398 patients.The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring system.RESULTS:The method provides:(1) the metrical extension in two-dimensions (the plane) of the residual hepatocellular set,including the area of vacuoles pertinent to abnormal lipid accumulation;(2) the geometric measure of the inflammation basin,which distinguishes intra-basin space and extra-basin dispersed parenchymal leukocytes;(3) the magnitude of collagen islets,(which were considered truncated fractals and classified into three degrees of magnitude);and (4)the tectonic index that quantifies alterations (disorders)in the organization of liver tissue.Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm2/s,scanning a whole section in 6-8 min.CONCLUSION:The results are the first standardized metrical evaluation of the geometric properties of the parenchyma,inflammation,fibrosis,and alterations in liver tissue tectonics of the biopsy sections.The present study confirms that biopsies are still valuable,not only for diagnosing chronic hepatitis,but also for quantifying changes in the organization and order of liver tissue structure.

  2. ASSOCIATION OF CAFFEINE INTAKE AND LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    Kalinca da Silva OLIVEIRA

    2015-03-01

    Full Text Available Background Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. Methods A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil. Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study Results There were 113 patients, 67 (59.3% females, 48 (42.5% were aged between 52 and 62 years, and 101 (89.4% were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62% patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. Conclusions The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

  3. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

    OpenAIRE

    Umemura, Toshitaka; Kawamura, Takahiko; Umegaki, Hiroyuki; Kawano, Naoko; Mashita, Shinichi; Sakakibara, Toshimasa; Hotta, Nigishi; Sobue, Gen

    2013-01-01

    Background/Aims In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD w...

  4. Baboon alcohol dehydrogenase isozymes: phenotypic changes in liver following chronic consumption of alcohol.

    Science.gov (United States)

    Holmes, R S; VandeBerg, J L

    1987-01-01

    According to the nomenclature of Vallee and Bazzone [1983] for mammalian alcohol dehydrogenase (ADH) isozymes, baboon ADHs comprise three major classes of activity, which were distinguished according to the following properties: Class I ADHs. These isozymes exhibited low-Km characteristics with ethanol as substrate, high isoelectric points (8.5-9.3), and sensitivity to 5 mM 4-methyl pyrazole inhibition, and were the major liver (ADH-2) and kidney (ADH-1) isozymes in the baboon. Class II ADHs. These isozymes showed high-Km values for ethanol, neutral isoelectric points (7.7 for the liver ADH-4 [pi-ADH] and 7.2 for the major stomach ADH [ADH-3], respectively), and were insensitive to inhibition with 5 mM 4-methyl pyrazole. Class III ADH. This enzyme was characterized by its inactivity with ethanol as substrate (up to 0.5 M), insensitivity to 4-methyl pyrazole inhibition, preference for medium-chain-length alcohols as substrate (trans-2-hexen-1-ol was routinely used in this study), and an isoelectric point (6.5) similar to that of the human liver chi-ADH (pI 6.4). Major activity variation of the liver pi-ADH (ADH-4) isozyme was observed among the 114 liver samples examined, with 34 percent exhibiting a null (or low-activity) phenotype. An electrophoretic variant phenotype for the major class II stomach isozyme (ADH-3) was also found in the population studied. The baboon was used as a model for studying alcohol-induced changes in liver ADH phenotype following chronic alcohol consumption. Prepuberal male baboons were pair-fed nutritionally adequate liquid diets containing ethanol (50 percent of calories) or isocaloric carbohydrates, and liver ADH isozyme patterns from biopsy samples were monitored for 20 weeks. Dramatic decreases in class II liver ADH activity (ADH-4, or pi-ADH) were observed within 4 weeks after the start of alcohol feeding, and a shift in liver class I isozymes was found during the later stages of alcohol consumption. These changes during chronic

  5. Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion.

    Science.gov (United States)

    Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

    2015-01-01

    Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0-3), but not the late stage after rUCCAO (day 4-32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD.

  6. Gender difference in motor impairments induced by chronic administration of vinblastine

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    Shahrnaz Parsania

    2014-06-01

    Full Text Available Objective(s:Neurotoxicity of anticancer drugs complicates treatment of cancer patients. Vinblastine (VBL is reported to induce motor and cognitive impairments in patients receiving chronic low-dose regimen. Materials and Methods: The effects of VBL treatment on motor, learning and memory functions of male and female Wistar rats were studied by behavioral related tests. Animals were given chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks from postnatal day 23 to 52. Motor function was evaluated using grasping test and balancing was evaluated by the rotarod. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM task and open field test, respectively. Results: Administration of VBL caused severe damage to motor and balance function of male rats in comparison to female rats treated with VBL and rats treated with saline. Memory and locomotion were affected in both male and female rats compared with saline treated rats, while a sex difference was also observed in these parameters; male rats showed more impairment compared with female ones. Both male and female rats showed cognitive impairments in MWM task and no sex differences were observed in these functions. Conclusion: Results revealed that VBL is a potent neurotoxic agent and despite the profound effect of VBL on motor and cognitive functions, it seems that male rats are more susceptible to motor deficits induced by VBL.

  7. Liver biopsy performance and histological findings among patients with chronic viral hepatitis: a Danish database study

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Krarup, Henrik Bygum; Møller, Axel;

    2007-01-01

    We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data......, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis...... had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis. Udgivelsesdato: 2007-null...

  8. Liver biopsy performance and histological findings among patients with chronic viral hepatitis

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Krarup, Henrik Bygum; Møller, Axel;

    2007-01-01

    We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data......, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis...... had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis....

  9. Multidetector CT findings of splenic artery aneurysm in children with chronic liver disease

    International Nuclear Information System (INIS)

    Splenic artery aneurysm (SAA) is a well-known complication of chronic liver disease and portal hypertension in adults. The incidence of SAA in children undergoing selective hepatic angiography prior to liver transplantation is reported as 4%, but there are few systematic studies. To investigate the SAAs detected by multidetector CT angiography (MDCTA) among children with chronic liver disease. A total of 124 children (71 girls, 53 boys; mean age 118 months; age range 5 days to 204 months) with chronic liver disease underwent MDCTA to display the vascular anatomy and any vascular complications during the pretransplantation period. Of these children, 23 also underwent coeliac angiography. The digital subtraction angiography (DSA) and MDCTA findings were compared. SAAs were detected in 13 children (10.4%); none was detectable by US. All patients had more than one aneurysm; ten patients had more than three. In all except one patient, the SAAs were located only in the intraparenchymal branches of the splenic artery; in one patient they were located in the intraparenchymal segment and in the distal third of the splenic artery. The mean size of the aneurysms was 6.5 mm (range 2.5-18 mm). All patients with aneurysms had splenomegaly and vascular collaterals. Nine of the children with SAAs had portal vein pathologies (two occlusions, two stenoses, five dilatations). A statistically significant difference existed with regard to the size of spleen (P < 0.05) and patient age (P < 0.05) between children with SAAs and children without SAAs. There was an increased risk of SAAs in patients with portal vein pathologies. In 19 patients without SAAs on MDCTA, no SAAs were seen on DSA. It is likely that the incidence of SAA in children with chronic liver disease will increase with improved survival of children with long-standing portal hypertension and chronic liver disease. MDCTA with multiplanar reconstruction is a noninvasive and effective means of imaging paediatric patients with

  10. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    Science.gov (United States)

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  11. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  12. Impaired cortical processing of inspiratory loads in children with chronic respiratory defects

    Directory of Open Access Journals (Sweden)

    Clément Annick

    2007-09-01

    Full Text Available Abstract Background Inspiratory occlusion evoked cortical potentials (the respiratory related-evoked potentials, RREPs bear witness of the processing of changes in respiratory mechanics by the brain. Their impairment in children having suffered near-fatal asthma supports the hypothesis that relates asthma severity with the ability of the patients to perceive respiratory changes. It is not known whether or not chronic respiratory defects are associated with an alteration in brain processing of inspiratory loads. The aim of the present study was to compare the presence, the latencies and the amplitudes of the P1, N1, P2, and N2 components of the RREPs in children with chronic lung or neuromuscular disease. Methods RREPs were recorded in patients with stable asthma (n = 21, cystic fibrosis (n = 32, and neuromuscular disease (n = 16 and in healthy controls (n = 11. Results The 4 RREP components were significantly less frequently observed in the 3 groups of patients than in the controls. Within the patient groups, the N1 and the P2 components were significantly less frequently observed in the patients with asthma (16/21 for both components and cystic fibrosis (20/32 and 14/32 than in the patients with neuromuscular disease (15/16 and 16/16. When present, the latencies and amplitudes of the 4 components were similar in the patients and controls. Conclusion Chronic ventilatory defects in children are associated with an impaired cortical processing of afferent respiratory signals.

  13. Effects of chronic renal failure on protein synthesis and albumin messenger ribonucleic acid in rat liver.

    OpenAIRE

    Zern, M A; Yap, S.H.; Strair, R K; Kaysen, G A; Shafritz, D A

    1984-01-01

    Previously we reported that chronic renal failure in rats leads to preferential disaggregation of liver membrane-bound polysomes associated with a decrease in albumin synthesis. To determine whether reduced albumin synthesis results from reduced cellular levels of albumin messenger RNA (mRNA) or some other molecular mechanism, we have employed mRNA-DNA hybridization in conjunction with cell-free protein synthesis to determine albumin mRNA sequence content and biological activity in subcellula...

  14. A case of chronic berylliosis using aspiration liver biopsy as a diagnostic aid

    International Nuclear Information System (INIS)

    Chronic berylliosis may occur in subjects who regularly handle or have handled the metal beryllium (workers in light bulb factories). Clinical symptoms (fatigue, loss of weight, coughing, increasing breathlessness upon exertion, pyrexia, cyanosis, clubbed fingers and certain radiological abnormalities) are non-specific. Pathological-anatomical examination reveals granulomatosis of the organs. A description is given of a case in which the diagnosis was made on the basis of the history, chest X-rays and liver biopsy findings. (author)

  15. Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

    OpenAIRE

    Hingorani, Sangeeta

    2008-01-01

    Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosc...

  16. PHARMACOECONOMIC ASSESSMENT OF USING INTERFERON-FREE REGIMENS FOR CHRONIC HEPATITIS C AFTER LIVER TRANSPLANTATION

    OpenAIRE

    A. A. Sukhoruk; E. V. Esaulenko

    2016-01-01

    This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical pract...

  17. Chronic mild stress alters circadian expressions of molecular clock genes in the liver.

    Science.gov (United States)

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki

    2013-02-01

    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  18. Effects of heparin on liver fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jun Shi; Jing-Hua Hao; Wan-Hua Ren; Ju-Ren Zhu

    2003-01-01

    AIM: To evaluate the effects of heparin on liver fibrosis in patients with chronic hepatitis B.METHODS: Fifty-two cases under study were divided into two groups, group A and group B. The two groups were given regular treatment and heparin/low molecular weight heparin (LMWH) treatment respectively. Hepatic functions,serum hyaluronic acid (HA) and type IV collagen levels were measured before and after the treatment, and six caseswere taken liver biopsy twice.RESULTS: After treatment, hepatic functions became significantly better in both groups. Serum HA and type IV collagen levels in group B compared with group A, decreased significantly after treatment. Collagen proliferation also decreased in group B after treatment.CONCLUSION: Heparin/LMWH can inhibit collagen proliferation in liver tissues with hepatitis B.

  19. Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

    Institute of Scientific and Technical Information of China (English)

    JFL Cobbold; S Morin; SD Taylor-Robinson

    2007-01-01

    Transient elastography is a recently developed noninvasive technique for the assessment of hepatic fibrosis.The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratification for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

  20. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.

    Directory of Open Access Journals (Sweden)

    Victoria L Gadd

    Full Text Available Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence.Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1 expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV (n = 39 or non-alcoholic fatty liver disease (NAFLD (n = 34 (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis and healthy controls (n = 11 by flow cytometry.The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46% of the decompensated patients who died within 8 months of recruitment.Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased

  1. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  2. Diagnosis of hepatoma using grayscale and Doppler ultrasound in patients with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Idris S

    2011-10-01

    Full Text Available Wasim A Memon, Zishan Haider, Mirza Amanullah Beg, Muhammad Idris, Tanveer-ul-Haq, Waseem Akhtar, Sidra IdrisRadiology Department, Aga Khan University Hospital, Karachi, Pakistan Every author contributed equally to the workObjective: To determine the diagnostic accuracy of liver ultrasound for the detection of hepatoma in chronic liver disease (CLD patients by either taking histopathology or serum α-fetoprotein levels or a biphasic computed tomography (CT scan (whichever is available as the gold standard.Study design: Cross-sectional.Place and duration of study: Radiology Department, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to January 2010.Methods: A total of 239 patients (156 males and 83 females with clinical suspicion or surveillance of hepatoma in CLD referred to the radiology department for ultrasound evaluation followed by either liver biopsy and histopathology or serum α-fetoprotein level or biphasic CT scan.Results: The sensitivity of ultrasound for hepatoma detection in CLD was 65%, specificity was 85%, and accuracy was 70%, and positive predictive value and negative predictive value were 92% and 45%, respectively.Conclusion: Ultrasound is a relatively quick, safe, reasonably accurate, and noninvasive imaging modality for the detection of hepatoma in CLD and can be complemented with clinical assessment of screening high-risk patients.Keywords: hepatoma, ultrasound, radiology, chronic liver disease

  3. In situ detection of lipid peroxidation by-products in chronic liver diseases.

    Science.gov (United States)

    Paradis, V; Kollinger, M; Fabre, M; Holstege, A; Poynard, T; Bedossa, P

    1997-07-01

    Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. The deleterious consequences of this mechanism are related in part to the formation of reactive aldehydic products that bind to intra- or extracellular molecules to form adducts. Specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, allowed us to investigate in situ, with an immunohistochemical procedure, the occurrence of lipid peroxidation in a panel of different chronic liver diseases. Intracellular HNE and MDA adducts were detected respectively in 24 of 39 cases (62%) and in 12 of 34 cases investigated (35%). They were localized mainly in the cytoplasm of hepatocytes, with the strongest staining observed in hemochromatosis, Wilson's disease, and in areas of acute alcoholic hepatitis in cases of alcoholic liver diseases. A peculiar pattern of immunostaining was observed in primary biliary cirrhosis where biliary cells of destroyed but also intact bile ducts strongly expressed HNE adducts. The liver extracellular matrix also displayed MDA adducts (30 of 34 cases, 88%) and HNE adducts (23 of 39 cases, 59%). While HNE adducts were specifically localized on large bundles of collagen fibers, MDA adducts were detected in a thin reticular network and in sinusoidal cells around portal tracts or fibrous septa. In conclusion, lipid peroxidation by-products are detectable in chronic liver diseases. Immunohistochemical results suggest that this mechanism is implicated very early in the pathogenesis of some of these diseases.

  4. Seroprevalence of Hepatitis E in Patients with Chronic Liver Disease from East Azerbaijan, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Somi

    2007-09-01

    Full Text Available Background and Aims: Superinfection with HEV in patients with chronic liver disease (CLD can cause severe hepatic decompensation leading to increased morbidity and mortality. This study aimed to determine seroprevalence of HEV infection among CLD patients compared to blood donors from Azerbaijan, north-west of Iran.Methods: CLD patients and a group of age matched blood donors with normal liver function tests were evaluated for the presence of anti-HEV IgG antibody in their sera for evidence of hepatitis E. The risk factors were estimated.Results: The mean age of CLD patients was 48 years (range: 10-87. 27.5% of patients were HEV IgG-positive. Among the controls 19.7% were positive for anti-HEV IgG. By multivariate analysis, there was no association between positive anti-HEV IgG and etiology of chronic liver disease, gender, literacy, accommodation, and number of family members in patients or controls. Mean age of patients infected with HEV in both groups was significantly more than the seronegative ones. Conclusions: We found high seroprevalence of HEV-antibody among blood donors and CLD patients in our study, so we recommend more attention to hygiene of food and water. In addition, such patients should be informed about the potential risks and simple ways to prevent the disease in their regular life and travels. This issue must be concerned in cases of "acute on chronic" hepatitis in CLD patients.

  5. Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR

    Directory of Open Access Journals (Sweden)

    Ewa Wunsch

    2015-01-01

    Full Text Available Background/Aim. Sulphotransferase 2A1 (SULT2A1 exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC and primary biliary cirrhosis (PBC. Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n=11, PBC (n=19, and control liver tissues (n=19. PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n=120 and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role.

  6. Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but also neuronal degeneration and cognitive impairment

    Science.gov (United States)

    Jing, Zhen; Shi, Changzheng; Zhu, Lihui; Xiang, Yonghui; Chen, Peihao; Xiong, Zhilin; Li, Wenxian; Ruan, Yiwen; Huang, Li'an

    2015-01-01

    Chronic cerebral hypoperfusion (CCH) induces cognitive impairment, but the compensative mechanism of cerebral blood flow (CBF) is not fully understood. The present study mainly investigated dynamic changes in CBF, angiogenesis, and cellular pathology in the cortex, the striatum, and the cerebellum, and also studied cognitive impairment of rats induced by bilateral common carotid artery occlusion (BCCAO). Magnetic resonance imaging (MRI) techniques, immunochemistry, and Morris water maze were employed to the study. The CBF of the cortex, striatum, and cerebellum dramatically decreased after right common carotid artery occlusion (RCCAO), and remained lower level at 2 weeks after BCCAO. It returned to the sham level from 3 to 6 weeks companied by the dilation of vertebral arteries after BCCAO. The number of microvessels declined at 2, 3, and 4 weeks but increased at 6 weeks after BCCAO. Neuronal degeneration occurred in the cortex and striatum from 2 to 6 weeks, but the number of glial cells dramatically increased at 4 weeks after BCCAO. Cognitive impairment of ischemic rats was directly related to ischemic duration. Our results suggest that CCH induces a compensative mechanism attempting to maintain optimal CBF to the brain. However, this limited compensation cannot prevent neuronal loss and cognitive impairment after permanent ischemia. PMID:25853908

  7. Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ping Liu; Mo-Bin Wan; Xiong Cai; Zhi-Qing Zhang; Jun Ye; Ren-Xing Zhou; Jia He; Bao-Zhang Tang; Yi-Yang Hu; Cheng Liu; Lie-Ming Xu; Cheng-Hai Liu; Ke-Wei Sun; De-Chang Hu; You-Kuan Yin; Xia-Qiu Zhou

    2005-01-01

    AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-Ⅲ-P, Ⅳ-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observedat wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, meanscore of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P<0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P<0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-Ⅲ-P and

  8. Impaired Gallbladder Motility and Increased Gallbladder Wall Thickness in Patients with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Colak, Yasar; Bozbey, Gulcin; Erim, Tolga; Caklili, Ozge Telci; Ulasoglu, Celal; Senates, Ebubekir; Mutlu, Hasan Huseyin; Mesci, Banu; Doğan, Mehmet Sait; Tasan, Guralp; Enc, Feruze Yilmaz; Tuncer, Ilyas

    2016-01-01

    Background/Aims Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. Methods An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. Results Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. Conclusions Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD. PMID:26932908

  9. Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury

    DEFF Research Database (Denmark)

    Godbolt, Alison K; Cancelliere, Carol; Hincapié, Cesar A;

    2014-01-01

    OBJECTIVE: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI) after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) using a previously published search strategy and predefined crit....... CONCLUSIONS: There is a lack of evidence of an increased risk of dementia after MTBI. In children, objective evidence of CCI exists only for complicated MTBI. More definitive studies are needed to inform clinical decisions, assessment of prognosis, and public health policy....

  10. Honey Bees' Behavior Is Impaired by Chronic Exposure to the Neonicotinoid Thiacloprid in the Field.

    Science.gov (United States)

    Tison, Léa; Hahn, Marie-Luise; Holtz, Sophie; Rößner, Alexander; Greggers, Uwe; Bischoff, Gabriela; Menzel, Randolf

    2016-07-01

    The decline of pollinators worldwide is of growing concern and has been related to the use of plant-protecting chemicals. Most studies have focused on three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) currently subject to a moratorium in the EU. Here, we focus on thiacloprid, a widely used cyano-substituted neonicotinoid thought to be less toxic to honey bees and of which use has increased in the last years. Honey bees (Apis mellifera carnica) were exposed chronically to thiacloprid in the field for several weeks at a sublethal concentration. Foraging behavior, homing success, navigation performance, and social communication were impaired, and thiacloprid residue levels increased both in the foragers and the nest mates over time. The effects observed in the field were not due to a repellent taste of the substance. For the first time, we present the necessary data for the risk evaluation of thiacloprid taken up chronically by honey bees in field conditions. PMID:27268938

  11. A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan

    Directory of Open Access Journals (Sweden)

    Yuki Inagaki

    2015-11-01

    Interpretation: The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation.

  12. Lower liver stiffness in patients with sustained virological response 4 years after treatment for chronic hepatitis C

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Mössner, Belinda Klemmensen; Christensen, Peer Brehm;

    2011-01-01

    Transient elastography (TE) is a noninvasive and well validated method for measurement of liver stiffness. The aim of this study was to use TE to evaluate whether patients with sustained virological response (SVR) have lower liver stiffness than patients with non-SVR after treatment for chronic...

  13. End-Stage Renal Disease after Liver Transplantation in Patients with Pre-Transplant Chronic Kidney Disease

    OpenAIRE

    Bahirwani, Ranjeeta; Forde, Kimberly A.; Mu, Yifei; Lin, Fred; Reese, Peter; Goldberg, David; Abt, Peter; Reddy, K. Rajender; Levine, Matthew

    2014-01-01

    Renal dysfunction prior to liver transplantation has a marked impact on post-transplant kidney outcomes. The aim of this study was to assess post-transplant renal function in patients with chronic kidney disease (CKD) receiving orthotopic liver transplantation (OLT) alone.

  14. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    Science.gov (United States)

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  15. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis.

    Science.gov (United States)

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  16. Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition.

    Directory of Open Access Journals (Sweden)

    Tae Yeob Kim

    Full Text Available To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium definitions.We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea.Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001. Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192. Patients with previous acute decompensation (AD within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001. Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391.The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.

  17. Effect of interferon therapy on radionuclide imaging in chronic liver diseases due to HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ghaffar, Y.; Dorgham, L.; Lotfy, N. [Ain Shams Univ., Imbaba, Giza (Egypt)]|[Menofia Unif., Shebin El Kom (Egypt)] [and others

    1995-09-01

    Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not received alpha-IFN. A {sup 99m}Tc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of the patients, compared to 8% in 20% of controls (p<0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p<0.001). Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon. 13 refs., 2 tabs.

  18. Cognitive impairment and depression in a population of patients with chronic kidney disease in Colombia: a prevalence study

    OpenAIRE

    Rodríguez-Angarita, Carlos Edgardo; Sanabria-Arenas, Rafael Mauricio; Vargas–Jaramillo, Juan Diego; Ronderos–Botero, Izcay

    2016-01-01

    Background Growth of the elderly population is linked to the increase of comorbid conditions such as chronic kidney disease (CKD), depression, and cognitive impairment (CI). Cognitive impairment can vary from minimal deficits in the normal aging, to mild cognitive impairment with a prevalence ranging from 1 to 29 % in people ≥ 65 years of age, up to severe impairment with a prevalence of 6 to 42 %. The CI induced by depression usually affects the functional performance of the elderly. Objecti...

  19. Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

    Institute of Scientific and Technical Information of China (English)

    Hsiu-Lung Fan; Po-Sheng Yang; Hui-Wei Chen; Teng-Wei Chen; De-Chuan Chan; Chi-Hong Chu; Jyh-Cherng Yu

    2012-01-01

    AIM:TO identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients.METHODS:We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus (ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy.Their demographic,clinical,and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test,Fisher's exact test,and a multiple logistic regression analysis.RESULTS:The study included 113 patients (87 men and 26 women) with a mean age of 49.84 years.Fiftytwo patients survived,and 61 patients died.Liver failure (85.2%),sepsis (34.4%),and multiple organ failure (39.3%) were the main causes of death.Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ scores ≥ 12[odds ratio (OR) =7.160,95% CI:2.834-18.092,P <0.001] and positive blood culture (OR =13.520,95%CI:2.740-66.721,P =0.001) on the day of diagnosis and model for end-stage liver disease (MELD) scores ≥ 28 (OR =8.182,95% CI:1.884-35.527,P =0.005)after the first week of treatment were independent predictors of mortality.CONCLUSION:APACHE Ⅱ scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF-HBV patients.

  20. Clinical Study on Treatment of Liver Fibrosis of Chronic Hepatitis B Patients with Ginkgo Leaf

    Institute of Scientific and Technical Information of China (English)

    何云; 袁凤仪; 王建宾; 邵淑莲; 袁红波; 黄晓欣

    2002-01-01

    Objective: To study the anti-liver fibrosis effect of Ginkgo leaf in patients with chronic hepatitis B.Methods: Eighty-six patients with chronic hepatitis B were randomly divided into two groups with similar general condition. The 42 patients in the treated group were treated with Ginkgo leaf tablet (GLT), and the 44 patients in the control group were treated with Yiganling tablet (益肝灵片). The treatment was conducted for 3 successive months in both groups. Changes in the histo-pathology of liver, serum levels of platelet activating factor (PAF), hyaluronic acid (HA), collagen type Ⅳ (C-Ⅳ), laminin (LN) and pro-collagen peptide type Ⅲ (PCⅢ)were observed before and after treatment. Results: The markedly effective rate and the total effective rate in the treated group were 45.1% and 76.2% respectively, while in the control group the corresponding rates were 18.2% and 43.2%. Comparison between the two groups showed significant difference (P<0.01). Serum levels of PAF, HA, C-Ⅳ, LN and PCⅢ were lowered significantly in the treated group after treatment. Compared with the corresponding parameters in the control group after treatment, the differences were all significant (P<0.01 or P<0.05). The pathological examination of liver showed improvement in both groups, the inflammation grade lowered in 10 patients (55.6%) of the treated group and in 5 patients (35.7%) of the control group, insignificant difference was shown between them. But in comparing the fibrosis staging lowering patients between the two groups, 12 patients (66.7%) vs 3 patients (21.4%), the difference was significant (P<0.05). Moreover, there were 4 patients in the control group with their fibrosis aggravated, while in the treated group, none was aggravated (P<0.05).Conclusion: Ginkgo leaf tablet has some liver protective and anti-liver fibrosis benefits.

  1. Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Soresi, M.; Bonfissuto, G.; Magliarisi, C.; Riili, A.; Terranova, A.; Di Giovanni, G.; Bascone, F.; Carroccio, A.; Tripi, S.; Montalto, G. E-mail: gmontal@unipa.it

    2003-05-01

    AIM: To retrospectively evaluate the prevalence of lymph nodes of the hepato-duodenal ligament in a group of patients with chronic liver disease of various aetiologies and to investigate what clinical, aetiological and laboratory data may lead to their appearance. MATERIALS AND METHODS: One thousand and three patients (554 men, 449 women) were studied, including 557 with chronic hepatitis and 446 with liver cirrhosis. The presence of lymph nodes near the trunk of the portal vein, hepatic artery, celiac axis, superior mesenteric vein and pancreas head was investigated using ultrasound. RESULTS: Lymph nodes were detected in 394 out of the 1003 study patients (39.3%); their number ranged from one to four, with a diameter ranging between 0.8 and 4 cm. The highest prevalence was in the subgroup of patients with primary biliary cirrhosis (87.5%), followed by patients with hepatitis C virus (HCV; 42%), patients with HCV and hepatitis B virus (HBV; 41.3%), autoimmune hepatitis (40%), and HBV alone (21.2%). In the alcoholic and idiopathic subgroups prevalence was 9.5%, while in the non-alcoholic steatohepatitis and haemochromatosis subgroups it was 0%. HCV RNA was present in 97 out of 103 lymph node-positive patients and in 141 out of 168 lymph node-negative HCV-negative patients (p<0.003). Lymphadenopathy frequency increased as the liver disease worsened ({chi}{sup 2} MH=74.3; p<0.0001). CONCLUSION: Despite the limitations of a retrospective study, our data indicate a high prevalence of lymphadenopathy in liver disease patients; ultrasound evidence of lymph nodes of the hepato-duodenal ligament in a given liver disease may most likely suggest a HCV or an autoimmune aetiology and a more severe histological picture.

  2. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    Science.gov (United States)

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  3. Population-representative Incidence of Acute-On-Chronic Liver Failure

    Science.gov (United States)

    Shao, Jian-Guo; Zhu, Yong-Chang; Xu, Ai-Dong; Yao, Jian-Hua; Wang, Xu-Lin; Qian, Yin-Kun; Wang, Hua-Yu; Shen, Yi; Lu, Peng; Wang, Lu-Jun

    2016-01-01

    Background: Acute-on-chronic liver failure (ACLF) is a major cause of hepatic death in the world, but no population-based studies have evaluated the incidence of ACLF. This study was conducted to determine the incidence and short-term outcomes of ACLF in a region of Eastern China. Methods: In this prospective cross-sectional study, we collected data from public hospitals in Nantong city between January 1, 2005, and December 31, 2014. All hospitals with admission potential for ACLF patients were included. The primary outcome was ACLF defined as severe jaundice and coagulopathy with underlying chronic liver disease, according to diagnostic and laboratory criteria suggested by Chinese Society for Hepatology (CSH). Results: During the 10-year period, a consecutive sample of 1934 ACLF patients was included in this study. The overall ACLF incidence rate over the 10-year period was 2.53 (95% confidence interval, 2.16-2.91) per 100,000 population per year, decreasing from 3.35 in 2005 to 2.06 in 2014. Chronic hepatitis B virus (HBV) infection was the leading cause of chronic liver disease and HBV reactivation was the most common cause of acute hepatic event. The 28-day mortality for the ACLF patients had a clear decline during the study period, form 50.39% in 2005 to 35.44% in 2014. Conclusions: In the Eastern China population, the incidence of ACLF is decreasing and the prognosis improving. Short-term mortality was associated with the presence of cirrhosis and growing age. While ACLF remains a life-threatening disorder, our findings suggest that nationwide and long-term cohorts should be conducted for the natural history of ACLF. PMID:27136963

  4. Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically

    Institute of Scientific and Technical Information of China (English)

    Joan Oliva; Jennifer Dedes; Jun Li; Samuel W French; Fawzia Bardag-Gorce

    2009-01-01

    AIM: To examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms. METHODS: Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 (Bortezomib, Velcade.) by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei. RESULTS: Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine, and, in particular, a significant decrease in the betainehomocysteine methyltransferase enzyme. This suggested that hypomethylation was associated with proteasome inhibition, as indicated by the decrease in histone methylation. CONCLUSION: The role of proteasome inhibition in regulating epigenetic mechanisms, and its link to liver injury in alcoholic liver disease, is thus a promising approach to study liver injury due to chronic ethanol consumption.

  5. Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia

    DEFF Research Database (Denmark)

    Junker, A E; Gluud, L; Holst, J J;

    2016-01-01

    OBJECTIVE: We evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia. METHODS: Four groups matched for age, sex and body mass index were studied: (i) 10 patients with normal glucose tolerance and NAFLD......; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect.......001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1) )] and without diabetes [7.5 pmol L...

  6. Subendocardial contractile impairment in chronic ischemic myocardium: assessment by strain analysis of 3T tagged CMR

    Directory of Open Access Journals (Sweden)

    Nagao Michinobu

    2012-02-01

    Full Text Available Abstract Background The purpose of this study was to quantify myocardial strain on the subendocardial and epicardial layers of the left ventricle (LV using tagged cardiovascular magnetic resonance (CMR and to investigate the transmural degree of contractile impairment in the chronic ischemic myocardium. Methods 3T tagged CMR was performed at rest in 12 patients with severe coronary artery disease who had been scheduled for coronary artery bypass grafting. Circumferential strain (C-strain at end-systole on subendocardial and epicardial layers was measured using the short-axis tagged images of the LV and available software (Intag; Osirix. The myocardial segment was divided into stenotic and non-stenotic segments by invasive coronary angiography, and ischemic and non-ischemic segments by stress myocardial perfusion scintigraphy. The difference in C-strain between the two groups was analyzed using the Mann-Whitney U-test. The diagnostic capability of C-strain was analyzed using receiver operating characteristics analysis. Results The absolute subendocardial C-strain was significantly lower for stenotic (-7.5 ± 12.6% than non-stenotic segment (-18.8 ± 10.2%, p Conclusions Analysis of tagged CMR can non-invasively demonstrate predominant impairment of subendocardial strain in the chronic ischemic myocardium at rest.

  7. Impaired cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Mikio C Aoi

    Full Text Available Dynamic cerebral autoregulation (dCA is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL, modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ([Formula: see text] = 0.029, faster gait speed ([Formula: see text] = 0.018 and lower IADL score ([Formula: see text]0.002. Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.

  8. High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.

    Science.gov (United States)

    Utzschneider, Daniel T; Alfei, Francesca; Roelli, Patrick; Barras, David; Chennupati, Vijaykumar; Darbre, Stephanie; Delorenzi, Mauro; Pinschewer, Daniel D; Zehn, Dietmar

    2016-08-22

    Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition of this chronic phenotype and how it impacts T cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing chronic lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that T cell differentiation and acquisition of a chronic or exhausted phenotype depend critically on the frequency of T cell receptor (TCR) engagement and less significantly on the strength of TCR stimulation. In fact, we noted that low-level antigen exposure promotes the formation of T cells with an acute phenotype in chronic infections. Unexpectedly, we found that T cell populations with an acute or chronic phenotype are maintained equally well in chronic infections and undergo comparable primary and secondary expansion. Thus, our observations contrast with the view that T cells with a typical chronic infection phenotype are severely functionally impaired and rapidly transition into a terminal stage of differentiation. Instead, our data unravel that T cells primarily undergo a form of phenotypic and functional differentiation in the early phase of a chronic LCMV infection without inheriting a net survival or expansion deficit, and we demonstrate that the acquired chronic phenotype transitions into the memory T cell compartment.

  9. Effect of WeiJia on carbon tetrachloride induced chronic liver injury

    Institute of Scientific and Technical Information of China (English)

    Pik-Yuen Cheung; Jay Chun; Hsiang-Fu Kung; Meng-su Yang; Qi Zhang; Ya-Ou Zhang; Gan-Rong Bai; Marie Chia-Mi Lin; Bernard Chan; Chi-Chun Fong; Lin Shi; Yue-Feng Shi

    2006-01-01

    AIM: To study the effect of WeiJia on chronic liver injury using carbon tetrachloride (CCl4) induced liver injury animal model.METHODS: Wistar rats weighing 180-220g were randomly divided into three groups: normal control group (Group A), CCl4 induced liver injury control group (Group B) and CCl4 induction with WeiJia treatment group (Group C). Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl4 in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week,Group C rats also received daily intraperitoneal injection of WeiJia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3 female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid (HA), type Ⅳ collagen (CIV), γ-glutamyl transferase (γ-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed.RESULTS: CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and Y-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L (P0.05) respectively, similar to normal control group (Group A), but significantly different from CCl4 induced liver injury control group (Group B). An increase in PCNA and decrease in a-SMA expression level was also observed.CONCLUSION: WeiJia could improve liver function and reduce liver fibrosis

  10. Effect of chronic intermittent hypoxia on theophylline metabolism in mouse liver

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-yang; ZENG Yi-ming; ZHANG Yi-xiang; WANG Wan-yu; WU Run-hua

    2013-01-01

    Background Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver,which is the most important organ for drug metabolism.This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.Methods Eight C57BL/6J mice were exposed to CIH for 12 weeks.Eight C57BL/6J mice were exposed to room air as a control group.Serum levels of alanine aminotransferase and aspartate aminotransferase were measured.Liver histology was observed by light and electron microscopy.Total hepatic cytochrome P450 concentration was measured.Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours.After incubation,the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.Results CIH did not affect the serum transaminase levels.Livers from mice exposed to CIH showed hepatocellular edema,and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope.The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60±2.43)% vs.(21.58±4.52)% (P=0.02).The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group;(0.83±0.08) vs.(1.13±0.21) mol/mg microsomal protein (P=0.004).Conclusion CIH decreases theophylline metabolism by mouse hepatocytes,which may correlate with the downregulation of cytochrome P450 expression by CIH.

  11. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    Science.gov (United States)

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  12. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    Science.gov (United States)

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  13. Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

    International Nuclear Information System (INIS)

    The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-α/β-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-γ-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-α/β-inducible genes (but not IFN-γ-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-α/β- and IFN-γ-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first

  14. Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease

    Institute of Scientific and Technical Information of China (English)

    Scott Grier; Adrian KP Lim; Nayna Patel; Jeremy FL Cobbold; Howard C Thomas; Isobel J Cox; Simon D Taylor-Robinson

    2006-01-01

    Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

  15. Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism.

    Science.gov (United States)

    Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2011-12-01

    The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism. PMID:21594680

  16. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome.

    Science.gov (United States)

    Ocon, Anthony J; Messer, Zachary R; Medow, Marvin S; Stewart, Julian M

    2012-03-01

    CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as 'mental fog'. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity). A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups. There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores. Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

  17. Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Fehmi Ate(s); Mehmet Yaln(i)z; Saadet Alan

    2011-01-01

    AIM: To evaluate the impact of liver steatosis upon response to given therapy in chronic hepatitis B (CHB) patients. METHODS: 84 consecutive CHB patients treated with 48-wk PEGylated interferon (PEG-IFN) therapy were enrolled. Baseline characteristics and sustained viral response (SVR) to PEG-IFN therapy were evaluated. RESULTS: Mean body mass index (BMI) was 27.36 ± 4.4 kg/m2. Six (7.1%) had hypertension and three (3.5%) had diabetes mellitus. Steatosis was present in 22.6% (19/84) of liver biopsy samples. Age, BMI, and triglyceride levels of the patients with hepatic steatosis were significantly higher than those without hepatic steatosis (P 0.05). CONCLUSION: Occurrence of hepatic steatosis is significantly high in CHB patients and this association leads to a trend of decreased, but statistically insignificant, SVR rates to PEG-IFN treatment.

  18. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Jiang-hua Wang

    2015-01-01

    Conclusions: The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients.

  19. Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

    Directory of Open Access Journals (Sweden)

    Angélica Luciana Nau

    2014-04-01

    Full Text Available Introduction Chronic hepatitis B virus (HBV infection and liver steatosis (LS are the most common causes of chronic liver disease, and their coexistence is frequently observed in clinical practice. Although metabolic syndrome is the main cause of LS, it has not been associated with HBV infection. The aims of this study were to describe the lipid profile and prevalence of LS among HBV carriers and to identify the characteristics associated with LS in this group. Methods This retrospective cross-sectional study included hepatitis B surface antigen (HBsAg-positive patients evaluated during 2011 and 2012. Results Of the 83 patients included, the mean age was 46.4±12.5 years, 53% were men, and 9.1% were hepatitis B e antigen (HBeAg -positive. These patients exhibited the following lipid profile: total cholesterol = 175.4±38.8mg/dL, low-density lipoprotein (LDL = 113.0±32.7mg/dL, and triglycerides = 91.1±45.2mg/dL. Their fasting glucose was 95.3±14.5g/dL, and fasting insulin was 6.1±5.9µIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of individuals. Factors associated with the presence of LS included higher levels of total cholesterol, prothrombin activity, fasting insulin, and body mass index (BMI as well as lower levels of aspartate aminotransferase (AST. Conclusions These findings suggest that LS in patients with chronic HBV appears to be a consequence of metabolic alterations and insulin action rather than of viral factors.

  20. Transcriptional Dysregulation of Upstream Signaling of IFN Pathway in Chronic HCV Type 4 Induced Liver Fibrosis

    Science.gov (United States)

    Ibrahim, Marwa K.; Salum, Ghada Maher; Bader El Din, Noha G.; Dawood, Reham M.; Barakat, Ahmed; Khairy, Ahmed; El Awady, Mostafa K.

    2016-01-01

    IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention. PMID:27135246

  1. The distressed (type D) personality is independently associated with impaired health status and increased depressive symptoms in chronic heart failure

    DEFF Research Database (Denmark)

    Schiffer, Angélique A; Pedersen, Susanne S.; Widdershoven, Jos W;

    2005-01-01

    Chronic heart failure (CHF) is a serious condition that is associated with impaired health status and a high prevalence of depressive symptoms. To date, little is known about the determinants of health status and depressive symptoms in CHF. Therefore, the aim of this study was to assess whether T...... Type D personality is associated with impaired health status and increased depressive symptoms in heart failure patients, independent of disease characteristics....

  2. Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B.

    Science.gov (United States)

    Huang, Haijun; Sun, Zeyu; Pan, Hongying; Chen, Meijuan; Tong, Yongxi; Zhang, Jiajie; Chen, Deying; Su, Xiaoling; Li, Lanjuan

    2016-01-01

    Chronic HBV (CHB) infected patients with intermediate necroinflammation and fibrosis are recommended to receive antiviral treatment. However, other than liver biopsy, there is a lack of sensitive and specific objective method to determine the necroinflammation and fibrosis stages in CHB patients. This study aims to identify unique serum metabolomic profile associated with histological progression in CHB patients and to develop novel metabolite biomarker panels for early CHB detection and stratification. A comprehensive metabolomic profiling method was established to compare serum samples collected from health donor (n = 67), patients with mild (G indicator for antiviral treatment for CHB management. PMID:27498553

  3. Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Yun Ma; Wen-Wei Yan

    2005-01-01

    Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients.Moreover, the incidence rate of post-liver transplantation diabetes mellitus (PTDM) also appears to be higher among patients with HCV infection. PTDM is often associated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

  4. PHARMACOECONOMIC ASSESSMENT OF USING INTERFERON-FREE REGIMENS FOR CHRONIC HEPATITIS C AFTER LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    A. A. Sukhoruk

    2016-01-01

    Full Text Available This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3. 

  5. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses.

    Science.gov (United States)

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A

    2015-11-20

    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  6. Treatment of chronic hepatitis C in liver transplantcandidates and recipients: Where do we stand?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The first generation direct antiviral agents (DAAs)highlighted substantial prognosis improvement amongliver transplant (LT) candidates and recipients withrecurrent hepatitis C virus (HCV) infection. During2014, second generation DAAs are associated withhigh sustained virological response rates (〉 95%),shortened duration courses and relatively few toxicities.In keeping with the currently available data, patientswith decompensated cirrhosis awaiting LT is preferableto be treated with interferon-free, new generationDAAs, with or without ribavirin combinations. Althoughdata about the safety of new DAAs combinations inthis patient population are limited, sofosbuvir anddaclatasvir pharmacokinetics do not appear to changesignificantly in moderate or severe liver impairment,while other new DAAs (simeprevir, asunaprevir)seem to be contraindicated in patients with severeliver impairment (Child-Pugh class C). On the otherhand, sofosbuvir should not be given in patients withglomerular filtration rate ≤ 30 mL/min, but ongoingtrials will clarify better this issue. With the objectivethat newer antiviral combinations will yield safer andmore efficient manipulation of HCV recurrence posttransplant,the European Association for the Study of theLiver has recently updated its recommendations towardsthis direction. Nevertheless the new antivirals' high costmay be the biggest challenge to their implementationworldwide.

  7. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    Science.gov (United States)

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

    2016-01-01

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

  8. Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

    Directory of Open Access Journals (Sweden)

    Mario Pirisi

    1993-01-01

    Full Text Available Phospholipase A2 (PLA2 modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P<0.001; Bonferroni’s test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (p<0.0 I and mild chronic liver disease (p<0.0S J. Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reacti ve protein, alkaline phosphatase and al-fetoprotein as predictor variables was significant (multiple R= 0.7056, multiple R2= 0.4978, F= 15.36, P= <0.0001. The standardized regression coefficients found to be significant were those of Creactive protein, blood urea nitrogen and al-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2 activity increases parallel to disease severity and accompanies the expression of proteins of the acute phase response that. like PLA2 activity, increase in serum while liver synthesis declines.

  9. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

    OpenAIRE

    Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Christine M Gall; Lynch, Gary; Baram, Tallie Z.

    2010-01-01

    Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly ...

  10. The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C.

    Science.gov (United States)

    Piche, T; Vandenbos, F; Abakar-Mahamat, A; Vanbiervliet, G; Barjoan, E M; Calle, G; Giudicelli, J; Ferrua, B; Laffont, C; Benzaken, S; Tran, A

    2004-01-01

    Recent attention has focused on the liver profibrogenic role of leptin in animal models. The purpose of this study was to evaluate the role of leptin and TNF-alpha in the severity of liver fibrosis in patients with chronic hepatitis C (CHC). We used a radioimmunoassay to determine serum leptin concentrations in 77 consecutive patients with CHC and 22 healthy controls. Leptin was correlated with liver histological (METAVIR) and metabolic indices. Sixty five patients had none to moderate liver fibrosis (F0-F2) and twelve severe fibrosis (F3-F4). Steatosis was observed in all but 27 patients. Leptin was significantly increased in patients compared with controls and was significantly more elevated in females both in patients and controls. The age, age at infection, prothrombin index, body mass index (BMI), triglycerides, glycaemia, ferritin, leptin and TNF-alpha, were associated with severe fibrosis. Steatosis was significantly more pronounced in patients with severe than those without or moderate fibrosis (P = 0.04). Only leptin was significantly and independently associated with severe fibrosis (OR = 1.2, CI 95%: 1.1-1.4, P = 0.03). Leptin was significantly associated with BMI (r = 0.64, P < 0.001) and glycaemia (r = 0.43, P < 0.001). Significant correlations were found between steatosis and BMI (r = 0.30, P < 0.01) and glycaemia (r = 0.30, P < 0.01). In patients with CHC and higher BMI and glycaemia levels, the severity of liver fibrosis is associated with serum leptin. TNF-alpha is a putative candidate involved in the mechanism. PMID:14738564

  11. Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Elegance Ting Pui Lam; Cindy Lo Kuen Lam; Ching Lung Lai; Man Fung Yuen; Daniel Yee Tak Fong

    2009-01-01

    AIM: To test the psychometric properties of a Chinese [(Hong Kong) HK] translation of the chronic liver disease questionnaire (CLDQ).METHODS: A Chinese (HK) translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B (CHB) patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese (HK) SF36Health Survey Version 2 (SF36v2).RESULTS: Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two (Fatigue and Systemic Symptoms) subscales tended to load on the same factor. Internal consistency and testretestreliabilities ranged from 0.580.90fordifferent subscales. Construct validity was confirmed by the expected correlations between the SF36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION: The Chinese (HK) CLDQ is valid,reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties.

  12. Prevalence of HBV and/or HDV markers using RIA in patients with chronic liver disease

    International Nuclear Information System (INIS)

    Sixty six with different chronic liver disease (CLD) were studied for the prevalence of HBV and/or HDV markers using radioimmunoassay. The total prevalence of HBV markers (i.e. when any of the markers is present) for chronic active hepatitis (CAH), post viral cirrhosis, chronic persistent hepatitis (CPH), cryptogenic cirrhosis, primary biliary cirrhosis (PBC), alcoholic cirrhosis, hepatocellular carcinoma (HCCA) and methyldopa induced chronic hepatitis were 6/13 (46.2%), 6/6 (100%), 7/9 (77.8%), 0/10, 0/2, 10/15 (66.7%), 7/10 (70%) and 0/1 respectively; whereas the total prevalence of anti-delta antibody was 0/13, 1/6 (16.7%), 3/9 (33.3%), 0/10 0/2, 0/15, 2/10 (20%) and 0/1 respectively, while the prevalence of anti-delta antibody for the control group was 4/102 (3.9%). Various patients with CLD, though they showed various viral markers yet they showed different pattern groups. 3 tabs

  13. Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications

    Directory of Open Access Journals (Sweden)

    Zsuzsa eSzondy

    2014-08-01

    Full Text Available In healthy individuals billions of cells die by apoptosis every day. Removal of the dead cells by phagocytosis (a process called efferocytosis must be efficient to prevent secondary necrosis and the consequent release of proinflammatory cell contents that damages the tissue environment and provokes autoimmunity. In addition, detection and removal of apoptotic cells generally induces an anti-inflammatory response. As a consequence improper clearance of apoptotic cells, being the result of either genetic anomalies and /or a persistent disease state, contributes to the establishment and progression of a number of human chronic inflammatory diseases such as autoimmune and neurological disorders, inflammatory lung diseases, obesity, type 2 diabetes or atherosclerosis. During the past decade our knowledge about the mechanism of efferocytosis has significantly increased, providing therapeutic targets through which impaired phagocytosis of apoptotic cells and the consequent inflammation could be influenced in these diseases.

  14. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Debmalya Sanyal

    2015-01-01

    Full Text Available Context: The perception of non-alcoholic fatty liver disease (NAFLD as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT, new onset treatment naive T2DM and normal glucose tolerance (NGT with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables, Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT 40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary

  15. Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity

    Institute of Scientific and Technical Information of China (English)

    Enver Mahir Gulcan; Ipek Tirit; Ayse Anil; Erdal Adal; Gulsen Ozbay

    2008-01-01

    AIM: To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease.METHODS: The study population comprised 48 patients with chronic active hepatitis B, 32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked irnmunosorbent assay.RESULTS: The mean ±SD serum neopterin levels were 14.2±5.6 nmol/L in patients with chronic hepatitis, 20.3±7.9 nmol/L in patients with liver cirrhosis and 5.2±1.4 nmol/L in control group. Serum neopterin levels were significantly higher in patients with chronic hepatitis (P = 0.005) and cirrhosis patients (P =0.008), than in control subjects. Cirrhotic patients had significantly higher serum neopterin levels than patients with chronic hepatitis (P=0.004). There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis (r = 0.41, P = 0.004) and cirrhotic patients (r = 0.39, P = 0.005). Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis (r = 0.51, P = 0.003) and cirrhotic patients (r = 0.49, P = 0.001).CONCLUSION: Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.

  16. The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

    Science.gov (United States)

    Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N

    2014-11-28

    Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

  17. Clinical Observation on Effect of Ruangan Granule (软肝颗粒剂 ) in Treating Chronic Hepatitic Liver Fibrosis

    Institute of Scientific and Technical Information of China (English)

    李秀惠; 赵春惠; 金荣华; 黄春

    2002-01-01

    Objective: To observe the clinical effect of Ruangan granule (RGG) in treating liver fibrosis.Methods: One hundred and twenty patients of chronic viral hepatitis B were randomly divided into two groups, 60 patients in the treated group and 60 patients in the control group. They were treated with RGG or composite Biejia Ruangan tablet (复方鳖甲软肝片) respectively for three months. The changes of liver function, liver fibrosis indices, including fibronectin (FN), laminin (LN) and hyaluronic acid (HA), as well as liver morphology by B-ultrasonic examination were observed after treatment. A three-month follow-up study was also conducted. Results: In the treated group, the markedly effective rate was 50.0% and effective rate was 41.7%, while in the control group, the corresponding rates were 26.7% and 55.0% respectively. Comparison of the markedly effective rate between the two groups showed significant difference (P<0.01). The serum levels of FN, LN, HA as well as splenomegaly and portal vein widening in the treated group after treatment were significantly improved (P<0.05), as compared with those in the control group after treatment; significant difference was shown in comparison of serum FN, LN and HA. Conclusion: RGG could improve effectively serum liver fibrosis indices and liver function in patients of chronic hepatitic fibrosis. It is helpful in alleviating and inhibiting the genesis and development of liver fibrosis so as to block the progression of liver cirrhosis.

  18. Graft loss following liver transplantation in patients with chronic hepatitis C.

    Science.gov (United States)

    Rosen, H R; O'Reilly, P M; Shackleton, C R; McDiarmid, S; Holt, C; Busuttil, R W; Martin, P

    1996-12-27

    Liver disease due to hepatitis C (HCV) is an increasingly frequent indication for orthotopic liver transplantation (OLT). The aim of the current study was to analyze the causes of graft loss following OLT for chronic hepatitis C and the longterm outcome following retransplantation in a large university program. Between January 1990 and December 1995, 1183 patients underwent primary OLT at our center. In 304 patients, HCV was diagnosed by seropositivity and/or polymerase chain reaction. Fifty-six (18.4%) of these patients underwent retransplantation. The 36 patients retransplanted for primary non-function were excluded from further analysis. The other indications for regrafting (>30 days following primary transplant) included hepatic artery thrombosis (5), chronic rejection (4), severe HCV recurrence (5), and other etiologies (6). The cumulative survival rates for the 248 patients who received 1 OLT (group 1) were 84% after one year and 75% after three years. The corresponding rates for the 20 non-PNF patients who were retransplanted (group 2) were 60% and 43%, respectively (Pindication for reOLT does not appear to impact ultimate outcome. Serious infectious complications were the leading cause of mortality in patients retransplanted. Furthermore, given the indolent natural history of HCV, longer follow-up is necessary to determine the ultimate rate of graft loss due to HCV recurrence.

  19. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.

    Science.gov (United States)

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-03-28

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. PMID:24696595

  20. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

    Science.gov (United States)

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  1. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood

    Directory of Open Access Journals (Sweden)

    Fernando Jáuregui-Huerta

    2011-01-01

    Full Text Available Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats′ audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5΄bromodeoxiuridine (BrdU, and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG, cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean΁standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.

  2. Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide.

    Science.gov (United States)

    Stanley, Dara A; Smith, Karen E; Raine, Nigel E

    2015-01-01

    Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness. PMID:26568480

  3. Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide.

    Science.gov (United States)

    Stanley, Dara A; Smith, Karen E; Raine, Nigel E

    2015-11-16

    Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness.

  4. Liver transplantation for chronic graft-versus-host disease: case report with 10-year follow-up.

    Science.gov (United States)

    Orlando, Giuseppe; Ferrant, Augustin; Schots, Rik; Goffette, Pierre; Mathijs, Jules; Lemaire, Julien; Danse, Etienne; Talpe, Stéphanie; Latinne, Dominique; Lerut, Jan

    2005-01-01

    Graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). Chronic GVHD (cGVHD) may lead to irreversible liver failure. We report a case of successful liver transplantation (LT) for end-stage liver failure because of cGVHD that had developed 22 months after BMT in a 24-year-old male. Re-transplantation was necessary 6 months later because of intrahepatic ischaemic type biliary tract lesions. He is now in excellent condition 10 years after the first transplant. This experience and the review of literature indicate that LT can cure GVHD-related chronic liver failure. Recurrent GVHD in the allograft has not yet been reported. PMID:15612994

  5. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  6. Biochemical and histological alterations in liver following sub chronic exposure of arsenic

    Directory of Open Access Journals (Sweden)

    Madhuri Mehta

    2015-07-01

    Full Text Available Objective: Contamination of groundwater with arsenic is of global concern. The present work was aimed to evaluate the biochemical and histological changes in liver of female rats induced by sodium arsenite at doses naturally found in groundwater of Punjab. Method: Twenty four female rats were divided into four groups of 6 animals each. Group I animals received distilled water and served as control; Group II-IV received arsenic at the dose of 10, 30 and 50 ppb (μg/L dissolved in distilled water ad libitum for 30 days. At the end of experiment, animals were sacrificed and liver was collected for biochemical and histological evaluation. Results: Biochemical analysis showed an increase in the activity of hepatic marker enzymes including transferases, phosphatases and lactate dehydrogenase (LDH. Also, the levels of antioxidant enzymes (catalase, reduced glutathione and glutathione-S-transferase decreased significantly (P<0.05 in treated animals when compared to control. A significant (P<0.05 dose dependent increase in the levels of lipid peroxidation and arsenic concentration in liver tissue was observed. Histological examination showed the presence of pyknotic bodies (necrosis and sinusoidal dilation in hepatocytes of treated groups. Conclusion: Sub chronic exposure of arsenic at these doses induces hepatotoxicity leading to oxidative stress.

  7. Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Karam A Mahdy; Hanaa H Ahmed; Fathia Mannaa; Azza Abdel-Shaheed

    2007-01-01

    AIM: To investigate the association between serum insulin-like growth factor 1 (IGF-1), osteocalcin, and parathyroid hormone (PTH) levels with the etiology and clinical condition of patients with chronic liver disease.METHODS: Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection: bilharziasis (9 patients), hepatitis B virus (HBV, 12 patients) and hepatitis C virus (HCV, 29 patients). The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group. HBsAg, HBcAbIgM,HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). Antibilharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted.RESULTS: Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin (14.7 ± 0.54 vs 3.6± 0.10, P < 0.05), while that for PTH was positively correlated with total protein (70.1 ± 2.17 vs 6.7 + 0.10,P < 0.05) in patients with HCV infection.CONCLUSION: Low serum IGF-1 level seems to play a critical role in the bone loss in patients with chronic liver disease. Elevated biochemical markers of bone remodeling suggest high-turnover in patients with viral infection and reflect severity of the clinical stage.

  8. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

    Science.gov (United States)

    Valencia, C. Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R.; Moran, Molly C.; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E.; Witte, David; Huang, Taosheng; Miethke, Alexander G.

    2016-01-01

    Background & Aims The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Methods Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis. Results A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy. Conclusion Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF. PMID:27483465

  9. Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

    Indian Academy of Sciences (India)

    Sebnem Atici; Ismail Cinel; Leyla Cinel; Nurcan Doruk; Gulcin Eskandari; Ugur Oral

    2005-03-01

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group ( = 10). Morphine group ( = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group ( = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups ( < 0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage.

  10. Osseous and Nonosseous Bone Scan Findings in Liver Transplant Candidates with end-stage Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Seval Erhamamcı

    2013-08-01

    Full Text Available Objective: End-stage chronic liver disease (CLD adversely affects the function of multiple organ systems including the skeletal system. The aim of this study was to assess osseous and nonosseous bone scintigraphy (BS findings in liver transplant (LT candidates with end-stage CLD. Methods: We retrospectively evaluated BS findings in 50 consecutive patients with end-stage CLD who were undergoing preoperative assessment for LT from January 2006 to December 2011. All the patients were analyzed with respect to clinical and laboratory parameters, and BS findings. Scintigrams were visually assessed for the presence of osseous and nonosseous abnormalities. Osseous abnormalities were classified as those indicating bone metabolism changes or metastatic bone disease. Typical scintigraphic findings denoting to changes in bone metabolism were the presence of decreased osseous uptake, increased periarticular uptake, asymmetrical or unusual uptake patterns. Nonosseous findings were classified according to the degree of soft-tissue uptake as mild and severe. Results: The group consisted of 46 adult and 4 adolescent patients. All adolescent patients had normal skeletal accumulation with growth plate uptake and one had mildly increased renal cortical activity. A total of 46 adult patients had one or more of the following osseous findings: generalized decrease in osseous uptake (n=4, 8.7%; bilateral decrease in lower extremity uptake (n=26, 56.5%; symmetrically increased periarticular uptake (n=26, 56.5%; bilateral cortical/periosteal increased uptake in the lower extremity indicating hepatic hypertrophic osteoarthropathy (HOA (n=8, 17.4%; bilateral increased sacroiliac activity (n=16, 34.8%; sacral activity (n=10, 21.7%, coccygeal activity (n=2, 4.3%, focally increased uptake suggestive of metastases (n=5, 10.9%. Three rib metastases appeared to be linear. Nonosseous findings observed in adult patients were mild diffuse liver uptake (n=4, 8.7% and bilateral

  11. Effects of a cognitive behavioral self-help program on depressed mood for people with acquired chronic physical impairments : A pilot randomized controlled trial

    NARCIS (Netherlands)

    Garnefski, Nadia; Kraaij, Vivian; Schroevers, Maya

    2011-01-01

    Objective: Aim was to examine whether a new cognitive-behavioral self-help intervention program was effective in improving depressed mood in people with acquired chronic physical impairments. Methods: Participants were 32 persons with acquired chronic physical impairments and depressive symptoms, wh

  12. Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease.

    OpenAIRE

    Chapman, R W; Gorman, A; Laulicht, M; Hussain, M.A.; Sherlock, S; Hoffbrand, A V

    1982-01-01

    Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in ...

  13. Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Cristina Irimia

    Full Text Available Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT, a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

  14. Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Somaya Hashem

    2016-01-01

    Full Text Available Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0–F2 or advanced (F3-F4 fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy.

  15. Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice

    Institute of Scientific and Technical Information of China (English)

    Qi KE; Rui-na YANG; Feng YE; Yu-jia WANG; Qiong WU; Li LI; Hong BU

    2012-01-01

    Background and objective:Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors.A variety of genetic factors have been reported,whereas few investigations have focused on epigenetic regulation during liver regeneration.In the present study,valproic acid (VPA),a histone deacetylase (HDAC)inhibitor,was used to investigate the effect of HDAC on liver regeneration.Methods:VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration.The mice were sacrificed,and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment.DNA synthesis was detected via a BrdU assay,and cell proliferation was tested using Ki-67.The expressions of cyclin D1,cyclin E,cyclin dependent kinase 2 (CDK2),and CDK4 were detected by Western blot analysis.Chromatin immunoprecipitation (ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot.Results:Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased,and the peak of BrdU was delayed in the VPA-administered mice.Consistently,cyclin D1 expression was also delayed.We identified B-myc as a target gene of HDACs by complementary DNA (cDNA) microarray.The expression of B-myc increased in the VPA-administered mice after hepatectomy (PH).The ChIP assay confirmed the presence of HDACs at the B-myc promoter.Conclusions:HDAC activities are essential for liver regeneration,inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest,thereby causing an anti-proliferative effect on liver regeneration.

  16. Pathology of heart, lung, liver and kidney in broilers under chronic heat stress

    Directory of Open Access Journals (Sweden)

    Worapol Aengwanich

    2005-05-01

    Full Text Available The purpose of this experiment was to investigate pathological changes in broilers under chronic heat stress. Fifteen birds (n = 15, twenty-eight days old were kept at 33 + 1oC environmental temperature for 21 days. While broilers were maintained in environmental temperature at 33 + 1 oC, body temperature, respiratory rate and urine excretion rose. Macroscopic and microscopic lesions of heart, lung, liver and kidney were examined. Right atrium hypertrophy with excessive blood accumulation, heart enlargement and right ventricular hypertrophy were observed in 12 out of 15 broilers (80%. Congestion, edema and hyperemia in lung were present in all broilers. Yellow and pale livers were observed in 4 out of 15 broilers (26.67%. Kidneys were highly affected i.e. generalized edema and hemorrhage in subrenal capsule. Under microscopic examination of heart, massive myofibrillar degeneration with hemorrhage, general fatty degeneration /or/ vacuolation of myofibers and diffused myocarditis containing organisms were found in some areas. The principal histopathologic lesions in the lung were related to vein and arteriole massive congestion. Massive hemorrhage was largely observed in parabronchus and alveoli of all broilers. Liver cells showed “fatty degeneration” with dilation of sinusoid of all broilers. Besides, necrosis with heterophils and lymphocytes was observed in some parts of the liver, especially in the centritubular region. In the kidney, leukocytes such as heterophils accumulated in many inflammatory areas. Fatty degeneration was observed in renal tubular epithelia of all broilers. Glomeruli were damaged. A space between renal papillae increased and accumulated water. Moreover, ureters in 9 out of 15 (60% birds showed sac-like expansion “ureteral pseudobladder”. These sacs were filled with urine and similar to bladder in mammals.

  17. Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake.

    Science.gov (United States)

    Kim, Dongyeop; Kim, Gyeong-Woo; Lee, Seon-Ho; Han, Gi Dong

    2016-08-01

    Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia. Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo. Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95 g/kg of body weight/d) with or without LF extract (100 or 200 mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity. Results The EC50 value for the DPPH radical scavenging capacity of LF extract was 451.5 μg/mL, whereas the IC50 value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3 μg/mL without cell cytotoxicity. LF extract (200 mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-α, and attenuated alcohol-induced abnormal morphological changes. Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake. PMID:26799831

  18. Raltegravir, tenofovir, and emtricitabine in an HIV-Infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver Toxicity

    Directory of Open Access Journals (Sweden)

    Ortu F

    2010-02-01

    Full Text Available Abstract Background in HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options. Case Description we here describe the case of an HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects. Conclusions given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.

  19. The heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

    2009-01-01

    Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...... against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease...

  20. The soluble macrophage activation markers sCD163 and Mannose Receptor (sMR) predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Rødgaard-Hansen, Sidsel; Aagaard, Niels Kristian;

    2015-01-01

    INTRODUCTION: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose-receptor (sMR...

  1. Characteristics of highly impaired children with severe chronic pain: a 5-year retrospective study on 2249 pediatric pain patients

    Directory of Open Access Journals (Sweden)

    Zernikow Boris

    2012-05-01

    Full Text Available Abstract Background Prevalence of pain as a recurrent symptom in children is known to be high, but little is known about children with high impairment from chronic pain seeking specialized treatment. The purpose of this study was the precise description of children with high impairment from chronic pain referred to the German Paediatric Pain Centre over a 5-year period. Methods Demographic variables, pain characteristics and psychometric measures were assessed at the first evaluation. Subgroup analysis for sex, age and pain location was conducted and multivariate logistic regression applied to identify parameters associated with extremely high impairment. Results The retrospective study consisted of 2249 children assessed at the first evaluation. Tension type headache (48%, migraine (43% and functional abdominal pain (11% were the most common diagnoses with a high rate of co-occurrence; 18% had some form of musculoskeletal pain disease. Irrespective of pain location, chronic pain disorder with somatic and psychological factors was diagnosed frequently (43%. 55% of the children suffered from more than one distinct pain diagnosis. Clinically significant depression and general anxiety scores were expressed by 24% and 19% of the patients, respectively. Girls over the age of 13 were more likely to seek tertiary treatment compared to boys. Nearly half of children suffered from daily or constant pain with a mean pain value of 6/10. Extremely high pain-related impairment, operationalized as a comprehensive measure of pain duration, frequency, intensity, pain-related school absence and disability, was associated with older age, multiple locations of pain, increased depression and prior hospital stays. 43% of the children taking analgesics had no indication for pharmacological treatment. Conclusion Children with chronic pain are a diagnostic and therapeutic challenge as they often have two or more different pain diagnoses, are prone to misuse of

  2. Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of ...

  3. Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2014-09-01

    Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients.

  4. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    Science.gov (United States)

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  5. Chronic liver disease prevention strategies and liver transplantation Estratégias de prevenção da doença hepática crônica e transplante de fígado

    OpenAIRE

    Anderson Soares da Silva; Luciane Loures dos Santos; Afonso Dinis Costa Passos; Ajith Kumar Sankarankutty; Ana de Lourdes Candolo Martinelli; Orlando de Castro e Silva

    2006-01-01

    Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80% of the end st...

  6. TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mee Juhng Jeon; Jong Hee Shin; Soon Pal Suh; Yong Chai Lim; Dong Wook Ryang

    2003-01-01

    AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage.METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n= 110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n= 19).TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined.RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1% of HBsAg-positive donors, 20.3 % of antiHCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1% of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6% of patients with type B chronic liver disease, and 10.5% of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05),except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7% of TTV DNA-positive patients and 76.9% of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients.CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant

  7. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  8. Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Silvia Sookoian; Maria Alejandra Fernández; Gustavo Casta(n)o

    2005-01-01

    AIM: To evaluate the safety and efficacy of chronic administration of losartan on hepatic fibrosis in chronic hepatitis C patients.METHODS: Fourteen patients with chronic hepatitis C non-responders (n = 10), with contraindications (n = 2)or lack of compliance (n = 2) to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after losartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies (interval 6-14 mo).Histological activity index (HAI) with fibrosis stage was assessed under blind conditions by means of Ishak's score. Subendothelial fibrosis was evaluated by digital image analyses.RESULTS: The changes in the fibrosis stage were significantly different between losartan group (decrease of 0.5±1.3) and controls (increase of 0.89±1.27;P<0.03). In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients (P<0.04). A decrease in sub-endothelial fibrosis was observed in the losartan group. No differences were found in HAI after losartan administration. Acute and chronic decreases in systolic arterial pressures (P<0.05)were observed after the losartan administration, without changes in mean arterial pressure or renal function.CONCLUSION: Chronic AT-Ⅱ type 1 receptor (AT1R)blockade may reduce liver fibrosis in patients with chronic hepatitis C.

  9. [An establishment of theoretical structure of PRO questionnaire in treating chronic liver disease by Chinese medicine].

    Science.gov (United States)

    Wang, Li; Zhang, Hua; Yuan, Wei-An; Wang, Yi-Xing; Tang, Jie; Cui, Chen; Zeng, Jin; Miao, Ping; Jiang, Jian

    2014-11-01

    By reviewing research contents of patient-reported outcome (PRO) and discussing Chinese medicine (CM) theories related to chronic liver disease (CLD), we have followed international PRO questionnaire development specification, combined CM theories such as uniformed spirit and body, correspondence between human and the universe, yin in property and yang in function of Gan, and seven emotions, and constructed theoretical structure of PRO questionnaire of treating CLD, including four major areas as physiology, psychology, independence, and society and nature. Of them, the physiological field contained six aspects such as blood deficiency, yin deficiency, bleeding, disorder of qi movement, improper transformation and transportation of Pi-Wei, and abnormal biliary excretion. The psychological field contained two aspects: Gan-related emotions and general disease related emotions. The independence field contained two aspects: daily life and study and work. The field of society and nature contains three aspects: social relations, social environment, and natural adaptability. PMID:25566635

  10. Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jie Shao; Lai Wei; Hao Wang; Yan Sun; Lan-Fang Zhang; Jing Li; Jian-Qiang Dong

    2007-01-01

    AIM: To study the relationship between hepatitis B virus (HBV) DNA levels and liver histology in patients with chronic hepatitis B (CHB) and to determine the prevalence and characteristics of hepatitis B e antigen (HBeAg) negative patients.METHODS: A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage (liver histology and biochemistry) was explored.RESULTS: Of the 213 patients with serum HBV DNA levels higher than 105 copies/mL, 178 (83.6%) were HBeAg positive, 35 (16.4%) were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse (ALT),aspartate aminotrans-ferase (AST) in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT (r = 0.351, P = 0.042). The grade (G) of liver disease correlated with ALT and AST (P < 0.05, r = 0.205, 0.327 respectively)in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G (P < 0.01, and r = 0.862, 0.802 respectively). HBeAg negative patients were older (35 ± 9 years vs 30 ±9 years, P < 0.05 ) and had a longer history of HBV infection (8 ± 4 years vs 6 ± 4 years, P < 0.05) and a lower HBV DNA level than HBeAg positive patients (8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P <0.001). There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.CONCLUSION: Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 105 copies

  11. Is high AgNOR quantity in hepatocytes associated with increased risk of hepatocellular carcinoma in chronic liver disease?

    Science.gov (United States)

    Derenzini, M; Trerè, D; Oliveri, F; David, E; Colombatto, P; Bonino, F; Brunetto, M R

    1993-01-01

    AIMS--To evaluate whether high numbers of silver staining nucleolar organiser regions (AgNORs) in hepatocytes are associated with increased risk of hepatocellular carcinoma in chronic liver disease. METHODS--The quantitative distribution of AgNORs was studied in the liver biopsy specimens of 33 patients with chronic liver disease, 11 of whom developed hepatocellular carcinoma. The interval between liver biopsy and diagnosis of hepatocellular carcinoma was 26 months (range one to 61 months); the mean follow up of patients without hepatocellular carcinoma was 45 months (range 24-59 months). Quantitative evaluation of AgNORs was carried out on silver stained routine sections by morphometric analysis, using a computer assisted image analysis system. RESULTS--High interphase AgNOR values (> 3 microns2) were found in hepatocytes of nine out of the 11 (82%) patients in whom neoplastic transformation occurred. Of the remaining 22 patients, only seven (31%) had AgNOR values higher than > 3 microns2 (chi 2 4.83; p = 0.036). CONCLUSIONS--These results indicate that high numbers of interphase AgNORs are associated with increased risk of hepatocellular carcinoma in patients with chronic liver disease. Images PMID:8408696

  12. "Liverscore" is predictive of both liver fibrosis and activity in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Shoukat Ali Arain; Qamar Jamal; Amir Omair

    2011-01-01

    AIM: To formulate a noninvasive index predictive of severity of liver fibrosis and activity in chronic hepatitis C.METHODS: This cross sectional study was conducted on polymerase chain reaction positive, treatment na(i)ve patients. Fibrosis was staged on a five point scale from F0-F4 and activity was graded on a four point scale from A0-A3, according to the METAVIR system. Patients were divided into two overall severity groups, minimal disease (< F2 and < A2) and significant disease (≥ F2 or ≥ A2). Eleven markers were measured in blood. Statistically, the primary outcome variable was identification of minimal and significant overall disease. Indices were formulated using β regression values of different combinations of nine statistically significant factors.Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis.RESULTS: A total of 98 patients were included and of these 46 had an overall clinically significant disease. Our final six marker index, Liverscore for Hepatitis C, consisted of age, alanine transaminase, gamma-glutamyl transpeptidase, apolipoprotein A-1, alpha-2 macroglobulin and hyaluronic acid. The area under the curve was found to be 0.813. On a 0-1 scale, negative predictive value at a cutoff level of ≤ 0.40 was 83%, while positive predictive value at ≥ 0.80 remained 89%. Altogether,61% of the patients had these discriminative scores.CONCLUSION: This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical decision making.

  13. [A Case of Composite Hepatocellular Carcinoma and Neuroendocrine Carcinoma in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B].

    Science.gov (United States)

    Yun, Eun Young; Kim, Tae Hyo; Lee, Sang Soo; Kim, Hong Jun; Kim, Hyun Jin; Jung, Woon Tae; Lee, Ok Jae; Song, Dae Hyun

    2016-08-25

    Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis. PMID:27554219

  14. Personal view: a potential novel treatment for fatigue complicating chronic liver disease - how should its efficacy be evaluated?

    NARCIS (Netherlands)

    E.A. Jones

    2006-01-01

    Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagoni

  15. Hepatitis E virus genotype three infection of human liver chimeric mice as a model for chronic HEV infection

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn); S.D. Pas (Suzan); G. van der Net (Guido); R.A. de Man (Robert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); A. Boonstra (Andre); T. Vanwolleghem (Thomas)

    2016-01-01

    textabstractGenotype (gt) 3 hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vi

  16. Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

    OpenAIRE

    Gao, Dan-Dan; Fu, Jia; Qin, Bo; Huang, Wen-Xiang; Yang, Chun; Jia, Bei

    2016-01-01

    AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).

  17. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  18. Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

    International Nuclear Information System (INIS)

    Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-114Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls

  19. Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. (II Division of Gastroenterology, University of Rome La Sapienza (Italy))

    1991-07-01

    Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1{sup 14}Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls.

  20. Usefulness of non-invasive serum markers for predicting liver fibrosis in Egyptian patients with chronic HCV infection.

    Science.gov (United States)

    El Guesiry, Dalal; Moez, Pacinte; Hossam, Nermine; Kassem, Mohamed

    2011-01-01

    Accurate monitoring of liver fibrosis changes in patients with hepatitis C virus (HCV) infection would be helpful in defining the need to intervene, implement the appropriate response in treatment and to minimize the use of liver biopsy. We aimed to evaluate the diagnostic utility of the different serum markers and indices in detecting liver fibrosis in study patients. Initial liver biopsy, routine liver function tests, estimation of hyaluronic acid, MMP-1, and PIIINP levels was performed for 30 Egyptian patients with HCV and 15 controls. Marker algorithms based on common laboratory such APRI score, Fibrotest and Actitest. PIIINP and MMP-1 serum markers were combined and entered into a stepwise logistic regression analysis with formulation of a score equation for fibrosis staging. Combined PIIINP and MMP-1 yielded different cut off scores to estimate two clinically relevant fibrosis stages: "significant fibrosis" versus "extensive fibrosis. Apri score also showed AUC of 1.0 with 100 % sensitivity and specificity to exclude the presence of cirrhosis and was significantly correlated to Metavair fibrosis stage in early fibrosis. On the other hand, PIIINP, Fibrotest and acti test were significantly correlated to Metavair fibrosis stage in both early and late fibrosis. In conclusion, integrating PIIINP/MMP-1 score was able to provide reliable information about the degree of liver fibrosis in chronic hepatitis C patients using different cut-offs values. A combination of liver markers as well as its related indices is an emerging tool to differentiate early from advanced liver fibrosis in HCV patients. PMID:23082465

  1. Occurrence of chronic renal failure in liver transplantation: monitoring of pre- and posttransplantation renal function.

    Science.gov (United States)

    Umbro, I; Tinti, F; Piselli, P; Fiacco, F; Giannelli, V; Di Natale, V; Zavatto, A; Merli, M; Rossi, M; Ginanni Corradini, S; Poli, L; Berloco, P B; Mitterhofer, A P

    2012-09-01

    The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.

  2. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

    Science.gov (United States)

    Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

    2015-02-01

    Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.

  3. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  4. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

    Directory of Open Access Journals (Sweden)

    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  5. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  6. Trends of chronic liver disease in a tertiary care referral hospital in Eastern India

    Directory of Open Access Journals (Sweden)

    Gautam Ray

    2014-01-01

    Full Text Available Background: There is scarce Indian data on time trends of hepatitis, an impediment to formulate an effective public health policy on the matter. Objective: The aim was to study secular trends and burden of hepatitis in a railway population. Materials and Methods: Outdoor, indoor, endoscopy unit and mortality records of patients attending this hospital from January 2003 to December 2011 were searched manually and relevant parameters of hepatitis patients were noted, especially etiology, clinical features, treatment, and mortality. Cochran-Armitage trend test was used to test significance of any trend in these parameters. Binary logistic regression analysis of various factors was carried out to study their effect on the liver related mortality of hepatitis B and C cases and Kaplan-Meyer survival curves were generated for significant factors. Two-sided P < 0.05 was considered to be significant. Result: Chronic liver disease (CLD due to alcohol showed a significant rising trend with early age (mean 48.4 years and high percentage of decompensated disease (75% at presentation and high early mortality (63%. No trend was observed for hepatitis B and C, but significant reduction in mortality was observed when definitive therapy was given. Cryptogenic CLD showed a decreasing trend though overall it still remained the most important etiology and survival was better compared with alcohol even with conservative therapy. Only 4% patients had hepatocellular carcinoma. Conclusion: A menace of alcohol related liver disease affecting young productive work force in this part of India is foreseen, which might impact the country′s economy and mandates immediate containment policy.

  7. Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis?

    Institute of Scientific and Technical Information of China (English)

    Paulo; Herman; Marcos; V; Perini; Vincenzo; Pugliese; Julio; Cesar; Pereira; Marcel; Autran; C; Machado; William; A; Saad; Luiz; AC; D; Albuquerque; Ivan; Cecconello

    2010-01-01

    AIM:To evaluate the long-term results of liver resection for the treatment of primary intrahepatic lithiasis.Prognostic factors,especially the impact of bilioenteric anastomosis on recurrence of symptoms were assessed.METHODS:Forty one patients with intrahepatic stones and parenchyma fibrosis/atrophy and/or biliary stenosis were submitted to liver resection.Resection was associated with a Roux-en-Y hepaticojejunostomy in all patients with bilateral stones and in those with unilateral disease and dilation of...

  8. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  9. Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    Chunling Zhao; Yan Chen; Chunlai Zhang; Linya Lü; Qian Xu

    2011-01-01

    The present study established a rat model of chronic intermittent hypoxia (CIH) to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase (ChAT) and nicotinic acetylcholine receptor (nAChR) expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinergic activity may be involved in CIH-induced cognitive impairment in rats.

  10. Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior.

    Directory of Open Access Journals (Sweden)

    Austin Chou

    Full Text Available Traumatic brain injury (TBI is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior.

  11. Etiology of newly-diagnosed cases of chronic liver disease in Southern Italy: results of a prospective multicentric study

    Directory of Open Access Journals (Sweden)

    Antonio Ascione

    2013-11-01

    Full Text Available The pattern of liver diseases has radically changed in our country over the last few decades. We prospectively collected data on the newly-diagnosed cases of chronic liver diseases in a region of southern Italy after about a decade from the last epidemiological study. We conducted a multicentric prospective study that enrolled 631 patients from 21 Liver Centers of the Campania region (Southern Italy at their first hospital admission or at their first outpatient visit. In our cohort of 631 patients (367 males, 263 females, 397 (62.9% were hepatitis C virus (HCV positive, 75 (11.9% were hepatitis B virus (HBV positive, 8 (1.3% were co-infected by HBV and HCV, 73 (11.6% had an alcoholic liver disease and 64 (10.1% had a nonalcoholic fatty liver disease. HBV infection was present in young people with a higher-than-expected prevalence, despite the vaccination program which should have involved this population. HCV chronic hepatitis still remains the most common cause of liver disease in our region. HBV infection still continues to represent a health problem in young people, despite the vaccination program.

  12. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma.

    Science.gov (United States)

    Giannitrapani, Lydia; Soresi, Maurizio; Balasus, Daniele; Licata, Anna; Montalto, Giuseppe

    2013-04-28

    Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC. PMID:23674845

  13. Comparison of collagen proportionate areas in liver fibrosis quantification between chronic hepatitis B and C

    Science.gov (United States)

    Chen, Sheng-Hung; Peng, Cheng-Yuan; Chiang, I-Ping; Lai, Hsueh-Chou; Lee, Chiung-Ju; Su, Wen-Pang; Kao, Jung-Ta; Chuang, Po-Heng

    2016-01-01

    Abstract Few studies have compared the distinct hepatic collagen morphometrics of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). This study compared the discrepancies between CHB and CHC in liver fibrosis (F) quantification by using the collagen proportionate area (CPA) and liver stiffness (LS) measured with shear wave velocity (SWV). This study enrolled 274 eligible consecutive patients diagnosed with CHB (n = 137) or CHC (n = 137). Their ages ranged from 20 to 80 years (median = 50). In total, 154 patients (56.2%) were male. Participant LS was measured by using acoustic radiation force impulse elastography preceding an immediate percutaneous liver biopsy. The total proportion of the collagen stained with picrosirius red to the total tissue area was expressed as the CPA percentage, which was stratified into portal–bridging (PB) and perisinusoidal (PS) proportionate areas (PAs). Based on the METAVIR F staging system, 36 (26.3%), 36 (26.3%), 28 (20.4%), and 37 (27.0%) participants in the CHB group and 34 (24.8%), 45 (32.9%), 34 (24.8%), and 24 (17.5%) participants in the CHC group were staged as F1, F2, F3, and F4, respectively. Both the total CPAs and PBPAs were significantly (P < 0.05) higher in the CHC group than in the CHB group within all F-stratified subgroups. The SWVs were significantly (P < 0.05) higher in the CHC group than in the CHB group only within the F2, F3, and F4 subgroups. However, the PSPAs did not differ significantly between the CHC and CHB groups within all subgroups. Multiple regression analysis revealed that viral hepatitis etiology (P < 0.001), METAVIR F stages (P < 0.001), and platelet count (P = 0.007) were independent factors correlated with the CPA (R2 = 0.543, P < 0.001). In conclusion, both the F stage-stratified CPAs and SWVs tended to be higher in cases of CHC than in those of CHB. The type of viral hepatitis significantly affected both the CPA and SWV values. The PBPAs were more

  14. Impairment of liver and kidney functions in gamma irradiation rats suffering pesticide toxicity

    International Nuclear Information System (INIS)

    The effect of exposure to single whole body gamma irradiation dose at 6.5 Gy and/or either oral administration of 50 or 100 mg kelthane/kg kelthane/kg body weight/day for successively 3 days, or daily feeding with 200 mg kelthane/kg body weight for 3, 6, and 12 weeks has been studied on relative liver and kidney weights, certain serum and liver enzymes creatinine and inorganic phosphorous clearance, as well as percentage of tubular phosphorous reabsorption in male animals. The data obtained revealed that exposure to gamma-irradiation alone or combined with kelthane treatment caused significant increase in the relative spleen weight besides significant decrease in serum and liver alkaline phosphatase and serum cholinesterase. Exposure to gamma irradiation after orally administration of 100 mg or feeding dietary kelthane caused significant decrease in liver glucose-6-phosphatase. Non significant changes in aspartic and alanine transaminases could be recorded due to gamma-irradiation and/or kelthane treatment. Endogenous clearance of creatinine and phosphorous as well as tubular phosphorous reabsorption were determined to assess the glomerular filtration and tubular function. The data obtained revealed that exposure to gamma-irradiation either alone or after treatment with kelthane caused significant decrease in creatinine and phosphorous clearance while phosphorous reabsorption was not appreciably affected. 4 tabs

  15. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin...

  16. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  17. Determination of antibody to hepatitis B core antigen by radioimmunoassay in chronic liver disease.

    Directory of Open Access Journals (Sweden)

    Mizuno,Motowo

    1980-06-01

    Full Text Available Antibody to hepatitis B core antigen (anti-HBc was measured by radioimmunoassay using CORAB (Abbott Laboratories in 10 cases of chronic persistent hepatitis (CPH, 46 cases of chronic aggressive hepatitis (CAH, 33 cases of liver cirrhosis (LC and 53 cases of hepatocellular carcinoma (HCC in relation to hepatitis B surface antigen (HBsAg and its antibody (anti-HBs. Ninety-eight point four percent of patients with HBsAg and 93.8% of patients with anti-HBs were positive for anti-HBc and the titers of anti-HBc in patients with HBsAg were significantly higher than those with anti-HBs. Thirty-five point five percent of patients negative for either HBsAg or anti-HBs were positive for anti-HBc. The titers of anti-HBc in patients with CPH, CAH and LC were relatively low, whereas 7 (46.8% of the HCC patients negative for either HBsAg or anti-HBc had high titers of anti-HBc. The significance of the presence of anti-HBc alone is discussed.

  18. Plasma erythropoietin levels in anaemic and non-anaemic patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Cosimo Marcello Bruno; Sergio Neri; Claudio Sciacca; Gaetano Bertino; Pietro Di Prima; Danila Cilio; Rinaldo Pellicano; Luciano Caruso; Raffaello Cristaldi

    2004-01-01

    AIM: To investigate the serum erythropoietin (Epo) levels in patients with chronic liver diseases and to compare to subjects with iron-deficiency anaemia and healthy controls.METHODS: We examined 31 anaemic (ALC) and 22 nonanaemic (NALC) cirrhotic patients, 21 non- anaemic subjects with chronic active hepatitis (CAH), 24 patients with irondeficiency anaemia (ID) and 15 healthy controls. Circulating UK) and haemoglobin (Hb) concentration were determined in all subjects.RESULTS: Mean±SD of Epo values was 26.9±10.8 mU/mL in ALC patients, 12.5±8.0 mU/mL in NALC subjects,11.6±6.3 mU/mL in CAH patients, 56.4±12.7 mU/mL in the cases of ID and 9.3±2.6 mU/mL in controls. No significant difference (P>0.05) was found in Epo levels between controls, CAH and NALC patients. ALC individuals had higher Epo levels (P<0.01) than these groups whereas ID subjects had even higher levels (P<0.001) than patients suffering from ALC.CONCLUSION: Increased Epo values in cirrhotics, are only detectable when haemoglobin was lesser than 12 g/dL.Nevertheless, this rise in value is lower than that observed in anaemic patients with iron-deficiency and appears blunted and inadequate in comparison to the degree of anaemia.

  19. Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 μg.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration. (author)

  20. Liver mortality attributable to chronic hepatitis C virus infection in Denmark and Scotland - using spontaneous resolvers as the benchmark comparator

    DEFF Research Database (Denmark)

    Innes, H; Hutchinson, S J; Obel, N;

    2016-01-01

    Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviours is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group, to uncover the independent...... contribution of CHC on liver mortality. Using national HCV diagnosis and mortality registers from Denmark and Scotland, we calculated the liver mortality rate (LMR) for persons diagnosed with CHC infection (LMRchronic ) and spontaneously resolved infection (LMRresolved ), according to subgroups defined by: age...... (where 0.00=not attributable at all; and 1.00=entirely attributable) of liver mortality attributable to CHC in the diagnosed population. Our cohort comprised 7005, and 21729 persons diagnosed with HCV antibodies in Denmark and Scotland, respectively. The mean follow up duration was 6.3-6.9 years. The TAF...

  1. Value of the 8-oxodG/dG ratio in chronic liver inflammation of patients with hepatocellular carcinoma.

    Science.gov (United States)

    Li, Pengcheng; Ramm, Grant A; Macdonald, Graeme A

    2016-08-01

    The aim of this study was to examine the role of oxidative DNA damage in chronic liver inflammation in the evolution of hepatocellular carcinoma. The accumulated data demonstrated that oxidative DNA damage and chronic liver inflammation are involved in the transformation of normal hepatocytes and their evolution towards hepatocellular carcinoma. However, the levels of 8-oxy-2'-deoxy-guanosine (8-oxodG), a biomarker of oxidative DNA damage, were overestimated and underestimated in previous reports due to various technical limitations. The current techniques are not suitable to analyze the 8-oxodG levels in the non-malignant liver tissues and tumors of hepatocellular carcinoma patients unless they are modified. Therefore, in this study, the protocols for extraction and hydrolysis of DNA were optimized using 54 samples from hepatocellular carcinoma patients with various risk factors, and the 8-oxodG and 2'-deoxyguanosine (dG) levels were measured. The patients enrolled in the study include 23 from The Princess Alexandra Hospital and The Royal Brisbane and Women's Hospitals, Brisbane, Australia, and 31 from South Africa. This study revealed that the 8-oxodG/dG ratios tended to be higher in most non-malignant liver tissues compared to hepatocellular carcinoma tissue (p=0.2887). It also appeared that the ratio was higher in non-malignant liver tissue from Southern African patients (p=0.0479), but there was no difference in the 8-oxodG/dG ratios between non-malignant liver tissues and tumors of Australian hepatocellular carcinoma patients (p=0.7722). Additionally, this study also revealed a trend for a higher 8-oxodG/dG ratio in non-malignant liver tissues compared to tumoural tissues of patients with HBV. Significant differences were not observed in the 8-oxodG/dG ratios between non-cirrhotic and cirrhotic non-malignant liver tissues. PMID:26890046

  2. The use of DWI to assess spleen and liver quantitative ADC changes in the detection of liver fibrosis stages in chronic viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Cece, Hasan, E-mail: hasan_cece@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Ercan, Abdulbasit, E-mail: abdulbasitercan@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Yıldız, Sema, E-mail: drsemayildiz@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Ekrem, E-mail: karakasekrem@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Omer, E-mail: dromerkarakas@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Boyacı, Fatıma Nurefsan, E-mail: drnurefsan@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Aydogan, Timucin, E-mail: drtaydogan@yahoo.com.tr [Harran University, Faculty of Medicine, Department of Gastroenterology, Sanliurfa (Turkey); Karakas, Emel Yigit, E-mail: e.ygtkarakas@yahoo.com.tr [Sanliurfa Training and Research Hospital, Department of İnternal Medicine, Sanliurfa (Turkey); Cullu, Nesat, E-mail: nesatcullu77@gmail.com [Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Radiology, Mugla (Turkey); Ulas, Turgay, E-mail: turgayulas@yahoo.com [Harran University, Faculty of Medicine, Department of İnternal Medicine, Sanliurfa (Turkey)

    2013-08-15

    This study aimed to evaluate the changes in spleen and liver diffusion-weighted magnetic resonance imaging (DWI) in chronic viral hepatitis patients. The study comprised 47 patients and 30 healthy volunteers. DWIs were obtained. Apparent Diffusion Coefficient (ADC) measurements were made by transferring the images to the workstation. The measurements of value b 1000 were made from a total of five points of the liver and three points of the spleen. Liver biopsy was performed on the 47 patients. The fibrosis stages of the patients were defined according to the METAVIR scoring system. Student's t-test was used in the comparison of mean ages, liver and spleen ADC values between the patient and the control group. Kruskal–Wallis followed by Mann–Whitney U Test with Bonferroni adjustment was performed in the comparison of mean ADC values of the patients at different stages and the control group. A statistically significant difference was determined between the patient and control group in respect of liver and spleen mean ADC values (P < 0.05). F3 group showed a significant difference compared to control and F1 and F4 group showed a significant difference compared to control, F1, F2 and F3 group in terms of the mean liver ADC value (P < 0.01). F3 and F4 group showed a significant difference compared to control and F1 group in terms of the mean spleen ADC value (P < 0.01). As a result we believe that the measurement of liver and spleen ADC values may be an indicator in the determination of the level of fibrosis.

  3. Assessment of liver fibrosis with 2-D shear wave elastography in comparison to transient elastography and acoustic radiation force impulse imaging in patients with chronic liver disease.

    Science.gov (United States)

    Gerber, Ludmila; Kasper, Daniela; Fitting, Daniel; Knop, Viola; Vermehren, Annika; Sprinzl, Kathrin; Hansmann, Martin L; Herrmann, Eva; Bojunga, Joerg; Albert, Joerg; Sarrazin, Christoph; Zeuzem, Stefan; Friedrich-Rust, Mireen

    2015-09-01

    Two-dimensional shear wave elastography (2-D SWE) is an ultrasound-based elastography method integrated into a conventional ultrasound machine. It can evaluate larger regions of interest and, therefore, might be better at determining the overall fibrosis distribution. The aim of this prospective study was to compare 2-D SWE with the two best evaluated liver elastography methods, transient elastography and acoustic radiation force impulse (point SWE using acoustic radiation force impulse) imaging, in the same population group. The study included 132 patients with chronic hepatopathies, in which liver stiffness was evaluated using transient elastography, acoustic radiation force impulse imaging and 2-D SWE. The reference methods were liver biopsy for the assessment of liver fibrosis (n = 101) and magnetic resonance imaging/computed tomography for the diagnosis of liver cirrhosis (n = 31). No significant difference in diagnostic accuracy, assessed as the area under the receiver operating characteristic curve (AUROC), was found between the three elastography methods (2-D SWE, transient elastography, acoustic radiation force impulse imaging) for the diagnosis of significant and advanced fibrosis and liver cirrhosis in the "per protocol" (AUROCs for fibrosis stages ≥2: 0.90, 0.95 and 0.91; for fibrosis stage [F] ≥3: 0.93, 0.95 and 0.94; for F = 4: 0.92, 0.96 and 0.92) and "intention to diagnose" cohort (AUROCs for F ≥2: 0.87, 0.92 and 0.91; for F ≥3: 0.91, 0.93 and 0.94; for F = 4: 0.88, 0.90 and 0.89). Therefore, 2-D SWE, ARFI imaging and transient elastography seem to be comparably good methods for non-invasive assessment of liver fibrosis. PMID:26116161

  4. Health Related Quality of Life of Chronic Liver Patients: A Dutch Population-Based Study

    NARCIS (Netherlands)

    S.M. van der Plas (Simone)

    2004-01-01

    markdownabstract__Abstract__ Chronic illnesses form a spectrum of diseases. Some chronic illnesses are poorly understood and unpredictable, some are understood and manageable, some are progressively disabling and some are life threatening. Nevertheless, for all chronic patients chronic illnesses ha

  5. Magnetic Resonance Signal, Rather Than Tendon Volume, Correlates to Pain and Functional Impairment in Chronic Achilles Tendinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gaerdin, A.; Bruno, J.; Movin, T.; Kristoffersen-Wiberg, M.; Shalabi, A. [Karolinska Univ. Hospital, Stockholm (Sweden). Depts. of Radiology and Orthopedics

    2006-09-15

    Purpose: To depict abnormal tendon matrix composition using magnetic resonance imaging (MRI) in chronic Achilles tendinopathy, and correlate intratendinous signal alterations to pain and functional impairment. Material and Methods: MRI of the Achilles tendon was performed on 25 patients with chronic Achilles tendinopathy (median age 50, range 37-71 years). All patients suffered from pain in the mid-portion of the Achilles tendon. Intratendinous signal was calculated from five different sagittal sequences, using a computerized 3D seed-growing technique. Pain and functional impairment were evaluated using a questionnaire completed by patients. Results: Severity of pain and functional impairment correlated to increased mean intratendinous signal in the painful tendon in all MR sequences (P 0.05). Difference in mean intratendinous signal between symptomatic and contralateral asymptomatic tendons was highly significant in all sequences (P <0.05) except on T2-weighted images (P = 0.6). Conclusion: Severity of pain and disability correlated to increased MR signal rather than to tendon volume in patients with unilateral mid-portion chronic Achilles tendinopathy.

  6. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

    Directory of Open Access Journals (Sweden)

    Koo Edward H

    2007-07-01

    Full Text Available Abstract Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs is associated with a reduced incidence of Alzheimer's disease (AD. We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition

  7. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

    Science.gov (United States)

    Kukar, Thomas; Prescott, Sonya; Eriksen, Jason L; Holloway, Vallie; Murphy, M Paul; Koo, Edward H; Golde, Todd E; Nicolle, Michelle M

    2007-01-01

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its

  8. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Godavarthi, Swetha K; Dey, Parthanarayan; Sharma, Ankit; Jana, Nihar Ranjan

    2015-09-01

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural abnormalities is poorly understood. Here we have demonstrated significant impairment of adult hippocampal neurogenesis in AS mice brain. Although, the number of BrdU and Ki67-positive cell in the hippocampal DG region was nearly equal at early postnatal days among wild type and AS mice, they were significantly reduced in adult AS mice compared to wild type controls. Reduced number of doublecortin-positive immature neurons in this region of AS mice further indicated impaired neurogenesis. Unaltered BrdU and Ki67-positive cells number in the sub ventricular zone of adult AS mice brain along with the absence of imprinted expression of Ube3a in the neural progenitor cell suggesting that Ube3a may not be directly linked with altered neurogenesis. Finally, we show that the impaired hippocampal neurogenesis in these mice can be partially rescued by the chronic treatment of antidepressant fluoxetine. These results suggest that the chronic stress may lead to reduced hippocampal neurogenesis in AS mice and that impaired neurogenesis could contribute to cognitive disturbances observed in these mice. PMID:26231800

  9. 维生素D与慢性肝病%Relationship between vitamin D and chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    朱鸣; 徐列明

    2013-01-01

    维生素D是一种主要在肝脏合成并具有多重生物学效应的脂溶性维生素.目前发现多种慢性肝病(chronic liver disease,CLD)都与维生素D缺乏有关,而且补充维生素D能够影响治疗效果.本文通过回顾近年来维生素D与CLD之间的相关基础和临床试验研究,总结维生素D在CLD发病机制和治疗中的作用,为临床研究和治疗提供新的思路.%Vitamin D is a fat-soluble vitamin with multiple biological effects that is predominantly synthetized in the liver.Various kinds of chronic liver diseases are associated with vitamin D deficiency,and vitamin D supplementation may influence treatment outcome.This article summarizes the role of vitamin D in the pathogenesis and treatment of chronic liver diseases to provide new insight into the treatment of these diseases.

  10. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease.

    Science.gov (United States)

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G

    1976-01-01

    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  11. Evaluation of liver stiffness measurement by fibroscan as compared to liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C.

    Science.gov (United States)

    Awad, Mohiee El-Deen Abd El-Aziz; Shiha, Gamal Elsayed; Sallam, Fersan Abdallah; Mohamed, Amany; El Tawab, Abd

    2013-12-01

    The study evaluated liver stiffness measurement (LSM) using non-invasive transient elastography (TE) in comparison with liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C (CHC). Thirty children (mean age 10.13 +/- 3.4 years) with CHC were subjected to histopathological assessment of liver biopsy specimens using METAVIER score and LSM using TE (FibroScan) as well as appropriate laboratory investigations. The results showed a highly significant stepwise increase of the mean liver stiffness values with increasing histological severity of hepatic fibrosis with the highest level detected in patients with stage F4 "cirrhosis" and significant differences for F3 and F4 vs. other fibrosis stages. There were significant positive correlations between LSM and several parameters of activity and progression of the chronic liver disease including METAVIER fibrosis stages (r=0.774, p=0.0001), necroinflammatory activity grades, AST, ALT, total serum bilirubin, prothrombin time and Child-Pugh grades as well as biochemical serum fibrosis markers (Fibrotest, Actitest, AST-to-platelet ratio index, Forns index and hyaluronic acid). The variables significantly negatively associated with the LSM were platelets count and serum albumin. The highest predictive performance of LSM was detected for stage F4 "cirrhosis", followed by F3 "advanced fibrosis" where accuracy of(96.7%, 85.3%) and AUROC of (1.00, 0.815) were obtained for these fibrosis stages at cutoff values of 9.5 and 12.5 kPa, respectively. The negative predictive values to exclude advanced fibrosis and cirrhosis at these cutoffs were high, whereas positive predictive values were modest.

  12. [Monoethylglycinexylidide--a metabolite of lidocaine--as an index of liver function in chronic hepatic parenchymal diseases].

    Science.gov (United States)

    Kupcová, V; Turecký, L; Szántová, M; Schmidtová, K

    1999-01-01

    significant differences among Ci A, Ci B and Ci C. Statistically significant differences were also between the group of steatofibrosis and whole group of cirrhosis. The concentration of MEGX 15 and 30 minutes after lidocaine administration correlated significantly with the values of albumin, prothrombin time, cholinesterase, Child-Plugh score and bilirubin. MEGX test represents an appropriate and rapid method for the determination of functional liver capacity in patients with liver cirrhosis and liver steatofibrosis, not yet used in Slovak republic. It is a noninvasive test, low time consuming, and when repeated it may provide prognostic information about further development of the disease. MEGX test is an appropriate index of liver function and may contribute to early treatment of chronic liver diseases. (Tab. 9, Fig. 10, Ref. 47.)

  13. Proprioceptive changes impair balance control in individuals with chronic obstructive pulmonary disease.

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    Lotte Janssens

    Full Text Available INTRODUCTION: Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD. However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD. The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness. METHODS: Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision. Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control. RESULTS: Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037. Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047, decreased anterior body sway during back muscle vibration (p = 0.025, and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002. Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037. CONCLUSIONS: Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls. These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability. Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle

  14. Impaired gastric myoelectricity in patients with chronic pancreatitis: Role of maldigestion

    Institute of Scientific and Technical Information of China (English)

    Ching-Liang Lu; Chih-Yen Chen; Jiing-Chyuan Luo; Full-Young Chang; Shou-Dong Lee; Han-Chang Wu; JDZ Chen

    2005-01-01

    AIM: To investigate whether gastric myoelectricai activity was impaired in patients with chronic pancreatitis (CP)and to explore the role of pancreatic enzyme in regulating gastric myoeiectrical activity.METHODS: Twenty CP patients and 20 controls participated in the study. Gastric myoelectrical activity was recorded by a homemade electrogastrography (EGG) device. Two experiments were carried out. In experiment one, EGG was recorded in both controls and CP patients. While in experiment two, either pancreatic enzymes or placebo was given together with test meals. Spectral analysis was used to generate various EGG parameters.RESULTS: The control subjects, but not the CP patients,showed typically increased postprandial dominant frequency. The postprandial dominant power (DP)increment (2.24±1.13 vs 5.35±0.96 dB, P= 0.04) and the percentage of normal 2-4 cpm slow waves (63.0±3.8% vs 77.4 ±3.1%, P<0.05) were lower in CP patients when compared with the control. In the 20 CP patients, the DP increment (4.76±1.02 vs 2.53±1.20 dB, P<0.05) and the postprandial percentage of normal 2-4 cpm (74.4±2.8%vs 64.8 ±5.7%, P<0.05) were significantly higher with pancreatic enzyme replacement than the placebo.ONCLUSION: CP patients have an abnormal postprandial stomach myoelectricity showing poor response in dominant frequency/power and regularity, whereas these abnormalities are corrected after pancreatic enzyme replacement.Maldigestion is likely to be the factor leading to abnormal postprandial gastric myoelectriclty of CP patients.

  15. Chronic stress differentially affects antioxidant enzymes and modifies the acute stress response in liver of Wistar rats.

    Science.gov (United States)

    Djordjevic, J; Djordjevic, A; Adzic, M; Niciforovic, A; Radojcic, M B

    2010-01-01

    Clinical reports suggest close interactions between stressors, particularly those of long duration, and liver diseases, such as hepatic inflammation, that is proposed to occur via reactive oxygen species. In the present study we have used 21-day social isolation of male Wistar rats as a model of chronic stress to investigate protein expression/activity of liver antioxidant enzymes: superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR), and protein expression of their upstream regulators: glucocorticoid receptor (GR) and nuclear factor kappa B (NFkB). We have also characterized these parameters in either naive or chronically stressed animals that were challenged by 30-min acute immobilization. We found that chronic isolation caused decrease in serum corticosterone (CORT) and blood glucose (GLU), increase in NFkB signaling, and disproportion between CuZnSOD, peroxidases (CAT, GPx) and GLR, thus promoting H2O2 accumulation and prooxidative state in liver. The overall results suggested that chronic stress exaggerated responsiveness to subsequent stressor at the level of CORT and GLU, and potentiated GLR response, but compromised the restoration of oxido-reductive balance due to irreversible alterations in MnSOD and GPx. PMID:20406049

  16. The metabolism of menadione impairs the ability of rat liver mitochondria to take up and retain calcium.

    Science.gov (United States)

    Bellomo, G; Jewell, S A; Orrenius, S

    1982-10-10

    The ability of mitochondria to take up and retain Ca2+, and thereby to effect the free intracellular concentration of this ion, is well established. More recently, it has been reported (Lehninger, A. L., Vercesi, A., and Bababunmi, E. A. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1690-1696) that the redox state of pyridine nucleotides modulates mitochondrial Ca2+ balance, since the oxidation of mitochondrial NAD(P)H is associated with the release of Ca2+ from these organelles. The latter may be achieved by a variety of treatments including the incubation of Ca2+-loaded liver mitochondria with hydroperoxides, the metabolism of which by the glutathione peroxidase-glutathione reductase system results in NADPH consumption. The metabolism of menadione (2-methyl-1,4-naphthoquinone) by Ca2+-loaded rat liver mitochondria results in rapid oxidation and loss of pyridine nucleotides and a decrease in ATP level. It is also associated with Ca2+ release and an impaired ability of the mitochondria to take up and retain Ca2+. The effects of menadione on mitochondrial Ca2+ balance are more rapid and pronounced than those of t-butylhydroperoxide, and in contrast to those observed with the hydroperoxide, they are not abolished by pretreatment with a glutathione-depleting agent. The effects of menadione on Ca2+ homeostasis are probably initiated by NAD(P)H oxidation linked to the reduction of menadione by both NADH-ubiquinone oxidoreductase and NAD(P)H:(quinone-acceptor) oxidoreductase. PMID:7118897

  17. Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Feng Qu

    Full Text Available Patients with HBV-acute-on-chronic liver failure (HBV-ACLF have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL, 29 and 23 patients with chronic hepatitis B (CHB, and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0 was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05, and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0 may be a useful prognostic indicator for the early prediction of HBV-ACLF.

  18. CD36 genetic variation, fat intake and liver fibrosis in chronic hepatitis C virus infection

    Science.gov (United States)

    Ramos-Lopez, Omar; Roman, Sonia; Martinez-Lopez, Erika; Fierro, Nora A; Gonzalez-Aldaco, Karina; Jose-Abrego, Alexis; Panduro, Arturo

    2016-01-01

    AIM To analyze the association of the CD36 polymorphism (rs1761667) with dietary intake and liver fibrosis (LF) in chronic hepatitis C (CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype (G > A) was determined by a TaqMan real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography (Fibroscan®) and APRI score was classified as mild LF (F1-F2) and advanced LF (F3-F4). RESULTS Overall, the CD36 genotypic frequencies were AA (30.1%), AG (54.8%), and GG (15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase (AST) serum values were higher in AA genotype carriers compared to non-AA carriers (91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST (β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG (OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes (OR = 3.52, 95%CI: 1.18-10.45, P = 0.02). CONCLUSION This study suggests that the CD36 (rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients. PMID:27660673

  19. Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury.

    Science.gov (United States)

    Wang, Yuhua; Liu, Yanlong; Kirpich, Irina; Ma, Zhenhua; Wang, Cuiling; Zhang, Min; Suttles, Jill; McClain, Craig; Feng, Wenke

    2013-09-01

    The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose-dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4- and TLR5-mediated endotoxin activation. PMID:23618528

  20. Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry

    Directory of Open Access Journals (Sweden)

    Olschewski Manfred

    2006-04-01

    Full Text Available Abstract Background Hepatopulmonary syndrome (HPS is a rare complication of liver diseases of different etiologies and may indicate a poor prognosis. Therefore, a simple non-invasive screening method to detect HPS would be highly desirable. In this study pulse oximetry was evaluated to identify patients with HPS. Methods In 316 consecutive patients with liver cirrhosis (n = 245, chronic hepatitis (n = 69 or non-cirrhotic portal hypertension (n = 2 arterial oxygen saturation (SaO2 was determined using a pulse oximeter. In patients with SaO2 ≤92% in supine position and/or a decrease of ≥4% after change from supine to upright position further diagnostic procedures were performed, including contrast-enhanced echocardiography and perfusion lung scan. Results Seventeen patients (5.4% had a pathological SaO2. Four patients (1.3% had HPS. HPS patients had a significant lower mean SaO2 in supine (89.7%, SD 5.4 vs. 96.0%, SD 2.3; p = 0.003 and upright position (84.3%, SD 5.0 vs. 96.0%, SD 2.4; p = 0.001 and had a lower mean PaO2 (56.2 mm Hg, SD 15.2 vs. 71.2 mm Hg, SD 20.2; p = 0.02 as compared to patients without HPS. The mean ΔSaO2 (difference between supine and upright position was 5.50 (SD 7 in HPS patients compared to non-HPS patients who showed no change (p = 0.001. There was a strong correlation between shunt volume and the SaO2 values (R = -0.94. Conclusion Arterial SaO2 determination in supine and upright position is a useful non-invasive screening test for HPS and correlates well with the intrapulmonary shunt volume.

  1. Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?

    Institute of Scientific and Technical Information of China (English)

    Luis Aparisi; Luis Sabater; Juan Del-Olmo; Juan Sastre; MigueI-Angel Serra; Ricardo Campello; Daniel Bautista; Abdalla Wassel; José-Manuel Rodrigo

    2008-01-01

    AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (η = 53), LC (η = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r=-0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis.

  2. Clinical Pathologic Study on Effect of Qianggan Capsule (强肝胶囊)in Treating Patients of Chronic Hepatitis B With Liver Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    杨柳明; 赵延龙; 吴志荣; 陈杜芳; 岑卓英; 徐克成; 左建生; 危北海; 张万岱

    2002-01-01

    Objective: To explore the clinical therapeutic effect of Qianggan Capsule (QGC) in treating chronic hepatitis B with liver fibrosis from the pathological aspect. Methods: Sixty-three patients of chronic hepatitis B with liver fibrosis were randomly divided into the treated group (n=45) and the control group (n=18). Both groups were treated with general liver protective drugs, such as Glucurone and vitamins B complex for 6 months. To the treated group, QGC was used additionally. The levels of serum alanine transaminase and liver fibrosis indexes including hyaluronic acid (HA), collagen type Ⅳ (C-Ⅳ) and laminin (LN) as well as the pathological examination of liver biopsy were observed before and after treatment. Results: The liver cirrhosis indexes, HA, C-Ⅳ and LN, were improved significantly in the treated group after treatment, P0.05. Pathological examination showed that the effective rate of treatment on liver inflammatory necrosis activity grade in the treated group was 57.8% and that on liver fibrosis stage was 75.6%, which were significantly improved as compared with those before treatment (P0.05). Conclusion: QGC has marked effects in reversing liver fibrosis and alleviating hepatic inflammatory necrosis in patients of chronic hepatitis B with liver fibrosis, and could lower the serum liver fibrosis related indexes effectively.

  3. Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014

    Science.gov (United States)

    Saracco, Giorgio Maria; Evangelista, Andrea; Fagoonee, Sharmila; Ciccone, Giovannino; Bugianesi, Elisabetta; Caviglia, Gian Paolo; Abate, Maria Lorena; Rizzetto, Mario; Pellicano, Rinaldo; Smedile, Antonina

    2016-01-01

    AIM To assess the etiology of chronic liver diseases (CLD) from 1998 to 2014 at the outpatient clinic of Gastroenterology of the main hospital in Northwest of Italy among those dedicated to hepatology. METHODS A random sample of charts of patients referred to for increased liver enzymes between January 1998 and December 2006, and between January 2012 and December 2014 were reviewed. Etiology search included testing for hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatitis, primary biliary cirrhosis, Wilson’s disease and hereditary hemocromatosis. A risky alcohol consumption was also considered. Non-alcoholic fatty liver disease (NAFLD) was diagnosed in patients with histological and/or ultrasound evidence of steatosis/steatohepatitis, and without other causes of CLD. RESULTS The number of patients included was 1163. Of them, 528 (45%) had positivity for HCV and 85 (7%) for HBV. Among the virus-free patients, 417 (36%) had metabolic disorders whereas the remaining had history of alcohol abuse, less prevalent causes of CLD or concomitant conditions. In comparison to 1998-2000 (41%), a reduction of HCV alone-related cases was detected during the periods 2001-2003 (35%, OR = 0.75, 95%CI: 0.53-1.06), 2004-2006 (33%, OR = 0.70, 95%CI: 0.50-0.97) and 2012-2014 (31%, OR = 0.64, 95%CI: 0.46-0.91). On the contrary, in comparison to 1998-2000 (31%), metabolic-alone disorders increased in the period 2004-2006 (39%, OR = 1.37, 95%CI: 0.99-1.91) and 2012-2014 (41%, OR = 1.53, 95%CI: 1.09-2.16). The other etiologies remained stable. The increase of incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014 tended to be higher in older patients (≥ 50 years) compared to younger (P = 0.058). CONCLUSION In the Northwest of Italy, during this study period, the prevalence of HCV infection decreased notably whereas that of NAFLD increased. PMID:27688660

  4. Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

    Institute of Scientific and Technical Information of China (English)

    Yun-Kyoung Yim; Hyun Lee; Kwon-Eui Hong; Young-Il Kim; Byung-Ryul Lee; Tae-Han Kim; Ji-Young Yi

    2006-01-01

    AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats.METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34(Yanglingquan) 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index,biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted.RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes.CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats.

  5. Turnover rates of hepatic collagen and circulating collagen-associated proteins in humans with chronic liver disease.

    Directory of Open Access Journals (Sweden)

    Martin L Decaris

    Full Text Available Accumulation and degradation of scar tissue in fibrotic liver disease occur slowly, typically over many years. Direct measurement of fibrogenesis, the rate of scar tissue deposition, may provide valuable therapeutic and prognostic information. We describe here results from a pilot study utilizing in vivo metabolic labeling to measure the turnover rate of hepatic collagen and collagen-associated proteins in plasma for the first time in human subjects. Eight subjects with chronic liver disease were labeled with daily oral doses of 2H2O for up to 8 weeks prior to diagnostic liver biopsy and plasma collection. Tandem mass spectrometry was used to measure the abundance and fractional synthesis rate (FSR of proteins in liver and blood. Relative protein abundance and FSR data in liver revealed marked differences among subjects. FSRs of hepatic type I and III collagen ranged from 0.2-0.6% per day (half-lives of 4 months to a year and correlated significantly with worsening histologic fibrosis. Analysis of plasma protein turnover revealed two collagen-associated proteins, lumican and transforming growth factor beta-induced-protein (TGFBI, exhibiting FSRs that correlated significantly with FSRs of hepatic collagen. In summary, this is the first direct measurement of liver collagen turnover in vivo in humans and suggests a high rate of collagen remodeling in advanced fibrosis. In addition, the FSRs of collagen-associated proteins in plasma are measurable and may provide a novel strategy for monitoring hepatic fibrogenesis rates.

  6. Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    Kun Huang; Jin-Hua Hu; Hui-Fen Wang; Wei-Ping He; Jing Chen; Xue-Zhang Duan; Ai-Min Zhang; Xiao-Yan Liu

    2011-01-01

    AIM: To investigate the survival rates and prognostic ffactors in patients with hepatitis B virus-related acute-on-chronic liver ffailure (HBV-ACLF).METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted ffrom 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS: A total off 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014].The highest risk off death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001).CONCLUSION: Antiviral therapy has a strong effffect on the prognosis off the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances,and HE also affffect patient survival.

  7. Cisatracurium dose–response relationship in patients with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Mohamed Z. Ali

    2014-04-01

    Results: The preoperative laboratory parameters showed statistically significant differences between the two groups regarding serum albumin, total bilirubin, ALT, AST, PT, PC and INR. The operative data showed statistically insignificant difference between the two groups regarding the 1st dose response (p = 0.152, the estimated ED80 (p = 0.886 and the calculated 2nd dose (p = 0.886 and statistically significant differences between the two groups regarding the 2nd dose response (p = 0.006, the measured ED50 (p = 0.010 and the measured ED95 (p = 0.001. In conclusion, the measured ED50 and ED95 through two-dose dose–response curve technique were clinically insignificant from using the single-dose technique. The dose–response curve of cisatracurium in patients with chronic liver disease was clinically insignificant in comparison with healthy subjects.

  8. The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular locali...... is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

  9. Limb-salvage angioplasty in poor surgical chronic liver disease and diabetic patients.

    Science.gov (United States)

    Hamdy, Hussam; El-Kolly, M; Ezzat, H; Abbas, M; Farouk, Y; Naser, M; Magdy, M; Elraouf, A

    2013-08-01

    Critical limb ischemia (CLI) in high surgical risk patients with chronic liver diseases has a grave prognosis with a one-year mortality rate of 20% and a one-year amputation rate of 25% after the initial diagnosis. According to Trans-Atlantic Inter-Society Consensus (TASC)-II Guidelines, revascularization (surgical & endovascular) is the treatment of choice for patients with critical limb ischemia (CLI). The primary goal of revascularization is to relieve ischemic rest pain, heal ulcers, prevent amputation, improve patient's quality of life (limb salvage) and secondary goal was the periprocedural complications. Endovascular techniques include balloon angioplasty, stents, stent-grafts, and plaque debulking procedures. Surgical options, identification of patients at risk of postoperative complications could have an impact on the indications for a procedure as well as permitting modifications of treatment to reduce the surgical risk This study evaluated the treatment out comas after limb salvage angioplasty for patients who otherwise would be candidates for primary amputation due to poor co-morbid conditions as chronic liver disease and diabetes. The clinical evaluation, laboratory investigations and abdominal ultrasonography were performed to all patients to evaluate their liver status. Patients were classified according to Child-pugh classification into child A, B & C. All patients were subjected to either detailed arterial duplex or C.T. angiography to assess their arterial lesions from January 2008- January 2010. 95 patients with critical limb ischemia (Rutherford categories 4, 5, 6) were treated by primary percutaneous transluminal angioplasty (PTA). No patient was excluded on the basis of the extent of arterial occlusive disease. The primary end points were immediate technical success, clinical improvement and limb salvages rates. Secondary end points were periprocedural complications and mortality. Most of the patients were male (54.7%) with mean age 62 (48

  10. Prognostic value of 13C-phenylalanine breath test on predicting survival in patients with chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    I Gallardo-Wong; S Morán; G Rodríguez-Leal; B Casta(n)eda-Romero; R Mera; J Poo; M Uribe; M Dehesa

    2007-01-01

    AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure.METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox.RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78,0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI:0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin,creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival.CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease.

  11. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    Energy Technology Data Exchange (ETDEWEB)

    Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  12. Persistance of HBsAg and serum activities of liver enzymes among chronic carriers of hepatitis B

    OpenAIRE

    Mansoureh Momen-Heravi; Hossein Akbari

    2011-01-01

    Background: Hepatitis B virus (HBV) infection and its squeals are major global health problems. This study was conducted to evaluate HBsAg persistence, risk factors of HBV infection and changes of liver function tests among chronic HBV carriers in Kashan. Materials and Method: This descriptive study was performed in HBsAg positive blood donors who detected after blood donation since 10 years ago. They were requested to retest HBsAg. A questionnaire consisting demographic and history of risk ...

  13. Immune blot analysis of viral surface proteins in serum and liver of patients with chronic hepatitis B virus infection.

    Science.gov (United States)

    Gerken, G; Manns, M; Gerlich, W H; Hess, G; Meyer zum Büschenfelde, K H

    1989-12-01

    The small and the middle surface proteins of hepatitis virus form either the virion or the 22 nm particle both of which are secreted. The large surface protein by itself remains cell bound in artificially transfected cell culture unless it is accompanied by an excess of the smaller protens. Its behavior in vivo is not yet well studied. Using specific monoclonal antibodies for immunoblotting, we found an abundance of small surface protein in the serum of chronic virus carriers and moderate amounts in the liver irrespective of viremia. The large surface protein was present in the serum and the liver of viremic carriers. In nonviremic carriers, the large protein was absent from serum, but in the liver a shorter form of the large protein was readily detectable. These findings suggest a complex regulatory mechanism of the viral surface protein depending on the expression of other viral gene products. PMID:2621452

  14. The Role of Ultrasound Imaging in the Definition of the Stage of Liver Fibrosis in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Dmitry Konstantinov

    2014-09-01

    Full Text Available The aim of this research was to develop a method for noninvasive staging of liver fibrosis (LF in patients with chronic hepatitis C (CHC based on ultrasound imaging (UI of the abdominal cavity. We examined 124 patients with CHC. The diagnosis was verified on the basis of clinical and epidemiological, serological and molecular biological data. Direct ultrasonic parameters of the structure and hemodynamics of liver and spleen were supplemented with estimated indicators: square of the expected cross-section of the lobes of the liver and spleen, as well as their ratio. On the basis of the discriminant analysis of the survey data of 82 patients, we developed an analytical model (with predictive value of 95.2% for interval estimation of the fibrosis degree in CHC patients. We have concluded that UI performed on modern equipment, including Doppler, is able to determine the degree of LF without resorting to histological verification.

  15. Liver stiffness measurement among patients with chronic hepatitis B and C: results from a 5-year prospective study.

    Directory of Open Access Journals (Sweden)

    Karen M Christiansen

    Full Text Available Liver stiffness measurement (LSM is widely used to evaluate liver fibrosis, but longitudinal studies are rare. The current study was aimed to monitor LSM during follow-up, and to evaluate the association of LSM data with mortality and liver-related outcomes. We included all patients with chronic viral hepatitis and valid LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and clinical outcome was obtained from medical records and national registers. The study included 845 patients: 597 (71% with hepatitis C virus (HCV, 235 (28% with hepatitis B virus (HBV and 13 (2% with dual infection. The initial LSM distribution (20% and >2 kPa increase, with one measure >7 kPa were 3.4/100 person years (PY for HCV and 1.5/100 PY for HBV infected patients. Patients with LSM values of ≥ 17 kPa had the same liver-related complication incidence as patients with biopsy-proven cirrhosis (11.1 versus 12.1/100 PY. Thirteen liver-related deaths occurred among HCV patients (0.6/100 PY, but none among HBV patients. Among patients who died of liver-related causes, all but one had baseline LSM values of ≥ 17 kPa. Overall, patients with LSM values <17 kPa were not associated with adverse outcomes. In contrast, LSM values ≥ 17 kPa were associated with significant risk of liver-related problems. The results of the current study suggest that clinical decisions should not be taken based on a single LSM measurement.

  16. Interactions of the heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Bernardi, Mauro

    2013-01-01

    There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting...... the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should...... be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic...

  17. Impaired motor preparation and execution during standing reach in people with chronic stroke.

    Science.gov (United States)

    McCombe Waller, Sandy; Yang, Chieh-Ling; Magder, Laurence; Yungher, Don; Gray, Vicki; Rogers, Mark W

    2016-09-01

    Movement preparation of both anticipatory postural adjustments (APAs) and goal directed movement during a standing reaching task in adults with chronic hemiparesis and healthy controls was investigated. Using a simple reaction time paradigm, while standing on two separate force platforms, subjects received a warning light cue to "get ready to reach" followed 2.5s later by an imperative light cue to "reach as quickly as possible" with the paretic arm (matched arm for controls) to touch a target in front of them for a total of 90 trials. In 30 of the reaching trials a loud acoustic stimulus (LAS) of 123 dB was randomly - -200, or 0ms relative to the "go" cue. APA (postural) responses were characterized by the onset and maximal posterior displacement of center of pressure (CoP) and onset/offset of electromyography (EMG) from tibialis anterior (TA), soleus (SOL), while reach was characterized by onset and maximal forward displacement of the reach hand and onset of the anterior (AD), biceps brachii (BB) and middle deltoid (MD). Subjects with stroke, demonstrated a marked reduction in the occurrence of the StartReact responses for both APA and forward reach at all LAS time points indicating movement preparation dysfunction. Movement execution during a cued reach showed significant delays in APA and reach onsets, significant reduction in the magnitude of APA (posterior CoP displacement) and reach excursion, and an increased latency between the APA and reach compared to controls. EMG activation patterns for the TA and SOL demonstrated co contraction compared to the temporally sequenced pattern of control subjects. When LAS was provided at the "go" there were earlier but not significant differences in APA onset latency compared to reaching without LAS and significant delays in reach onset latency when compared to control subjects with or without LAS. An early burst of EMG in biceps brachii muscles with a further delay of the reach onset compared to reaching without LAS may

  18. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Directory of Open Access Journals (Sweden)

    Kieran A Brune

    Full Text Available Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD. We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1 and activated extracellular signal-regulated kinase (ERK. We demonstrate that HIV

  19. Cardiovascular and respiratory dysfunction in chronic obstructive pulmonary disease complicated by impaired peripheral oxygenation

    Directory of Open Access Journals (Sweden)

    Chuang ML

    2015-02-01

    Full Text Available Ming-Lung Chuang,1,2 Shih-Feng Huang,1 Chun-Hung Su2,3 1Division of Pulmonary Medicine and Department of Critical Care Medicine, 2School of Medicine, 3Division of Cardiology and Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China Background: Impaired peripheral oxygenation (IPO-related variables readily achieved with cardiopulmonary exercise testing (CPET represent cardiovascular dysfunction. These variables include peak oxygen uptake (VO2 <85% predicted, anaerobic threshold <40%  VO2max predicted, VO2-work rate slope <8.6 mL/watt, oxygen pulse <80% predicted, and ventilatory equivalents for O2 and CO2 at nadir of >31 and >34, respectively. Some of these six variables may be normal while the others are abnormal in patients with chronic obstructive pulmonary disease (COPD. This may result in confusion when using the interpretation algorithm for diagnostic purposes. We therefore hypothesized that patients found to have abnormal values for all six variables would have worse cardiovascular function than patients with abnormal values for none or some of these variables.Methods: In this cross-sectional comparative study, 58 COPD patients attending a university teaching hospital underwent symptom-limited CPET with multiple lactate measurements. Patients with abnormal values in all six IPO-related variables were assigned to an IPO group while those who did not meet the requirements for the IPO group were assigned to a non-IPO group. Cardiovascular function was measured by two-dimensional echocardiography and Δlactate/ΔVO2, and respiratory dynamics were compared between the two groups.Results: Fourteen IPO and 43 non-IPO patients were entered into the study. Both groups were similar with regard to left ventricular ejection fraction and right ventricular morphology (P>0.05 for both. At peak exercise, both groups reached a similar heart rate level and Δlactate/ΔVO2. The IPO patients had an

  20. Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    Matthias Ocker; Marion Ganslmayer; Steffen Zopf; Susanne Gahr; Christopher Janson; Eckhart G. Hahn; Christoph Herold

    2005-01-01

    AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF).METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG)was performed before and 3 mo after initiation of antiviral therapy.RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCI and ICG) were not affected by antiviral therapy. In the 14 non-responders,no changes in QTLF values were observed during the treatment period.CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antivJral treatment in hepatitis C.

  1. Comparison of the effectiveness of preoperative portal vein embolization in patients with chronic liver disease: Gelfoam versus gelfoam coil

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sung Wook; Chang, Il Soo; Do, Young Soo; Park, Hong Suk; Park, Kwang Bo; Cho, Sung Ki; Choo, In Wook [Dept. of Radiology, and Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Choo, Sung Wook [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2015-05-15

    To compare the effectiveness of portal vein embolization (PVE) performed using gelfoam or a gelfoam-coil combination before major hepatic resection in patients with chronic liver disease. PVE using gelfoam or a gelfoam-coil combination was performed in 37 patients. From April 2003 to September 2007, PVE was performed using gelfoam (n = 17) and a gelfoam-coil combination (n = 20) to induce hypertrophy. Computed tomography volumetry was performed 2-4 weeks after PVE to assess the changes in liver volume. The mean percentage increase in future liver remnant volume was 23.7 +/- 23.7% in the gelfoam group and 36.7 +/- 18.5% in the gelfoam-coil group (p = 0.02). Recanalization was found in 15 gelfoam group patients and 8 gelfoam-coil group patients (p = 0.003). The mean tumor size increased from 4.5 +/- 2.9 cm before PVE to 5.0 +/- 3.5 cm after PVE in the gelfoam group and from 4.3 +/- 2.2 cm before PVE to 4.7 +/- 2.5 cm after PVE in the gelfoam-coil group (p = 0.80). The gelfoam-coil combination was more effective than gelfoam alone for induction of compensatory hypertrophy by PVE in patients with chronic liver disease.

  2. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Liu, Jianping; Als-Nielsen, Bodil;

    2003-01-01

    Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation.......Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation....

  3. Assessment of prognosis and curative effect in patients with chronic severe hepatitis using the model for end-stage liver disease scores

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Severe hepatitis is the most severe liver disease, with poor prognosis and high mortality. We explored the practical use of the model for end-stage liver disease (MELD) on clinical and the molecular adsorbents recirculating system (MARS) on chronic severe hepatitis to predict the short-term prognosis of patients with chronic severe hepatitis using the MELD score and the curative effect of MARS treatment.

  4. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.;

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... activity in the colon and small intestine of the rat. METHODS: Rats were fed ethanol in a liquid diet for six weeks. Control rats received a similar diet but with ethanol isocalorically replaced by carbohydrates. Retinol dehydrogenase was analyzed from cell cytosol samples from the small and the large...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p retinol...

  5. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Andre Castro Lyra; Bernd Genser; Ricardo Ribeiro dos Santos; Luiz Guilherme Costa Lyra; Milena Botelho Pereira Soares; Luiz Flavio Maia da Silva; Marcos Fraga Fortes; André Goyanna Pinheiro Silva; Augusto César de Andrade Mota; Sheilla A Oliveira; Eduardo Lorens Braga; Wilson Andrade de Carvalho

    2007-01-01

    AIM:To evaluate the safety and feasibility of bone marrow cell(BMC)transplantation in patients with chronic liver disease on the waiting list for liver transplantation.METHODS:Ten patients(eight males)with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells.Seven patients were classified as Child-Pugh B and three as Child-Pugh C.Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI.Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient.At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors.Patients were followed up for adverse events up to 4 mo.RESULTS:The median age of the patients was 52 years(range 24-70 years).All patients were discharged 48 h after BMC infusion.Two patients complained of mild pain at the bone marrow needle puncture site.No other complications or specific side effects related to the procedure were observed.Bilirubin levels were lower at 1(2.19 ± 0.9)and 4 mo(2.10 ± 1.0)after cell transplantation that baseline levels(2.78 ± 1.2).Albumin levels 4 mo after BMC infusion(3.73 ± 0.5)were higher than baseline levels(3.47 ± 0.5).International normalized ratio(INR)decreased from 1.48(SD = 0.23)to 1.43(SD = 0.23)one month after cell transplantation.CONCLUSION:BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible.In addition,a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed.Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

  6. Effects of Acute Exercise and Chronic Exercise on the Liver Leptin-AMPK-ACC Signaling Pathway in Rats with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Xuejie Yi

    2013-01-01

    Full Text Available Aim. To investigate the effects of acute and chronic exercise on glucose and lipid metabolism in liver of rats with type 2 diabetes caused by a high fat diet and low dose streptozotocin (STZ. Methods. Animals were classified into control (CON, diabetes (DC, diabetic chronic exercise (DCE, and diabetic acute exercise (DAE groups. Results. Compared to CON, the leptin levels in serum and liver and ACC phosphorylation were significantly higher in DC, but the levels of liver leptin receptor, AMPKα1/2, AMPKα1, and ACC proteins expression and phosphorylation were significantly lower in DC. In addition, the levels of liver glycogen reduced significantly, and the levels of TG and FFA increased significantly in DC compared to CON. Compared to DC, the levels of liver AMPKα1/2, AMPKα2, AMPKα1, and ACC phosphorylation significantly increased in DCE and DAE. However, significant increase of the level of liver leptin receptor and glycogen as well as significant decrease of the level of TG and FFA were observed only in DEC. Conclusion. Our study demonstrated that both acute and chronic exercise indirectly activated the leptin-AMPK-ACC signaling pathway and increased insulin sensitivity in the liver of type 2 diabetic rats. However, only chronic and long-term exercise improved glucose and lipid metabolism of the liver.

  7. Serum Vitamin D Levels are not Predictive of the Progression of Chronic Liver Disease in Hepatitis C Patients with Advanced Fibrosis

    OpenAIRE

    Mendez-Navarro, Jorge; Delgado-Borrego, Aymin; Corey, Kathleen Elizabeth; Zheng, Zheng; Dienstag, Jules Leonard; Chung, Raymond Taeyong

    2012-01-01

    In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course...

  8. Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis

    Directory of Open Access Journals (Sweden)

    Daniela Cabibi

    2015-01-01

    Full Text Available Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT, Sirius Red (SR, and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA by Digital Image Analysis (DIA and correlate them with transient elastography (TE. Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein. Results. MT, SR, and orcein staining showed concordant results in 89.6% of cases in staging CHC, without significant difference in both semiquantitative and quantitative evaluations of fibrosis. TE values were concordant with orcein levels in 86.5% of the cases and with MT/RS in 77.5% (P<0.001. No significant correlation between the grade of necroinflammatory activity and TE values was found. Conclusion. In CHC, SR/MT and orcein stainings are almost concordant and when discordant, orcein staining is better related to TE values than MT/RS. This suggests that elastic fibers play a more important role than reticular or collagenous ones in determining stiffness values in CHC.

  9. Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet.

    Science.gov (United States)

    Britton, Laurence; Jaskowski, Lesley; Bridle, Kim; Santrampurwala, Nishreen; Reiling, Janske; Musgrave, Nick; Subramaniam, V Nathan; Crawford, Darrell

    2016-06-01

    Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe(+/-) mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC Hfe(+/-) mice demonstrated raised fasting serum glucose concentrations and HOMA-IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparα, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model. PMID:27354540

  10. A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Tohru Utsunomiya; Hiroshi Inoue; Graham F Barnard; Masaki Mori; Masahiro Okamoto; Shigeki Wakiyama; Masaji Hashimoto; Kengo Fukuzawa; Takahiro Ezaki; Shinichi Aishima; Yasuji Yoshikawa; Taizo Hanai

    2007-01-01

    AIM: To study a more accurate quantification of hepatic fibrosis which would provide clinically useful information for monitoring the progression of chronic liver disease.METHODS: Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azan stained: total area, and determined the morphologic fibrosis index (MFI), as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis.RESULTS: We identified 39 genes that collectively showed a good correlation (r>0.50) between geneexpression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis,we developed a new genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples (r= 0.76, 2.2% VS 2.8%, P<0.0001) and 12 independent additional test samples (r = 0.75, 9.8% vs 8.6%, P<0.005). It was far better in assessing liver fibrosis than blood markers such as prothrombin time (r= -0.53),type Ⅳ collagen 7s (r = 0.48), hyaluronic acid (r = 0.41),and aspartate aminotransferase to platelets ratio index(APRI) (r= 0.38).CONCLUSION: Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.

  11. Insulin and C peptide response, and antibody levels in hepatitis C related chronic liver disease

    International Nuclear Information System (INIS)

    Objective: Patients with cirrhosis due to hepatitis C (HC) have an increased prevalence of diabetes mellitus. The pathogenic mechanism by which HC predisposes to DM is not clear. The objective of this study was to determine the insulin and C-peptide response to 75 gram oral glucose load and measure anti phospholipid antibody levels in patients with chronic liver disease due to HC. Design: a prospective study. Place and duration of study: This study was conducted at the department of medicine, Jinnah postgraduate medical centre over period of three months. Subjects and methods: An analytical case control study was carried out on 37 patients (m-18,f=19); none of these patients had received interferon. They were divided into four groups: (a) HC cirrhosis with DM (n=9 ), (b) HC cirrhosis without DM (n=11), (c) hepatitis B (HB) cirrhosis without DM (n=7), (d) chronic hepatitis C without DM (n=10). Group C and D were taken as controls. Fasting blood samples were taken and repeated after 2 hours of 75 gram oral glucose load (2 h PG). Result: mean ages of group A,B,C and D were (yr +- SD) 51.3 +- 7.6,48.9 +- 2.4, 33.7 +-10.8 and 31.7 +- 8.8 respectively. There was no statistically significant difference in the age, Pugh score and body mass index of HC cirrhotic patients with and without DM. Patients of group A had higher fasting and 2 h PG glucose levels (P=0.003 and 0.000) and higher fasting insulin level (p=0.045). However, increments in insulin and c peptide levels 2 h PG were much less (p=0.048 and 0.003). HB cirrhotics without diabetes (group C behaved just like HC cirrhotic without diabetes (group B). Patients of group D had normal glucose tolerance and insulin and C peptide levels. All four groups had normal anti phospholipid antibody levels. Conclusion: Patients with cirrhosis due to HC nd HB show evidence of glucose intolerance in spite of hyperinsulinaemia probably due to insulin resistance. HC cirrhotics with diabetes have fasting hyperglycemia in spite of

  12. Health care costs, work productivity and activity impairment in non-malignant chronic pain patients

    DEFF Research Database (Denmark)

    Kronborg, Christian; Handberg, Gitte; Axelsen, Flemming

    2009-01-01

    This study explores the costs of non-malignant chronic pain in patients awaiting treatment in a multidisciplinary pain clinic in a hospital setting. Health care costs due to chronic pain are particular high during the first year after pain onset, and remain high compared with health care costs...

  13. Arrhythmia risk in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ioana Mozos

    2015-01-01

    Interactions between the functioning of the heart andthe liver have been described, with heart diseasesaffecting the liver, liver diseases affecting the heart,and conditions that simultaneously affect both. Theheart is one of the most adversely affected organs inpatients with liver cirrhosis. For example, arrhythmiasand electrocardiographic changes are observed inpatients with liver cirrhosis. The risk for arrhythmia isinfluenced by factors such as cirrhotic cardiomyopathy,cardiac ion channel remodeling, electrolyte imbalances,impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT intervalprolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions.

  14. Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

    Science.gov (United States)

    Schaefer, Benedikt; Haschka, David; Finkenstedt, Armin; Petersen, Britt-Sabina; Theurl, Igor; Henninger, Benjamin; Janecke, Andreas R; Wang, Chia-Yu; Lin, Herbert Y; Veits, Lothar; Vogel, Wolfgang; Weiss, Günter; Franke, Andre; Zoller, Heinz

    2015-11-01

    Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with hepatic iron overload in a subgroup of patients. The underlying cause for this association is unknown. The aim of the present study was to define the genetics of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the expression of the iron hormone hepcidin. Full exome and candidate gene sequencing were carried out in a family with A1ATD and hepatic iron overload. Regulation of hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co-transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model to investigate the molecular mechanism of this regulation. Observed familial clustering of hepatic iron overload with A1ATD suggests a genetic cause, but genotypes known to be associated with hemochromatosis were absent. Individuals homozygous for the A1AT Z-allele with environmental or genetic risk factors such as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA expression in a dose-dependent manner. Experiments in overexpressing cells show that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co-receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute-phase protein A1AT is an inducer of hepcidin expression. Through this mechanism, A1ATD could be a trigger of hepatic iron overload in genetically predisposed individuals or patients with environmental risk factors for hepatic siderosis. PMID:26310624

  15. [Therapeutic correction of mild cognitive impairment in patients with chronic cerebral ischemia].

    Science.gov (United States)

    Odinak, M M; Kashin, A V; Ememlin, A Iu; Lupanov, I A

    2013-01-01

    Neurodegenerative and cerebrovascular diseases are the most significant among the main reasons leading to the cognitive impairment of the elderly. Vascular cognitive impairment is not limited to only dementia, representing a heterogeneous group both in pathogenic and clinical terms. The article dwells upon new principles of vascular cognitive impairment's classification and the review of their possible therapeutic correction that was conducted. The article includes the results of the 12-week open therapeutic (randomized with the control group) study of efficiency and safety of vitrum memory for patients with mild vascular cognitive impairment. It is shown that the therapy significantly improved the state of neurodynamic and regulatory functions of the patients with I--II stage dyscirculatory encephalopathy. PMID:23739499

  16. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure

    OpenAIRE

    Lu, Cai-Ling; Tang, Shen; Meng, Zhi-Juan; He, Yi-Yuan; Song, Ling-Yong; Liu, Yin-Pin; Ma, Ning; Li, Xi-Yi; Guo, Song-Chao

    2014-01-01

    Background Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. Results The escape latency in the Morris Water Maz...

  17. Construction and characterization of a cDNA library from human liver tissue with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-hong; CHEN Zhi; YAO Hang-ping; CHEN Feng; ZHU Hai-hong; ZHOU Hong-juan

    2005-01-01

    Objective: To construct a cDNA library from human liver tissue with chronic hepatitis B and check its quality for investigating the expression level of liver tissue infected by hepatitis B virus. This will then be used to find the relevant genes and interesting proteins associated with the development of hepatitis B. Methods: The total RNA from liver tissue with chronic hepatitis B was extracted and the mRNA was purified using TRIZOL method. Switching mechanism at 5' end of the RNA transcript(SMART) technique and CDS Ⅲ/3' primer were used for first-strand cDNA synthesis. Long distance polymerase chain reaction(LD PCR) was then used to synthesize the double-strand cDNA that was then digested by Sfi I and fractionated by CHROMA SPIN-400 column. The longer than 0.4 kb cDNAs were collected and ligated to λTriplEx2 vector. Then λ phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries were strictly checked by conventional titer determination. Fourteen plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. Results: The titers of unamplifed and amplified libraries were 1.94×106 pfu/ml and1.49×109 pfu/ml respectively. The percentages of recombinants from both libraries were 98.15% in unamplified library and98.76% in amplified library. The lengths of the inserts were 1.23 kb in average, 1-2 kb in 64.29%, and 0.5-1.0 kb in 35.71%.Conclusion: A high quality cDNA library from human liver tissue with chronic hepatitis B was successfully constructed.

  18. Clinical, Laboratory and Bacterial Profile of Spontaneous Bacterial Peritonitis in Chronic Liver Disease Patients

    International Nuclear Information System (INIS)

    Objective: To determine the clinical and laboratory features, bacterial profile and antibiotic sensitivity pattern of Spontaneous Bacterial Peritonitis (SBP) in Chronic Liver Disease (CLD) patients presenting at a tertiary care hospital of Karachi. Study Design: Cross-sectional study. Place and Duration of Study: PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi, from April 2010 to March 2012. Methodology: CLD patients with ascites were recruited from PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi. Basic demographics, symptoms and clinical signs of patients were recorded. Patients with the history of antibiotic use within last 3 days or any intra-abdominal source of infection were excluded. Diagnostic paracentesis was done for ascitic fluid detailed report (D/R) and culture. Blood sample was collected for total leukocyte count, serum proteins and billirubin levels. Results: Out of a total 152 CLD patients, 38 (25%) were diagnosed with SBP. Eight (24.2%) patients presented with classical SBP, 20 (52.6%) had culture negative neutrocytic ascites and 10 (26%) had bacterascites. Fever, abdominal tenderness and constipation were common in SBP patients. Ascitic fluid culture was positive in 19 (50%) patients. E. coli (65%) was the predominant pathogen followed by Enterococcus species (15%). Resistance was high against cephalosporins (78%) and fluoroquinolones (69.6%) and least against amikacin (13%) and meropenem (12%). Conclusion: Ascitic fluid D/R and culture together can lead to the accurate diagnosis of SBP and can guide for the right antibiotic choice as resistance to commonly prescribed antibiotic is common in such patients. (author)

  19. Nosocomial candiduria in chronic liver disease patients at a hepatobilliary center

    Directory of Open Access Journals (Sweden)

    Neha Rathor

    2014-01-01

    Full Text Available Background: Nosocomial urinary tract infections (UTIs are common in catheterized patients. Fungal UTI has become an important nosocomial problem over the past decade. The microbiology of candiduria is rapidly evolving and new trends are being reported. Aims: To study the microbiological trends and antifungal resistance profile of Candida in urine of catheterized chronic liver disease (CLD patients at a super specialty hepatobiliary tertiary-care center. Materials and Methods: urine samples were collected by sterile technique, processed by semi-quantitative method as per the standard protocols. Direct microscopic examination of urine sample was also done to look for the presence of pus cells, red blood cells, casts, crystals or any bacterial or fungal element. Result: A total of 337 yeast isolates were obtained from catheterized patients, non-albicans Candida spp. emerged as the predominant pathogen and was responsible for 67.06% of nosocomial fungal UTI. Candida tropicalis accounted for 34.71% of the cases, whereas Candida albicans grew in 32.93%, Candida glabrata 16.32%, rare Candida spp. Nearly 11.5% (Candida hemolunii to be confirmed by molecular methods. Antifungal sensitivity varied non-albicans species except C. tropicalis, Candida parapsilosis were more often resistant to antifungal drugs. Conclusion: Nosocomial Candida UTIs in CLD patients is common, due to the cumulative pressure of contributing factors such as urinary instrumentation and prolonged use of broad-spectrum antibiotics. Non-albicans Candida were found to outnumber C. albicans in catherized CLD patients. Risk of strain persistence is also higher with non-albicans Candida. Thus, species identification and susceptibility testing is a must for appropriate management of such patients.

  20. Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities.

    Science.gov (United States)

    Musso, Giovanni; Cassader, Maurizio; Cohney, Solomon; De Michieli, Franco; Pinach, Silvia; Saba, Francesca; Gambino, Roberto

    2016-10-01

    Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium. PMID:27660122

  1. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    International Nuclear Information System (INIS)

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility

  2. Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities.

    Science.gov (United States)

    Musso, Giovanni; Cassader, Maurizio; Cohney, Solomon; De Michieli, Franco; Pinach, Silvia; Saba, Francesca; Gambino, Roberto

    2016-10-01

    Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium.

  3. Diagnosis of spontaneous bacterial peritonitis in infants and children with chronic liver disease: A cohort study

    Directory of Open Access Journals (Sweden)

    Abdel-Latif Zainab

    2011-05-01

    Full Text Available Abstract Background Spontaneous bacterial peritonitis (SBP is a serious complication in infants and children with chronic liver disease (CLD; however its diagnosis might be difficult. We aimed to study the feasibility of diagnosing SBP by routine ascitic fluid tapping in infants and children with CLD. Methods We enrolled thirty infants and children with biopsy-proven CLD and ascites. Ascitic fluid was examined for biochemical indices, cytology and cell count. Aerobic and anaerobic bacteriological cultures of ascitic fluid were preformed. Direct smears were prepared from ascitic fluid deposit for Gram and Zheil-Nelson staining. Results Patients were divided into three groups: Group I included five patients with SBP in which the cell count was ≥ 250/mm3 and culture was positive (16.7%, Group II, eight patients with culture negative neutrocytic ascites (CNNA with cells ≥ 250/mm3 and negative culture (26.7% and Group III, seventeen negative patients (56.6% in which cells were 3 and culture was negative. None of our patients had bacteriascites (i.e. culture positive with cells 3. Presence of fever was significantly higher in SBP and CNNA. The mean lactate dehydrogenase (LDH level was significantly higher in ascitic fluid in the infected versus sterile cases (p Conclusions SBP is a rather common complication in children with CLD. Culture of the ascitic fluid is not always diagnostic of infection. Biochemical parameters of the ascitic fluid definitely add to the diagnostic accuracy. LDH ascitic/serum ratio ≥ 0.5, an arterial-ascitic pH gradient ≥ 0.1 and total ascitic fluid protein ≤ 1 gm/dl are the most significant parameters suggesting infection.

  4. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, F.A. [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattar, R. [1Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Facincani, I. [Departamento de Pediatria e Neonatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramalho, L.N.Z. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Jorgetti, V. [Departamento de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Volpon, J.B. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Paula, F.J.A. de [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-14

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

  5. Acute and chronic wound fluids inversely influence adipose-derived stem cell function: molecular insights into impaired wound healing.

    Science.gov (United States)

    Koenen, Paola; Spanholtz, Timo A; Maegele, Marc; Stürmer, Ewa; Brockamp, Thomas; Neugebauer, Edmund; Thamm, Oliver C

    2015-02-01

    Wound healing is a complex biological process that requires a well-orchestrated interaction of mediators as well as resident and infiltrating cells. In this context, mesenchymal stem cells play a crucial role as they are attracted to the wound site and influence tissue regeneration by various mechanisms. In chronic wounds, these processes are disturbed. In a comparative approach, adipose-derived stem cells (ASC) were treated with acute and chronic wound fluids (AWF and CWF, respectively). Proliferation and migration were investigated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and transwell migration assay. Gene expression changes were analysed using quantitative real time-polymerase chain reaction. AWF had a significantly stronger chemotactic impact on ASC than CWF (77·5% versus 59·8% migrated cells). While proliferation was stimulated by AWF up to 136·3%, CWF had a negative effect on proliferation over time (80·3%). Expression of b-FGF, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was strongly induced by CWF compared with a mild induction by AWF. These results give an insight into impaired ASC function in chronic wounds. The detected effect of CWF on proliferation and migration of ASC might be one reason for an insufficient healing process in chronic wounds.

  6. An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine-induced chronic liver injury model in rats

    Institute of Scientific and Technical Information of China (English)

    Jang-Woo Shin; Myong-Min Lee; Xiao Ping Hu; Chang-Gue Son; Jin-Young Son; Se-Mi Oh; Seung-Hyun Han; Jing-Hua Wang; Jung-Hyo Cho; Chong-Kwan Cho; Hwa-Seung Yoo; Yeon-Weol Lee

    2006-01-01

    AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats.METHODS: Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15th d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides,hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis,were analyzed using real-time PCR.RESULTS: CGX administration restored the spleen weight to normal after having been increased by DMN treatment.Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P< 0.05), ALT (P < 0.01), and AST (P < 0.01) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β, TIMP-1, TIMP-2,PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration.CONCLUSION: CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.

  7. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver

    DEFF Research Database (Denmark)

    Frey, Simone K; Nagl, Britta; Henze, Andrea;

    2008-01-01

    The levels of retinol-binding protein 4 (RBP4) - the carrier protein for Vitamin A in plasma - are tightly regulated under healthy circumstances. The kidney, the main site of RBP4 catabolism, contributes to an elevation of RBP4 levels during chronic kidney disease (CKD) whereas during chronic liver...

  8. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2014-04-01

    The irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder world wide that lasts for decades. The human gut harbors a diverse population of microbial organisms which is symbiotic and important for well being. However, studies on conventional, germ-free, and obese animals have shown that alteration in normal commensal gut microbiota and an increase in pathogenic microbiota-termed "dysbiosis", impact gut function, homeostasis, and health. Diarrhea, constipation, visceral hypersensitivity, and abdominal pain arise in IBS from the gut-induced dysfunctional metabolic, immune, and neuro-immune communication. Dysbiosis in IBS is associated with gut inflammation. Gut-related inflammation is pivotal in promoting endotoxemia, systemic inflammation, and neuroinflammation. A significant proportion of IBS patients chronically consume alcohol, non-steroidal anti-inflammatories, and fatty diet; they may also suffer from co-morbid respiratory, neuromuscular, psychological, sleep, and neurological disorders. The above pathophysiological substrate is underpinned by dysbiosis, and dysfunctional bidirectional "Gut-Brain Axis" pathways. Pathogenic gut microbiota-related systemic inflammation (due to increased lipopolysaccharide and pro-inflammatory cytokines, and barrier dysfunction), may trigger neuroinflammation enhancing dysfunctional brain regions including hippocampus and cerebellum. These as well as dysfunctional vago-vagal gut-brain axis may promote cognitive impairment. Indeed, inflammation is characteristic of a broad spectrum of neurodegenerative diseases that manifest demntia. It is argued that an awareness of pathophysiological impact of IBS and implementation of appropriate therapeutic measures may prevent cognitive impairment and minimize vulnerability to dementia. PMID:24590859

  9. MDMA Pretreatment Leads to Mild Chronic Unpredictable Stress-induced Impairments in Spatial Learning

    OpenAIRE

    Cunningham, Jacobi I.; Raudensky, Jamie; Tonkiss, John; Yamamoto, Bryan K.

    2009-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse world-wide and a selective serotonin (5-HT) neurotoxin. An important factor in the risk of drug abuse and relapse is stress. Although multiple parallels exist between MDMA abuse and stress including effects on 5-HTergic neurotransmission, few studies have investigated the consequences of combined exposure to MDMA and chronic stress. Therefore, rats were pretreated with MDMA and exposed 7 days later to 10 days of mild chronic unpredic...

  10. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy

    OpenAIRE

    Tackenberg, Björn; Jelčić, Ilijas; Baerenwaldt, Anne; Wolfgang H Oertel; Sommer, Norbert; Nimmerjahn, Falk; Lünemann, Jan D.

    2009-01-01

    The inhibitory Fc-γ receptor FcγRIIB, expressed on myeloid and B cells, has a critical role in the balance of tolerance and autoimmunity, and is required for the antiinflammatory activity of intravenous Ig (IVIG) in various murine disease models. However, the function of FcγRIIB and its regulation by IVIG in human autoimmune diseases are less well understood. Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy, and IVIG is wide...

  11. Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice

    OpenAIRE

    Babygirija, Reji; Zheng, Jun; Ludwig, Kirk; Takahashi, Toku

    2009-01-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. The development of gastric symptoms may depend on how humans adapt to the stressful events in their daily lives. Although acute stress delays gastric emptying and alters upper gastrointestinal motility in rodents, the effects of chronic stress on gastric motility and its adaptation mechanism remains unclear. Central oxytocin has been shown to have antistress effects. We studied whether central oxytocin is i...

  12. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani; Alessandro Vario; Maria Guido; Alfredo Alberti

    2007-01-01

    AIM: To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F ≥ 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB).METHODS: One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 ± 11.3) with CHB undergoing diagnostic liver biopsy were included. ASTto-Platelet ratio (APRI), Forns' index, AST-to-ALT Ratio,Goteborg University Cirrhosis Index (GUCI), Hui's model and Fibrotest were measured on the day of liver biopsy.The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC).RESULTS: PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI,Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibrotest had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76,respectively). Stepwise combination algorithms of APRI,Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC,98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy.CONCLUSION: In CHB sequential combination of APRI,Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

  13. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

    Directory of Open Access Journals (Sweden)

    Papa Saliou Mbaye

    Full Text Available BACKGROUND AND AIMS: Despite the high prevalence of chronic hepatitis B (CHB in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM and two biochemical scores (FibroTest®, Fibrometer® to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10 IU/mL and normal alanine aminotransferase (ALT values. METHODS: LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB. Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. RESULTS: 225 patients were evaluated (84% male and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT, and Fibrometer® (FM using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. CONCLUSION: In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.

  14. Sensorimotor impairments of paretic upper limb correlates with activities of daily living in subjects with chronic stroke

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    Ng S.M. Shamay

    2011-02-01

    Full Text Available The  main objective  of  this  study  was  to  investigate  the correlations  between sensorimotor  impairments  of  paretic  upper  limb  and the  hand  functions of  activities of daily  living  (ADLs  scores  in  persons  with chronic stroke.This is a cross-sectional  study  with  19  chronic  stroke  survivors.  Hand function was measured by the Jebsen-Taylor Hand Function Test (JTHFT. Impairments in upper extremity motor function were measured by upper limb items  of  Fugl-Meyer  Assessment  (FMA-UE.  Forearm  muscles  strength, handgrip  and  pinch  grip  power  were  assessed  using  handheld  dynamo-meters. Tactile sensation threshold was measured by monofilaments.Significant differences were found between the affected and unaffected side in the total JTHFT scores, forearm muscle strength, handgrip and pinch grip (p≤0.017, but not the tactile sensa-tion threshold.  The total JTHFT scores were found to be correlated with total score of FMA-UE (rs = -0.789, hand-grip  power  (rs = -0.588 and pinch grip power (rs = -0.657 on the affected side, but not the tactile sensation. The total JTHFT scores were correlated with FMA-UE scores, handgrip and pinch grip of the affected side.  This is the first study in documenting the correlation between the sensorimotor impairments and JTHFT scores in persons with  chronic stroke. Our findings highlights the importance of including upper limb and grip strength training in stroke rehabilitation program in order to improve hand functions in activities of daily living in patients with chronic stroke.

  15. The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

    Science.gov (United States)

    Qiu, Wenhui; Shen, Yang; Pan, Chenyuan; Liu, Shuai; Wu, Minghong; Yang, Ming; Wang, Ke-Jian

    2016-08-01

    Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10μg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000μg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it. PMID:27104808

  16. Acetaldehyde Adducts in Alcoholic Liver Disease

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    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  17. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

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    Toshitaka Umemura

    2013-07-01

    Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

  18. Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment

    Science.gov (United States)

    Bernasconi, Davide Paolo; Casari, Salvatore; Maggiolo, Franco; Cauda, Roberto; Di Pietro, Massimo; Ladisa, Nicoletta; Sighinolfi, Laura; Dal Zoppo, Sarah; Sabbatini, Francesca; Soria, Alessandro; Pezzoli, Chiara; Mondi, Annalisa; Costarelli, Silvia; Valsecchi, Maria Grazia; Torti, Carlo; Gori, Andrea

    2016-01-01

    Background Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear. Methods Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89–60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF. Conclusions Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage. PMID:27632369

  19. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

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    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  20. TNFR1 determines progression of chronic liver injury in the IKK gamma/Nemo genetic model

    NARCIS (Netherlands)

    Cubero, F.J.; Singh, A.; Borkham-Kamphorst, E.; Nevzorova, Y.A.; Masaoudi, Al M.; Haas, U.; Boekschoten, M.V.; Gassler, N.; Weiskirchen, R.; Muller, M.; Liedtke, C.; Trautwein, C.

    2013-01-01

    Death receptor-mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral and alcoholic hepatitis, ischemia/reperfusion injury, fulminant hepatic failure, cholestatic liver injury, as well as cancer. Deletion of NF-kappa B essential modulator in hepatocytes (IKK ga

  1. New insights into the coagulopathy of liver disease and liver transplantation

    Institute of Scientific and Technical Information of China (English)

    M Senzolo; P Burra; E Cholongitas; AK Burroughs

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis.Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore,these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

  2. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Young Eun Chon

    Full Text Available Transient elastography (TE, a non-invasive tool that measures liver stiffness, has been evaluated in meta-analyses for effectiveness in assessing liver fibrosis in European populations with chronic hepatitis C (CHC. However, these data cannot be extrapolated to populations in Asian countries, where chronic hepatitis B (CHB is more prevalent. In this study, we performed a meta-analysis to assess the overall performance of TE for assessing liver fibrosis in patients with CHB.Studies from the literature and international conference abstracts which enrolled only patients with CHB or performed a subgroup analysis of such patients were enrolled. Combined effects were calculated using area under the receiver operating characteristic curves (AUROC and diagnostic accuracy values of each study.A total of 18 studies comprising 2,772 patients were analyzed. The mean AUROCs for the diagnosis of significant fibrosis (F2, severe fibrosis (F3, and cirrhosis (F4 were 0.859 (95% confidence interval [CI], 0.857-0.860, 0.887 (95% CI, 0.886-0.887, and 0.929 (95% CI, 0.928-0.929, respectively. The estimated cutoff for F2 was 7.9 (range, 6.1-11.8 kPa, with a sensitivity of 74.3% and specificity of 78.3%. For F3, the cutoff value was determined to be 8.8 (range, 8.1-9.7 kPa, with a sensitivity of 74.0% and specificity of 63.8%. The cutoff value for F4 was 11.7 (range, 7.3-17.5 kPa, with a sensitivity of 84.6% and specificity of 81.5%.TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB.

  3. Liver shear-wave velocity and serum fibrosis markers to diagnose hepatic fibrosis in patients with chronic viral hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jian Xue; Ji, Yong Hao; Zhao Junzhi; Zhang, Yao Ren; Dun, Guo Liang; Ning, Bo [Dept. of Ultrasonography, Baoji Central Hospital, Baoji (China); Ai, Hong [Dept. of Ultrasonography, The First Affiliated Hospital of Medical College, Xi' an Jiaotong University, Xi' an (China)

    2016-06-15

    To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis.

  4. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke

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    Meadmore Katie L

    2012-06-01

    Full Text Available Abstract Background Novel stroke rehabilitation techniques that employ electrical stimulation (ES and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL, a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.

  5. Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: computed tomography is useful for evaluation

    OpenAIRE

    HIRAOKA, ATSUSHI; Aibiki, Toshihiko; Okudaira, Tomonari; Toshimori, Akiko; Kawamura, Tomoe; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki; Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi

    2015-01-01

    Background/Aim The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings. Methods We enrolled 988 CLD (736 with naïve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm2)/...

  6. Medical management of chronic liver diseases in children (part I): focus on curable or potentially curable diseases.

    Science.gov (United States)

    El-Shabrawi, Mortada H F; Kamal, Naglaa M

    2011-12-01

    The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic

  7. Studies on the hepatic hemodynamics of the patients with fatty liver by hepatic blood flow mapping

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Shuichi; Okajima, Tugio; Yamazaki, Yasurou (Toho Univ., Tokyo (Japan). School of Medicine)

    1991-12-01

    To investigate intrahepatic hemodynamics of the patients with fatty liver, the time to reach maximal enhancement (PT) of every 3 x 3 pixel was depicted by a gray scale throughout an area of maximal horizontal slice of CT of the liver to obtain blood flow mapping of the liver, and compared with those of normal, chronic hepatitis and cirrhosis. Mottles of deep gray, light gray or black pixels were distributed throughout the liver slice of fatty liver. Although the mean PT of a ROI of fatty liver was longer than normal and shorter than that of cirrhosis and the same as that of chronic hepatitis, the map of fatty liver was different from that of chronic hepatitis. When the distribution of PT was expressed by their histogram, it was known that PT of fatty liver had a wider range than that of chronic hepatitis. The range was the same as that of cirrhosis. In one case of fatty liver, the deep gray pixels was increased when fatty infiltration of the liver was improved. It was concluded that the intrahepatic blood flow of fatty liver was impaired in a way not similar to chronic hepatitis or liver cirrhosis, which could be clearly seen by hepatic blood flow mapping, and which seemed to be reversible with the improvement of fatty liver. (author).

  8. Chronic Liver Disease and the Detection of Hepatocellular Carcinoma by [18F]fluorocholine PET/CT

    Directory of Open Access Journals (Sweden)

    Sandi A. Kwee

    2015-05-01

    Full Text Available Positron emission tomography (PET using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh can elucidate tumors based on differences in choline phospholipid metabolism between tumor and surrounding tissue. The feasibility of detecting hepatocellular carcinoma (HCC using FCh PET has been shown despite constitutively high parenchymal choline metabolism in the liver. Since HCC frequently develops in the setting of chronic liver disease, we comparatively evaluated FCh PET/CT between cirrhotic and non-cirrhotic patients with HCC to investigate the effects of hepatic dysfunction on tumor detection and the tumor-to-background ratio (TBR of FCh uptake. FCh PET/CT was performed prospectively in 22 consecutive patients with HCC (7 newly diagnosed, 15 previously treated. Of these 22 patients, 14 were cirrhotic and 8 non-cirrhotic. Standardized uptake value (SUV measurements were obtained by region of interest analysis of the PET images. Tumor FCh uptake and the TBR were compared between cirrhotic and non-cirrhotic patients. Liver lesions were confirmed to be HCC by biopsy in 10 patients and by Barcelona criteria in 4 patients. There was correspondingly increased liver tumor FCh uptake in 13/14 of those patients, and iso-intense tumor FCh uptake (TBR 0.94 in one non-cirrhotic patient with newly diagnosed HCC. FCh PET/CT also showed metastatic disease without local tumor recurrence in 2 previously treated patients, and was negative in 6 treated patients without tumor recurrence by radiographic and clinical follow-up. Tumor maximum SUV ranged from 6.4 to 15.3 (mean 12.1 and liver TBR ranged from 0.94 to 2.1 (mean 1.6, with no significant differences between cirrhotic and non-cirrhotic patients (SUVmax 11.9 vs. 12.2, p = 0.83; TBR 1.71 vs. 1.51, p = 0.29. Liver parenchyma mean SUV was significantly lower in cirrhotic patients (6.4 vs. 8.7, p < 0.05. This pilot study supports the general feasibility of HCC detection by FCh PET/CT. However, a broad

  9. FibroScan对慢性药物性肝损害肝纤维化的诊断价值研究%Diagnostic value of FibroScan for liver fibrosis in patients with chronic drug-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    李梵; 闫涛; 周燕萍; 张健; 邵清; 李忠斌; 李冰; 陈国凤

    2013-01-01

    目的 探讨FibroScan对于慢性药物性肝损害(drug-induced liver injury,DILI)肝纤维化的诊断准确性.方法 选择2009年4月-2011年1月在我院住院的经肝脏穿刺病理诊断的慢性DILI患者49例,进行FibroScan检测得到肝脏硬度测量(liver stiffness measurement,LSM)值.以肝脏活体组织检查病理结果为“金标准”绘制受试者工作特征(receiver operating characteristic,ROC)曲线,计算ROC曲线下面积(area under the receiver operating characteristic curve,AUROC),以评价FibroScan对慢性DILI肝纤维化的诊断价值.结果 LSM值与肝脏病理分期呈正相关,Kendall相关系数为0.607,P<0.001.FibroScan诊断慢性DILI肝纤维化≥S2期、≥S3期、S4期的AUROC分别为0.878、0.944、0.993.结论 FibroScan对诊断慢性DILI肝纤维化程度有较好的准确性.%Objective To investigate the diagnostic accuracy of FibroScan for liver fibrosis in patients with chronic drug-induced liver injury (DILI).Methods Forty-nine inpatients with chronic DILI,who were treated in our hospital and underwent liver biopsy from Apr.2009 to Jan.2011,were enrolled in this study.The values of liver stiffness measurement (LSM) were obtained using FibroScan.With liver biopsy as the gold standard,the receiver operating characteristic (ROC) curves were drawn,and the areas under the receiver operating characteristic curves (AUROC) were calculated to evaluate the diagnostic accuracy of FibroScan for liver fibrosis in patients with chronic DILI.Results Liver stiffness was positively correlated with liver fibrosis stage with a Kendall coefficient of 0.607 (P<0.001).Using FibroScan for the assessment of liver fibrosis in patients with chronic DILI,the AUROCs were 0.878 for the patients with ≥ S2,0.944 for those with ≥ S3 and 0.993 for those with S4.Conclusion FibroScan can assess liver fibrosis in patients with chronic DILI with a high accuracy.

  10. Prospective validation of FibroTest in comparison with liver stiffness for predicting liver fibrosis in Asian subjects with chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Beom Kyung Kim

    Full Text Available Diagnostic values of FibroTest (FT for hepatic fibrosis have rarely been assessed in Asian chronic hepatitis B (CHB patients. We aimed to validate its diagnostic performances in comparison with liver stiffness (LS.From 2008 to 2010, 194 CHB patients who underwent liver biopsies along with FT and transient elastography were prospectively enrolled. Fibrosis stage was assessed according to the Batts and Ludwig system.To predict significant fibrosis (F≥2, advanced fibrosis (F≥3, and cirrhosis (F = 4, areas under receiver operating characteristic curves (AUROCs of FT were 0.903, 0.907, and 0.866, comparable to those of LS (0.873, 0.897, and 0.910, respectively. Optimized cutoffs of FT to maximize sum of sensitivity and specificity were 0.32, 0.52, and 0.68 for F≥2, F≥3, and F = 4, while those of LS were 8.8, 10.2, and 14.1 kPa, respectively. According to FT and LS cutoffs, 123 (63.4% and 124 (63.9% patients were correctly classified consistent with histological fibrosis (F1, F2, F3, and F4, respectively. Overall concordance between each fibrosis stage estimated by FT and LS was observed in 111 patients, where 88 were correctly classified with histological results. A combination formula adding LS to FT (LS+FT showed similar AUROC levels (0.885, 0.905, and 0.915, while another multiplying LS by FT (LS×FT showed the best AUROCs (0.941, 0.931, and 0.929 for F≥2, F≥3, and F4, respectively.FT provides good fibrosis prediction, with comparable outcomes to LS in Asian CHB patients. FT substantially reduces need for liver biopsy, especially when used in combination with LS.

  11. Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Li-Qun Yang; Shen-Jing Li; Yun-Fei Cao; Xiao-Bo Man; Wei-Feng Yu; Hong-Yang Wang; Meng-Chao Wu

    2003-01-01

    AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P<0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.

  12. Impact of Il28b-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection.

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    Magdalena Ydreborg

    Full Text Available BACKGROUND AND AIMS: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. METHODS: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860 and HCV genotyping. RESULTS: CC(rs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001. Additionally CC(rs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004, and higher AST to platelet ratio index (APRI; p = 0.02 as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CC(rs12979860 was significantly associated with higher viral load (P = 0.001, with a similar non-significant trend noted among HCV genotype 3 infected patients. CONCLUSION: This study confirms previous reports that the CC(rs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.

  13. Comparison on Efficacy between Astragalus-Polygonum Anti-Fibrosis Decoction and Jinshuibao (金水宝) Capsule in Treating Liver Fibrosis of Chronic Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To observe the efficacy of Astragalus-Polygonum Anti-Fibrosis decoction (APAFD)and Jinshuibao capsule (JSBC) in treating liver fibrosis of chronic hepatitis B. Methods: Ninety-two cases of liver fibrosis of chronic hepatitis B were randomly divided into group A and group B. Patients in group A received APAFD for 48 weeks, and in group B, they received JSBC for 48 weeks. The effects on the level change of hyaluronic acid (HA), laminin (LN), pro-collagen Ⅲ (PCⅢ) and collagen Ⅳ (CⅣ) as well as liver functional tests and liver biochemical parameters before and after treatment were observed.Results: Level of serum HA, LN, PCⅢ and CⅣ in group A declined more obviously than that of group B, the difference was significant (P<0.01). The liver functional tests such as total bilirubin (TB), alanine aminotransferase (ALT), albumin/globulin (A/G) ratio, hepatitis related serum biochemical parameters such as cholylglycine (CG), serum ferritin (SF), prealbumin (PC) of group A were all improved more significantly than that of group B (P<0.01).Conclusion: APAFD is more effective than JSBC in treating liver fibrosis of chronic hepatitis B and in the inhibition of hepatic inflammation, hence it is a good composite Chinese herbal preparation against liver fibrosis.

  14. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood