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Sample records for hepatic nutritional fibrosis

  1. Autophagy in Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Yang Song

    2014-01-01

    Full Text Available Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.

  2. Nutritional Issues in Cystic Fibrosis.

    Science.gov (United States)

    Solomon, Missale; Bozic, Molly; Mascarenhas, Maria R

    2016-03-01

    The importance of maintaining adequate nutrition in patients with cystic fibrosis has been well known for the past 3 decades. Achieving normal growth and maintaining optimal nutrition is associated with improved lung function. Comprehensive and consistent nutritional assessments at regular intervals can identify those at risk of nutritional failure and uncover micronutrient deficiencies contributing to malnutrition. Management of malnutrition in cystic fibrosis should follow a stepwise approach to determine the causes and comorbidities and to develop a nutritional plan. Nutritional management is crucial at every stage in a person's life with cystic fibrosis and remains a cornerstone of management.

  3. Hepatitis C: Diet and Nutrition

    Science.gov (United States)

    ... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

  4. Cystic fibrosis - nutrition

    Science.gov (United States)

    ... in recipes. Add marshmallows to fruit or hot chocolate. Add raisins, dates, or chopped nuts and brown ... AP, Quinton H. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic ...

  5. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions,and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accuracy for predicting significant fibrosis and cirrhosis in chronic hepatitis C. Based on available data, the performance of simple tests derived from routine laboratory parameters appears to be similar to that of more complex and expensive fibrosis panels. Transient elastography seems more accurate than blood tests for diagnosing cirrhosis.

  6. HIV Infection Accelerates Hepatitis C-Related Liver Fibrosis

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    ... HIV Infection Accelerates Hepatitis C–Related Liver Fibrosis HIV Infection Accelerates Hepatitis C–Related Liver Fibrosis Email ... the progression of other chronic diseases as well. HIV and Fibrosis Dr. Kirk and his team tapped ...

  7. Inhibition of SIRT2 suppresses hepatic fibrosis.

    Science.gov (United States)

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

  8. Nutritional assessment in children with cystic fibrosis

    Science.gov (United States)

    Optimal nutrition, including consuming 35–40% of calories (kcal) as fat, is a vital part of the management of cystic fibrosis (CF), and involves accurate assessment of dietary intake. We compared 3 methods of nutritional assessment in 8– to 14-year-old children (n=20) with CF: 1) a 24-h Dietary Reca...

  9. [Congenital hepatic fibrosis: apropos of 12 cases].

    Science.gov (United States)

    Murga, M L; Jara, P; Díaz, M C; de la Rubia, L; Arroba, M L; Larrauri, J; Vázquez, C

    1988-02-01

    Twelve patients with congenital hepatic fibrosis have been retrospectively studied and followed for 1 to 14 years. Clinical features, hepatic function tests and biopsy have been analyzed. Presence of portal hypertension and congenital malformation have been investigated. Clinical presentations varies from newborn to nine years of age without male or female predominance. Most frequent clinical form has been hypertensive type. Cholangitic type has worse prognosis. Familiar recurrence rate is 20%. Congenital malformations are associated in 92% most frequently infantile polycystic kidney disease. Hepatic biopsy has confirmed diagnosis in all patients.

  10. Hepatic fibrosis: Concept to treatment.

    Science.gov (United States)

    Trautwein, Christian; Friedman, Scott L; Schuppan, Detlef; Pinzani, Massimo

    2015-04-01

    Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases.

  11. Cystic Fibrosis: Diet and Nutrition

    Science.gov (United States)

    ... as ice cream, pudding, and cheesecake. Top hot chocolate, pudding, and other desserts with whipped cream. Avoid ... energy or trouble gaining weight, even with good nutrition and supplements. For these teens, doctors may recommend ...

  12. [Nutrition, cystic fibrosis and the digestive tract].

    Science.gov (United States)

    Olveira, Gabriel; Olveira, Casilda

    2008-05-01

    The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

  13. Imaging findings in congenital hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Akhan, Okan [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)]. E-mail: akhano@tr.net; Karaosmanoglu, Ali Devrim [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey); Ergen, Bilge [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)

    2007-01-15

    Congenital hepatic fibrosis (CHF) is a rare congenital multisystemic disorder, mostly inherited in autosomal recessive fashion, primarily affecting renal and hepatobiliary systems. Main underlying process of the disease is the malformation of the ductal plate, the embryological precursor of the biliary system, and secondary biliary strictures and periportal fibrosis ultimately leading to portal hypertension. The natural course of the disease is highly variable ranging from minimally symptomatic disease to true cirrhosis of the liver. However, in most patients the most common manifestations of the diseases that are related to portal hypertension, particularly splenomegaly and bleeding varices. Many other disease processes may co-exist with the disease including Caroli's disease, choledochal cysts and autosomal recessive polycystic kidney disease (ARPKD) reflecting the mulstisystemic nature of the disease. The associating biliary ductal disease led the authors to think that all these entities are a continuum and different reflections of the same underlying pathophysiological process. Although, conventional method of diagnosis of CHF is the liver biopsy the advent of imaging technologies and modalities, today, may permit the correct diagnosis in a non-invasive manner. Characteristic imaging features are generally present and recognition of these findings may obviate liver biopsy while preserving the diagnostic accuracy. In this article, it is aimed to increase the awareness of the practising radiologists to the imaging findings of this uncommon clinical disorder and trail the blaze for future articles relating to this issue.

  14. Increased caffeine consumption is associated with reduced hepatic fibrosis

    National Research Council Canada - National Science Library

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E; Liang, T. Jake; Hoofnagle, Jay H

    2010-01-01

    Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically...

  15. Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys.

    Science.gov (United States)

    Manes, J L; Kissane, J M; Valdes, A J

    1977-06-01

    In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells.

  16. Expression of integrin in hepatic fibrosis and intervention of resveratrol

    Institute of Scientific and Technical Information of China (English)

    Jianye WU; Chuanyong GUO; Jun LIU; Xuanfu XUAN

    2009-01-01

    The aim of this study was to explore the expression of integrin-β1 in different stages of hepatic fibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepatic fibrosis. Hepatic fibrosis models of male Sprague Dawley (SD) rats were created and intragastric administration of resveratrol was given in low (40 mg/kg), middle (120mg/kg) and high (200 mg/kg) dose groups. The expression of integrin-β1, transforming growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of hepatic fibrosis was detected by using RT-PCR. The expression of hexadecenoic acid (HA) and precollagen Ⅲ (pc Ⅲ) was assayed by radioimmunoassay. The expression of integrin-β1, TGF-β and TIMP-1 was determined in each group. Liver function and pathological sections of each group in different stages of hepatic fibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses. The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepatic fibrosis, but it was increased in other groups. The expression levels of integrin-β1 in the model control group (0.878±0.03, P 0.05). The expression levels of integrin-β1 and TGF-β in middle dose group and high dose group were higher than other groups (P<0.01). The expression levels of integrin-β1 and TGF-β in model control group and low dose group were lower than the normal control group (P < 0.01). The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups (P < 0.01). The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group (P<0.01). The expression of integrin-β1 existed in all stages of hepatic fibrosis of SD rats, and it was increased with the development of hepatic fibrosis. The expression of TGF-β and TIMP-1 was consistent with that ofintegrin-β1 in different stages of

  17. The Immune Interplay between Thyroid Papillary Carcinoma and Hepatic Fibrosis.

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    Nidal Muhanna

    Full Text Available A high prevalence of thyroid papillary cancer was reported in hepatitis-C-virus (HCV positive patients. However, the mechanistic role of hepatic-fibrosis in thyroid malignancy progressions is still unclear.We aimed to study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis.Hepatic-fibrosis was induced in nude-nu-male mice by intra-peritoneal administration of carbon-tetrachloride. To induce thyroid-tumor, a thyroid papillary carcinoma cell line (NPA was injected subcutaneously in the backs. Fibrotic profile was estimated by α-smooth-muscle-actin (αSMA expression in liver tissue extracts using western-blots and RT-PCR. Intra-hepatic NK cells were isolated and stained for NK activity (CD107a by flow cytometry. Liver histopathology (H&E staining, thyroid tumor mass and serum alanine aminotransferase (ALT, serum vascular endothelial growth factor (VEGF and free-T4 levels were also assessed.Ex-vivo: NPA cells were co-cultured with intra-hepatic NK cells isolated from fibrotic mice with/without the tumor were analyzed for CFSE-proliferations. Both tumor groups (with/without hepatic-fibrosis excreted higher serum free T4 levels. Hepatic-fibrosis increased tumor weight and size and serum free-T4 levels. In addition, tumor induction increased liver injury (both hepatic-fibrosis, necro-inflammation and serum ALT levels. In addition, tumor-bearing animals with hepatic-fibrosis had increased NK activity. NPA tumor-bearing animals increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum free-T4 excretions. Serum VEGF levels were significantly increased in the fibrotic- bearing tumor groups compared to the non-fibrotic groups. In-vitro, NK cells from fibrotic tumor-bearing animals reduced proliferation of NPA cells. This decrease is attributed to increase NK cells activity in the fibrotic animals with the NPA tumors.Our results propose that NK cells although were

  18. growth and nutrition in south african children with cystic fibrosis

    African Journals Online (AJOL)

    Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasian ... effective pancreatic enzyme replacement formulations has made it possible to ... That this deficit was nutritional in origin is supported by the similar ...

  19. Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

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    Liana Codes

    2007-06-01

    Full Text Available The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from non-proliferating cells to proliferating cells that express a- smooth-muscle actin (a-SMA, a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

  20. Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

    Directory of Open Access Journals (Sweden)

    Liana Codes

    Full Text Available The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from non-proliferating cells to proliferating cells that express a- smooth-muscle actin (a-SMA, a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

  1. Increased caffeine consumption is associated with reduced hepatic fibrosis.

    Science.gov (United States)

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E; Liang, T Jake; Hoofnagle, Jay H

    2010-01-01

    Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P = 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis.

  2. Increased caffeine consumption is associated with reduced hepatic fibrosis

    Science.gov (United States)

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E.; Liang, T. Jake; Hoofnagle, Jay H.

    2009-01-01

    Background Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. Aim To use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Methods Patients undergoing liver biopsy completed a detailed caffeine questionnaire on 3 occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. Results 177 patients (99 male, 104 Caucasian, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75th percentile for the cohort (308 mg ~2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (OR 0.33, 95% CI: 0.14-0.80, p=0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index and alcohol intake in all patients (OR 0.25, 95% CI: 0.09-0.67, p=0.006), as well as the subset with HCV infection (OR 0.19, 95% CI: 0.05-0.66, p=0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. Conclusion A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. PMID:20034049

  3. 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

  4. A family of congenital hepatic fibrosis and atypical retinitis pigmentosa

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    Sunil Pawar

    2015-11-01

    Full Text Available Congenital hepatic fibrosis is a rare cause of portal hypertension and esophageal varices in children. We report cases of siblings with biopsy proven congenital hepatic fibrosis and with atypical retinitis pigmentosa. They presented with repeated episodes of jaundice along with progressive decrease of vision in night. They had hepatosplenomegaly and portal hypertension with esophageal varices. One of the siblings had a large regenerating nodule replacing the entire right lobe of the liver and other one developed repeated hematemesis. This constellation of diagnosis belongs to the ciliopathy group of disorders. The spectrum of ciliopathy disorders has been evolving, and it varies from mild to severe manifestations.

  5. Nutritional therapy in cirrhosis or alcoholic hepatitis

    DEFF Research Database (Denmark)

    Fialla, Annette D; Israelsen, Mads; Hamberg, Ole

    2015-01-01

    BACKGROUND & AIMS: Patients with cirrhosis and alcoholic hepatitis are often malnourished and have a superimposed stress metabolism, which increases nutritional demands. We performed a systematic review on the effects of nutritional therapy vs. no intervention for patients with cirrhosis or alcoh......BACKGROUND & AIMS: Patients with cirrhosis and alcoholic hepatitis are often malnourished and have a superimposed stress metabolism, which increases nutritional demands. We performed a systematic review on the effects of nutritional therapy vs. no intervention for patients with cirrhosis...... or alcoholic hepatitis. METHODS: We included trials on nutritional therapy designed to fulfil at least 75% of daily nutritional demand. Authors extracted data in an independent manner. Random-effects and fixed-effect meta-analyses were performed and the results expressed as risk ratios (RR) with 95% confidence...... analysis. Fixed-effect analysis suggested that nutrition prevented overt hepatic encephalopathy (0.73; 95% CI, 0.55 to 0.96) and infection (0.66; 95% CI, 0.45 to 0.98, respectively), but the results were not confirmed in random-effects analyses. CONCLUSION: Our review suggests that nutritional therapy may...

  6. Assessment of hepatic fibrosis in pediatric cases with hepatitis C virus in Egypt

    Institute of Scientific and Technical Information of China (English)

    Manal A El-Hawary; Abdel Aziz Shaheen; Hanaa El-Karaksy; Mona S El-Raziky; Gamal Esmat; Hanan Soliman; Amr Abouzied; Maissa El-Raziky; Wafaa El-Akel; Rokaya El-Sayed; Fatma Shebl

    2007-01-01

    AIM:To assess hepatic fibrosis and factors associated with its progression in children with HCV infection.METHODS: At the Hepatology Unit, Cairo University Children's Hospital, a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 ± 4.3 years.RESULTS: Among the 43 patients'biopsies, 12 (27.9%)were having no fibrosis, 20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo, P = 0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 my/dL,P = 0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P =0.33).CONCLUSION: Hepatic fibrosis was present in 72.1%of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age, duration of infection, risk factors, comorbid conditions and most biochemical parameters.

  7. Serum YKL-40 is increased in patients with hepatic fibrosis

    DEFF Research Database (Denmark)

    Johansen, J S; Christoffersen, P; Møller, S

    2000-01-01

    with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg...

  8. Congenital Hepatic Fibrosis: An Uncommon Cause of Chronic Renal Failure

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    A Azarfar

    2014-04-01

    Full Text Available Congenital Hepatic Fibrosis (CHF is a rare disease that affects both the liver and kidneys.  Congenital hepatic fibrosis (CHF is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts. Affected individuals also have impaired renal function, usually caused, in children and teenagers, by an autosomal recessive polycystic kidney disease (ARPKD. Impaired renal function associated with CHF in adults is caused by an autosomal dominant polycystic kidney disease (ADPKD. Case presentation: We report the case of a 8-year-old Iranian girlwas admitted to our hospital for evaluation ofrenal failure. In patient hepatomegaly was noted incidentally on a routine physical examination and then kidney biopsy showed global sclerosis and   A liver biopsy revealed proliferation of collagen fibres surrounding the portal area, a finding that was compatible with congenital hepatic fibrosisand our patient was scheduled for kidney and  liver transplantation. Conclusion: The relationship of ARPKD to CHF is the subject of substantial controversy. Some clinicians suggest that the two conditions represent one disorder with a range of clinical/pathological presentations Key word: Congenital Hepatic Fibrosis Polycystic Kidney Disease, CRF.

  9. Prediction of fibrosis progression in chronic viral hepatitis

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    Grace Lai-Hung Wong

    2014-09-01

    Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

  10. Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis.

    Science.gov (United States)

    Wood, Marnie J; Crawford, Darrell H G; Wockner, Leesa F; Powell, Lawrie W; Ramm, Grant A

    2017-09-01

    Ferritin is purported to have proinflammatory and profibrogenic effects on hepatic stellate cells. Thus, rather than acting as a passive indicator of hepatic iron concentration (HIC) in haemochromatosis, ferritin may directly influence fibrosis. This study evaluated whether serum ferritin is a better predictor of hepatic fibrosis compared to variables previously associated with increased fibrosis risk in haemochromatosis. We identified 291 C282Y HFE-homozygous patients who had undergone liver biopsy for histological fibrosis staging and measurement of HIC. Ordinal logistic regression determined the best model for fibrosis stage not including serum ferritin. Then, serum ferritin was introduced into this model to assess whether the predictive power of the model was significantly increased and to evaluate the effect on other predictors of fibrosis. Ordinal logistic regression analyses without serum ferritin demonstrated that log HIC (OR 2.89; P serum ferritin in multivariate analysis substantially improved the predictive power of the model (χ(2 ) = 37.15; P serum ferritin in this model rendered the effects of HIC, gender, alcohol and steatosis to non-significance. In haemochromatosis, serum ferritin is a better predictor of fibrosis stage than HIC, gender, steatosis and alcohol. These data support a hypothesis that ferritin may play a role in fibrosis rather than simply acting as a passive indicator of iron storage. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. [Non-invasive evaluation of liver fibrosis in hepatitis C].

    Science.gov (United States)

    de Lédinghen, V; Poynard, T; Wartelle, C; Rosenthal, E

    2008-03-01

    In 2007, the recommended FibroScan, FibroTest or liver biopsy for the initial diagnosis of fibrosis in patients with hepatitis C without co morbidities. These methods have to be interpreted according to the clinical situation, keeping in mind negative and positive false results. For FibroTest, hemolysis, Gilbert syndrome or acute inflammation can modify the result. Pre-analytical and analytical conditions of FibroTest have to be respected according to manufactory recommendations. For FibroScan, the numbers of measurements, the rate of successful measurements, and the interquartile range have to be correct. In case of suspicious results, FibroTest or FibroScan have to be done again. The liver biopsy, FibroTest, and FibroScan are less relevant for the distinction of two adjacent stages of fibrosis. However, their performances are excellent for the diagnosis of severe fibrosis or cirrhosis compared to moderate fibrosis.

  12. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

    Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients d

  13. Serum hyaluronic acid as a noninvasive marker of hepatic fibrosis in chronic hepatitis B

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    Geramizadeh Bita

    2008-01-01

    Full Text Available Background/Aims: Chronic hepatitis B is a serious global health problem. Liver biopsy is currently recommended as the gold standard for the evaluation of the degree of fibrosis in patients with chronic hepatitis B. This procedure, however, is invasive and has potential complications. In this study, we attempted to validate the level of hyaluronic acid as a simple laboratory test to discriminate between patients with and without significant fibrosis in chronic hepatitis B. Methods: This study included 93 patients with chronic hepatitis B who had undergone percutaneous liver biopsy from 2003 to 2006. At the time of biopsy, a sample of serum was taken for the hyaluronic acid (HA assay. Histological assessment consisted of the semiquantitative analysis of the degree of fibrosis according to the criteria proposed by the Ishak system. These findings were then compared by using statistical analysis. Results: HA levels and stage groups of fibrosis were well correlated (Spearman r = 0.945, P < 0.005. There was a significant increase in HA levels when considering S0 to S6. The mean values of HA concentrations were 59.7 ± 10.5 ng/mL for stages 0-2, 149.4 ± 15.9 ng/mL for stages 3-4 , and 284.5 ± 14.5 ng/mL for the last group (stages 5-6. There were significant differences between the three groups. Serum HA levels of cases with extensive fibrosis were significantly higher than in those with mild and moderate fibrosis ( P = 0.0001, P = 0.0005, and P = 0.0001, respectively. Conclusion: Serum HA level is a precise predictor of extensive liver fibrosis in chronic hepatitis B. HA is well correlated with the stage of fibrosis and can reflect the severity of fibrosis. Thus, it can be used as a noninvasive test to monitor these patients.

  14. Epigenetic regulation of hepatic stellate cell activation and liver fibrosis.

    Science.gov (United States)

    El Taghdouini, Adil; van Grunsven, Leo A

    2016-12-01

    Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i.e DNA methylation, histone modifications and the functional role of non-coding RNAs that accompany this key event in the development of chronic liver disease. Expert commentary: Although great progress has been made, our understanding of the epigenetic regulation of hepatic stellate cell activation is limited and, thus far, insufficient to allow the development of epigenetic drugs that can selectively interrupt liver fibrosis.

  15. Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Tsung-Jung Lin; Li-Ying Liao; Shyr-Yi Lin; Chih-Lin Lin; Ting-An Chang

    2006-01-01

    AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CHC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Peris' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patientswith mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P= 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.

  16. Quantitative Assessment of Hepatic Fibrosis by Contrast-enhanced Ultrasonography

    Institute of Scientific and Technical Information of China (English)

    Ming-bo Zhang; En-ze Qu; Ji-Bin Liu; Jin-rui Wang

    2011-01-01

    Objective To explore the contrast-enhanced ultrasonographic features for quantitative assessment of hepatic fibrosis.Methods 86 patients with chronic viral hepatitis B were enrolled in this study from March 2007 to August 2009.The patients were classified into 5 groups (S0-S4) according to fibrosis stage evaluated with ultrasound guided liver biopsy.New contrast-enhanced ultrasonography (CEUS) features including area under the time-intensity curve (TIC) of portal venous phase/hepatic arterial phase (Qp/Qa) and intensity of portal venons phase/hepatic arterial phase (Ip/Ia) were used to detect the blood supply ratio (portal vein/hepatic artery) in each group.Arrival time of portal vein trunk (Tp) and decreasing rate of TIC (β) were also analyzed.Results Qp/Qa and Ip/Ia decreased from So to S4,while Tp and β increased These 4 features were significantly correlated with the degree of fibrosis (P<0.001) and were significantly different among the five groups (P<0.001).Sensitivity and specificity of Ip/Ia were 80% and 86% for groups ≥S1,75% and 86% for groups ≥ S2,71% and 84% for groups ≥ S3,and 76% and 80% for group S4,respectively.Sensitivity and specificity of Qp/Qa were 70% and 88% for groups ≥ S1,80% and 76% for groups ≥ S2,74% and 70% for groups ≥ S3,and 81% and 95% for group S4,respectively.Conclusion Ip/Ia and Qp/Qa could be adopted as reliable,non-invasive features for quantitative assessment of hepatic fibrosis.

  17. Molecular therapy for hepatic injury and fibrosis: Where are we?

    Institute of Scientific and Technical Information of China (English)

    Colette C Prosser; Roy D Yen; Jian Wu

    2006-01-01

    Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents,and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver.These factors lead to activation of hepatic stellate cells,which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury,signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepaticinjury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.

  18. MODERN DIAGNOSTIC TOOLS FOR DETECTING HEPATIC FIBROSIS IN CHILDREN

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    A.N. Surkov

    2009-01-01

    Full Text Available The present review highlights the new diagnostic tools for detecting hepatic fibrosis against the backdrop of different liver pathologies in children. They are characterized by a variety of the clinical forms, progressive course along with the fibroid changes in liver and possible result in the liver cirrhosis. The authors considered the modern methods of the needle liver biopsy and noninvasive visualization, as well as justified the necessity to look for the noninvasive markers of the fibroid liver by means of the antibody'mediated diagnostic methods. Such tests are based on identification of various molecular compounds, which are fibrogenesis activators and take part in the formation of the extracellular matrix components. They also described changes of such fibroid liver markers, as hyaluronic acid, collagen type IV, matrix metalloproteinases 2 and 9, tissular inhibitor of the matrix metalloproteinases'1, transforming growth factor–1, which may be recommended for the noninvasive monitoring of the hepatic fibrosis in children.Key words: hepatic fibrosis, antibody'mediated fibrosis markers, children.

  19. Clinical Study of Dahuang Zhechong Pill (大黄Zhe虫丸) in Treating Posthepatitis B Hepatic Fibrosis

    Institute of Scientific and Technical Information of China (English)

    陈孝银; 李恩庆; 杨钦河; 章群; 孙立; 徐云生; 沈强

    2004-01-01

    Hepatic fibrosis is the only way for all kinds of chronic hepatic diseases to develop into liver cirrhosis. How to block and reverse hepatic fibrosis is the key issue for treatment of all kinds of chronic hepatic disease. After many years arduous effort in treating hepatic fibrosis, no satisfactory results in western medical treatment have been obtained. Though hepatic fibrosis could be definitely reversed by colchicines, the strong toxicity of colchicines limited its clinical application.

  20. ROC curves in evaluation of serum fibrosis indices for hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Min Zheng; Wei-Min Cai; Hong-Lei Weng; Rong-Hua Liu

    2002-01-01

    AIM: Use Receiver operating characteristic (ROC) curves to find out the relationship between serum level of hyaluronic acid (HA), type Ⅲ procollagen (PCⅢ), N-terminal procollagen Ⅲ peptide (PⅢNP), laminin (LN), type Ⅳ collagen (C-Ⅳ) and hepatic fibrosis, as well as to determine their value in clinical practice.METHODS: 114 serum samples from chronic hepatitis patients were assayed for fibrosis indices including HA, PCⅢ, PⅢNP, LN and Ⅳ-C with radioimmunoassay (RIA). Liver biopsy was also performed in all these patients and the biopsy material was examined histopathologically.RESULTS: ROC curves analysis showed that area under the curve (AUC) of PⅢNP, HA, PCⅢ, C-Ⅳ and LN was 0.800,0.728, 0.727, 0.583 and 0.463, respectively. The analysis also showed that PⅢNP (r=0.452), HA (r=0.497) and PCⅢ (r=0.404) have greater diagnosis performances than C-Ⅳ (r=0.238) and LN (r=0.128) according to fibrosis staging. The sensitivity of HA plus PⅢNP was 55.1%, it was the most sensitive combination. Combined three or more than three indices that based on HA, the specificity was 100 %.Using combination assays can improve the specificity, but its sensitivity was not high. Serum fibrosis indices increased as the grade of inflammation aggravated. But only PⅢNP and PCⅢ had significant difference between G1 and G2 (PⅢNP: 13.16±8.07 VS8.32±5.09; PCⅢ: 164.22±65.69 VS 138.23±77.63). The coefficient correlation of the results of inflammation grade and fibrosis staging to HA was 0.525 and 0.553 respectively, that to PCⅢ, 0.446 and 0.412, that to LN, 0.234 and 0.194, and that to Ⅳ-C, 0.363 and 0.351, respectively.CONCLUSION: Serum fibrosis indices can indicate tendency of hepatic fibrosis, but it cannot replace liver biopsy. However, as diagnostic markers, more efficient serum fibrosis indices for the diagnosis of hepatic fibrosis need to be explored.

  1. Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells.

    Science.gov (United States)

    Feng, Yi; Ying, Hai-Yan; Qu, Ying; Cai, Xiao-Bo; Xu, Ming-Yi; Lu, Lun-Gen

    2016-09-01

    Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 μmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.

  2. Hepatic PPARs: their role in liver physiology, fibrosis and treatment.

    Science.gov (United States)

    Zardi, E M; Navarini, L; Sambataro, G; Piccinni, P; Sambataro, F M; Spina, C; Dobrina, A

    2013-01-01

    Complex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease.

  3. Reversal of hepatic fibrosis: pathophysiological basis of antifibrotic therapies

    Directory of Open Access Journals (Sweden)

    Ismail MH

    2011-07-01

    Full Text Available Mona H Ismail1, Massimo Pinzani21Department of Internal Medicine, Division of Gastroenterology, King Fahad University Hospital, Al-Khobar, Saudi Arabia; 2Dipartimento di Medicina Interna Center for Research, High Education and Transfer, Università degli Studi di Firenze, Florence, ItalyAbstract: Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible.Keywords: liver fibrosis, cirrhosis, fibrogenesis, antifibrotic agents

  4. Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Rong-Li Piao; David R Brigstock; Jie Zhu; Man-Li Zhang; Run-Ping Gao

    2012-01-01

    AIM:To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1 (TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r =0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r =0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.

  5. Nutritional Assesment in Cystic Fibrosis Patients( Iran and Newzeland

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    V Moeeni

    2014-04-01

    Full Text Available Introduction: Patients with Cystic Fibrosis have increased risk of malnutrition. Early detection of nutritional deterioration enables prompt intervention and correction. The aims of this project were to: - Define the nutritional status of CF patients in Iran and New Zealand -    Compare and contrast the MacDonald Nutritional Screening tool  with the Australasian guidelines for Nutrition in Cystic Fibrosis -    Validate these results in comparison with patient’s evaluation by their CF clinical team.   Materials and Methods: 69 CF patients (2-18 years were assessed during routine outpatient visits over one year. Anthropometric measurements were obtained. Both tools were applied for each patient and the results compared to their clinical evaluation (as gold standard with calculation of specificity and sensitivity. Results: Under-nutrition was more frequent in Iranian than NZ patients (39% versus 0%, p=0.0001, whereas over-nutrition was more prevalent in NZ children (9% versus 17%, p=0.05. At the first visit, MacDonald and Australasian guidelines were able to recognize 77% and 61% of under-nourished Iranian patients, respectively. The mean sensitivity and specificity for all visits for the MacDonald tool were 83% & 73% (Iran and 65% & 86% (NZ. Sensitivity and specificity for the Australasian guidelines were 79% & 79% (Iran and 70% & 90% (NZ. Conclusions: Both tools successfully recognised patients at risk of malnutrition. The MacDonald tool had comparable sensitivity and specificity to that described previously, especially in Iranian patients. This tool may be helpful in recognizing at risk CF patients, particularly in developing countries with fewer resources. Key words: Iran, Cystic Fibrosis Patient, Newzeland, Nutritional Assesment.

  6. Influence of Hepatic Inflammation on FibroScan Findings in Diagnosing Fibrosis in Patients with Chronic Hepatitis B.

    Science.gov (United States)

    Zeng, Xianghua; Xu, Cheng; He, Dengming; Zhang, Huiyan; Xia, Jie; Shi, Dairong; Kong, Lingjun; He, Xiaoqin; Wang, Yuming

    2015-06-01

    Hepatic inflammation may affect the performance of FibroScan. This prospective study investigated the influence of hepatic inflammation on liver stiffness measurement (LSM) values by assessing FibroScan and liver biopsy findings in 325 patients with chronic hepatitis B. Liver fibrosis and inflammation were classified into five stages (S0-S4) and grades (G0-G4) according to the Scheuer scoring system. LSM values were correlated with fibrosis stage and inflammation grade (r = 0.479, p inflammation grade, no significant differences were found between patients with significant fibrosis (S2-S4) (p > 0.05). For inflammation grades G0, G1, G2 and G3, areas under receiver operating characteristic curves of FibroScan for significant fibrosis were 0.8267 (p Inflammation has a significant influence on LSM values in patients with chronic hepatitis B with mild fibrosis, but not in those with significant fibrosis.

  7. NUTRITIONAL SUPPORT FOR FULMINANT HEPATITIS.

    Science.gov (United States)

    Ramos Figueira, Estela Regina; Rocha Filho, Joel Avancini; Souto Nacif, Lucas; Carneiro D'Albuquerque, Luiz; Linetzky Waitzberg, Dan

    2015-12-01

    Introducción: la hepatitis fulminante se asocia a un exacerbado hipercatabolismo, la hipoglicemia y la hiperamonemia están acompañadas por la liberación de citocinas proinflamatorias y hormonas catabólicas en la circulación sistémica, empeorando la condición clínica del paciente. El apoyo nutricional es un elemento crucial para la recuperación de estos pacientes. Objetivos: el objetivo de esta revisión es actualizar el apoyo nutricional para la hepatitis fulminante. Métodos: la revisión se llevó a cabo mediante la búsqueda electrónica en Medline-PubMed, utilizando malla de términos. Resultados y discusión: no hay muchos datos disponibles sobre el apoyo nutricional para lahepatitis fulminante o fallo hepático agudo. Las estrategias de intervención nutricional inicial se centran en el control de los trastornos metabólicos de la hepatitis fulminante descritos anteriormente, que deben ser individualizadas de acuerdo a la gravedad de la situación clínica del paciente. Energía y proteína se pueden proporcionar en cantidades de 25‑40 kcal / kg / día y 0,8-1,2 g / kg / día, respectivamente. La terapia nutricional enteral está indicada en pacientes con encefalopatía avanzada o para aquellos que no pueden ser adecuadamente alimentados por vía oral. Se debe obtener una euglicemia y la ingesta de proteínas puede estar basada en fórmulas de BCAA. Los lípidos se pueden administrar como suplemento energético con precaución. Una terapia nutricional adecuada puede potencialmente reducir la morbilidad y la mortalidad de los pacientes con hepatitis fulminante.

  8. 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.

  9. Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Ming-Liang Zhang; Zuo-Jiong Gong

    2004-01-01

    AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS: Rat hepatic fibrosis was induced by carbon tet:achloride (CCl4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PⅠ, PⅡ) groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCl4, twice a wk for 8 wk. Rats in PⅠ and PⅡ groups were also treated with pioglitazone of 3 mg/kg, daily via gastrogavage beginning on the 1st day and at the end of the 2nd week,administration of CCl4 respectively. Liver functions (ALT,AST), serum fibrotic markers (HA, LN, PCⅢ) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for α-smooth muscle actin (α-SMA) were performed.Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST, HA, LN and PCⅢ (P<0.05 or <0.01). The HP concentrations in PⅠ (210.90±24.07 μg/g), and PⅡ (257.36±30.55 μg/g) groups were also lower than those in model group (317.80±36.44 μg/g) (P<0.01). Histologic examination showed that PⅠ and PⅡ groups had milder hepatocellular degeneration, necrosis and infiltration of inflammatory cells, and thinner or less fibrotic septa than did model group. The scores for necroinflammation in PⅠ (2.80±1.03), and PⅡ (3.00±1.05) groups were significantly reduced as compared with model group (4.88±2.30) (P<0.05 or <0.01); the fibrosis scores in PⅠ (3.40±1.65), and PⅡ (4.60±1.35) groups were also markedly lower than those in model group (7.00±3.21)(P<0.05 or <0.01). Immunohistochemical staining showed that expression of α-SMA in PⅠ and PⅡ groups was ameliorated

  10. 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.

  11. Advances of Hepatic Fibrosis-Associated Serological Markers in the View of Translational Medicine

    Directory of Open Access Journals (Sweden)

    Lin LIU

    2016-03-01

    Full Text Available Hepatic fibrosis is the dysplasia of intra-hepatic fiber. The pathological outcome of various acute and chronic hepatic diseases marked by excessive deposition of extracellular matrix (EMC, and is an inevitable process of chronic hepatitis developing into liver cirrhosis and HCC. Translational medicine is the ultimate target of medical research, the specific reflection of technological innovation on combined road of production, knowledge and research, and the inevitable tendency of basic medicine translated into applicable medicine. How to change the massive information discovered in omics era into applicable techniques in clinic is a challenge urgent to be resolved, and is also critical to further improve the therapeutic efficacy of hepatocellular carcinoma (HCC. The present hepatic fibrosis-associated serological markers include hyaluronic acid (HA, collagen, lominin (LN, matrix metalloproteinases (MMPs and their inhibitors (TIMPs and transforming growth factors (TGF β l. Though they are all associated with hepatic fibrosis, they have their own disadvantages. Ideal serological markers for hepatic fibrosis should have higher specificity, sensitivity and accuracy to liver. In recent years, with new advances achieved in the research of body protein level, metabolic level and immune response level, and some new potential hepatic fibrosis-associated serological markers have been discovered, which are expected to improve the diagnosis of hepatic fibrosis. This study, in the view of translational medicine, mainly summarized the serological markers like HA and collagen, hoping to provide clinical references for the prevention and treatment of hepatic fibrosis and the prevention of HCC.

  12. New gene therapy strategies for hepatic fibrosis.

    Science.gov (United States)

    Salazar-Montes, Adriana M; Hernández-Ortega, Luis D; Lucano-Landeros, Martha S; Armendariz-Borunda, Juan

    2015-04-07

    The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with a high co-morbidity and mortality without effective treatment, and much research has been aimed at developing new therapeutic strategies to guarantee recovery. Liver-based gene therapy has been used to downregulate specific genes, to block the expression of deleterious genes, to delivery therapeutic genes, to prevent allograft rejection and to augment liver regeneration. Viral and non-viral vectors have been used, with viral vectors proving to be more efficient. This review provides an overview of the main strategies used in liver-gene therapy represented by non-viral vectors, viral vectors, novel administration methods like hydrodynamic injection, hybrids of two viral vectors and blocking molecules, with the hope of translating findings from the laboratory to the patient's bed-side.

  13. Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

    Directory of Open Access Journals (Sweden)

    Y. Wan

    2014-08-01

    Full Text Available Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg was injected iv into mice 30 min after concanavalin A (Con A challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST. Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg. Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and transforming growth factor beta (TGF-β pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR. NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

  14. Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Areeba Ahmad

    2012-01-01

    Full Text Available Hepatic fibrosis (HF is a progressive condition with serious clinical complications arising from abnormal proliferation and amassing of tough fibrous scar tissue. This defiance of collagen fibers becomes fatal due to ultimate failure of liver functions. Participation of various cell types, interlinked cellular events, and large number of mediator molecules make the fibrotic process enormously complex and dynamic. However, with better appreciation of underlying cellular and molecular mechanisms of fibrosis, the assumption that HF cannot be cured is gradually changing. Recent findings have underlined the therapeutic potential of a number of synthetic compounds as well as plant derivatives for cessation or even the reversal of the processes that transforms the liver into fibrotic tissue. It is expected that future inputs will provide a conceptual framework to develop more specific strategies that would facilitate the assessment of risk factors, shortlist early diagnosis biomarkers, and eventually guide development of effective therapeutic alternatives.

  15. Hyperplasia of elastic tissue in hepatic schistosomal fibrosis

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    Zilton A. Andrade

    1991-12-01

    Full Text Available Elastic tissue hyperplasia, revealed by means of histological, immunocytochemical and ultrastructural methods, appeared as a prominent change in surgical liver biopsies taken from 61 patients with schistosomal periportal and septal fibrosis. Such hyperplasia was absent in ecperimental murine schistosomiasis, including mice with "pipe-stem" fibrosis. Displaced connective tissue cells in periportal areas, such as smooth muscle cells, more frequently observed in human material, could be the site of excessive elastin synthesis, and could explain the differences observed in human and experimental materials. Elastic tissue, sometimes represented by its microfibrillar components, also appeared to be more condensed in areas of matrix (collagen degradation, suggesting a participation of this tissue in the remodelling of the extracellular matrix. By its rectratile properties elastic tissue hyperplasia in hepatic schistosomiasis can cause vascular narrowing and thus play a role in the pathogenesis of portal hypeertension.

  16. Familial congenital hepatic fibrosis: report of a family with three affected children.

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    Fatemeh Farahmand

    2013-09-01

    Full Text Available Congenital hepatic fibrosis (CHF is a developmental disorder of the biliary system, characterized by defective remodeling of the ductal plate. Herein a family of three children, from consanguineous parents, with minor thalassemia is presented who suffered from congenital hepatic fibrosis (CHF. Prompt diagnosis and appropriate treatment are necessary to avoid further complications in the affected patients.

  17. Experience of a single center with congenital hepatic fibrosis:A review of the literature

    Institute of Scientific and Technical Information of China (English)

    Ali; Shorbagi; Yusuf; Bayraktar

    2010-01-01

    Congenital hepatic fibrosis(CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts.It is one of the fibropolycystic diseases,which also include Caroli disease,autosomal dominant polycystic kidney disease,and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis,portal hypertension,and renal cystic disease.CHF is known to occur in association with a ran...

  18. Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

    DEFF Research Database (Denmark)

    Nielsen, M J; Karsdal, Morten A; Kazankov, K

    2016-01-01

    . AIM: To investigate whether differences in extracellular matrix (ECM) composition of the liver during fibrogenesis in two seemingly similar types of viral hepatitis could be reflected by differences in ECM turnover. METHODS: Utilising a cross-sectional design, we measured specific ECM protein...... fragments in plasma from 197 chronic hepatitis B (CHB) patients and 403 chronic hepatitis C (CHC) patients matched for inflammation grade and fibrosis stage. Markers of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3, P4NP7S...... and fibrosis only in CHC. Basement membrane collagen fragments P4NP7S and C4M were significantly higher in matched activity and fibrosis cohorts within CHB vs CHC. CONCLUSION: The main parameters to determine extracellular matrix biomarker levels are inflammation, fibrosis, and type of viral insult. Compared...

  19. Inverse association between hepatic stellate cell apoptosis and fibrosis in chronic hepatitis C virus infection.

    Science.gov (United States)

    Gonzalez, S A; Fiel, M I; Sauk, J; Canchis, P W; Liu, R-C; Chiriboga, L; Yee, H T; Jacobson, I M; Talal, A H

    2009-02-01

    Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection (n = 44) and HCV-negative controls with normal liver histology (n = 9). We used immunohistochemical techniques to identify activated (alpha-smooth muscle actin+), proliferative (Ki-67+) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, x 200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0-3.1 vs 1.1, 0.2-3.5 cells/HPF, P = 0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis (P = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01-0.28 cells/HPF) per increase in fibrosis stage (P = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.

  20. Serum osteopontin predicts degree of hepatic fibrosis and serves as a biomarker in patients with hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Matsue

    Full Text Available Osteopontin (OPN is a matricellular protein that upregulates during pathogenesis of hepatic fibrosis. The present study was aimed to evaluate whether serum OPN could be used as a biomarker to assess the degree of hepatic fibrosis in patients with hepatitis C virus (HCV infection.Needle biopsy was performed on HCV patients and scored as zero fibrosis (F0, mild fibrosis (F1, moderate fibrosis (F2, severe fibrosis (F3 and liver cirrhosis (F4 based on Masson's trichrome and α-smooth muscle actin (α-SMA staining. Serum OPN levels were measured using ELISA and correlated with the degree of fibrosis. Furthermore, the OPN values were correlated and evaluated with platelets count, serum hyaluronic acid (HA, and collagen type IV and subjected to receiver operating characteristic (ROC curve analysis.Serum OPN levels were remarkably increased from F0 through F4 in a progressive manner and the differences were significant (P < 0.001 between each group. The data were highly correlated with the degree of hepatic fibrosis. The ROC curve analysis depicted that serum OPN is an independent risk factor and an excellent biomarker and a prognostic index in HCV patients.The results of the present study indicate that serum OPN levels reflect the degree of hepatic fibrosis and could be used as a biomarker to assess the stage of fibrosis in HCV patients which would help to reduce the number of liver biopsies. Furthermore, serum OPN serves as a prognostic index towards the progression of hepatic fibrosis to cirrhosis and hepatocellular carcinoma.

  1. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients

    DEFF Research Database (Denmark)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike;

    2016-01-01

    BACKGROUND: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim...... in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without......). CONCLUSIONS: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic...

  2. Maintenance of nutritional status in patients with cystic fibrosis: new and emerging therapies

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    Kalnins D

    2012-06-01

    Full Text Available Daina Kalnins,1 Michael Wilschanski21Clinical Dietetics, Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada; 2Pediatric Gastroenterology Unit, Hadassah University Hospitals, Jerusalem, IsraelAbstract: Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health.Keywords: cystic fibrosis, nutrition, fat-soluble vitamins, pancreatic enzymes

  3. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN

    2012-01-01

    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  4. [Effect of decoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C on indices of hepatic fibrosis in chronic hepatitis B].

    Science.gov (United States)

    Zhang, Lijuan; Chang, Yijie

    2012-01-01

    To evaluate the effect of decoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C on the indices of hepatic fibrosis in chronic hepatitis B. The 94 cases of chronic viral hepatitis B patients were randomly divided into two groups. The treatment group was treated with stronger neo-minophagen C 100 mL dissolved in 10% dextrose 250 ml once a day intravenously, combined with decoction of turtle shell for anti-fibrosis one powder daily. And the control group was treated with stronger neo-minophagen C alone, 3 months as a course. Liver fibrosis indexes and liver function index were tested for two groups of patients before and after the treatment. Both the difference of liver fibrosis indexes between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P turtle shell for anti-fibrosis combined with stronger neo-minophagen C could significantly improve the clinical efficacy and the liver fibrosis indexes and liver function index in chronic hepatitis B.

  5. Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C.

    Science.gov (United States)

    Pungpapong, Surakit; Nunes, David P; Krishna, Murli; Nakhleh, Raouf; Chambers, Kyle; Ghabril, Marwan; Dickson, Rolland C; Hughes, Christopher B; Steers, Jeffery; Nguyen, Justin H; Keaveny, Andrew P

    2008-09-01

    Although recurrent hepatitis C virus (HCV) after liver transplantation (LT) is universal, a minority of patients will develop cirrhosis within 5 years of surgery, which places them at risk for allograft failure. This retrospective study investigated whether 2 serum fibrosis markers, serum hyaluronic acid (HA) and YKL-40, could be used to predict rapid fibrosis progression (RFP) post-LT. These markers were compared with conventional laboratory tests, histological assessment, and hepatic stellate cell activity (HSCA), a key step in fibrogenesis, as assessed by immunohistochemical staining for alpha-smooth muscle actin. Serum and protocol liver biopsy samples were obtained from 46 LT recipients at means of 5 +/- 2 (biopsy 1) and 39 +/- 6 (biopsy 2) months post-LT, respectively. RFP was defined as an increase in the fibrosis score >or= 2 from biopsy 1 to biopsy 2 (a mean interval of 33 +/- 6 months). The ability of parameters at biopsy 1 to predict RFP was compared with the areas under receiver operating characteristic curves (AUROCs). Of the 46 subjects, 15 developed RFP. Serum HA and YKL-40 performed significantly better than conventional parameters and HSCA in predicting RFP post-LT for HCV at biopsy 1, with AUROCs of 0.89 and 0.92, respectively. The accuracy of serum HA >or= 90 microg/L and YKL-40 >or= 200 microg/L in predicting RFP at biopsy 1 was 80% and 96%, respectively. In conclusion, we found that elevated levels of serum HA and YKL-40 within the first 6 months after LT accurately predicted RFP. Larger studies evaluating the role of serum HA and YKL-40 in post-LT management are warranted.

  6. The improving effects on hepatic fibrosis of interferon-γ liposomes targeted to hepatic stellate cells.

    Science.gov (United States)

    Li, Qinghua; Yan, Zhiqiang; Li, Feng; Lu, Weiyue; Wang, Jiyao; Guo, Chuanyong

    2012-07-05

    No satisfactory anti-fibrotic therapies have yet been applied clinically. One of the main reasons is the inability to specifically target the responsible cells to produce an available drug concentration and the side-effects. Exploiting the key role of the activated hepatic stellate cells (HSCs) in both hepatic fibrogenesis and over-expression of platelet-derived growth factor receptor- (PDGFR- ), we constructed targeted sterically stable liposomes (SSLs) modified by a cyclic peptide (pPB) with affinity for the PDGFR- to deliver interferon (IFN)- to HSCs. The pPB-SSL-IFN- showed satisfactory size distribution. In vitro pPB-SSL could be taken up by activated HSCs. The study of tissue distribution via living-body animal imaging showed that the pPB-SSL-IFN- mostly accumulated in the liver until 24 h. Furthermore, the pPB-SSL-IFN- showed more significant remission of hepatic fibrosis. In vivo the histological Ishak stage, the semiquantitative score for collagen in fibrotic liver and the serum levels of collagen type IV-C in fibrotic rats treated with pPB-SSL-IFN- were less than those treated with SSL-IFN- , IFN- and the control group. In vitro pPB-SSL-IFN- was also more effective in suppressing activated HSC proliferation and inducing apoptosis of activated HSCs. Thus the data suggest that pPB-SSL-IFN- might be a more effective anti-fibrotic agent and a new opportunity for clinical therapy of hepatic fibrosis.

  7. Clinical Study of Dahuang Zhechong Pill(大黄 虫丸)in Treating Posthepatitis B Hepatic Fibrosis

    Institute of Scientific and Technical Information of China (English)

    陈孝银; 李恩庆; 杨钦河; 章群; 孙立; 徐云生; 沈强

    2004-01-01

    @@ Hepatic fibrosis is the only way for all kinds of chronic hepatic diseases to develop into liver cirrhosis. How to block and reverse hepatic fibrosis is the key issue for treatment of all kinds of chronic hepatic disease. After many years arduous effort in treating hepatic fibrosis, no satisfactory results in western medical treatment have been obtained.Though hepatic fibrosis could be definitely reversed by colchicines, the strong toxicity of colchicines limited its clinical application. Studies in recent years showed that Chinese herbal medicine has made promising progress in treating hepatic fibrosis. Both experimental and clinical studies have confirmed that many Chinese herbal prescriptions have good effect in anti-hepatic fibrosis(1,2).

  8. Scanning electron microscopic observation: three-dimensional architecture of the collagen in hepatic fibrosis rats

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hong; ZHAO Jing; ZHANG Wei-guang; ZHANG Li-ying; MA Rui-qiong; WANG Li-qin; ZHANG Shu-yong; TIAN Long

    2007-01-01

    Background In the process of hepatic fibrosis, the accumulation of collagen fibers is strongly related to the hepatic function. The aim of this study was to investigate the three-dimensional architecture of the collagen network in the liver of rats with hepatic fibrosis.Methods Healthy adult male Wistar rats (n=32) were randomly divided into a control group (n=16) and a hepatic fibrosis group (n=16). In the control group, the rats were treated with peanut oil while the rats in hepatic fibrosis group were treated for 10 weeks with 60% CCl4 diluted in peanut oil. The quantity of collagen fibers was detected by Western blotting; distribution of the collagen was detected by sirius red staining and polarized microscope; the three-dimensional architecture of collagen in the liver was observed under the scanning electron microscope after fixed tissues were treated with cell-maceration using NaOH. Statistical analysis was performed using the u test.Results The quantity of collagen fibers increased significantly in the hepatic fibrosis group. With the aggravation of hepatic fibrosis, collagen fibers gradually accumulated. They interlaced the reticulation compartment and formed a round or ellipse liver tissue conglomeration like a grape framework that was disparate and wrapped up the normal liver Iobule.The deposition of collagen fibers was obvious in adjacent hepatic parenchyma, especially around the portal tracts.Conclusion Our experiment showed the collagen proliferation and displays clearly the three-dimensional architecture of collagen fibers in rat liver with hepatic fibrosis by scanning electron microscope. It can provide a morphological foundation for the mechanisms of changed haemodynamics and portal hypertension in hepatic fibrosis.

  9. Correlation analysis of hepatic fibrosis related indicators with HBV-DNA level in patients with hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yan Zhang; Bo Wu

    2017-01-01

    Objective:To observe the correlation of HBV-DNA level with hepatic fibrosis related indicators in patients with chronic hepatitis B.Methods: Real-time RT-PCR was used to detect HBV-DNA level. Chemiluminescence was used to detect the hepatic fibrosis related indicators, including PCⅢ, HA, CⅣ, and LN.Results:The serum HBV-DNA level, PCⅢ, HA, CⅣ, and LN in the observation group were significantly higher than those in the control group (P0.05). The serum HBV-DNA level had no linear correlation with HA, PCⅢ, and CⅣ, but was positively correlated with LN (r=0.290,P<0.05).Conclusions:Effective anti-viral therapy and controlling of serum HBV-DNA level can play a positive role in delaying the hepatic fibrosis progression in patients with chronic hepatitis B.

  10. Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Hiroki Wagatsuma; Fumihiko Yokoya; Qing-Wei Zhang; Mutsuyo Yamaguchi; Hiroyuki Aburatani; Norifumi Kawada

    2006-01-01

    AIM: To determine the gene expression profile data for the whole liver during development of dimethylnitrosamine (DMN)-induced hepatic fibrosis.METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells),and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells.RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSCspecific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis,suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocytespecific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis.CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

  11. OPTIMIZATION OF TETRANDRINE TREATMENT IN RAT HEPATIC FIBROSIS MODEL

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To optimize the therapeutic dosage of tetrandrine (Tet) in rat hepatic fibrosis model. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of l0mg·kg-1 ·d-1, 5mg·kg-1 ·d-1 and 2.5mg·kg-1 ·d-1 ( n =10 in each group). All rats,except for the normal controls, were injected with axenic porcine serum (0. 5ml each time, twice a week) intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid (HA) , laminin ( LM) , and procollagen type Ⅲ (PCⅢ) were tested. Collagen type Ⅰ and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase (ALT), aspartate aminotransferase ( AST), albumin (ALB), albumin/globulin ratio (A/G) and alkaline phosphatase (ALP) improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase (γ-GT) and total bilirubin (TBIL). Secondly, markedly lowered levels of HA, LM and collagen type Ⅰ, Ⅲ were also detected by radioimmunology and immunohistochemistry in the 5 mg · kg- 1 · d- 1 Tet-treated model group. Moreover, pathological findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg · kg- 1 · d-1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg·kg-1 ·d-1 to 10mg·kg 1 ·d-1, and 5mg·kg-1 ·d-1 may be theoptimum one among all doses.

  12. 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

  13. Diagnosis of hepatic fibrosis in hepatitis B patients by logistic regression modeling based on plasma amino acid ratio and age

    Institute of Scientific and Technical Information of China (English)

    张占卿

    2013-01-01

    Objective To explore the efficacy of logistic regression modeling based on plasma amino acid profile and patient age,for diagnosing hepatic fibrosis in patients with chronic hepatitis B (CHB) .Methods One-hundredand-forty-eight patients (108 males;mean age:38.1±11.9 years,range:16—72 years) histologically

  14. Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis.

    Science.gov (United States)

    Liu, Fen; Wang, Xiwei; Wu, Gang; Chen, Ling; Hu, Peng; Ren, Hong; Hu, Huaidong

    2015-01-01

    Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed. The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs) of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption. Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45-0.84). For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47-0.92). High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42-0.68). The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58-0.92). The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV) infection. Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis.

  15. Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Fen Liu

    Full Text Available Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed.The Medline, Web of Science, and Embase databases (from inception to June 2015 were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption.Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45-0.84. For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47-0.92. High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42-0.68. The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58-0.92. The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV infection.Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis.

  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. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models.

    Science.gov (United States)

    Zheng, Ze; Zhang, Xuebao; Wang, Jiemei; Dandekar, Aditya; Kim, Hyunbae; Qiu, Yining; Xu, Xiaohua; Cui, Yuqi; Wang, Aixia; Chen, Lung Chi; Rajagopalan, Sanjay; Sun, Qinghua; Zhang, Kezhong

    2015-12-01

    Hepatic fibrosis, featured by the accumulation of excessive extracellular matrix in liver tissue, is associated with metabolic disease and cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome. In this study, we investigated the effect and mechanism of PM2.5 exposure on hepatic fibrogenesis. Both inhalation exposure of mice and in vitro exposure of specialized cells to PM2.5 were performed to elucidate the effect of PM2.5 exposure on hepatic fibrosis. Histological examinations, gene expression analyses, and genetic animal models were utilized to determine the effect and mechanism by which PM2.5 exposure promotes hepatic fibrosis. Inhalation exposure to concentrated ambient PM2.5 induces hepatic fibrosis in mice under the normal chow or high-fat diet. Mice after PM2.5 exposure displayed increased expression of collagens in liver tissues. Exposure to PM2.5 led to activation of the transforming growth factor β-SMAD3 signaling, suppression of peroxisome proliferator-activated receptor γ, and expression of collagens in hepatic stellate cells. NADPH oxidase plays a critical role in PM2.5-induced liver fibrogenesis. Exposure to PM2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5 exposure on promoting hepatic fibrosis. Copyright © 2015. Published by Elsevier B.V.

  18. Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis

    OpenAIRE

    Fen Liu; Xiwei Wang; Gang Wu; Ling Chen; Peng Hu; Hong Ren; Huaidong Hu

    2015-01-01

    Background and Aim Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed. Methods The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds rat...

  19. The association between indirect bilirubin levels and liver fibrosis due to chronic hepatitis C virus infection.

    Science.gov (United States)

    Cengiz, Mustafa; Yılmaz, Guldal; Ozenirler, Seren

    2014-08-01

    We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients' demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤ 2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patients (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28 ± 0.02 mg/dl vs. 0.44 ± 0.032 mg/dl, pbilirubin level was negatively correlated with advanced fibrosis scores (r=-0.416 and pbilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0-0.005, pbilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.

  20. Determination of serum fibrosis indexes in patients with chronic hepatitis and its significance

    Institute of Scientific and Technical Information of China (English)

    郑敏; 蔡卫民; 翁红雷; 刘荣华

    2003-01-01

    Objectives To study the relationship between serum levels of hyaluronic acid (HA), type Ⅲ procollagen (PCⅢ), laminin (LN), type Ⅳ collagen (Ⅳ-C) and hepatic fibrosis and to determine their value in clinical practice. Methods 2600 serum samples from chronic hepatitis patients were assayed for fibrosis indexes including HA, PCⅢ, LN and Ⅳ-C with RIA. Liver biopsy was performed in 280 of those patients and the biopsy material was examined histopathologically. The inflammation grade of the liver, stage of fibrosis and degree of chronic hepatitis were recorded and were compared with fibrotic indexes. Results Among 2600 chronic hepatitis patients, every fibrotic index had a significant correlation with the inflammation grade, fibrosis staging and the degree of chronic hepatitis (P<0.01). The coefficient correlation of the results of histopathological examinations to HA was 0.544, 0.548 and 0.468 respectively, that to PCⅢ, 0.495, 0.424 and 0.335, that to LN, 0.214, 0.204 and 0.184, and that to Ⅳ-C, 0.406, 0.404 and 0.412, respectively. Conclusions Serum fibrosis indexes are fairly well correlated with the inflammation grade of the liver, fibrosis staging and the degree of chronic hepatitis. However, as diagnostic markers, they should be considered in combination with liver function tests, ultrasonography and clinical manifestations.

  1. Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT in Renal and Hepatic Fibrosis

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    Anusha H. Tennakoon

    2015-12-01

    Full Text Available Epithelial to mesenchymal transition (EMT, particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis, the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs, as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data.

  2. Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

    Science.gov (United States)

    Tennakoon, Anusha H.; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-01-01

    Epithelial to mesenchymal transition (EMT), particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis), the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs), as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data. PMID:26729181

  3. Diagnosis and quantification of hepatic fibrosis in children with diffusion weighted MR imaging

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    Razek, Ahmed Abdel Khalek Abdel, E-mail: arazek@mans.eun.eg [Diagnostic Radiology Department, Mansoura Faculty of Medicine, 62 ElNokrasi Street Meet Hadr, Mansoura 3512 (Egypt); Abdalla, Ahmed [Pediatric Department, Mansoura Faculty of Medicine, Mansoura (Egypt); Omran, Eman [Diagnostic Radiology Department, Mansoura Faculty of Medicine, 62 ElNokrasi Street Meet Hadr, Mansoura 3512 (Egypt); Fathy, Abeer [Pediatric Department, Mansoura Faculty of Medicine, Mansoura (Egypt); Zalata, Khaled [Diagnostic Pathology Department, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2011-04-15

    Purpose: To evaluate the accuracy of diffusion weighted MR imaging in diagnosis and quantification of hepatic fibrosis in children with chronic hepatitis. Materials and methods: Sixty-three consecutive children (40 boys, 23 girls, median age 9.3 years), with chronic hepatitis and thirty age matched volunteers underwent diffusion weighted MR imaging of the liver using a single shot echoplanar imaging with b-value = 0, 250, and 500 s/mm{sup 2}. Liver biopsy was obtained with calculation of METAVIR score. The ADC value of the liver was correlated with METAVIR score. Receiver operating characteristic curve was done for diagnosis and grading of hepatic fibrosis. Results: There was statistical difference in the mean ADC value between volunteers and patients with hepatic fibrosis (P = 0.001) and in patients with different grades of METAVIR scores (P = 0.002). There was correlation between the mean ADC value and METAVIR score (r = 0.807, P = 0.001). The cut off point to predict fibrosis (1.7 x 10{sup -3} mm{sup 2}/s) revealed 83% accuracy, 85% sensitivity, 82% specificity, 83% PPV, and 85% NPV. The area under the curve was 0.91 for F1, 0.85 for F2, 0.86 for F3 and 0.90 for F4. Conclusion: The apparent diffusion coefficient value is a promising quantitative parameter used for diagnosis and quantification of hepatic fibrosis in children with chronic hepatitis.

  4. Clinical Study on Reversing Hepatic Fibrosis with Handan Ganle (汉丹肝乐) Capsule

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To observe the therapeutic effect on hepatic fibrosis of chronic hepatitis B by Chinese medicine Handan Ganle capsule (HDGLC).Methods: A total of 104 patients with chronic hepatitis B has been treated by HDGLC for 6 months, liver fibrosis indexes and the serum biochemical indexes were detected before treatment, during the curative period and by the end of treatment. Hepatic biopsy was performed before or after the treatment.Results: The improvement rate of clinical symptoms was 79.0%-90.6%, and the recovery rate of ALT was 72.6%, serum fibrosis indexes such as HA, type Ⅳ collagen and LN were significantly decreased along with the extending course of disease (P<0.05). The pathohistological score of liver was decreased from 7.82±6.22 before treatment to 5.16±3.75 after treatment (P<0.05) and the score of hepatic fibrosis was decreased from 7.49±5.45 before treatment to 5.16±4.26 after treatment (P<0.05).Conclusion: HDGLC has remarkable therapeutic and reversing effect on chronic hepatitis B induced hepatic fibrosis.

  5. Segmental Difference of the Hepatic Fibrosis from Chronic Viral Hepatitis due to Hepatitis B versus C Virus Infection: Comparison Using Dual Contrast Material-Enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jae Ho; Yu, Jeong Sik; Chung, Jae Joon; Kim, Joo Hee; Kim, Ki Whang [Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-08-15

    We wanted to identify the geographic differences in hepatic fibrosis and their associations with the atrophy-hypertrophy complex in patients with chronic viral hepatitis using the dual-contrast material-enhanced MRI (DC-MRI) with gadopentetate dimeglumine and ferucarbotran. Patients with chronic C (n = 22) and B-viral hepatitis (n = 35) were enrolled for determining the subjective grade of fibrosis (the extent and thickness of fibrotic reticulations) in the right lobe (RL), the caudate lobe (CL), the medial segment (MS) and the lateral segment (LS) of the liver, with using a 5-grade scale, on the gradient echo T2-weighted images of DC-MRI. The fibrosis grades of different segments were compared using the Kruskal-Wallis test followed by post-hoc analysis to establish the segment-by-segment differences. The incidences of two pre-established morphologic signs of cirrhosis were also compared with each other between the two groups of patients. There were significant intersegmental differences in fibrosis grades of the C-viral group (p = 0.005), and the CL showed lower fibrosis grades as compared with the grades of the RL and MS, whereas all lobes were similarly affected in the B-viral group (p = 0.221). The presence of a right posterior hepatic notch was significantly higher in the patients with intersegmental differences of fibrosis between the RL and the CL (19 out of 25, 76%) than those without such differences (6 out of 32, 19%) (p < 0.001). An expanded gallbladder fossa showed no significant relationship (p = 0.327) with the segmental difference of the fibrosis grades between the LS and the MS. The relative lack of fibrosis in the CL with more advanced fibrosis in the RL can be a distinguishing feature to differentiate chronic C-viral hepatitis from chronic B-viral hepatitis and this is closely related to the presence of a right posterior hepatic notch.

  6. Nutritional support treatment for severe chronic hepatitis and posthepatitic cirrhosis.

    Science.gov (United States)

    Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (Pcirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  7. The improving effects on hepatic fibrosis of interferon-γ liposomes targeted to hepatic stellate cells

    Science.gov (United States)

    Li, Qinghua; Yan, Zhiqiang; Li, Feng; Lu, Weiyue; Wang, Jiyao; Guo, Chuanyong

    2012-07-01

    No satisfactory anti-fibrotic therapies have yet been applied clinically. One of the main reasons is the inability to specifically target the responsible cells to produce an available drug concentration and the side-effects. Exploiting the key role of the activated hepatic stellate cells (HSCs) in both hepatic fibrogenesis and over-expression of platelet-derived growth factor receptor-β (PDGFR-β), we constructed targeted sterically stable liposomes (SSLs) modified by a cyclic peptide (pPB) with affinity for the PDGFR-β to deliver interferon (IFN)-γ to HSCs. The pPB-SSL-IFN-γ showed satisfactory size distribution. In vitro pPB-SSL could be taken up by activated HSCs. The study of tissue distribution via living-body animal imaging showed that the pPB-SSL-IFN-γ mostly accumulated in the liver until 24 h. Furthermore, the pPB-SSL-IFN-γ showed more significant remission of hepatic fibrosis. In vivo the histological Ishak stage, the semiquantitative score for collagen in fibrotic liver and the serum levels of collagen type IV-C in fibrotic rats treated with pPB-SSL-IFN-γ were less than those treated with SSL-IFN-γ, IFN-γ and the control group. In vitro pPB-SSL-IFN-γ was also more effective in suppressing activated HSC proliferation and inducing apoptosis of activated HSCs. Thus the data suggest that pPB-SSL-IFN-γ might be a more effective anti-fibrotic agent and a new opportunity for clinical therapy of hepatic fibrosis.

  8. Deficiency of DJ-1 Ameliorates Liver Fibrosis through Inhibition of Hepatic ROS Production and Inflammation

    Science.gov (United States)

    Yu, Yingxue; Sun, Xuehua; Gu, Jinyang; Yu, Chang; Wen, Yankai; Gao, Yueqiu; Xia, Qiang; Kong, Xiaoni

    2016-01-01

    Liver fibrosis is a global health problem and previous studies have demonstrated that reactive oxygen species (ROS) play important roles in fibrogenesis. Parkinson disease (autosomal recessive, early onset) 7 (Park7) also called DJ-1 has an essential role in modulating cellular ROS levels. DJ-1 therefore may play functions in liver fibrogenesis and modulation of DJ-1 may be a promising therapeutic approach. Here, wild-type (WT) and DJ-1 knockout (DJ-1 KO) mice were administrated with carbon tetrachloride (CCl4) to induce liver fibrosis or acute liver injury. Results showed that DJ-1 depletion significantly blunted liver fibrosis, accompanied by marked reductions in liver injury and ROS production. In the acute CCl4 model, deficiency of DJ-1 showed hepatic protective functions as evidenced by decreased hepatic damage, reduced ROS levels, diminished hepatic inflammation and hepatocyte proliferation compared to WT mice. In vitro hepatic stellate cells (HSCs) activation assays indicated that DJ-1 has no direct effect on the activation of HSCs in the context of with or without TGFβ treatment. Thus our present study demonstrates that in CCl4-induced liver fibrosis, DJ-1 deficiency attenuates mice fibrosis by inhibiting ROS production and liver injury, and further indirectly affecting the activation of HSCs. These results are in line with previous studies that ROS promote HSC activation and fibrosis development, and suggest the therapeutic value of DJ-1 in treatment of liver fibrosis.

  9. Synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis.

    Science.gov (United States)

    Ouyang, Jingfeng; Gao, Zuming; Ren, Zihua; Hong, Dongsheng; Qiao, Hongxiang; Chen, Yan

    2010-08-01

    Rat mesenchymal stem cells (rMSCs) and salidroside have been applied in the treatment of hepatic fibrosis. The present study aimed to investigate the mechanism of hepatic differentiation of rMSCs in vitro and synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis in rats. rMSCs treated with 10 microg/mL, 20 microg/mL and 50 microg/mL salidroside were taken at 14 days and the proteins were subjected to western blot analysis. Hepatic fibrosis was induced in rats by administration of porcine serum for 8 weeks. Then, rats were randomly divided into 6 groups: control group, hepatic fibrosis group (model), salidroside group, rMSCs group and rMSCs plus salidroside group. Four weeks later, the localization and differentiation of rMSCs were determined. To evaluate the improvement of liver injury, the pathology of hepatocytes (or liver) and serum transforming growth factor-beta1 (TGF-beta1) were assessed. Induced rMSCs expressed alpha-fetoprotein (AFP) and albumin (ALB), which suggested rMSCs differentiated towards hepatocytes; moreover, E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. In experiments of rMSCs transplantation, the amount of collagen in the liver of rMSCs plus salidroside treated rats was significantly lowered accompanied by reduced expression of TGF-beta1, when compared to the control group and rMSCs group. These findings suggested the synergistic effects of rMSCs transplantation and salidroside on hepatic fibrosis. Salidroside could differentiate rMSCs towards hepatocytes and E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. Treatment with rMSCs transplantation and salidroside exerted synergistic effects on the experimental hepatic fibrosis via suppressing the expression of TGF-beta1.

  10. [Effect of metformin on the formation of hepatic fibrosis in type 2 diabetic rats].

    Science.gov (United States)

    Qiang, Gui-Fen; Zhang, Li; Xuan, Qi; Yang, Xiu-Ying; Shi, Li-Li; Zhang, Heng-Ai; Chen, Bai-Nian; Du, Guan-Hua

    2010-06-01

    The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.

  11. ASSOCIATION OF THE NUTRITIONAL PROFILE WITH HISTOLOGICAL FINDINGS OF PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C INFECTION

    Directory of Open Access Journals (Sweden)

    Vanessa Aparecida de SANTIS E SILVA

    2015-12-01

    Full Text Available Background - Different factors are responsible for the progression of hepatic fibrosis in chronic infection with hepatitis C virus, but the role of nutritional factors in the progression of the disease is not clearly defined. This study aimed to evaluate the nutritional status and dietary profile among patients with chronic hepatitis C who were candidates for treatment and its association with histopathological features. Methods - A crossectional study was conducted on treatment-naïve patients with chronic hepatitis C genotype 1, between 2011 and 2013. The following assessments were performed before treatment: liver biopsy, anthropometric measurements and qualitative/quantitative analysis of food intake. Results - Seventy patients were studied. The majority of patients was classified as obese (34% or overweight (20% according to body mass index [BMI] and as at risk for cardiovascular diseases by waist circumference (79%. Unhealthy food intake was presented by 59% according to qualitative parameters and several patients showed an insufficient intake of calories (59%, excessive intake of protein (36% and of saturated fat (63%, according to quantitative analysis. With respect to histology, 68% presented activity grade ≥2, 65% had steatosis and 25% exhibited fibrosis stage >2. Comparative analysis between anthropometric parameters and histological features showed that elevated waist circumference was the only variable associated to hepatic steatosis ( P =0.05. There was no association between qualitative and quantitative food intake parameters with histological findings. Conclusion - In this study, most of the patients with hepatitis C presented inadequate qualitative food intake and excessive consumption of saturated fat; in addition, excess of abdominal fat was associated to hepatic steatosis. Therefore, nutritional guidance should be implemented prior to treatment in patients with chronic hepatitis C, in order to avoid nutritional disorders

  12. Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats?

    Science.gov (United States)

    Hajiasgharzadeh, Khalil; Tavangar, Seyed Mohammad; Javan, Mohammad; Dehpour, Ahmad R; Mani, Ali R

    2014-10-01

    Recent studies have shown that vagus nerve activation inhibits cytokine production in a variety of non-neural cells though activation of α7 nicotinic acetylcholine receptor (α7nAChR). Since chronic inflammation plays a pivotal role in liver fibrosis, this study was designed to investigate the role of hepatic vagus nerve in the progression of hepatic fibrosis in rats. Cirrhosis was induced by chronic ligation of the bile duct. Hepatic hydroxyproline level, portal pressure, serum transaminase level, hepatic TIMP-1 (tissue inhibitor of metalloproteinase-1) and MCP-1 (monocyte chemoattractant peptide-1) expression were measured in order to assess the progression of liver cirrhosis. α7nAChR expression was assessed using RT-PCR as well as immunostaining. RT-PCR analysis of the liver showed that α7nAChR mRNA is expressed in rat liver. Immunostaining study demonstrated that hepatic α7nAChR is mainly expressed in the hepatocytes of cirrhotic liver with minimum α7nAChR expression in biliary epithelium or myofibroblasts. Bile duct ligation was associated with portal hypertension, increased hepatic hydroxyproline level as well as TIMP-1 and MCP-1 expression in the liver. However neither selective hepatic vagotomy nor methyllycaconitine (an α7nAChR antagonist) could significantly affect development of portal hypertension or hepatic fibrosis in rats. Selective hepatic vagotomy could only attenuate serum aspartate aminotransferase level in bile duct ligated rats but did not have a significant effect on hepatic inflammation as assessed by MCP-1 mRNA expression. Our study provides evidence against a crucial role for the hepatic vagus nerve as an intrinsic protective mechanism in modulation of hepatic fibrosis in a rat model of biliary cirrhosis.

  13. Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Run-Xuan Shao; Takao Kawabe; Masao Omata; Yujin Hoshida; Motoyuki Otsuka; Naoya Kato; Ryosuke Tateishi; Takuma Teratani; Shuichiro Shiina; Hiroyoshi Taniguchi; Masaru Moriyama

    2005-01-01

    AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis.METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV)infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade F1-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed:normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios.RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC.CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.

  14. Human amniotic epithelial cell transplantation induces markers of alternative macrophage activation and reduces established hepatic fibrosis.

    Directory of Open Access Journals (Sweden)

    Ursula Manuelpillai

    Full Text Available Chronic hepatic inflammation from multiple etiologies leads to a fibrogenic response that can progress to cirrhosis and liver failure. Transplantation of human amniotic epithelial cells (hAEC from term delivered placenta has been shown to decrease mild to moderate hepatic fibrosis in a murine model. To model advanced human liver disease and assess the efficacy of hAEC therapy, we transplanted hAEC in mice with advanced hepatic fibrosis. Immunocompetent C57BL/6 mice were administered carbon tetrachloride (CCl(4 twice weekly resulting in bridging fibrosis by 12 weeks. hAEC (2 × 10(6 were infused via the tail vein at week 8 or weeks 8 and 10 (single and double dose, respectively. Human cells were detected in mouse liver four weeks after transplantation showing hAEC engraftment. CCl(4 treated mice receiving single or double hAEC doses showed a significant but similar decrease in liver fibrosis area associated with decreased activation of collagen-producing hepatic stellate cells and decreased hepatic protein levels of the pro-fibrogenic cytokine, transforming growth factor-beta1. CCl(4 administration caused hepatic T cell infiltration that decreased significantly following hAEC transplantation. Hepatic macrophages play a crucial role in both fibrogenesis and fibrosis resolution. Mice exposed to CCl(4 demonstrated increased numbers of hepatic macrophages compared to normal mice; the number of macrophages decreased significantly in CCl(4 treated mice given hAEC. These mice had significantly lower hepatic protein levels of the chemokine monocyte chemoattractant protein-1 than mice given CCl(4 alone. Alternatively activated M2 macrophages are associated with fibrosis resolution. CCl(4 treated mice given hAEC showed increased expression of genes associated with M2 macrophages including YM-1, IL-10 and CD206. We provide novel data showing that hAEC transplantation induces a wound healing M2 macrophage phenotype associated with reduction of established

  15. Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review.

    Science.gov (United States)

    Mauch, Renan Marrichi; Kmit, Arthur Henrique Pezzo; Marson, Fernando Augusto de Lima; Levy, Carlos Emilio; Barros-Filho, Antonio de Azevedo; Ribeiro, José Dirceu

    2016-12-01

    To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review

    Science.gov (United States)

    Mauch, Renan Marrichi; Kmit, Arthur Henrique Pezzo; Marson, Fernando Augusto de Lima; Levy, Carlos Emilio; Barros-Filho, Antonio de Azevedo; Ribeiro, José Dirceu

    2016-01-01

    Abstract Objective: To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. Data source: A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. Data synthesis: Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. Conclusions: The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. PMID:27181343

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

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    Ryuta Shigefuku

    2016-09-01

    Full Text Available 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.

  18. Nutritional Support Treatment for Severe Chronic Hepatitis and Posthepatitic Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    QIN Huimin; LI Hongtao; XING Mingyou; WU Chunming; LI Guojun; SONG Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT) +PN; group C subject to CT+ EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-biil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D,the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  19. Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Shawky Abdelhamid Fouad; Serag Esmat; Dalia Omran; Laila Rashid; Mohamed H Kobaisi

    2012-01-01

    AIM:To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection.METHODS:One hundred and fifty-four patients with chronic HCV infection were included in this study; 124patients were non-cirrhotic,and 30 were cirrhotic.The following measurements were obtained in all patients:serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),albumin,total bilirubin,prothrombin time and concentration,complete blood count,hepatitis B surface antigen (HBsAg),HCVAb,HCV-RNA by quantitative polymerase chain reaction,abdominal ultrasound and ultrasonic-guided liver biopsy.The following ratios,scores and indices were calculated and compared with the results of the histopathological examination:AST/ALT ratio (AAR),age platelet index (API),AST to platelet ratio index (APRI),cirrhosis discriminating score (CDS),Pohl score,G(o)teborg University Cirrhosis Index (GUCI).RESULTS:AAR,APRI,API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%,79.2%,76.6% and 80.5%,respectively); P values were:< 0.01,< 0.05,< 0.001 and < 0.001,respectively.Among the studied parameters,AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5,respectively.APRI,API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P <0.001,< 0.001 and < 0.005,respectively),while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P >0.05).In addition,we found significant correlations for the AAR,APRI,API,GUCI and Pohl score between the non-cirrhotic (F0,F1,F2,F3) and cirrhotic (F4) groups (P values:< 0.001,< 0.05,< 0.001,< 0.001 and <0.005,respectively; CDS did not demonstrate significant correlation (P > 0.05).CONCLUSION:The use of AAR,APRI,API,GUCI and Pohl score measurements may decrease the need for liver biopsies

  20. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum.

    Science.gov (United States)

    Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

    2016-04-01

    In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.

  1. Inhibitory effect of leflunomide on hepatic fibrosis induced by CC14 in rats

    Institute of Scientific and Technical Information of China (English)

    Hong-wei YAO; Jun LI; Ji-qiang CHEN; Shu-yun XU

    2004-01-01

    AIM: To study the effect of leflunomide on CCl4-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50 % CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-β1(TGF-β1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-κB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-κB expression in liver tissue, and reduced elevated serum TGF-β1 and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CC14 in rats.

  2. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum

    Directory of Open Access Journals (Sweden)

    Yan-Rong Yu

    2016-04-01

    Full Text Available In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4+ Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.

  3. Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats.

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    Yoshitaka Fujimoto

    Full Text Available Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB-induced right heart failure model and investigated whether cardiac output (CO is responsible for the progression of hepatic fibrosis.Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01. Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01. Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2 were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05.Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.

  4. Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

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    Hai Nhung Truong

    2014-02-01

    Full Text Available Liver injury causes nodule and scar tissue formation and diffuse fibrosis, which are characteristic of liver cirrhosis. Since there are currently no efficacious therapies to prevent fibrosis, the development of animal models of liver fibrosis is necessary to facilitate further in vivo studies of this pathology. In this study, a mouse model of liver fibrosis was generated using Swiss mice and carbon tetrachloride (CCl4 treatment. Induction of liver fibrosis was analyzed using 0.8, 1.0, or 1.2 mL/kg CCl4 to determine the effective dose. In this study, we aimed to develop a standardized hepatic fibrosis mouse model by using CCl4 induction to facilitate further studies in this field. In Swiss mice, we evaluated the dose of CCl4 and the criteria of fibrosis, such as serum markers, fibrosis marker genes, and histopathology. Mice were administered CCl4 three times per week for 8 consecutive weeks. Body weights, survival rates, levels of serum markers (aspartate aminotransferase/alanine aminotransferase [AST/ALT] and fibrosis markers (fibronectin, procollagen, nt5e, transforming growth factor-beta [TGF-beta], and integrin, and histopathology (using hematoxylin and eosin [H and E] staining were analyzed to determine the optimal dose of CCl4 for induction of liver fibrosis. Results showed that 1.0 mL/kg CCl4 was the most efficient dose for the establishment of a liver fibrosis mouse model. In a standardized liver fibrosis model, mice were treated with 1.0 mL/kg CCl4 three times per week for 11 consecutive weeks, and levels of serum markers (AST, ALT, bilirubin, and albumin, expression of fibrosis marker genes (using quantitative reverse transcription polymerase chain reaction [RT-PCR], histopathology (using Hematoxylin and eosin staining, and connective tissue formation (using Massive trichrome staining were analyzed. The outcomes showed that serum markers and the levels of fibrosis marker genes were significantly increased in the standardized liver

  5. Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

    Directory of Open Access Journals (Sweden)

    Hai Nhung Truong

    2014-05-01

    Full Text Available Liver injury causes nodule and scar tissue formation and diffuse fibrosis, which are characteristic of liver cirrhosis. Since there are currently no efficacious therapies to prevent fibrosis, the development of animal models of liver fibrosis is necessary to facilitate further in vivo studies of this pathology. In this study, a mouse model of liver fibrosis was generated using Swiss mice and carbon tetrachloride (CCl4 treatment. Induction of liver fibrosis was analyzed using 0.8, 1.0, or 1.2 mL/kg CCl4 to determine the effective dose. In this study, we aimed to develop a standardized hepatic fibrosis mouse model by using CCl4 induction to facilitate further studies in this field. In Swiss mice, we evaluated the dose of CCl4 and the criteria of fibrosis, such as serum markers, fibrosis marker genes, and histopathology. Mice were administered CCl4 three times per week for 8 consecutive weeks. Body weights, survival rates, levels of serum markers (aspartate aminotransferase/alanine aminotransferase [AST/ALT] and fibrosis markers (fibronectin, procollagen, nt5e, transforming growth factor-beta [TGF-β], and integrin, and histopathology (using hematoxylin and eosin [H&E] staining were analyzed to determine the optimal dose of CCl4 for induction of liver fibrosis. Results showed that 1.0 mL/kg CCl4 was the most efficient dose for the establishment of a liver fibrosis mouse model. In a standardized liver fibrosis model, mice were treated with 1.0 mL/kg CCl4 three times per week for 11 consecutive weeks, and levels of serum markers (AST, ALT, bilirubin, and albumin, expression of fibrosis marker genes (using quantitative reverse transcription polymerase chain reaction [RT-PCR], histopathology (using Hematoxylin and eosin staining, and connective tissue formation (using Massive trichrome staining were analyzed. The outcomes showed that serum markers and the levels of fibrosis marker genes were significantly increased in the standardized liver fibrosis

  6. Effect of Green Tea Extract Encapsulated Into Chitosan Nanoparticles on Hepatic Fibrosis Collagen Fibers Assessed by Atomic Force Microscopy in Rat Hepatic Fibrosis Model.

    Science.gov (United States)

    Safer, Abdel-Majeed A; Hanafy, Nomany A; Bharali, Dhruba J; Cui, Huadong; Mousa, Shaker A

    2015-09-01

    The present study examined the effect of Green Tea Extract (GTE) encapsulated into Chitosan Nanoparticles (CS-NPs) on hepatic fibrosis in rat model as determined by atomic force microscopy (AFM). The bioactive compounds in GTE encapsulated into CS-NPs were determined using LC-MS/MS method. Additionally, the uptake of GTE-CS NPs in HepG2 cells showed enhanced uptake. In experimental fibrosis model, AFM was used as a high resolution microscopic tool to investigate collagen fibers as an indicator of hepatic fibrosis induced by treatment with CCl4. Paraffin sections of fibrotic liver tissues caused by CC4 treatment of rats and the effect of GTE-CS NPs treatment with or without CCl4 on hepatic fibrosis were examined. Liver tissues from the different groups of animals were de-waxed and processed as for normal H/E staining and Masson's trichrome staining to locate the proper area of ECM collagen in the CCl4 group versus collagen in liver tissues treated with the GTE-CS NPs with or without CCl4. Selected areas of paraffin sections were trimmed off and fixed flat on top of mica and inserted in the AFM stage. H/E staining, Masson's trichrome stained slides, and AFM images revealed that collagen fibers of 250 to 300 nm widths were abundant in the fibrotic liver samples while those of GTE-CS NPs were clear as in the control group. Data confirmed the hypothesis that GTE-CS NPs are effective in removing all the extracellular collagen caused by CCl4 in the hepatic fibrosis rat liver.

  7. Three-year follow-up study on hepatic fibrosis due to chronic hepatitis Btreated by interferon-α1b and traditional medicine preparation

    Institute of Scientific and Technical Information of China (English)

    Ming Liang Cheng; Yin Ying Lu; Jun Wu; Tian Ying Luo; Ke Fu Huang; Yi Sheng Ding; Ran Cai Liu; Jia Li; Zhong Li

    2000-01-01

    AIM To investigate the short-term and long-term therapeutic effect of traditional medicine preparation andIFN-α1 b on hepatic fibrosis due to chronic hepatitis B.METHODS Fifty-two patients with hepatic fibrosis of hepatitis B were treated by IFN-alb and traditionalmedicine preparation, then observed the change of serum indexes of hepatic fibrosis, liver biopsy,ultrasonography and fibergastroscopy.RESULTS The serum indexes of hepatic fibrosis decreased significantly after 3-month treatment(P<0.05). The improvement of liver fibrosis was confirmed by liver biopsy, ultrasonography andfibergastroscopy. After 3-year continuous follow-up, the conditions of patients were got better. Symptomsand signs were disappeared. The pathohistologic change of liver, serum index of hepatic fibrosis and liverfunction were continuously improved.CONCLUSION The good short-term and long-term effects were obtained by using IFN-α1b to suppressduplication of hepatitis B virus and traditional medicine preparation to reverse hepatic fibrosis.

  8. Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

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    Fábio Heleno de Lima Pace

    2012-08-01

    Full Text Available INTRODUCTION: Approximately 30% of hepatitis C virus (HCV monoinfected patients present persistently normal alanine aminotransferase (ALT levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive with known time of HCV infection (intravenous drugs users were selected. Patients with hepatitis B surface antigen (HBsAg positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80% were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26% patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001 periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001 and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

  9. Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

    OpenAIRE

    Nassef, Yasser E.; Mones M. Abu Shady; Essam M Galal; Hamed,Manal A

    2013-01-01

    The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transformi...

  10. MELD-XI Scores Correlate with Post-Fontan Hepatic Biopsy Fibrosis Scores.

    Science.gov (United States)

    Evans, William N; Acherman, Ruben J; Ciccolo, Michael L; Carrillo, Sergio A; Galindo, Alvaro; Rothman, Abraham; Winn, Brody J; Yumiaco, Noel S; Restrepo, Humberto

    2016-10-01

    We tested the hypothesis that MELD-XI values correlated with hepatic total fibrosis scores obtained in 70 predominately stable, post-Fontan patients that underwent elective cardiac catheterization. We found a statistically significant correlation between MELD-XI values and total fibrosis scores (p = 0.003). Thus, serial MELD-XI values may be an additional useful clinical parameter for follow-up care in post-Fontan patients.

  11. qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients

    Science.gov (United States)

    Tai, Dean C.S.; Wang, Shi; Cheng, Chee Leong; Peng, Qiwen; Yan, Jie; Chen, Yongpeng; Sun, Jian; Liang, Xieer; Zhu, Youfu; Rajapakse, Jagath C.; Welsch, Roy E.; So, Peter T.C.; Wee, Aileen; Hou, Jinlin; Yu, Hanry

    2014-01-01

    Background & Aims There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. Methods qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p biopsies (p biopsies: 10–44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p <0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p = 0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. Conclusions qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice. PMID:24583249

  12. Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

    Science.gov (United States)

    Li, Shu; Wang, Lina; Yan, Xiuchuan; Wang, Qinglan; Tao, Yanyan; Li, Junxia; Peng, Yuan; Liu, Ping; Liu, Chenghai

    2012-01-01

    The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs) in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) and α-smooth muscle actin (α-SMA) production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation. PMID:23243430

  13. Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

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    Shu Li

    2012-01-01

    Full Text Available The renin-angiotensin system (RAS plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B, one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN- induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I and α-smooth muscle actin (α-SMA production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β, and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.

  14. Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

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    Lindsey J. Reese

    2012-01-01

    Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

  15. Effect of hepatic iron concentration reduction on hepatic fibrosis and damage in rats with cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Gil Peretz; Gabriela Link; Orit Pappo; Rafael Bruck; Zvi Ackerman

    2006-01-01

    AIM: To assess the effect of iron reduction after phlebotomy in rats with "normal" hepatic iron concentration (HIC) on the progression of hepatic fibrosis, as a result of bile duct ligation (BDL).METHODS: Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated.RESULTS: Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects.CONCLUSION: Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats.However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.

  16. Pediatric MR elastography of hepatic fibrosis: principles, technique and early clinical experience

    Energy Technology Data Exchange (ETDEWEB)

    Binkovitz, Larry A.; Glaser, Kevin J.; Yin, Meng; Ehman, Richard L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); El-Youssef, Mounif [Mayo Clinic, Pediatric Gastroenterology, Rochester, MN (United States); Binkovitz, Anna K. [Macalaster College, St. Paul, MN (United States)

    2012-04-15

    Numerous pediatric conditions result in hepatic fibrosis. As treatments develop for the underlying disorders, a non-invasive assessment of liver fibrosis would be beneficial as an adjunct or possible replacement for the traditional gold standard, liver biopsy. Magnetic resonance elastography is a noninvasive imaging technique that has been used successfully in adults for identification and assessment of liver fibrosis. This review describes the basic principles of MR elastography as well as the technical aspects specific to children. Clinical pediatric applications, limitations and areas for future research are described. (orig.)

  17. Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis.

    Science.gov (United States)

    Bennett, Robert G; Simpson, Ronda L; Hamel, Frederick G

    2017-06-14

    To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis. Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type I collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smooth muscle actin (SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha (PGC1α) was determined by Western blotting. Treatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels (ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels (P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen (P < 0.05). These results were supported by immunohistochemistry for type I collagen, in which only combination treatment reduced fibrillar collagen levels (P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels. The combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy.

  18. Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach

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    Hicham Khallafi

    2015-01-01

    Full Text Available Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infections has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weaknesses of each modality is needed to correctly interpret the results in appropriate clinical context.

  19. Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

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    Gattu Mahanandeeshwar

    2007-07-01

    Full Text Available Abstract Background Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC virus infection and fibrosis. Methods Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1 and 23 with advanced fibrosis (F3, F4 were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups. Results Seven individual protein spots were identified as either significantly increased (α2-macroglobulin, haptoglobin, albumin or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α2-macroglobulin, are included in existing non-invasive serum marker panels. Conclusion Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.

  20. Relevance of activated hepatic stellate cells in predicting the development of pediatric liver allograft fibrosis.

    Science.gov (United States)

    Venturi, Carla; Reding, Raymond; Quinones, Jorge Abarca; Sokal, Etienne; Rahier, Jacques; Bueno, Javier; Sempoux, Christine

    2016-06-01

    Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in liver fibrogenesis. With the purpose of analyzing their presence and relevance in predicting liver allograft fibrosis development, 162 liver biopsies of 54 pediatric liver transplantation (LT) recipients were assessed at 6 months, 3 years, and 7 years after LT. The proportion of activated HSCs, identified by α-smooth muscle actin (ASMA) immunostaining, and the amount of fibrosis, identified by picrosirius red (PSR%) staining, were determined by computer-based morphometric analysis. Fibrosis was also staged by using the semiquantitative liver allograft fibrosis score (LAFSc), specifically designed to score fibrosis in the pediatric LT population. Liver allograft fibrosis displayed progression over time by PSR% (P ASMA expression decreased in the long term, with inverse evolution with respect to fibrosis (P ASMA-positive HSCs area ≥ 8% at 6 months (n = 20) developed a higher fibrosis proportion compared to those with ASMA-positive HSCs area ≤ 8% (n = 34) at the same period of time and in the long term (P = 0.03 and P ASMA expression ≥ 8% at 6 months was found to be an independent risk factor for 7-year fibrosis development by PSR% (r(2) = 0.5; P ASMA expression ≥ 8% at 3 years showed an association with the development of fibrosis at 7 years (P = 0.02). In conclusion, there is a high proportion of activated HSCs in pediatric LT recipients. ASMA ≥ 8% at 6 months seems to be a risk factor for early and longterm fibrosis development. In addition, activated HSCs showed inverse evolution with respect to fibrosis in the long term. Liver Transplantation 22 822-829 2016 AASLD.

  1. Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis

    Science.gov (United States)

    Zhang, Bin; Liang, Long; Dong, Yuhao; Lian, Zhouyang; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Objectives To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). Methods We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Results Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83–4.09, P = 0.006; WMD 13.10, 95% CI 9.53–16.67, P < 0.001; WMD 14.34, 95% CI 10.26–18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06–3.18, P = 0.027; WMD 5.63, 95% CI 2.74–8.52, P < 0.001; WMD 3.30, 95% CI 2.10–4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). Conclusions IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF. PMID:26820668

  2. Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    Full Text Available To determine the potential of intravoxel incoherent motion (IVIM MR imaging for staging of hepatic fibrosis (HF.We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D. The effect estimate was expressed as a pooled weighted mean difference (WMD with 95% confidence interval (CI, using the fixed-effects model.Overall, we included six papers (406 patients in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83-4.09, P = 0.006; WMD 13.10, 95% CI 9.53-16.67, P < 0.001; WMD 14.34, 95% CI 10.26-18.42, P < 0.001, respectively. Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06-3.18, P = 0.027; WMD 5.63, 95% CI 2.74-8.52, P < 0.001; WMD 3.30, 95% CI 2.10-4.50, P < 0.001, respectively. However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively.IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.

  3. The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies.

    Directory of Open Access Journals (Sweden)

    Jun eXu

    2014-07-01

    Full Text Available Liver fibrosis results from dysregulation of normal wound healing, inflammation, activation of myofibroblasts and deposition of extracellular matrix (ECM. Chronic liver injury causes death of hepatocytes and formation of apoptotic bodies, which in turn, release factors that recruit inflammatory cells (neutrophils, monocytes, macrophages, and lymphocytes to the injured liver. Hepatic macrophages (Kupffer cells produce TGF1 and other inflammatory cytokines that activate Collagen Type I producing myofibroblasts, which are not present in the normal liver. Secretion of TGF1 and activation of myofibroblasts play a critical role in the pathogenesis of liver fibrosis of different etiologies. Although the composition of fibrogenic myofibroblasts varies dependent on etiology of liver injury, liver resident Hepatic Stellate Cells (HSCs and Portal Fibroblasts (PFs are the major source of myofibroblasts in fibrotic liver in both experimental models of liver fibrosis and in patients with liver disease. Several studies have demonstrated that hepatic fibrosis can reverse upon cessation of liver injury. Regression of liver fibrosis is accompanied by the disappearance of fibrogenic myofibroblasts followed by resorption of the fibrous scar. Myofibroblasts either apoptose or inactivate into a quiescent-like state (e.g. stop collagen production and partially restore expression of lypogenic genes. Resolution of liver fibrosis is associated with recruitment of macrophages that secrete matrix-degrading enzymes (matrix metalloproteinase, collagenases and are responsible for fibrosis resolution. However, prolonged/repeated liver injury may cause irreversible crosslinking of ECM and formation of uncleavable collagen fibers. Advanced fibrosis progresses to cirrhosis and hepatocellular carcinoma (HCC. The current review will summarize the role and contribution of different cell types to populations of fibrogenic myofibroblasts in fibrotic liver.

  4. Nutritional decline in cystic fibrosis related diabetes: the effect of intensive nutritional intervention.

    LENUS (Irish Health Repository)

    White, H

    2012-02-01

    BACKGROUND: Reports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD. METHODS: 48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD. RESULTS: No important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n=17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg\\/m(2) (CFRD) v 20.8 kg\\/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout. CONCLUSION: Pre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.

  5. Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

    Directory of Open Access Journals (Sweden)

    Clarice Neuenschwander Lins de Morais

    2010-07-01

    Full Text Available Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-γ, TNF-α and TGF-β, platelets, bilirubins (Bil, alanine aminotransferase (ALT and aspartate aminotransferase (AST, total proteins, γ-glutamil transferase (γ-GT and alkaline phosphatase (AP, that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39, HC/hepatosplenic schistosomiasis (HSS (n = 19, HSS (n = 22 and a control group (n = 13. ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-α (p = 0.020 and AP (p = 0.005 could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002, γ-GT (p = 0.034 and AP (p = 0.001 were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008 was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

  6. Artificial neural network aided non-invasive grading evaluation of hepatic fibrosis by duplex ultrasonography

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2012-06-01

    Full Text Available Abstract Background Artificial neural networks (ANNs are widely studied for evaluating diseases. This paper discusses the intelligence mode of an ANN in grading the diagnosis of liver fibrosis by duplex ultrasonogaphy. Methods 239 patients who were confirmed as having liver fibrosis or cirrhosis by ultrasound guided liver biopsy were investigated in this study. We quantified ultrasonographic parameters as significant parameters using a data optimization procedure applied to an ANN. 179 patients were typed at random as the training group; 60 additional patients were consequently enrolled as the validating group. Performance of the ANN was evaluated according to accuracy, sensitivity, specificity, Youden’s index and receiver operating characteristic (ROC analysis. Results 5 ultrasonographic parameters; i.e., the liver parenchyma, thickness of spleen, hepatic vein (HV waveform, hepatic artery pulsatile index (HAPI and HV damping index (HVDI, were enrolled as the input neurons in the ANN model. The sensitivity, specificity and accuracy of the ANN model for quantitative diagnosis of liver fibrosis were 95.0%, 85.0% and 88.3%, respectively. The Youden’s index (YI was 0.80. Conclusions The established ANN model had good sensitivity and specificity in quantitative diagnosis of hepatic fibrosis or liver cirrhosis. Our study suggests that the ANN model based on duplex ultrasound may help non-invasive grading diagnosis of liver fibrosis in clinical practice.

  7. Artificial neural network aided non-invasive grading evaluation of hepatic fibrosis by duplex ultrasonography.

    Science.gov (United States)

    Zhang, Li; Li, Qiao-Ying; Duan, Yun-You; Yan, Guo-Zhen; Yang, Yi-Lin; Yang, Rui-Jing

    2012-06-20

    Artificial neural networks (ANNs) are widely studied for evaluating diseases. This paper discusses the intelligence mode of an ANN in grading the diagnosis of liver fibrosis by duplex ultrasonogaphy. 239 patients who were confirmed as having liver fibrosis or cirrhosis by ultrasound guided liver biopsy were investigated in this study. We quantified ultrasonographic parameters as significant parameters using a data optimization procedure applied to an ANN. 179 patients were typed at random as the training group; 60 additional patients were consequently enrolled as the validating group. Performance of the ANN was evaluated according to accuracy, sensitivity, specificity, Youden's index and receiver operating characteristic (ROC) analysis. 5 ultrasonographic parameters; i.e., the liver parenchyma, thickness of spleen, hepatic vein (HV) waveform, hepatic artery pulsatile index (HAPI) and HV damping index (HVDI), were enrolled as the input neurons in the ANN model. The sensitivity, specificity and accuracy of the ANN model for quantitative diagnosis of liver fibrosis were 95.0%, 85.0% and 88.3%, respectively. The Youden's index (YI) was 0.80. The established ANN model had good sensitivity and specificity in quantitative diagnosis of hepatic fibrosis or liver cirrhosis. Our study suggests that the ANN model based on duplex ultrasound may help non-invasive grading diagnosis of liver fibrosis in clinical practice.

  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. Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease

    DEFF Research Database (Denmark)

    Pavlov, Chavdar S; Casazza, Giovanni; Nikolova, Dimitrinka

    2015-01-01

    fibrosis in people with liver diseases. Transient elastography is a non-invasive method for assessing and staging hepatic fibrosis. OBJECTIVES: To determine the diagnostic accuracy of transient elastography for diagnosis and staging hepatic fibrosis in people with alcoholic liver disease when compared...... with liver biopsy. To identify the optimal cut-off values for differentiating the five stages of hepatic fibrosis. SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled and Diagnostic Test Accuracy Studies Registers, The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation...... Index Expanded (last search August 2014). SELECTION CRITERIA: Diagnostic cohort and diagnostic case-control study designs that assessed hepatic fibrosis in participants with alcoholic liver disease with transient elastography and liver biopsy, irrespective of language or publication status. The study...

  10. Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Andreia Ferreira Barros

    2014-04-01

    Full Text Available Undernourished mice infected (UI submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation and host (growth curves, biology, collagen synthesis and characteristics of the immunological response were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

  11. Beneficial effects of yam on carbon tetrachloride-induced hepatic fibrosis in rats.

    Science.gov (United States)

    Chan, Yin-Ching; Chang, Shih-Chieh; Liu, Sin-Yie; Yang, Hsin-Ling; Hseu, You-Cheng; Liao, Jiunn-Wang

    2010-01-15

    In a previous study, lyophilised yam reduced brain amyloid beta-protein (Abeta) accumulation and improved the antioxidative defence system in senescence-accelerated (SAMP8) mice. Therefore, the aim of this study was to investigate the hepatic protection of yam in the carbon tetrachloride-induced hepatic fibrosis of rats. Hepatic fibrosis was induced in rats via intraperitoneal injections of CCl(4) at a dose of 1 mL kg(-1) body weight (BW) twice weekly for 8 weeks. Three groups of rats were gavaged daily with yams at doses of 0.5, 1 and 2 g kg(-1) BW for 8 weeks, respectively. Yam treatments significantly decreased the ratio of liver/body weight, levels of gamma-glutaminotranspeptidase (GGT), low-density lipoprotein, and triglyceride in serum when compared with those administered CCl(4) alone. Treatment with yams significantly elevated antioxidant activities of glutathione peroxidase (GSH-Px) and superoxidase dismutase (SOD) in livers. Microscopically, yam-treated groups presented with low histoscores of CCl(4)-induced liver injury and fibrosis. Additionally, yam treatment reduced the area of GGT-positive foci and the index of proliferating cell nuclear antigen (PCNA) in liver. Daily administration of yam attenuates CCl(4)-induced hepatic fibrosis in rats in a dose-dependent manner; this attenuation may be related to the antioxidant properties of yams. Copyright (c) 2009 Society of Chemical Industry.

  12. IMMUNOHISTOCHEMICAL STUDY OF HEPATIC-FIBROSIS INDUCED IN RATS BY MULTIPLE GALACTOSAMINE INJECTIONS

    NARCIS (Netherlands)

    JONKER, AM; DIJKHUIS, FWJ; HARDONK, MJ; MOERKERK, P; TENKATE, J

    Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and

  13. Oxymatrine could promote mesenchymal stem cell therapy in hepatic fibrosis rats:an experimental research

    Institute of Scientific and Technical Information of China (English)

    柴宁莉

    2013-01-01

    Objective To investigate whether oxymatrine (OM) could promote mesenchymal stem cell (MSC) therapy in CCl4-induced hepatic fibrosis (HF) in rats and to initially explore its mechanisms.Methods Totally 50 male SD rats were randomly divided into five groups,i.e.,nor-

  14. Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Tung-Hung Su

    2014-06-01

    Full Text Available Hepatic fibrosis is a wound-healing response to various chronic stimuli, including viral hepatitis B or C infection. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs, regulate the balance between matrix metalloproteinases and their tissue inhibitors to maintain extracellular matrix homeostasis. Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involves angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic regulations. Hepatic inflammation is the driving force behind liver fibrosis; however, host single nucleotide polymorphisms and viral factors, including the genotype, viral load, viral mutation, and viral proteins, have been associated with fibrosis progression. Eliminating the underlying etiology is the most crucial antifibrotic therapy. Growing evidence has indicated that persistent viral suppression with antiviral therapy can result in fibrosis regression, reduced liver disease progression, decreased hepatocellular carcinoma, and improved chances of survival. Preclinical studies and clinical trials are currently examining several investigational agents that target key fibrogenic pathways; the results are promising and shed light on this debilitating illness.

  15. Liposomal oxymatrine in hepatic fibrosis treatment: formulation, in vitro and in vivo assessment.

    Science.gov (United States)

    Zhang, Shujuan; Wu, Jun; Wang, Hua; Wang, Tiechuang; Jin, Lina; Shu, Dandan; Shan, Weiguang; Xiong, Subin

    2014-06-01

    The aim was to develop a liposomal oxymatrine conjugating D-alpha tocopheryl polyethylene glycol 1000 succinate (OMT-LIP) for enhanced therapeutics of hepatic fibrosis. OMT-LIP was prepared using the remote loading method. The influences of formulation compositions on the encapsulation efficiency of OMT-LIP were investigated. Mean particle size, zeta potential, morphology, in vitro release, fibrotic liver targeting, and therapeutics of OMT-LIP were thoroughly assessed. The intraliposomal buffer composition and concentration, extraliposomal phase composition and pH, types of phospholipid, lipid molar ratio composition, and theoretical drug loading are crucial factors to entrap OMT into liposomes. The optimum OMT-LIP presented spherically unilamellar microstructures with entrapment efficiency of 79.7 ± 3.9%, mean particle size of 121.6 ± 52.9 nm, and zeta potential of -5.87 mV. OMT-LIP significantly increased the accumulation of OMT in the fibrotic liver with an 11.5-fold greater AUC than OMT solution in the dimethylnitrosamine (DMN)-induced hepatic fibrosis animals. OMT-LIP could be a potential strategy to improve treatment outcomes for hepatic fibrosis, showing the protective effects to mice given CCl4 and the enhanced therapeutics to mice with either DMN or CCl4-induced hepatic fibrosis.

  16. Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

    Science.gov (United States)

    Zhang, Zhengping; Wang, Chunming; Zha, Yinhe; Hu, Wei; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2015-03-24

    Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.

  17. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice

    Science.gov (United States)

    Chow, Leola N.; Schreiner, Petra; Ng, Betina Y. Y.; Lo, Bernard; Hughes, Michael R.; Scott, R. Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M.; Crawford, Jason; Webb, Murray; Underhill, T. Michael

    2016-01-01

    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID:26998906

  18. Erythropoietin decreases carbon tetrachloride-induced hepatic fibrosis by inhibiting transforming growth factor-beta

    Institute of Scientific and Technical Information of China (English)

    Soo Young Park; Joo Young Lee; Won Young Tak; Young Oh Kweon; Mi Suk Lee

    2012-01-01

    Background In addition to hematopoietic effect,the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities.The purpose of this study was to evaluate the effect of recombinant human erythropoietin (rhEPO) on hepatic fibrosis and hepatic stellate cells (HSCs).Methods Carbon tetrachloride (CCl4) induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study.CCl4 and rhEPO (0,200 or 1000 U/kg) was injected intraperitoneally in BALB/c mice three times a week for 4 weeks.Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β31 (TGF-β1),α-smooth muscle actin (α-SMA),and fibronectin in explanted liver.Immunoblotting of α-SMA,phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO.Results Expressions of TGF-β1,α-SMA,and fibronectin were increased in CCl4 injected mice livers,but significantly attenuated by co-treatment with CCl4 and rhEPO.Co-treatment of rhEPO markedly suppressed fibrosis in Masson's trichrome compared with treatment of only CCl4.TGF-β1 increased phosphorylated α-SMA,Smad-2 expressions in HSCs,which were decreased by rhEPO co-treatment.Conclusions Treatment of rhEPO effectively suppressed fibrosis in CCl4-induced liver fibrosis mice models.Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.

  19. Advances of Hepatic Fibrosis-Associated Serological Markers in the View of Translational Medicine

    Institute of Scientific and Technical Information of China (English)

    LIU Lin; ZHANG Jing; XIE Dong-hao; CUI Jian-wei

    2016-01-01

    Hepatic ifbrosis is the dysplasia of intra-hepatic ifber. The pathological outcome of various acute and chronic hepatic diseases marked by excessive deposition of extracellular matrix (EMC), and is an inevitable process of chronic hepatitis developing into liver cirrhosis and HCC. Translational medicine is the ultimate target of medical research, the specific reflection of technological innovation on combined road of production, knowledge and research, and the inevitable tendency of basic medicine translated into applicable medicine. How to change the massive information discovered in omics era into applicable techniques in clinic is a challenge urgent to be resolved, and is also critical to further improve the therapeutic efifcacy of hepatocellular carcinoma (HCC). The present hepatic ifbrosis-associated serological markers include hyaluronic acid (HA), collagen, lominin (LN), matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) and transforming growth factors (TGF) β l. Though they are all associated with hepatic fibrosis, they have their own disadvantages. Ideal serological markers for hepatic ifbrosis should have higher speciifcity, sensitivity and accuracy to liver. In recent years, with new advances achieved in the research of body protein level, metabolic level and immune response level, and some new potential hepatic ifbrosis-associated serological markers have been discovered, which are expected to improve the diagnosis of hepatic ifbrosis. This study, in the view of translational medicine, mainly summarized the serological markers like HA and collagen, hoping to provide clinical references for the prevention and treatment of hepatic ifbrosis and the prevention of HCC.

  20. Hepatitis C and insulin resistance: steatosis, fibrosis and non-response Hepatitis C y resistencia a la insulina: esteatosis, fibrosis y no respuesta

    Directory of Open Access Journals (Sweden)

    M. Romero-Gómez

    2006-08-01

    Full Text Available Insulin resistance is more often seen in hepatitis C than in other liver diseases, including non-alcoholic steatohepatitis. The Homeostasis Model for Assessment [HOMA= fasting insulin (mUI/ml * fasting glucose (mmol/L / 22.5] has proved useful in the measurement of insulin sensitivity in euglycemic patients. Cross-sectional and case-cohort studies support a role for hepatitis C as a factor implied in the development of type-2 diabetes in high-risk patients (male patients, older than 40 years, and overweight. In transgenic mice models the HCV core protein has been found to induce insulin resistance via TNF production. Insulin resistance has been associated with steatosis development and fibrosis progression in a genotype-dependent manner. In genotype-1 patients, the mechanisms by which insulin resistance promotes fibrosis progression include: a steatosis; b hyperleptinemia; c increased TNF production; and d impaired expression of PPARγ receptors. Indeed, insulin resistance has been found as a common denominator to the majority of features associated with difficult-to-treat patients. Patients with cirrhosis, obesity, coinfected with HIV, and Afro-American, all of them showed insulin resistance. Insulin resistance strongly influences sustained response rates, at least in genotype-1 patients. Insulin resistance decreases during and after treatment in patients that achieved virus C clearance. Moreover, the incidence of type-2 diabetes seems to be lower in responders than in non-responders. In summary, hepatitis C promotes insulin resistance and insulin resistance induces steatosis, fibrosis, and interferon resistance. The treatment of insulin resistance by decreasing hyperinsulinemia could improve sustained response rates in patients with chronic hepatitis C treated with peginterferon plus ribavirin.

  1. Noninvasive assessment of hepatic fibrosis in patients with chronic hepatic B viral Infection using magnetic resonance elastography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Dept. of Radiology, Chungnam National University Hospital, Daejeon (Korea, Republic of); Lee, Jeong Min; Yoon, Jeong Hee; Shin, Cheong Il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Kyung Bun [Dept. of Pathology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-04-15

    To evaluate the diagnostic performance of magnetic resonance elastography (MRE) for staging hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection. Patients with chronic HBV infection who were suspected of having focal or diffuse liver diseases (n = 195) and living donor candidates (n = 166) underwent MRE as part of the routine liver MRI examination. We measured liver stiffness (LS) values on quantitative shear stiffness maps. The technical success rate of MRE was then determined. Liver cell necroinflammatory activity and fibrosis were assessed using histopathologic examinations as the reference. Areas under the receiver operating characteristic curve (Az) were calculated in order to predict the liver fibrosis stage. The technical success rate of MRE was 92.5% (334/361). The causes of technical failure were poor wave propagation (n = 12), severe respiratory motion (n = 3), or the presence of iron deposits in the liver (n = 12). The mean LS values, as measured by MRE, increased significantly along with an increase in the fibrosis stage (r = 0.901, p < 0.001); however, the mean LS values did not increase significantly along with the degree of necroinflammatory activity. The cutoff values of LS for ≥ F1, ≥ F2, ≥ F3, and F4 were 2.45 kPa, 2.69 kPa, 3.0 kPa, and 3.94 kPa, respectively, and with Az values of 0.987-0.988. MRE has a high technical success rate and excellent diagnostic accuracy for staging hepatic fibrosis in patients with chronic HBV infection.

  2. Pathogenesis of hepatic septal fibrosis associated with Capillaria hepatica infection of rats.

    Science.gov (United States)

    Santos, A B; Tolentino, M; Andrade, Z A

    2001-01-01

    Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

  3. Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B.

    Science.gov (United States)

    Zhijian, Yu; Hui, Li; Weiming, Yao; Zhanzhou, Lin; Zhong, Chen; Jinxin, Zheng; Hongyan, Wang; Xiangbin, Deng; Weizhi, Yang; Duoyun, Li; Xiaojun, Liu; Qiwen, Deng

    2015-01-01

    This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI) to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.

  4. Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Yu Zhijian

    2015-01-01

    Full Text Available This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.

  5. Association of caffeine intake and liver fibrosis in patients with chronic hepatitis C.

    Science.gov (United States)

    Oliveira, Kalinca da Silva; Buss, Caroline; Tovo, Cristiane Valle

    2015-01-01

    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. 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. 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. The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

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

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    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.

  7. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

    Institute of Scientific and Technical Information of China (English)

    Caterina; Sagnelli; Salvatore; Martini; Mariantonietta; Pisaturo; Giuseppe; Pasquale; Margherita; Macera; Rosa; Zampino; Nicola; Coppola; Evangelista; Sagnelli

    2015-01-01

    Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.

  8. Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro

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    Quanfang Huang

    2016-11-01

    Full Text Available Background/Aims: Raf kinase inhibitory protein (RKIP is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS in rats and primary hepatic stellate cells (HSCs were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

  9. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

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    Silvia Affò

    Full Text Available Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+ and mature dendritic (MHCII+CD11c+ cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  10. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

    Science.gov (United States)

    Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  11. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

    Science.gov (United States)

    Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857

  12. Loss of Discoidin Domain Receptor 2 Promotes Hepatic Fibrosis after Chronic Carbon Tetrachloride through Altered Paracrine Interactions between Hepatic Stellate Cells and Liver-Associated Macrophages

    OpenAIRE

    Olaso, Elvira; ARTETA, BEATRIZ; BENEDICTO, AITOR; Crende, Olatz; Friedman, Scott L.

    2011-01-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl4) to DDR2+/+ and DDR2−/− mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after...

  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. Role of the receptor for advanced glycation end products in hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Christina Lohwasser; Daniel Neureiter; Yury Popov; Michael Bauer; Detlef Schuppan

    2009-01-01

    AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGEBSA) and Nε-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-α (TNF-α). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1(Ⅰ) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.

  15. Group IVA phospholipase A2 participates in the progression of hepatic fibrosis.

    Science.gov (United States)

    Ishihara, Keiichi; Miyazaki, Akira; Nabe, Takeshi; Fushimi, Hideaki; Iriyama, Nao; Kanai, Shiho; Sato, Takashi; Uozumi, Naonori; Shimizu, Takao; Akiba, Satoshi

    2012-10-01

    Group IVA phospholipase A2 (IVA-PLA2) is an enzyme that intiates the arachidonic acid pathway and plays an important role in inflammation. We demonstrate that IVA-PLA2 deficiency suppresses lipid deposition in the liver, which was induced by administration of a high-fat and -cholesterol diet (HFCD) for 16 wk in mice. Herein, we performed 2-dimensional gel-based comparative proteomics to further define the suppressive effect of IVA-PLA2 deficiency on fatty liver formation. In comparisons among 4 groups, wild-type (WT)/normal diet (ND), IVA-PLA2-deficient knockout (KO)/ND, WT/HFCD, and KO/HFCD, 4 proteins, 3 of which are associated with hepatic fibrosis, were identified as molecules, of which altered expression by HFCD was suppressed in KO mice compared to WT mice. Therefore, we assessed the effect of IVA-PLA2 deficiency on hepatic fibrosis induced by HFCD or carbon tetrachloride (CCl4) in mouse models. Biochemical and histological analyses revealed that IVA-PLA2 deficiency markedly reduced overall collagen accumulation in the liver of HFCD- and CCl4-derived mouse models. We found that IVA-PLA2 deficiency prevented activation of hepatic stellate cells and infiltration of F4/80-positive macrophages without affecting other immunocytes such as CD8+ lymphocytes and natural killer cells. In summary, IVA-PLA2 deficiency attenuates not only lipid deposition in the liver but also hepatic fibrosis formation.

  16. Role of iron in hepatic fibrosis: One piece in the puzzle

    Institute of Scientific and Technical Information of China (English)

    Marie A Philippe; Richard G Ruddell; Grant A Ramm

    2007-01-01

    Iron is an essential element involved in various biological pathways. When present in excess within the cell, iron can be toxic due to its ability to catalyse the formation of damaging radicals, which promote cellular injury and cell death. Within the liver, iron related oxidative stress can lead to fibrosis and ultimately to cirrhosis. Here we review the role of excessive iron in the pathologies associated with various chronic diseases of the liver. We also describe the molecular mechanism by which iron contributes to the development of hepatic fibrosis.

  17. Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

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    Paul Calès

    2015-01-01

    Full Text Available Background: Liver fibrosis staging provides prognostic value, although hampered by observer variability. We used digital analysis to develop diagnostic morphometric scores for significant fibrosis, cirrhosis and fibrosis staging in chronic hepatitis C. Materials and Methods: We automated the measurement of 44 classical and new morphometric descriptors. The reference was histological METAVIR fibrosis (F staging (F0 to F4 on liver biopsies. The derivation population included 416 patients and liver biopsies ≥20 mm-length. Two validation population included 438 patients. Results: In the derivation population, the area under the receiver operating characteristic (AUROC for clinically significant fibrosis (F stage ≥2 of a logistic score combining 5 new descriptors (stellar fibrosis area, edge linearity, bridge thickness, bridge number, nodularity was 0.957. The AUROC for cirrhosis of 6 new descriptors (edge linearity, nodularity, portal stellar fibrosis area, portal distance, granularity, fragmentation was 0.994. Predicted METAVIR F staging combining 8 morphometric descriptors agreed well with METAVIR F staging by pathologists: k = 0.868. Morphometric score of clinically significant fibrosis had a higher correlation with porto-septal fibrosis area (rs = 0.835 than METAVIR F staging (rs = 0.756, P < 0.001 and the same correlations with fibrosis biomarkers, e.g., serum hyaluronate: rs = 0.484 versus rs = 0.476 for METAVIR F (P = 0.862. In the validation population, the AUROCs of clinically significant fibrosis and cirrhosis scores were, respectively: 0.893 and 0.993 in 153 patients (biopsy < 20 mm; 0.955 and 0.994 in 285 patients (biopsy ≥ 20 mm. The three morphometric diagnoses agreed with consensus expert reference as well as or better than diagnoses by first-line pathologists in 285 patients, respectively: significant fibrosis: 0.733 versus 0.733 (k, cirrhosis: 0.900 versus 0.827, METAVIR F: 0.881 versus 0.865. Conclusion: The new automated

  18. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

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    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  19. SERUM MARKERS FOR ASSESSING LIVER FIBROSIS IN EGYPTIAN PA- TIENTS WITH CHRONIC HEPATITIS B AND C CO-INFECTION VERSUS CHRONIC HEPATITIS C.

    Science.gov (United States)

    Mobarak, Lamiaa

    2016-04-01

    Chronic hepatitis B and C can progress to hepatic fibrosis and cirrhosis. The stage of liver fibrosis is critical for decision of treatment and prediction of outcomes, as life threatening complications highly develop in cirrhotic patients. The aim of this study was to evaluate the diagnostic accuracy of non-invasive serum markers in the assessment of liver fibrosis in patients with combined chronic hepatitis B and C versus those with chronic hepatitis C. This study included 2 groups; Gl: combined chronic hepatitis B & C, which included 71 patients and G2: chronic hepatitis C, which included 70 patients. Liver biopsy results from both groups were recorded. Three validated blood indices Fibro Q, Fibro alpha, and Biotechnology Research Center (BRC) were tested for optimal cut off values for assessing liver fibrosis in both groups. The results showed that the area under receiver operating characteristic curves (AUROC) for Fibro Q in differentiating significant fibrosis (> F2) from non-significant fibrosis (≤ F2) was 0.79 (95% CI: 0.60-0.89) in the first group and 0.85 (95% CI: 0.71-0.98) in the second group. AUROC for BRC was 0.76 (95% CI: 0.63-0.89) in the first group and 0.75 (CI: 0.60-0.89) in the second group. Fibro alpha performed less in both groups based on AUROC 0.69 and 0.68 in the first and second group respectively.

  20. 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.

  1. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

    Institute of Scientific and Technical Information of China (English)

    Linda; Hammerich; Frank; Tacke

    2015-01-01

    Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11 b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11 b and Gr1(Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins(SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma(HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.

  2. [Nutritional status of adults with cystic fibrosis - current methods of assessment].

    Science.gov (United States)

    Szabla, Anna; Skorupa, Wojciech; Milewska, Magdalena; Weker, Halina

    2015-11-01

    Cystic fibrosis (CF) is one of the most frequent monogenic disease in the Caucasian population, inherited in an autosomal recessive pattern. This is a multiple organ disease and its main manifestations include pulmonary and gastrointestinal dysfunction. The exocrine pancreatic deficiency results in impaired digestion and absorption what may lead to malnutrition and vitamins and minerals deficiencies. The life expectancy of cystic fibrosis patients has been increasing over the past years, so there is a need to verify usefulness of existing or create new methods of nutritional status assessment. The aim of this paper was presentation current data on the methods of assessment and monitoring of nutritional status. Particular attention has been paid to appropriate nutritional support in prevention and treatment of malnutrition patients with cystic fibrosis. On the basis of recent literature we can conclude that the advanced nutritional status assessment is recommended in patient with CF by using anthropometrical methods, body composition analysis and biochemical data. Good nutritional status is connected with pulmonary functions, quality and life length.

  3. Noninvasive estimation of fibrosis in chronic viral hepatitis

    DEFF Research Database (Denmark)

    Risum, Malene; Barfod, Toke Seierøe; Lindhardt, Bjarne Orskov

    2013-01-01

    In chronic viral hepatitis the liver biopsy helps the clinician to decide when to start treatment and plan follow-up. However, the execution of a liver biopsy is associated with discomfort, and sampling error can lead to misinterpretation. Serum markers and transient elastography (TE) are being...

  4. Regulation of decoction shugan bushen on testosterone and ACTH in ratswith hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Zhong Pang Fan; Jian Cheng Wu; Xing Zhu; Qian Hong Wan; Ting Zan Li

    2000-01-01

    AIM To observe the regulating effect of decoction shugan bushen (SGBS) on testosterone (Te) andadrenocortiotropin (ACTH).METHODS Fifty wistar male rats divided into four groups randomly, that is, normal group, hepaticfibrosis group, and two Chinese herb medicine treatment groups. The model of toxic hepatic fibrosis wasinduced by 0.5% dimethylnitrosamine (DMN). The decoction SGBS is composed of such herbs as bupleurumRoot. Dodder Seed, curcuma rood indianmulberry etc. According to the different doses of the drugs, ratsare divided into two groups in the treatment groups. The Chinese herb medicine treatment begins in a weekafter the second celiac injection of DMN, lastiong 8 weeks. The rats of normal group and hepatic fibrosisgroup are fed with distilled water once a day. After 11 weeks of Chinese herb medicine treatment, the Teand ACTH were tested insera of rats, and the livers were dissected for the pathology examination.RESULTS The results of pathology examination in rat livers of each group show that the hepatocytes of thenormal group have normal array, no degeneration and fibrosis. Those in the pathology group have obviousdegenerative necrosis and hepatic fibrosis, and in some cases show the evidence of cirrosis. The results intreatment groups are essentially similar to those of normal group. Variance analysis of least significantdifference (LSD) method is employed to compare the hormone level between groups. The serum levels of Teand ACTH in the normal group are 75.30±45.25 ng/dl and 141.02±68.70 ng/L. The levels in hepaticfibrosis group are obviously lower than those of normal group, as 19.77±16.92 ng/dl and 92.85±27.24ng/L, respectivite and with statistically different (P 0.05).Two different doses make no obvious difference between the treatment groups (P>0.05).CONCLUSION SGBS can correct the hormone disturbance and shows the effect of anti-hepatic fibrosis.

  5. Structural changes of the diaphragmatic peritoneum in patients with schistosomal hepatic fibrosis: its relation to ascites.

    Science.gov (United States)

    Ismail, A H; Mohamed, F S

    1986-06-01

    The histopathologic changes of the peritoneum of the hemidiaphragm were studied in 30 patients with schistosomal liver disease and compared with ten control subjects. The diaphragmatic peritoneum of patients with ascites was markedly thickened with infiltration of inflammatory cells and collagen bundles resembling the interstitial changes of peripheral lymphedema. Obliteration of diaphragmatic lymphatic stomata with restricted lymph flow as well as excess lymph formation from portal hypertension are both major factors in the magnitude and intractability of ascites associated with schistosomal hepatic fibrosis.

  6. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    Science.gov (United States)

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  7. Liposomal Oxymatrine in Hepatic Fibrosis Treatment: Formulation, In Vitro and In Vivo Assessment

    OpenAIRE

    Zhang, Shujuan; Wu, Jun; Wang, Hua; Wang, Tiechuang; Jin, Lina; Shu, Dandan; Shan, Weiguang; Xiong, Subin

    2014-01-01

    The aim was to develop a liposomal oxymatrine conjugating d-alpha tocopheryl polyethylene glycol 1000 succinate (OMT-LIP) for enhanced therapeutics of hepatic fibrosis. OMT-LIP was prepared using the remote loading method. The influences of formulation compositions on the encapsulation efficiency of OMT-LIP were investigated. Mean particle size, zeta potential, morphology, in vitro release, fibrotic liver targeting, and therapeutics of OMT-LIP were thoroughly assessed. The intraliposomal buff...

  8. Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis

    Science.gov (United States)

    Abdelmegeed, Mohamed A.; Choi, Youngshim; Godlewski, Grzegorz; Ha, Seung-Kwon; Banerjee, Atrayee; Jang, Sehwan; Song, Byoung-Joon

    2017-01-01

    Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE. PMID:28051126

  9. Performance of real-time elastography for the staging of hepatic fibrosis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Huisuo Hong

    Full Text Available BACKGROUND: With the rapid development of real-time elastography (RTE, a variety of measuring methods have been developed for the assessment of hepatic fibrosis. We evaluated the overall performance of four methods based on RTE by performing meta-analysis of published literature. METHODS: Online journal databases and a manual search from April 2000 to April 2014 were used. Studies from different databases that meet inclusion criteria were enrolled. The statistical analysis was performed using a random-effects model and fixed-effects model for the overall effectiveness of RTE. The area under the receiver operating characteristic curve (AUROC was calculated for various means. Fagan plot analysis was used to estimate the clinical utility of RTE, and the heterogeneity of the studies was explored with meta-regression analysis. RESULTS: Thirteen studies from published articles were enrolled and analyzed. The combined AUROC of the liver fibrosis index (LFI for the evaluation of significant fibrosis (F≥2, advanced fibrosis (F≥3, and cirrhosis (F = 4 were 0.79, 0.94, and 0.85, respectively. The AUROC of the elasticity index (EI ranged from 0.75 to 0.92 for F≥2 and 0.66 to 0.85 for F = 4. The overall AUROC of the elastic ratio of the liver for the intrahepatic venous vessels were 0.94, 0.93, and 0.96, respectively. The AUROC of the elastic ratio of the liver for the intercostal muscle in diagnosing advanced fibrosis and cirrhosis were 0.96 and 0.92, respectively. There was significant heterogeneity in the diagnostic odds ratio (DOR for F≥2 of LFI mainly due to etiology (p<0.01. CONCLUSION: The elastic ratio of the liver for the intrahepatic vein has excellent precision in differentiating each stage of hepatic fibrosis and is recommend to be applied to the clinic.

  10. Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells.

    Science.gov (United States)

    Kim, Kang Ho; Lee, Jae Man; Zhou, Ying; Harpavat, Sanjiv; Moore, David D

    2016-08-01

    Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GR(LysM)) or HSC (GR(hGFAP)): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GR(LysM) mice, whereas the suppression of fibrotic gene expression was diminished in GR(hGFAP) mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis.

  11. Berberine Inhibition of Fibrogenesis in a Rat Model of Liver Fibrosis and in Hepatic Stellate Cells

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2016-01-01

    Full Text Available Aim. To examine the effect of berberine (BBR on liver fibrosis and its possible mechanisms through direct effects on hepatic stellate cells (HSC. Methods. The antifibrotic effect of BBR was determined in a rat model of bile duct ligation- (BDL- induced liver fibrosis. Multiple cellular and molecular approaches were introduced to examine the effects of BBR on HSC. Results. BBR potently inhibited hepatic fibrosis induced by BDL in rats. It exhibited cytotoxicity to activated HSC at doses nontoxic to hepatocytes. High doses of BBR induced apoptosis of activated HSC, which was mediated by loss of mitochondrial membrane potential and Bcl-2/Bax imbalance. Low doses of BBR suppressed activation of HSC as evidenced by the inhibition of α-smooth muscle actin (α-SMA expression and cell motility. BBR did not affect Smad2/3 phosphorylation but significantly activated 5′ AMP-activated protein kinase (AMPK signalling, which was responsible for the transcriptional inhibition by BBR of profibrogenic factors α-SMA and collagen in HSC. Conclusion. BBR is a promising agent for treating liver fibrosis through multiple mechanisms, at least partially by directly targeting HSC and by inhibiting the AMPK pathway. Its value as an antifibrotic drug in patients with liver disease deserves further investigation.

  12. SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice.

    Science.gov (United States)

    Li, Min; Hong, Wenxuan; Hao, Chenzhi; Li, Luyang; Wu, Dongmei; Shen, Aiguo; Lu, Jun; Zheng, Yuanlin; Li, Ping; Xu, Yong

    2017-09-26

    Hepatic stellate cells (HSCs) are a major source of fibrogenesis in the liver contributing to cirrhosis. When activated, HSCs transdifferentiate into myofibroblast and undergo profound functional alterations paralleling an overhaul of the transcriptome, the mechanism of which remains largely undefined. We investigated the involvement of the class III deacetylase sirtuin (silent information regulator 1, SIRT1) in HSC activation and liver fibrosis. SIRT1 levels were down-regulated in the livers in mouse models of liver fibrosis, in patients with cirrhosis, and in activated HSCs as opposed to quiescent HSCs. SIRT1 activation halted whereas SIRT1 inhibition promoted HSC trans-differentiation into myofibroblast. Liver fibrosis was exacerbated in mice with HSC-specific deletion of SIRT1 (conditional knockout, cKO), receiving CCl4 (1 mg/kg) injection or subjected to bile duct ligation, compared to wild-type littermates. SIRT1 regulated peroxisome proliferator activated receptor γ (PPARγ) transcription by deacetylating enhancer of zeste homolog 2 (EZH2) in quiescent HSCs. Finally, EZH2 inhibition or PPARγ activation ameliorated fibrogenesis in cKO mice. In summary, our data suggest that SIRT1 plays an essential role guiding the transition of HSC phenotypes.-Li, M., Hong, W., Hao, C., Li, L., Wu, D., Shen, A., Lu, J., Zheng, Y., Li, P., Xu, Y. SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice. © FASEB.

  13. Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats

    Institute of Scientific and Technical Information of China (English)

    Ali Riza Soylu; Huseyin Baloglu; Mevlut Ture; Kemal Kutlu; Kadir Kaymak; Nurettin Aydogdu; Umit Nusret Basaran; Semsi Altaner; Orhan Tarcin; Nursal Gedik; Hasan Umit; Ahmet Tezel; Gulbin Dokmeci

    2006-01-01

    AIM:To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats.METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 rog/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELTSA method.RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 ± 1.2, 33.8 ±2.9, 36.7 ± 0.5 μg collagen/mg protein, respectively)compared to BDL (48.3 ± 0.6 mg collagen/g protein) (P< 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% ± 1.1%, 6.2% ± 1.7%, 12.3% ±2.0%, respectively) compared to BDL (17.4% ± 5.6%) (P< 0.05 for each). The same beneficial effect of vitamin C,vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 ± 0.8 vs BDL: 3.1 ± 0.7;P < 0.05).CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic

  14. Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ryuta Shigefuku

    2014-01-01

    Full Text Available Aims: The present study evaluated the utility of xenon computed tomography (Xe-CT as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF in patients with nonalcoholic fatty liver disease (NAFLD or chronic hepatitis C (CH-C. Methods: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results: In group 1, portal venous TBF (PVTBF, hepatic arterial (HATBF, and total hepatic TBF (THTBF were significantly lower in patients with in nonalcoholic steatohepatitis (NASH than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively. In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively. In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

  15. Matrix-derived serum markers in monitoring liver fibrosis in children with chronic hepatitis B treated with interferon alpha

    Institute of Scientific and Technical Information of China (English)

    Dariusz Marek Lebensztejn; Maria El(z)bieta Sobaniec-Lotowska; Maciej Kaczmarski; Michael Voelker; Detlef Schuppan

    2006-01-01

    AIM: To evaluate prospectively 4 selected serum fibrosis markers (tenascin, hyaluronan, collagen Ⅵ, TIMP-1)before, during and 12 mo after IFN treatment of children with chronic hepatitis B.METHODS: Forty-seven consecutive patients wit-h chronic hepatitis B (range 4-16 years, mean 8 years) underwent IFN treatment (3 MU tiw for 20 wk). Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated assays.RESULTS: IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis(r = 0.3383, P = 0.021).Basal fibrosis markers did not differ between responders (42.5%) and nonresponders(57.5% ). During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in responders.CONCLUSION: Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.

  16. Diagnostic accuracy of serum biochemical fibrosis markers in children with chronic hepatitis B evaluated by receiver operating characteristics analysis.

    Science.gov (United States)

    Lebensztejn, Dariusz Marek; Skiba, Elzbieta; Tobolczyk, Jolanta; Sobaniec-Lotowska, Maria Elzbieta; Kaczmarski, Maciej

    2005-12-07

    To investigate the diagnostic accuracy of potent serum biochemical fibrosis markers in children with chronic hepatitis B evaluated by receiver operating characteristics (ROC) analysis. We determined the serum level of apolipoprotein A-I (APO A-I), haptoglobin (HPT) and a-2 macroglobulin (A2M) with an automatic nephelometer in 63 children (age range 4-17 years, mean 10 years) with biopsy-verified chronic HBeAg-positive hepatitis B. Fibrosis stage and inflammation grade were assessed in a blinded fashion according to Batts and Ludwig. We defined mild liver fibrosis as a score < or =2 and advanced fibrosis as a score equal to 3. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis (AccuROC, Canada). Serum concentrations of APO A-I, HPT and A2M were not significantly different in patients with chronic hepatitis B compared to controls. However, APO A-I level of 1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% (AUC = 0.7117, P = 0.035) to predict advanced fibrosis. All other serum biochemical markers and their combination did not allow a useful prediction. None of these markers was a good predictor of histologic inflammation. Apolipoprotein A-I may be a suitable serum marker to predict advanced liver fibrosis in children with chronic hepatitis B.

  17. Matrix-derived serum markers in monitoring liver fibrosis in children with chronic hepatitis B treated with interferon alpha.

    Science.gov (United States)

    Lebensztejn, Dariusz-Marek; Sobaniec-Lotowska, Maria-Elzbieta; Kaczmarski, Maciej; Voelker, Michael; Schuppan, Detlef

    2006-06-07

    To evaluate prospectively 4 selected serum fibrosis markers (tenascin, hyaluronan, collagen VI, TIMP-1) before, during and 12 mo after IFN treatment of children with chronic hepatitis B. Forty-seven consecutive patients with chronic hepatitis B (range 4-16 years, mean 8 years) underwent IFN treatment (3 MU tiw for 20 wk). Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated assays. IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis(r = 0.3383, P = 0.021). Basal fibrosis markers did not differ between responders (42.5%) and nonresponders(57.5%). During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in responders. Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.

  18. Diagnostic accuracy of serum biochemical fibrosis markers in children with chronic hepatitis B evaluated by receiver operating characteristics analysis

    Institute of Scientific and Technical Information of China (English)

    Dariusz Marek Lebensztejn; El(z)bieta Skiba; Jolanta Tobolczyk; Maria El(z)bieta Sobaniec-Lotowska; Maciej Kaczmarski

    2005-01-01

    AIM: To investigate the diagnostic accuracy of potent serum biochemical fibrosis markers in children with chronic hepatitis B evaluated by receiver operating characteristics (ROC) analysis.METHODS: We determined the serum level of apolipoprotein A-I (APO A-I), haptoglobin (HPT) and a-2macroglobulin (A2M) with an automatic nephelometer in 63 children (age range 4-17 years, mean 10 years)with biopsy-verified chronic HBeAg-positive hepatitis B.Fibrosis stage and inflammation grade were assessed in a blinded fashion according to Batts and Ludwig. We defined mild liver fibrosis as a score ≤2 and advanced fibrosis as a score equal to 3. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis (AccuROC, Canada).RESULTS: Serum concentrations of APO A-I, HPT and A2M were not significantly different in patients with chronic hepatitis B compared to controls. However, APO A-I level of 1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% (AUC = 0.7117, P = 0.035) to predict advanced fibrosis. All other serum biochemical markers and their combination did not allow a useful prediction.None of these markers was a good predictor of histologic inflammation.CONCLUSION: Apolipoprotein A-I may be a suitable serum marker to predict advanced liver fibrosis in children with chronic hepatitis B.

  19. Chronic viral hepatitis C in pediatric age group; assessment of viral activity and hepatic fibrosis by 1H magnetic resonance spectroscopy and diffusion weighted imaging in asymptomatic

    Directory of Open Access Journals (Sweden)

    Shereen Mansour Galal

    2016-09-01

    Conclusion: Early diagnosis of asymptomatic chronic hepatitis C is essential to prevent or delay end stage chronic parenchymal liver disease. 1H MRS may be a potential noninvasive helpful diagnostic tool in the assessment of staging and fibrosis of asymptomatic chronic hepatitis C. The increase in metabolites were correlated with histopathological changes. DW-MRI can be considered as an effective predictor in the assessment of activity in chronic hepatitis C.

  20. Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis.

    Science.gov (United States)

    Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Kohl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A; Eisenacher, Martin; Borchers, Christoph H; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2015-05-01

    Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.

  1. Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

    Directory of Open Access Journals (Sweden)

    Yasser E Nassef

    2013-11-01

    Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

  2. Inhibitory effects of capsaicin on hepatic stellate cells and liver fibrosis.

    Science.gov (United States)

    Yu, Fu-Xiang; Teng, Yin-Yan; Zhu, Qian-Dong; Zhang, Qi-Yu; Tang, Yin-He

    2014-10-01

    Hepatic stellate cells (HSCs) play an important role in the process of liver fibrosis. In this study, we investigated the inhibitory effects of capsaicin on HSCs and liver fibrosis. Cultured HSCs were incubated with various concentrations of capsaicin. Cell proliferation was examined using a cell counting kit. Production of hydrogen peroxide was determined using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay. The mRNA and protein expression of target genes was analyzed by reverse transcription PCR and Western blot analysis, respectively. Cell apoptosis was evaluated by annexin V-FITC and propidium iodide (PI) costaining followed by flow cytometric analysis. A CCl4 rat liver fibrosis model was used to assess in vivo effects of capsaicin by histological examination and measurement of liver fibrosis markers, including hydroxyproline content, serum type III collagen, and hyaluronic acid (HA) levels. Our results show that capsaicin dose-dependently inhibited cell proliferation, suppressed cell activation, and decreased hydrogen peroxide production in cultured HSCs. Capsaicin reduced the mRNA levels of tissue inhibitors of metalloproteinase 1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in HSCs. Moreover, capsaicin-induced cell apoptosis was associated with increased expression of Bax, cytochrome c (cyt c), and caspase-3, but reduced levels of Bcl-2. The animal studies further revealed that capsaicin efficiently reduced the extent of liver fibrosis, inhibited HSC proliferation, and promoted cell apoptosis. Our findings suggest that capsaicin might inhibit fibrogenesis by inhibiting the activities of HSCs.

  3. Upregulation of TNF-α mRNA in hepatic fibrosis rats induced by dimethylnitrosamine

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To observe the expression level of TNF-α mRNA in rats with hepatic fibrosis induced by dimethylnitrosamine (DMN) and to explore its relationship with collagen metabolism and its diagnostic value for hepatic fibrosis. Methods: Twenty-five male Wistar rats were randomly divided into normal control group (n=10) and model group (n=15). Model rats were induced by DMN for 4 weeks and at final stage were executed. TNF-α mRNA were detected by RT-PCR and the inflammatory necrosis and collagen deposition in hepatic tissue were observed by HE stain and Sirius red stain. The liver functions were determined by automatic biochemical analytic device. The serum marks of liver fibrosis, such as HA, LN and Ⅳ-C were measured with ELISA and RIA. Results: In this study, the rat model of liver fibrosis induced by DMN was successfully constructed. RT-PCR reveals that TNF-α mRNA expression in control group is lower than that of model group. The liver functions of model group were impaired compared with those of the control group (P<0. 01). Semi-quantitive analysis revealed that TNF-α/β-actin of normal rats was 0. 39±0. 12, while 0. 93±0. 05 of model rats. The concentration of HA (434. 44±98. 81 vs 252. 9± 26. 59ng/ml, P<0. 01), LN (70. 67±6. 32 vs 37. 90±5. 97 ng/ml, P<0. 01) and Ⅳ-C (79. 39±10. 52 vs 21. 40±4.17 ng/ml, P<0. 01) were significantly increased in the model group as well. Changes of the indexes were similar to the pathological damage of the liver. Conclusion: The results suggested that activation of TNF-α in liver tissues may be the common pathogenic mechanism of liver fibrosis. TNF-α may be a useful index for the diagnosis of hepatic fibrosis which worthies further investigation.

  4. Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B

    Science.gov (United States)

    Liu, Ping; Hu, Yi-Yang; Liu, Cheng; Zhu, Da-Yuan; Xue, Hui-Ming; Xu, Zhi-Qiang; Xu, Lie- Ming; Liu, Cheng-Hai; Gu, Hong-Tu; Zhang, Zhi-Qing

    2002-01-01

    AIM: To evaluate the clinical efficacy of salvianolic acid B (SA-B) on liver fibrosis in chronic hepatitis B. METHODS: Sixty patients with definite diagnosis of liver fibrosis with hepatitis B were included in the trial. Interferon-γ (IFN-γ) was used as control drug. The patients took orally SA-B tablets or received muscular injection of IFN-γ in the double blind randomized test. The complete course lasted 6 mo. The histological changes of liver biopsy specimen before and after the treatment were the main evidence in evaluation, in combination with the results of contents of serum HA, LN, IV-C, P-III-P, liver ultrasound imaging, and symptoms and signs. RESULTS: Reverse rate of fibrotic stage was 36.67% in SA-B group and 30.0% in IFN-γ group. Inflammatory alleviating rate was 40.0% in SA-B group and 36.67% in IFN-γ group. The average content of HA and IV-C was significantly lower than that before treatment. The abnormal rate also decreased remarkably. Overall analysis of 4 serological fibrotic markers showed significant improvement in SA-B group as compared with the IFN-γ group. Score of liver ultrasound imaging was lower in SA-B group than in IFN-γ group (HA 36.7% vs 80%, IV-C 3.3% vs 23.2%). Before the treatment, ALT AST activity and total bilirubin content of patients who had regression of fibrosis after oral administration of SA-B, were significantly lower than those of patients who had aggravation of fibrosis after oral administration of SA-B. IFN-γ showed certain side effects (fever and transient decrease of leukocytes, occurrence rates were 50% and 3.23%), but SA-B showed no side effects. CONCLUSION: SA-B could effectively reverse liver fibrosis in chronic hepatitis B. SA-B was better than IFN-γ in reduction of serum HA content, overall decrease of 4 serum fibrotic markers, and decrease of ultrasound imaging score. Liver fibrosis in chronic hepatitis B with slight liver injury was more suitable to SA-B in anti-fibrotic treatment. SA-B showed no

  5. 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 ...

  6. CD133(+) human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis.

    Science.gov (United States)

    Elkhafif, Nagwa; El Baz, Hanan; Hammam, Olfat; Hassan, Salwa; Salah, Faten; Mansour, Wafaa; Mansy, Soheir; Yehia, Hoda; Zaki, Ahmed; Magdy, Ranya

    2011-01-01

    The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.

  7. Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Qing-Wei Zhang; Hirotaka Wagatsuma; Maiko Mori; Akihiro Tamori; Susumu Shiomi; Shuhei Nishiguchi

    2008-01-01

    AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients.METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis.RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients.CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.

  8. [Effects of acupuncture intervention on hepatic platelet-derived growth factor signaling pathway in CCl4-induced hepatic fibrosis rats].

    Science.gov (United States)

    Kong, De-Song; Ma, Jin; Lu, Yin; Ni, Guang-Xia; Ni, Chun-Yan; Zhang, Xue-Jiao; Wang, Ai-Yun; Chen, Wen-Xing; Zheng, Shi-Zhong

    2012-04-01

    To observe the effect of acupuncture stimulation of "Taichong" (LR 3), "Qimen" (LR 14), etc. on hepatic platelet-derived growth factor (PDGF) signal pathway activity at the protein and mRNA levels in hepatic fibrosis rats. Forty-six SD rats were randomly divided into control (10 rats), model (12 rats), acupuncture (12 rats) and non-acupoint (12 rats) groups. Hepatic fibrosis model was established by intraperitoneal injection of mixture solution of 50% CCl4 and olive oil [1:1, 3 times on the 1st week (W), twice/W thereafter for 5 more weeks]. During modeling, acupuncture stimulation of "Taichong" (LR 3), "Qimen" (LR 14), "Ganshu" (BL 18) and "Zusanli" (ST 36) was conducted simultaneously. At the end of the experiments, all the rats were sacrificed for collecting their liver and blood samples, followed by separation of the hepatic stellate cells (HSCs). ELISA, Western blot and Real-time quantitative PCR techniques were used to detect the content of serum PDGF and expression levels of PDGF-beta receptor (PDGF-beta R), extracellular signal-regulated kinase (ERK1/2), c-jun N-terminal kinase (JNK) and P 38 genes and proteins of HSCs, respectively. Compared to the control group, serum PDGF content, and expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein and P 38 protein of HSCs in the model group were upregulated significantly (P acupuncture group were down-regulated apparently (P acupuncture and non-acupoint groups in serum PDGF content and between the model group and non-acupoint group in the expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein, JNK protein and P 38 protein of HSCs, as well as between the model group and acupuncture group in the expression levels of JNK protein and P 38 protein of HSCs (P > 0.05). Acupuncture intervention can effectively down-regulate serum PDGF content, and expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein of HSCs in liver fibrosis rats, which may contribute to its effect in

  9. Reproductive Status Is Associated with the Severity of Fibrosis in Women with Hepatitis C

    Science.gov (United States)

    Villa, Erica; Vukotic, Ranka; Cammà, Calogero; Petta, Salvatore; Di Leo, Alfredo; Gitto, Stefano; Turola, Elena; Karampatou, Aimilia; Losi, Luisa; Bernabucci, Veronica; Cenci, Annamaria; Tagliavini, Simonetta; Baraldi, Enrica; De Maria, Nicola; Gelmini, Roberta; Bertolini, Elena; Rendina, Maria; Francavilla, Antonio

    2012-01-01

    Introduction Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men. Materials and Methods A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis. Results Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001). Conclusions The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging

  10. Reproductive status is associated with the severity of fibrosis in women with hepatitis C.

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    Erica Villa

    Full Text Available INTRODUCTION: Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men. MATERIALS AND METHODS: A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis. RESULTS: Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001 or premenopausal (P = 0.042 group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052. Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048 and early menopausal (P = 0.004 but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001 and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001. In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001. CONCLUSIONS: The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol

  11. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

    Science.gov (United States)

    2012-01-01

    The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis. PMID:22559721

  12. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Gao Hong-Ying

    2012-05-01

    Full Text Available Abstract The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, hexadecenoic acid (HA, laminin (LN, hydroxyproline (Hyp, and glutathione (GSH, malondialdehyde (MDA, superoxide dismutase (SOD in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E staining and Masson Trichrome (MT examination. The expression of transforming growth factor-β1 (TGF-β1 and α-smooth muscle actin (α-SMA was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

  13. Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2.

    Science.gov (United States)

    Zakaria, Sherin; El-Sisi, Alaa

    2016-07-01

    Prostaglandin E2 (PGE2) is a potent physiological suppressor of liver fibrosis. Because the anti-ulcer drug rebamipide can induce the formation of endogenous PGE2, this study investigated the potential effects of rebamipide on development of a hepatic fibrosis that was inducible by carbon tetrachloride (CCl4). Groups of Wistar rats received intraperitoneal (IP) injections of CCl4 (0.45 ml/kg [0.72 g CCl4/kg]) over the course of for 4 weeks. Sub-sets of CCl4-treated rats were also treated concurrently with rebamipide at 60 or 100 mg/kg. At 24 h after the final treatments, liver function and oxidative stress were indirectly assessed. The extent of hepatic fibrosis was evaluated using two fibrotic markers, hyaluronic acid (HA) and pro-collagen-III (Procol-III); isolated liver tissues underwent histology and were evaluated for interleukin (IL)-10 and PGE2 content. The results indicated that treatment with rebamipide significantly inhibited CCl4-induced increases in serum ALT and AST and also reduced oxidative stress induced by CCl4. Fibrotic marker assays revealed that either dose of rebamipide decreased the host levels of Procol-III and HA that had become elevated due to the CCl4. At the higher dose tested, rebamipide appeared to be able to permit the hosts to have a normal liver histology and to minimize any CCl4-induced collagen precipitation in the liver. Lastly, the use of rebamipide was seen to be associated with significant increases in liver levels of both PGE2 and the anti-inflammatory cytokine IL-10. Based on these findings, it is concluded that rebamipide can retard hepatic fibrosis induced by CCl4 and that this effect may, in part, be mediated by an induction of PGE2 and IL-10 in the liver itself.

  14. THE ROLE OF ENALAPRIL IN PATHOGENESIS OF CCL4 INDUCED HEPATIC FIBROSIS

    Institute of Scientific and Technical Information of China (English)

    魏红山; 李定国; 陆汉明; 展玉涛; 王志荣; 黄新; 徐芹芳

    2001-01-01

    Objective The present study was designed to examine whether the renin-angiotensin system would be implicated in the development of hepatic fibrosis induced by CCl4. The effects of enalapril on the expression of platelet derived growth factor receptor (PDGFR) in liver tissue were also investigated. Methods 50 Sprague-Dawley rats were randomly divided into 5 groups (control group, model group, and 3 enalapril treated groups ). Except rats of the model group, all rats received subcutanous injection of 40% CCl4 (every 3d for 6 weeks). Rats of enalapril treated groups were given enalapril (10mg/kg, 5mg/kg, 2.5mg/kg per day, orally) for 6 weeks before they were killed. Serum levels of hyaluronic acid (HA) and laminin ( LN) were deterrnined by radioimmunoassay techniques. Van Gieson collagen staining was used to evaluate the extracellular matrix of the liver. The expressions of PDGFR and a-smooth muscle actin ( α-SMA ) were confirmed by immunohistochemical methods. Results Compared with those in the model group, it was found in enalapril treated groups: (1) serum levels of collagen type Ⅳ and LN were significantly reduced (P<0.01); (2) the progression of fibrosis was delayed (P<0.01); (3) the expressions of PDGFR and a-SMA were decreased. Conclusion The renin-angiotensin system was involved in the development of hepatic fibrosis induced by CCl4. Angiotensin-converting enzyme (ACE) inhibitor and enalapril could slow down the rate of hepatic fibrosis. This effect might be due to the ability of this drug in suppressing the expression of PDGFR of liver tissue.

  15. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling.

    Directory of Open Access Journals (Sweden)

    Ikuo Nakamura

    Full Text Available Brivanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR and fibroblast growth factor receptor (FGFR tyrosine kinases, which are both involved in mechanisms of liver fibrosis. We hypothesized that inhibition of VEGFR and FGFR by brivanib would inhibit liver fibrosis. We therefore examined the effect of brivanib on liver fibrosis in three mouse models of fibrosis.In vivo, we induced liver fibrosis by bile duct ligation (BDL, chronic carbon tetrachloride (CCl4, and chronic thioacetamide (TAA administration. Liver fibrosis was examined by immunohistochemistry and Western immunoblotting. In vitro, we used LX-2 human hepatic stellate cells (HSCs to assess the effect of brivanib on stellate cell proliferation and activation.After in vivo induction with BDL, CCl4, and TAA, mice treated with brivanib showed reduced liver fibrosis and decreased expression of collagen Iα1 and α-smooth muscle actin in the liver. In vitro, brivanib decreased proliferation of HSCs induced by platelet-derived growth factor (PDGF, VEGF, and FGF. Brivanib also decreased stellate cell viability and inhibited PDGFBB-induced phosphorylation of its cognate receptor.Brivanib reduces liver fibrosis in three different animal models and decreases human hepatic stellate cell activation. Brivanib may represent a novel therapeutic approach to treatment of liver fibrosis and prevention of liver cancer.

  16. 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.

  17. Congenital hepatic fibrosis associated with von Recklinghausen's disease Fibrosis hepática congénita asociada a enfermedad de von Recklinghausen

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    O. A. Jorge

    2006-09-01

    Full Text Available Congenital hepatic fibrosis is characterized by a ductal plate malformation with duct-like structures and fibrosis. It manifests clinically with portal hypertension and may be associated with multiple congenital defects. We present the case of a 16-year-old male with splenomegaly, leukopenia and thrombocytopenia, esophageal varices, and a histopathological diagnosis of congenital hepatic fibrosis. He exhibits "café au lait' spots and "Lisch' nodules, with a diagnosis of von Recklinghausen's disease. Congenital hepatic fibrosis belongs to the so-called fibropolycystic diseases, in which there is a disordered interaction between cells and the extracellular matrix. Von Recklinghausen's disease affects tissues derived from the neural crest and its diagnosis is based on clinical criteria. It is associated with multiple diseases. We describe its association with congenital hepatic fibrosis for the first time.La fibrosis hepática congénita se origina como consecuencia de una malformación de la placa ductal con estructuras tipo ductales acompañadas de fibrosis. Se manifiesta con hipertensión portal y puede asociarse a múltiples defectos congénitos. Presentamos un varón de 16 años con esplenomegalia, leuco- y plaquetopenia, varices esofágicas y diagnóstico histopatológico de fibrosis hepática congénita. La exploración física mostraba la existencia de manchas de "café con leche' y nódulos de "Lisch' con diagnóstico de enfermedad de von Recklinghausen. La fibrosis hepática congénita forma parte de las enfermedades fibropoliquísticas donde existiría una alteración en la interacción entre las células y la matriz extracelular. La enfermedad de von Recklinghausen afecta a los tejidos derivados de la cresta neural y su diagnóstico se basa en criterios clínicos. Se asocia a múltiples patologías. Presentamos por primera vez su asociación con fibrosis hepática congénita.

  18. Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

    Science.gov (United States)

    Hegazy, Sahar K; El-Bedewy, Mohamed; Yagi, Akira

    2012-01-01

    AIM: To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis. METHODS: Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation. Fifteen healthy volunteers as the control group and 40 patients were included. The patients were randomly subdivided into two equal groups: the conventional group was treated with placebo (starch), and AHM group was treated with 0.15 gm/d AHM, both for 12 consecutive weeks. The patients were investigated before and after treatment. Serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hyaluronic acid (HA), transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined. The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA) was identified by immunohistochemistry. RESULTS: At the start of the study, the hematoxylin and eosin staining revealed fibro-proliferated bile ductules, thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment. The use of AHM for 12 wk significantly ameliorated the fibrosis, inhibited the inflammation, and resulted in minimal infiltration and minimal fibrosis compared to the conventional group. The enzyme activities of the liver (ALT, AST and ALP) were attenuated after treatment in both groups, and the decrease in the AHM group was more significant as compared with the conventional group. Similar to the AST, the MDA levels were significantly higher before treatment, and were attenuated after treatment in both groups. In contrast, the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls. The serum levels of the fibrosis markers (HA, TGF-β and MMP-2) were also reduced

  19. Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

    Institute of Scientific and Technical Information of China (English)

    Sahar K Hegazy; Mohamed El-Bedewy; Akira Yagi

    2012-01-01

    AIM:To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS:Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation.Fifteen healthy volunteers as the control group and 40 patients were included.The patients were randomly subdivided into two equal groups:the conventional group was treated with placebo (starch),and AHM group was treated with 0.15 gm/d AHM,both for 12 consecutive weeks.The patients were investigated before and after treatment.Serum activity of aspartate aminotransferase (AST),alanine aminotransferase (ALT),alkaline phosphatase (ALP),hyaluronic acid (HA),transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined.The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA)was identified by immunohistochemistry.RESULTS:At the start of the study,the hematoxylin and eosin staining revealed fibro-proliferated bile ductules,thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment.The use of AHM for 12 wk significantly ameliorated the fibrosis,inhibited the inflammation,and resulted in minimal infiltration and minimal fibrosis compared to the conventional group.The enzyme activities of the liver (ALT,AST and ALP) were attenuated after treatment in both groups,and the decrease in the AHM group was more significant as compared with the conventional group.Similar to the AST,the MDA levels were significantly higher before treatment,and were attenuated after treatment in both groups.In contrast,the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls.The serum levels of the fibrosis markers (HA,TGF-β and MMP-2) were also reduced significantly after treatment

  20. Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Jan eGörtzen

    2015-12-01

    Full Text Available Introduction:In liver fibrosis activation of hepatic stellate cells (HSC comprises phenotypical change into profibrotic and myofibroplastic cells with increased contraction and secretion of extracellular matrix (ECM proteins. The small GTPase RhoA orchestrates cytoskeleton formation, migration and mobility via non-receptor tyrosine-protein kinase c-SRC (cellular sarcoma in different cells. Furthermore, RhoA and its downstream effector Rho-kinase also play a crucial role in hepatic stellate cells and hepatic fibrogenesis. Matrix stiffness promotes HSC activation via cytoskeleton modulation. This study investigated the interaction of c-SRC and RhoA under different matrix stiffness conditions.Methods:Liver fibrosis was induced in rats using bile duct ligation (BDL, thioacetamide (TAA or carbon tetrachloride (CCl4 models. mRNA levels of albumin, PDGF-R, RHOA, COL1A1 and αSMA were analyzed via qRT-PCR. Western Blots using phospho-specific antibodies against p-c-SRC418 and p-c-SRC530 analyzed the levels of activating and inactivating c-SRC respectively. LX2 cells and hepatocytes were cultured on acrylamide gels of 1kPa and 12kPa or on plastic to mimic non-fibrotic, fibrotic or cirrhotic environments, then exposed to SRC-inhibitor PP2. Overexpression of RhoA was performed by transfection using RhoA-plasmids. Additionally, samples from cirrhotic patients and controls were collected at liver transplantations and tumor resections were analyzed for RhoA and c-SRC protein expression by Western Blot.Results:Transcription of albumin and RhoA was decreased, whereas transcription and activation of c-SRC was increased in hepatocytes cultured on 12kPa compared to 1kPa gels. LX2 cells cultured on 12kPa gels showed upregulation of RHOA, COL1A1 and αSMA mRNA levels. Inhibition of c-SRC by PP2 in LX2 cells led to an increase in COL1A1 and αSMA most prominently in 12kPa gels. In LX2 cells with RhoA overexpression, c-SRC inhibition by PP2 failed to improve fibrosis

  1. Suppressive effects of 17β-estradiol on hepatic fibrosis in CCl4-induced rat model

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Liu; Ding-Guo Li; Xin Huang; Chun-Hua Zong; Qin-Fang Xu; Han-Ming Lu

    2004-01-01

    AIM: To investigate the pathway via which 17β-estradiol (β-Est) exerts suppressive effects on rat hepatic fibrosis.METHODS: In vivo study was done in CCl4-induced female hepatofibrotic rats. Fibrosis-suppressive effect of β-Est rat models. Six weeks after the treatment, all the rats were sacrificed and specimens of serum or liver tissue were collected for the studies. Serum liver enzymes,fibrosis markers and estradiol levels were determined by standard enzymatic methods, ELISA and RIA, respectively.Degrees of fibrosis and areas of hepatic stellate cells (HSCs) positive for alpha-smooth muscle actin (α-SMA) in the liver were determined by van Gieson (VG) stain and immunohistochemistry.In vitro studies, HSCs were isolated by a combination of pronase-collagenase perfusion and density gradient centrifugation. First-passage HSCs were randomly divided into 10 groups, and different concentrations of β-Est, 2-hydroxyestradiol (2OHE) or 2-methoxyestradiol (2MeOE) were separately added to the cell groups. After incubation for 72 h, the degree of cell proliferation, collagen production, α-SMA or estrogen receptor (ER) expression was determined by MTT assay, ELISA and immunohistochemistry,respectively.RESULTS: β-Est treatment reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA) and type Ⅳ collagen (C Ⅳ) in sera, suppressed hepatic collagen content, decreased the areas of HSCs positive for α-SMA significantly in both intact and ovariectomized female hepatofibrotic rats. There was a negative correlation between the percentage of fibrotic area of liver tissue and the serum estradiol level; the calculated correlation coefficient was -0.57 (P<0.01). β-Est and its metabolites concentration-dependently (10-9 mol/L-10-7 mol/L) inhibited HSC proliferation and collagen synthesis. At the concentration of 10-7 mol/L, they could inhibit α-SMA expression. The order of potency was 2MeOE>2OHE>β-Est.CONCLUSION: β-Est may suppress

  2. (18)F-FBHGal for asialoglycoprotein receptor imaging in a hepatic fibrosis mouse model.

    Science.gov (United States)

    Kao, Hao-Wen; Chen, Chuan-Lin; Chang, Wen-Yi; Chen, Jenn-Tzong; Lin, Wuu-Jyh; Liu, Ren-Shyan; Wang, Hsin-Ell

    2013-02-15

    Quantification of the expression of asialoglycoprotein receptor (ASGPR), which is located on the hepatocyte membrane with high-affinity for galactose residues, can help assess ASGPR-related liver diseases. A hepatic fibrosis mouse model with lower asialoglycoprotein receptor expression was established by dimethylnitrosamine (DMN) administration. This study developed and demonstrated that 4-(18)F-fluoro-N-(6-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexyl)benzamide ((18)F-FBHGal), a new (18)F-labeled monovalent galactose derivative, is an asialoglycoprotein receptor (ASGPR)-specific PET probe in a normal and a hepatic fibrosis mouse models. Immunoassay exhibited a linear correlation between the accumulation of GalH-FITC, a fluorescent surrogate of FBHGal, and the amount of ASGPR. A significant reduction in HepG2 cellular uptake (P ASGPR blocking agent. Animal studies showed the accumulation of (18)F-FBHGal in fibrosis liver (14.84±1.10 %ID/g) was appreciably decreased compared with that in normal liver (20.50±1.51 %ID/g, P ASGPR-related liver dysfunction.

  3. Enhanced HBsAg synthesis correlates with increased severity of fibrosis in chronic hepatitis B patients.

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    Mei-Zhu Hong

    Full Text Available BACKGROUND AND AIMS: Little is known about whether low serum HBsAg levels result from impaired HBsAg synthesis or a reduced number of hepatocytes caused by advanced liver fibrosis. Therefore, we investigated the capacity for HBsAg synthesis in a cross-sectional cohort of treatment-naïve chronic hepatitis B patients. METHODS: Chronic hepatitis B patients (n = 362 were enrolled; liver biopsies were performed and liver histology was scored, and serum HBsAg and HBV DNA levels were investigated. In the enrolled patients, 183 out of 362 have quantitative serum HBsAg levels. Tissue HBsAg was determined by immunohistochemistry. RESULTS: A positive correlation between serum HBsAg and HBV DNA levels was revealed in HBeAg(+ patients (r = 0.2613, p = 0.0050. In HBeAg(+ patients, serum HBsAg and severity of fibrosis were inversely correlated (p = 0.0094, whereas tissue HBsAg levels correlated positively with the stage of fibrosis (p = 0.0280. After applying the mean aminopyrine breath test as a correction factor, adjusted serum HBsAg showed a strong positive correlation with fibrosis severity in HBeAg(+ patients (r = 0.5655, p<0.0001. The adjusted serum HBsAg values predicted 'moderate to severe' fibrosis with nearly perfect performance in both HBeAg(+ patients (area under the curve: 0.994, 95% CI: 0.983-1.000 and HBeAg(- patients (area under the curve: 1.000, 95% CI: 1.000-1.000. CONCLUSIONS: Although serum HBsAg levels were negatively correlated with fibrosis severity in HBeAg(+ patients, aminopyrine breath test-adjusted serum HBsAg and tissue HBsAg, two indices that are unaffected by the number of residual hepatocytes, were positively correlated with fibrosis severity. Furthermore, adjusted serum HBsAg has an accurate prediction capability.

  4. The efficacy of aspartate aminotransferase-toplatelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice

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    Earl Kim

    2013-01-01

    Full Text Available Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD, and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST-to-platelet ratio index (APRI have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement &gt;5.9 kPa Fibroscan were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (&gt;5.9 kPa. In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875 presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

  5. Nutrición, fibrosis quística y aparato digestivo Nutrition, cystic fibrosis and the digestive tract

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    Gabriel Olveira

    2008-05-01

    empleo no está avalado en evidencias científicas sólidas. Los preparados más empleados suelen ser poliméricos e hipercalóricos. Las indicaciones de soporte nutricional enteral por sonda (especialmente gastrostomía o parenteral son similares a las empleadas en otras patologías. El control dietético y nutricional debe incluirse en un programa multidisciplinar que permita mejorar la capacidad funcional, la calidad de vida y reducir, al menos teóricamente, la morbi-mortalidad asociada a la malnutrición en estos pacientes.The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m², and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients. Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition

  6. Anti-hepatitis C virus treatment may prevent the progression of liver fibrosis in non-responder human immunodeficiency virus/hepatitis C virus coinfected patients

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    Caterina Sagnelli

    2014-04-01

    Full Text Available AIM: To evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon+Ribavirine regimen. MATERIALS AND METHODS: We investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon+Ribavirine treatment (Group hepatitis C virus Rx administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula. RESULTS: Liver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16% patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups. CONCLUSION: Liver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy.

  7. Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy

    Science.gov (United States)

    Wang, Tong-Hong; Chen, Tse-Ching; Teng, Xiao; Liang, Kung-Hao; Yeh, Chau-Ting

    2015-08-01

    Liver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi-quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining, and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P 0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method.

  8. Hepatic stellate cell-specific deletion of SIRT1 exacerbates liver fibrosis in mice.

    Science.gov (United States)

    Li, Min; Hong, Wenxuan; Hao, Chenzhi; Li, Luyang; Xu, Huihui; Li, Ping; Xu, Yong

    2017-09-14

    Liver fibrosis is widely perceived as a host defense mechanism that aids tissue repair following liver injury. Excessive fibrogenesis, however, serves to disrupts normal liver structure and precedes such irrevocable human pathologies as cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrosis. In the present study we investigated the mechanism by which the lysine deacetylase SIRT1 regulates HSC activation. We report here that SIRT1 levels were decreased in the liver in different mouse models and in cultured HSCs undergoing activation. SIRT1 down-regulation paralleled HDAC4 up-regulation. HDAC4 was recruited to the SIRT1 promoter during HSC activation and removed acetylated histones H3 and H4 from the SIRT1 promoter leading to SIRT1 trans‑repression. HDAC4 silencing restored SIRT1 expression and attenuated HSC activation in SIRT1-dependent manner. More important, selective deletion of SIRT1 in HSCs exacerbated CCl4-induced liver fibrosis in mice. Mechanistically, SIRT1 deacetylated PPARγ to block HSC activation. Together, our data reveal an HDAC4-SIRT1-PPARγ axis that contributes to the regulation of HSC activation and liver fibrosis. Copyright © 2017. Published by Elsevier B.V.

  9. Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways.

    Science.gov (United States)

    Seifert, Lena; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Werba, Gregor; Pansari, Mridul; Pergamo, Matthew; Ochi, Atsuo; Torres-Hernandez, Alejandro; Levie, Elliot; Tippens, Daniel; Greco, Stephanie H; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Eisenthal, Andrew; van Heerden, Eliza; Avanzi, Antonina; Barilla, Rocky; Zambirinis, Constantinos P; Rendon, Mauricio; Daley, Donnele; Pachter, H Leon; Hajdu, Cristina; Miller, George

    2015-12-01

    Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Lena Seifert

    2015-12-01

    Full Text Available Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1–/– mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

  11. Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Yongchen Wang

    2016-06-01

    Full Text Available Demethyleneberberine (DMB is an essential metabolite of Berberine (BBR in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs and induce cell apoptosis through the nuclear factor-κB (NF-κB cascade. Immunohistochemical (IHC and quantitative polymerase chain reaction (qPCR analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor β 1 (TGF-β1-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs and tissue inhibitors of MMP (TIMPs. These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation.

  12. Comparing the role of shape and texture on staging hepatic fibrosis from medical imaging

    Science.gov (United States)

    Zhang, Xuejun; Louie, Ryan; Liu, Brent J.; Gao, Xin; Tan, Xiaomin; Qu, Xianghe; Long, Liling

    2016-03-01

    The purpose of this study is to investigate the role of shape and texture in the classification of hepatic fibrosis by selecting the optimal parameters for a better Computer-aided diagnosis (CAD) system. 10 surface shape features are extracted from a standardized profile of liver; while15 texture features calculated from gray level co-occurrence matrix (GLCM) are extracted within an ROI in liver. Each combination of these input subsets is checked by using support vector machine (SVM) with leave-one-case-out method to differentiate fibrosis into two groups: normal or abnormal. The accurate rate value of all 10/15 types number of features is 66.83% by texture, while 85.74% by shape features, respectively. The irregularity of liver shape can demonstrate fibrotic grade efficiently and texture feature of CT image is not recommended to use with shape feature for interpretation of cirrhosis.

  13. The pharmacological approach to reverse portal hypertention and hepatic schistosomal fibrosis in Egypt, control experimental study.

    Science.gov (United States)

    Helmy, Ahmed Hazem I; Abdel-Hady, Afaf Ahmed; el-Shanawany, Faten; Hammam, Olfat; Abdel-Hady, Ahmed

    2005-12-01

    Schistosoma mansoni is the most prevalent cause of liver fibrosis in Egypt. It is characterized by hepatocyte damage, inflammation and chronic parasite egg-induced granuloma formation leading to fibrosis. Its management, particularly fibrosis, has focused primarily on treating and preventing the complications of portal hypertension. Unfortunately, there is no therapy that has been proved to prevent progressive hepatic fibrosis which is associated with a significant morbidity and mortality due to granulomatous hypersensitivity to parasite eggs. However, recent developments in understanding hepatic fibrogenesis confirm that recovery from advanced fibrosis is possible. There is a considerable imperative to develop anti-fibrotic strategies that are applicable to liver fibrosis. It was noted that a marked increase in the amount of different interstitial collagens types are associated with the development of fibrotic liver diseases. Meanwhile, it has been suggested that as long as the relative portions of liver collagen are still within the normal limits, the fibrosis may still be reversible. If it exceeds the normal limits fibrogenesis will proceed to its end stage, even if the etiological agent is removed. Collagen type IV and procollagen type III are two of the most accurate fibrosis markers which allow reliable non-invasive diagnosis. The T lymphocytes and the immuno-regulatory cytokines may be important in the host response to S. mansoni granuloma formation and fibrosis. Chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Corticosteroids and prostaglandins interfere with both efferent and afferent mechanisms of immune function. These data indicate that this adjuvant therapy can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a balance between Th1 and Th2 cells response as will be documented by the fibrosis markers. One hundred S. mansoni

  14. 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.

  15. Insulin resistance, steatosis, and fibrosis in Egyptian patients with chronic Hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Ahlam M Ahmed

    2011-01-01

    Full Text Available Background/Aim: Both nonalcoholic fatty liver disease (NAFLD and chronic hepatitis C virus (HCV infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC (necroinflammation and fibrosis and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection. Patients and Methods: Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. Results: Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST level were 42 ± 7.7 years (range 20-56 and 68 ± 41.7 U/L (range 16-214, respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4 and 5.9 ± 15.2 (range 0.9-136.2, respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis. Conclusions: Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.

  16. The role of mutations in core protein of hepatitis B virus in liver fibrosis

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    Abbasi Shahsanam

    2009-11-01

    Full Text Available Abstract The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 ± 9 years old with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 ± 0.8 vs 1.9 ± 1.4 for mean stage of fibrosis P = 0.05. Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both. Patients with mutation in C-terminal domain had higher serum ALT (62 ± 17 vs 36 ± 12 IU/l, p = 0.02. Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.

  17. Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Kang, Bo-Kyeong; Lee, Seung Soo; Cheong, Hyunhee; Hong, Seung Mo; Jang, Kiseok; Lee, Moon-Gyu

    2015-12-01

    The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis. Among the histologic and biomolecular findings, the fibrosis stage and the collagen RNA level were significant independent factors associated with liver elasticity (p steatohepatitis (NASH) and in determining fibrosis stage, and the corresponding areas under the receiver operating characteristic curves were 0.963 and 0.927-0.997, respectively. In conclusion, SWE is a potential non-invasive method for the detection of NASH and staging of hepatic fibrosis in patients with NAFLD.

  18. The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals.

    Science.gov (United States)

    Kim, H Nina; Crane, Heidi M; Rodriguez, Carla V; Van Rompaey, Stephen; Mayer, Kenneth H; Christopoulos, Katerina; Napravnik, Sonia; Chander, Geetanjali; Hutton, Heidi; McCaul, Mary E; Cachay, Edward R; Mugavero, Michael J; Moore, Richard; Geng, Elvin; Eron, Joseph J; Saag, Michael S; Merrill, Joseph O; Kitahata, Mari M

    2016-12-29

    We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

  19. Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

    DEFF Research Database (Denmark)

    Pincikova, T; Nilsson, Kristine Kahr; Moen, I E;

    2011-01-01

    Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

  20. Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles.

    Science.gov (United States)

    Yang, D; Gao, Y-H; Tan, K-B; Zuo, Z-X; Yang, W-X; Hua, X; Li, P-J; Zhang, Y; Wang, G

    2013-12-01

    We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (Pliposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

  1. HuR contributes to Hepatic Stellate Cell activation and liver fibrosis

    OpenAIRE

    Woodhoo, A.; Iruarrizaga-Lejarreta, M.; Beraza, N.; García-Rodríguez, J.L.; Embade, N.; Fernández-Ramos, D.; Matinez-Lopez, N.; Gutiérrez, Virginia; Arteta, B; Caballeria, J.; Lu, S.C. (Shelly C.); Mato, J.M. (José María); Varela-Rey, M.; Martinez-Chantar, M.L.

    2012-01-01

    RNA-binding proteins (RBPs) play a major role in control of mRNA turnover and translation rates. We examined the role of the RBP human antigen R (HuR) during cholestatic liver injury and hepatic stellate cells (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and α-SMA (α-smooth muscle actin) expression. HuR expression increased in activated HSC from BDL mice and during HSC activation in vitro...

  2. Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ping Liu; Zhi-Qing Zhang; Yi-Yang Hu; Cheng Liu; Da-Yuan Zhu; Hui-Ming Xue; Zhi-Qiang Xu; Lie- Ming Xu; Cheng-Hai Liu; Hong-Tu Gu

    2002-01-01

    AIM: To evaluate the clinical efficacy of salvianolic acidB (SA-B) on liver fibrosis in chronic hepatitis B.METHODS: Sixty patients with definite diagnosis of liverfibrosis with hepatitis B were included in the trial.Interferon-γ (IFN-γ) was used as control drug. Thepatients took orally SA-B tablets or received muscularinjection of IFN-γ in the double blind randomized test,The complete course lasted 6 months. The histologicalchanges of liver biopsy specimen before and after thetreatment were the main evidence in evaluation, incombination with the results of contents of serum HA,LN, Ⅳ-C, P-Ⅲ-P, liver ultrasound imaging, andsymptoms and signs.RESULTS: Reverse rate of fibrotic stage was 36.67 % inSA-B group and 30.0 % in IFN-γgroup. Inflammatoryalleviating rate was 40.0 % in SA-B group and 36.67 %in IFN-γ group. The average content of HA and Ⅳ-Cwas significantly lower than that before treatment. Theabnormal rate also decreased remarkably. Overallanalysis of 4 serological fibrotic markers showedsignificant improvement in SA-B group as comparedwith the IFN-γgroup. Score of liver ultrasound imagingwas lower in SA-B group than in IFN-γgroup (HA 36.7 %vs80 %,Ⅳ-C 3.3 % vs23.2 %). Before the treatment,ALT AST activity and total bilirubin content of patientswho had regression of fibrosis after oral administrationof SA-B, were significantly lower than those of patientswho had aggravation of fibrosis after oraladministration of SA-B. IFN-γ showed certain sideeffects (fever and transient decrease of leukocytes,occurrence rates were 50 % and 3.23 %), but SA-Bshowed no side effects.CONCLUSION: SA-B could effectively reverse liverfibrosis in chronic hepatitis B. SA-B was better than IFN-γ in reduction of serum HA content, overall decrease of4 serum fibrotic markers, and decrease of ultrasoundimaging score. Liver fibrosis in chronic hepatitis B withslight liver injury was more suitable to SA-B in anti-fibrotic treatment. SA-B showed no obvious side effects.

  3. 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.

  4. Proteomic Profiling of Human Liver Biopsies: Hepatitis C Virus-Induced Fibrosis and Mitochondrial Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Diamond, Deborah L.; Jacobs, Jon M.; Paeper, Bryan; Proll, Sean; Gritsenko, Marina A.; Carithers, Jr., Robert L.; Larson , Anne M.; Yeh, Matthew M.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2007-09-01

    Liver biopsies from HCV-infected patients offer the unique opportunity to study human liver biology and disease in vivo. However, the low protein yields associated with these small samples present a significant challenge for proteomic analysis. In this study we describe the application of an ultra-sensitive proteomics platform for performing robust quantitative proteomic studies on microgram amounts of HCV-infected human liver tissue from 15 patients at different stages of fibrosis. A high quality liver protein data base containing 5,920 unique protein identifications supported high throughput quantitative studies using 16O:18O stable isotope labeling in combination with the accurate mass and time (AMT) tag approach. A total of 1,641 liver biopsy proteins were quantified and ANOVA identified 210 proteins exhibiting statistically significant differences associated with fibrosis stage. Hierarchical clustering revealed that biopsies representative of later fibrosis stages (e.g. Batts-Ludwig stages 3-4) exhibited a distinct protein expression profile indicating an apparent down-regulation of many proteins when compared to samples from earlier fibrosis stages (e.g. Batts-Ludwig stages 0-2). Functional analysis of these signature proteins suggests that impairment of key mitochondrial processes including fatty acid oxidation and oxidative phosphorylation, and response to oxidative stress and reactive oxygen species occurs during advanced stage 3-4 fibrosis. In conclusion, the results reported here represent a significant advancement in clinical proteomics providing to our knowledge, the first demonstration of global proteomic alterations accompanying liver disease progression in patients chronically infected with HCV. Our findings contribute to a generally emerging theme associating oxidative stress and hepatic mitochondrial dysfunction with HCV pathogenesis.

  5. Viscoelasticity-based magnetic resonance elastography for the assessment of liver fibrosis in hepatitis C patients after liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kamphues, C.; Bova, R.; Yahyazadeh, A.; Bahra, M.; Neuhaus, P. [Charite, Campus Virchow Klinikum, Berlin (Germany). Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie; Klatt, D.; Braun, J.; Sack, I.; Asbach, P. [Charite - Universitaetsmedizin, Berlin (Germany). Klinik fuer Radiologie; Klauschen, F. [Charite - Universitaetsmedizin, Berlin (Germany). Inst. fuer Pathologie

    2012-11-15

    Purpose: Despite advantages in antiviral therapy of hepatitis C (HCV) in recent years, progressing liver fibrosis remains a major problem for patients suffering from hepatitis C after liver transplantation. Therefore, effective non-invasive methods for the assessment of liver fibrosis are needed in order to guide treatment decisions and predict prognosis in these patients. The aim of this study was to prospectively assess the diagnostic accuracy of viscoelasticity-based magnetic resonance (MR) elastography for the assessment of liver fibrosis in HCV patients after liver transplantation. Materials and Methods: After IRB approval, a total of 25 patients, who had received a liver graft due to chronic hepatitis C underwent both liver biopsy and MR elastography. Two viscoelastic constants, the shear elasticity {mu} and the powerlaw exponent {alpha} were calculated by fitting the frequency function of the complex shear modulus with the viscoelastic springpot-model. Results: A strong positive correlation between shear elasticity {mu} and the stage of fibrosis could be found (R = 0.486, p = 0.0136). The area under the receiver operating curve (AUROC) of MR elastography based on {mu} for diagnosis of severe fibrosis (F {>=} 3) was 0.87 and 0.65 for diagnosis of significant fibrosis (F {>=} 2). The powerlaw exponent {alpha} did not correlate with the stage of fibrosis. Conclusion: MR elastography represents a promising non-invasive procedure for the assessment of higher grades of fibrosis in HCV patients after liver transplantation. The poor correlation for lower grades of fibrosis suggests unknown mechanical interactions in the transplanted liver. (orig.)

  6. 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

  7. Relationship between hepatic CTGF expression and routine blood tests at the time of liver transplantation for biliary atresia: hope or hype for a biomarker of hepatic fibrosis

    Directory of Open Access Journals (Sweden)

    Haafiz A

    2011-04-01

    Full Text Available Allah Haafiz1, Christian Farrington1, Joel Andres1, Saleem Islam21Hepatology and Liver Transplantation, Division of Pediatric Gastroenterology, Hepatology and Nutrition, 2Division of Pediatric Surgery, University of Florida College of Medicine, Gainesville, FL, USABackground: Progressive hepatic fibrosis (HF is a prominent feature of biliary atresia (BA, the most common indication for liver transplantation (LT in children. Despite its importance in BA, HF is not evaluated in routine patient care because the invasiveness of liver biopsy makes histologic monitoring of fibrosis unfeasible. Therefore, the identification of noninvasive markers to assess HF is desirable especially in children.Purpose: The main goal of this pilot project was to establish an investigational framework correlating hepatic expression of fibrogenic markers with routine blood tests in BA.Methods: Using liver explants from patients with BA (n = 26, immune-expression of connective tissue growth factor (CTGF, a key fibrogenic cytokine was determined using horseradish-labeled antibodies. Expression intensities of lobular (L-CTGF and portal (P-CTGF CTGF were determined by using ImageJ software. These CTGF intensities were correlated with blood tests performed at the time of LT. Correlation coefficients were determined for each blood test variable versus mean L-CTGF and P-CTGF expression intensities. A P-value of less than 0.05 was considered statistically significant.Results: All patients had end-stage liver disease and persistent cholestasis at the time of LT. Kendall tau (t rank correlation coefficient for L-CTGF and white blood cell (WBC was inversed (—0.52; P ≤ 0.02. Similar but statistically nonsignificant inverse relationships were noted between L-CTGF and prothrombin time (PT (—0.15; P ≤ 0.4, international normalized ratio (INR (—0.14; P ≤ 0.5, and platelet count (—0.36; P ≤ 0.09. Inversed (t rank correlation coefficients were also evident between P

  8. [Results of nutritional intervention in children and adolescents with cystic fibrosis].

    Science.gov (United States)

    Gaspar, Maria Cristina A; Chiba, Sônia M; Gomes, Clóvis E T; Juliano, Yara; Novo, Neil F; Ancona-Lopez, Fabio

    2002-01-01

    Few studies have verified longitudinally the evolution of the nutritional status of patients with cystic fibrosis. The objective of this study is to follow the evolution of the nutritional status, body composition and energy consumption, macronutrients and micronutrients ingested by children and adolescents by means of nutritional interventions at the Clinic of Cystic Fibrosis/Pediatric Pneumology of the Department of Pediatrics of Universidade Federal de São Paulo. 18 patients were involved in this study, thirteen males and five females with ages ranging from 0.3 to 18.4 years. We performed three evaluations: evaluation 1 (M1--prenutritional intervention), M2 after 6 months, and M3 after 12 months. In these three instances we verified: the z score for weight/age, weight/height and height/age and the calculation of a 3-day diet record. We verified the body composition (anthropometry) in M1 and M3. The nutritional interventions were hypercaloric, hyperproteic, with adequate amount of ingested macronutrients and micronutrients. We observed an increase in the z score for height/age (M1=-1.07; M2=-0.69; M3=-0.50) and fat-free mass after the nutritional interventions, without improvement in the z score for weight/height and fat mass. We verified an increase in the energy intake during M2 (139%) and M3 (132%) compared to M1 (106%). Remarkable increase in the intake of protein, calcium, iron and vitamin C by the patients was found. The occurrence of anemia was found in 44% (8/18) of the patients. The improvement of the z score in height/age and fat-free mass was probably due to the increase in energy consumption after the nutritional intervention. A significant improvement in the z score for weight/height and fat mass was not found, probably due to a gain in height and fat-free mass.

  9. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations.

  10. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study.

    Science.gov (United States)

    Ghavamzadeh, Ardeshir; Mirzania, Mehrzad; Kamalian, Naser; Sedighi, Nahid; Azimi, Parisima

    2015-04-01

    Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls' Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation.

  11. Long-term, maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C.

    Science.gov (United States)

    Manzia, Tommaso Maria; Angelico, Roberta; Toti, Luca; Bellini, Maria Irene; Sforza, Daniele; Palmieri, Giampiero; Orlando, Giuseppe; Tariciotti, Laura; Angelico, Mario; Tisone, Giuseppe

    2011-05-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

  12. Hepatitis B virus sequencing and liver fibrosis evaluation in HIV/HBV co-infected Nigerians.

    Science.gov (United States)

    Grant, Jennifer; Agbaji, Oche; Kramvis, Anna; Yousif, Mukhlid; Auwal, Mu'azu; Penugonda, Sudhir; Ugoagwu, Placid; Murphy, Robert; Hawkins, Claudia

    2017-06-01

    Molecular characteristics of hepatitis B virus (HBV), such as genotype and genomic mutations, may contribute to liver-related morbidity and mortality. The association of these characteristics with liver fibrosis severity in sub-Saharan Africa is uncertain. We aimed to characterise molecular HBV features in human immunodeficiency virus (HIV)/HBV co-infected Nigerians and evaluate associations between these characteristics and liver fibrosis severity before and after antiretroviral therapy (ART) initiation. HIV/HBV co-infected Nigerians underwent liver fibrosis estimation by transient elastography (TE) prior to and 36 months after ART initiation. Basal core promoter/precore (BCP/PC) and preS1/preS2/S regions of HBV were sequenced from baseline plasma samples. We evaluated associations between HBV mutations and liver fibrosis severity by univariate and multivariable regression. At baseline, 94 patients underwent TE with median liver stiffness of 6.4 (IQR 4.7-8.7) kPa. Patients were predominantly infected with HBV genotype E (45/46) and HBe-antigen negative (75/94, 79.8%). We identified BCP A1762T/G1764A in 15/35 (43%), PC G1896A in 20/35 (57%), 'a' determinant mutations in 12/45 (26.7%) and preS2 deletions in 6/16 (37.5%). PreS2 mutations were associated with advanced fibrosis in multivariable analysis. At follow-up, median liver stiffness was 5.2 (IQR 4.1-6.6) kPa. No HBV molecular characteristics were associated with lack of fibrosis regression, although HIV virologic control, body mass index (BMI) and baseline CD4+ T-cell count were associated with a decline in fibrosis stage. Frequent BCP/PC and preS1/preS2/S mutations were found in ART-naïve HIV/HBV co-infected Nigerians. Median liver stiffness declined after initiation of ART, regardless of pre-ART HBV mutational pattern or virologic characteristics. © 2017 John Wiley & Sons Ltd.

  13. 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.

  14. The stress-regulated transcription factor CHOP promotes hepatic inflammatory gene expression, fibrosis, and oncogenesis.

    Directory of Open Access Journals (Sweden)

    Diane DeZwaan-McCabe

    Full Text Available Viral hepatitis, obesity, and alcoholism all represent major risk factors for hepatocellular carcinoma (HCC. Although these conditions also lead to integrated stress response (ISR or unfolded protein response (UPR activation, the extent to which these stress pathways influence the pathogenesis of HCC has not been tested. Here we provide multiple lines of evidence demonstrating that the ISR-regulated transcription factor CHOP promotes liver cancer. We show that CHOP expression is up-regulated in liver tumors in human HCC and two mouse models thereof. Chop-null mice are resistant to chemical hepatocarcinogenesis, and these mice exhibit attenuation of both apoptosis and cellular proliferation. Chop-null mice are also resistant to fibrosis, which is a key risk factor for HCC. Global gene expression profiling suggests that deletion of CHOP reduces the levels of basal inflammatory signaling in the liver. Our results are consistent with a model whereby CHOP contributes to hepatic carcinogenesis by promoting inflammation, fibrosis, cell death, and compensatory proliferation. They implicate CHOP as a common contributing factor in the development of HCC in a variety of chronic liver diseases.

  15. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

    Science.gov (United States)

    Parikh, Pathik; Ryan, John D.

    2017-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care. PMID:28251119

  16. Hepatic fibrosis in biliary-obstructed rats is prevented by Ginkgo biloba treatment

    Institute of Scientific and Technical Information of China (English)

    G(o)ksel Pener; Levent Kabasakal; Meral Yüksel; Nursal Gedik; (Y)nci Alican

    2005-01-01

    AIM: To assess the antioxidant and antifibrotic effects of long-term Ginkgo biloba administration on liver fibrosis induced by biliary obstruction in rats.METHODS: Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). Ginkgo administered for 28 d. At the end of the treatment period,all rats were killed. Serum aspartate aminotransferase (AST),alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-α (TNF-α) was also assayed in serum samples. Liver tissues were taken for determination of the hepatic malondialdehyde (MDA) and glutathione (GSH) levels,myeloperoxidase (MPO) activity and collagen content.Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Serum AST, ALT, LDH, and TNF-α levels were elevated in the BDL group as compared to control group and were significantly decreased by EGb treatment.RESULTS: Hepatic GSH level, depressed by BDL, was elevated back to control level in EGb-treated BDL group.Increase in tissue MDA level, MPO activity and collagen content due to BDL were also attenuated by EGb treatment.Furthermore, luminol and lucigenin CL values in BDL group increased dramatically compared to control and reduced by EGb treatment.CONCLUSION: Our results suggest that Ginkgo biloba protects the liver from oxidative damage following BDL in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation; thus, restoration of oxidant and antioxidant status in the tissue.

  17. The Role of TGF-β1 in Mice Hepatic Fibrosis by Schistosomiasis Japonica

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the role of transforming growth factor-β1 (TGF-β1) in mice with hepatic fibrosis caused by Schistosomiasis Japonica, ELISA ,VG staining and multimedia color hieroglyph quantitative analysis were used to study the change of the serum TGF-β1, liver collagen fiber and reticular fiber in mice. The level of serum TGF-β1 in experimental group was significantly higher than that in control group (P<0.01 orP<0.05) 8, 10, 12 weeks after infected by schistosomiasis. After infection, the level of liver collagen fiber and reticular fiber, and that of TGF -β1 increased over time (P< 0.01 or P<0. 05). In mice infected by Schistosomiasis Japonica, the level of TGF-β1 increased with prolongation of infection time, and with the increase of liver collagen fiber and reticular fiber. TGFβ1 plays an important role of immunomodulation in hepatic fibrosis formation caused by Schistosomiasis Japonica.

  18. Antihepatic Fibrosis Effect of Active Components Isolated from Green Asparagus (Asparagus officinalis L.) Involves the Inactivation of Hepatic Stellate Cells.

    Science.gov (United States)

    Zhong, Chunge; Jiang, Chunyu; Xia, Xichun; Mu, Teng; Wei, Lige; Lou, Yuntian; Zhang, Xiaoshu; Zhao, Yuqing; Bi, Xiuli

    2015-07-08

    Green asparagus (Asparagus officinalis L.) is a vegetable with numerous nutritional properties. In the current study, a total of 23 compounds were isolated from green asparagus, and 9 of these compounds were obtained from this genus for the first time. Preliminary data showed that the ethyl acetate (EtOAc)-extracted fraction of green asparagus exerted a stronger inhibitory effect on the growth of t-HSC/Cl-6 cells, giving an IC50 value of 45.52 μg/mL. The biological activities of the different compounds isolated from the EtOAc-extracted fraction with respect to antihepatic fibrosis were investigated further. Four compounds, C3, C4, C10, and C12, exhibited profound inhibitory effect on the activation of t-HSC/Cl-6 cells induced by TNF-α. The activation t-HSC/Cl-6 cells, which led to the production of fibrotic matrix (TGF-β1, activin C) and accumulation of TNF-α, was dramatically decreased by these compounds. The mechanisms by which these compounds inhibited the activation of hepatic stellate cells appeared to be associated with the inactivation of TGF-β1/Smad signaling and c-Jun N-terminal kinases, as well as the ERK phosphorylation cascade.

  19. Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Phaedra M Tachtatzis

    Full Text Available Chronic Hepatitis B virus (HBV infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.Liver samples from patients with chronic HBV (n = 91, normal liver (n = 55 and regenerating liver (n = 15 were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro.13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9% in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect.Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

  20. Loss of discoidin domain receptor 2 promotes hepatic fibrosis after chronic carbon tetrachloride through altered paracrine interactions between hepatic stellate cells and liver-associated macrophages.

    Science.gov (United States)

    Olaso, Elvira; Arteta, Beatriz; Benedicto, Aitor; Crende, Olatz; Friedman, Scott L

    2011-12-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl(4)) to DDR2(+/+) and DDR2(-/-) mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after chronic CCl(4) administration, DDR2(-/-) livers had increased collagen deposition, gelatinolytic activity, and HSC density. Increased basal gene expression of osteopontin, transforming growth factor-β1, monocyte chemoattractant protein-1, and IL-10 and reduced basal gene expression of matrix metalloproteinase-2, matrix metalloproteinase-13, and collagen type I in quiescent DDR2(-/-) HSCs were amplified further after chronic CCl(4). In concordance, DDR2(-/-) HSCs isolated from chronically injured livers had enhanced in vitro migration and proliferation, but less extracellular matrix degradative activity. Macrophages from chronic CCl(4)-treated DDR2(-/-) livers showed stronger chemoattractive activity toward DDR2(-/-) HSCs than DDR2(+/+) macrophages, increased extracellular matrix degradation, and higher cytokine mRNA expression. In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that DDR2 normally orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis.

  1. Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C.

    Science.gov (United States)

    Wu, Li-Yuan; Liu, Shuhong; Liu, Yuan; Guo, Chaonan; Li, Hanwei; Li, Wenshu; Jin, Xueyuan; Zhang, Keming; Zhao, Ping; Wei, Lai; Zhao, Jingmin

    2015-05-01

    Interleukin-22 (IL-22) is known to play a critical role in liver immunity. However, the role of IL-22 in HCV-associated liver fibrosis is poorly understood. In this study, patients with HCV infection disclosed significant increases in peripheral numbers of IL-22-producing cells as well as in IL-22 plasma levels. In the liver, the increased intrahepatic IL-22(+) cells were positively correlated with fibrotic staging scores and clinical progression from CHC to cirrhosis. Moreover, the majority of IL-22(+) cells were located in fibrotic areas in the liver of patients with cirrhosis and co-localized with α-smooth muscle actin (α-SMA) positive hepatic stellate cells (HSCs). In vitro, administration of IL-22 was accompanied with inhibited LX-2 cell apoptosis, promoted LX-2 cell proliferation, increased expression of α-SMA, and up-regulated collagen production by LX-2 cells. Collectively, our data provide evidence that IL-22 may contribute to the fibrogenesis of HCV-associated liver fibrosis by activating HSCs.

  2. Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Fatima Khaja

    2016-01-01

    Full Text Available Since its discovery, small interfering RNA (siRNA has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA not easily accessed by conventional drugs. Hence, RNA interference (RNAi therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs. This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF, an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP, showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases.

  3. Fibrose cística: uma abordagem clínica e nutricional Cystic fibrosis: a clinical and nutritional approach

    Directory of Open Access Journals (Sweden)

    Fernanda Ribeiro Rosa

    2008-12-01

    produce thick and viscous mucus secretions that obstruct the lungs, pancreas and bile duct. Many patients have pancreatic insufficiency which leads to malabsorption of nutrients, especially proteins and fats and to gastrointestinal complications such as rectal prolapse, intestinal obstruction syndrome, constipation and hepatic cirrhosis. Cystic fibrosis is usually diagnosed during childhood by neonatal screening programs or sweat test. Because of the multiple systems involved and the variability and chronicity of the disease, a multidisciplinary team is essential to help patients and their families understand the disease and adhere to treatment. Current cystic fibrosis therapy includes maintaining the nutritional status, clearing the airways with physiotherapy and mucolytics, preventing and treating infections with antibiotics and prescribing energy supplements, high-fat and high-protein diets, as well as minerals and fat-soluble vitamins. The purpose of this study was to present a brief literature review of the clinical and nutritional aspects of cystic fibrosis.

  4. Protective effects of seed melon extract on CCl4-induced hepatic fibrosis in mice.

    Science.gov (United States)

    Zhan, Yuan-Yuan; Wang, Jin-Hui; Tian, Xing; Feng, Shi-Xiu; Xue, Lin; Tian, Li-Ping

    2016-12-04

    Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao, was also known as watermelon belongs to family Cucurbitaceae, variously used as healthy food and in the treatment of liver and lungs problems. Currently, Citrullus lanatus has become a major economic crop of medicinal and edible effects with regional characteristics. This study was designed to evaluate the hepatoprotective and antioxidant activity of the seed melon (Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao) extract (SME) against carbon tetrachloride (CCl4) induced hepatic fibrosis in mice. In this study, mice were randomly divided into 7 groups, including normal control, model, silymarin tablets as the positive control, SME 100, 200, 400, and 800mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), hyaluronic acid (HA) and laminin (LN) were checked. The levels of antioxidant enzymes such as superoxide dismutase (SOD), glutataion (GSH) and glutathione peroxidase (GSH-Px) were determined after SME administration. The hydroxyproline (HYP) levels, malondialdehyde (MDA) levels and histopathologic examinations of hepatocyte fibrosis were also determined. Additionally, effects of SME on alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1(TGF-β1) protein expressions were determined. We found that SME could significantly lower the serum levels of hepatic enzyme markers AST, ALT, HA and LN (P<0.01). Compared with the CCl4-only treatment group, levels of hepatic SOD and GSH-Px were significantly increased, and the MDA levels were remarkably decreased in mice treated by SME at medium dose (400mg/kg) and high dose (800mg/kg) (P<0.01). A histological examination of the liver showed that lesions, including necrosis, lymphocyte infiltration and fatty degeneration, were partially healed by treatment with SME. The results of protein expressions studies displayed that SME could inhibit α-SMA and TGF-β1

  5. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

    Institute of Scientific and Technical Information of China (English)

    Ru-Tao Hong; Jian-Ming Xu; Qiao Mei

    2009-01-01

    AIM:To investigate the protective effects of melatonin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats. METHODS:All rats were randomly divided into normal control group, model control group treated with CCl4 for 12 wk, CCl4 + NAC group treated with CCl4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl4 + MEL-1 group treated with CCl4 + melatonin (2.5 mg/kg) for 12 wk, CCl4 + MEL-2 group treated with CCl4 + melatonin (5.0 mg/kg) for 12 wk, and CCl4 + MEL-3 group treated with CCl4 + melatonin (10 mg/kg). Rats in the treatment groups were injected subcutaneously with sterile CCl4 (3 mL/kg, body weight) in a ratio of 2:3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and protein concentration were measured with routine laboratory methods using an autoanalyzer. Hydroxyproline (HYP) content in liver and malondialdehyde (MDA) and glutathione peroxidase (GPx) levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid (HA), laminin (LN), and procollagen Ⅲ N-terminal peptide (PⅢNP) were determined by radioimmunoassay. RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl4 + MEL3 group than in model control group ( u = 2.172, P < 0.05), indicating that melatonin (10 mg/kg) can significantly ameliorate CCl4-induced hepatic fibrotic changes. The serum levels of ALT and AST were markedly lower in CCl4 + MEL treatment groups (5, 10 mg/kg) than in model control group (ALT:286.23 serum laminin (LN) and hyaluronic acid (HA) levels and hydroxyproline (HYP) contents in liver were significantly lower in CCl4 + MEL-3 group (10

  6. Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Liu; Jian-Lin Wu; Jian Liang; Tao Zhang,; Qing-Shou Sheng

    2012-01-01

    AIM:To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.METHODS:We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals.Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis.A new fibrosis index [globulin/platelet (GP) model] was developed,including globulin (GLOB) and platelet count (PLT).GP model =GLOB (g/mL) x 100/PLT (x 109/L).We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.RESULTS:Thirteen clinical biochemical and hematological variables [sex,age,PLT,alanine aminotransferase,aspartate aminotransferase (AST),albumin,GLOB,total bilirubin (T.bil),direct bilirubin (D.bil),glutamyl transferase,alkaline phosphatase,HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1,F2-F3 and F4).Bivariate Spearman's rank correlation analysis showed that six variables,including age,PLT,T.bil,D.bil,GLOB and PT,were correlated with the three fibrosis stages (FS).Correlation coefficients were 0.23,-0.412,0.208,0.220,0.314 and 0.212; and P value was 0.014,< 0.001,0.026,0.018,0.001 and 0.024,respectively.Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT:F =11.772,P <0.001; GLOB:F =6.612,P =0.002).Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R2 =0.237).By Spearman's rank correlation analysis,GP model was significantly correlated with the three FS (r =0.466,P < 0.001).The median values in F0-F1,F2-F3 and F4 were 1.461,1.720 and 2.634.Compared with the six available models (fibrosis index,AST-platelet ratio,FIB-4,fibrosis-cirrhosis index and age-AST model and age-PLT ratio),GP model showed a highest correlation

  7. Hepatic CEACAM1 Overexpression Protects Against Diet-induced Fibrosis and Inflammation in White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Sumona Ghosh Lester

    2015-08-01

    Full Text Available CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1–/–, C57/BL6J mice fed a high-fat diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by hyperinsulinemia, insulin resistance and visceral obesity. Conversely, forced liver-specific expression of CEACAM1 protected insulin sensitivity and energy expenditure, and limited gain in total fat mass by high-fat diet in L-CC1 mice. Because CEACAM1 protein is barely detectable in white adipose tissue, we herein investigated whether hepatic CEACAM1-dependent insulin clearance pathways regulate adipose tissue biology in response to dietary fat. While high-fat diet caused a similar body weight gain in L-CC1, this effect was delayed and less intense relative to wild-type mice. Histological examination revealed less expansion of adipocytes in L-CC1 than wild-type by high-fat intake. Immunofluorescence analysis demonstrated a more limited recruitment of crown-like structures and qRT-PCR analysis showed no significant rise in TNFα mRNA levels in response to high-fat intake in L-CC1 than wild-type mice. Unlike wild-type, high-fat diet did not activate TGF-β in white adipose tissue of L-CC1 mice, as assessed by Western analysis of Smad2/3 phosphorylation. Consistently, high-fat diet caused relatively less collagen deposition in L-CC1 than wild-type mice, as shown by Trichome staining. Coupled with reduced lipid redistribution from liver to visceral fat, lower inflammation and fibrosis could contribute to protected energy expenditure against high-fat diet in L-CC1 mice. The data underscore the important role of hepatic insulin clearance in the regulation of adipose tissue inflammation and fibrosis.

  8. Histomorphometry of hepatic portal fibrosis in patients with surgical schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Brandt Carlos Teixeira

    2002-01-01

    Full Text Available The usual histology report of hepatic fibrosis in patients with hepatosplenic schistosomiasis mansoni presents no association with hemodynamic and clinical liver parameters. Histomorphometry is adding a new tool of investigation for measuring density of portal fibrosis in these patients. This investigation was set up for assessing a possible agreement between the well-accepted international classification and the fibrosis density grades measured by histomorphometry. Thirty-five children and equal number of adults were included in this study. All patients underwent splenectomy and ligature of the left gastric vein. Histology findings were assessed in surgical liver biopsy stained with Masson trichrome. The official histology report was used as reference. The histomorphometric studies were done by semi-automatic morphometry. The mean percentage (X of portal fibrosis plus or minus one standard deviation (SD was classified as grade II (7.06% up to 34.72%; grade I was up to 7.06%; and grade III above 34.72%. Although, not reaching statistical significance, there is a tendency of the fibrosis to be more intense in children than adults (X±SD - 22.02±13.46% versus 20.63%±15.33% "t" = 0.379 p>0.05. Seven out of nine (77.8% patients classified as grade I, by morphometry, had the same result on the official report, however, two (22.2% were described as grade III. Sixteen out of forty-four (36.4% classified as grade II on morphometry had the same classification as the histology grade, but, twenty seven (61.4% were classified as grade III and one (2.3% as grade I. Fifteen (21.4% out of 70 patients had grade III on both classifications, but, two (11.8% out of seventeen G III on morphometry were grade II. The kappa (k measurement of agreement between both classification was k = 0.319, showing a fair strength of association. The histomorphometric measurements of Symmers fibrosis in surgical patients with mansonic schistosomiasis partially support the report

  9. Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor.

    Science.gov (United States)

    Duan, Xingping; Meng, Qiang; Wang, Changyuan; Liu, Zhihao; Liu, Qi; Sun, Huijun; Sun, Pengyuan; Yang, Xiaobo; Huo, Xiaokui; Peng, Jinyong; Liu, Kexin

    2017-02-15

    Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH. The C57BL/6 male mice were fed with methionine choline deficient (MCD) diet for 4 weeks to induce NASH and treated with or without calycosin by oral gavage for 4 weeks. The body weight, liver weight and the liver to body weight ratios were measured. Serum ALT, AST, TG, TC, FFA, MCP-1 and mKC levels were accessed by biochemical methods. H&E staining and Oil red O staining were used to identify the amelioration of liver histopathology. Immunohistochemistry of a-SMA, Masson trichrome staining and Sirius red staining were used to identify the amelioration of hepatic fibrosis. The quantitative real-time-PCR and Western blot were applied to observe the expression changes of key factors involved in triglyceride synthesis, free fatty acid β-oxidation and hepatic fibrosis. Calycosin significantly inhibited body weight loss induced by MCD diet, decreased the ALT and AST activities, MCP-1 and mKC in a dose-dependent manner. The H&E and Oil red O staining indicated calycosin effectively improved hepatic steatosis, improved the degree of triglyceride accumulation. Masson trichrome and Sirius red staining indicated that calycosin treatment remarkably attenuated the degree of hepatic fibrosis. Immunohistochemistry of a-SMA demonstrated that calycosin attenuated hepatic fibrosis by inhibiting hepatic stellate cell activation. Further, calycosin inhibited the expression of SREBP-1c, FASN, ACC and SCD1 involved in triglyceride synthesis, promoted the expression of PPARa, CPT1, Syndecan-1 and LPL involved in free fatty

  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. Intrahepatic gene expression profiles and alpha-smooth muscle actin patterns in hepatitis C virus induced fibrosis.

    Science.gov (United States)

    Lau, Daryl T-Y; Luxon, Bruce A; Xiao, Shu-Yuan; Beard, Michael R; Lemon, Stanley M

    2005-08-01

    To gain insight into pathogenic mechanisms underlying fibrosis in hepatitis C virus (HCV)-mediated liver injury, we compared intrahepatic gene expression profiles in HCV-infected patients at different stages of fibrosis and alpha-smooth muscle actin (alpha-SMA) staining patterns. We studied 21 liver biopsy specimens: 5 had no fibrosis (Ludwig-Batts stage 0); 10 had early portal or periportal fibrosis (stages 1 and 2); and 6, advanced fibrosis (stages 3 and 4). None of the patients had hepatocellular carcinoma. Transcriptional profiles were determined by high-density oligonucleotide microarrays. ANOVA identified 157 genes for which transcript abundance was associated with fibrosis stage. These defined three distinct hierarchical clusters of patients. Patients with predominantly stage 0 fibrosis had increased abundance of mRNAs linked to glycolipid metabolism. PDGF, a potent stellate cell mitogen, was also increased. Transcripts with increased abundance in stages 1 and 2 fibrosis were associated with oxidative stress, apoptosis, inflammation, proliferation, and matrix degradation, whereas transcripts increased in stages 3 and 4 were associated with fibrogenesis and cellular proliferation. Cells staining for alpha-SMA were detectable at all stages but infrequent in advanced fibrosis without active inflammation. A high frequency of such cells was associated with mRNAs linked to glycolipid metabolism. In conclusion, the presence of alpha-SMA-positive HSCs and expression of PDGF in stage 0 fibrosis suggests that stellate cells are activated early in HCV-mediated injury, possibly in response to oxidative stress resulting from inflammation and lipid metabolism. Increased abundance of transcripts linked to cellular proliferation in advanced fibrosis is consistent with a predisposition to cancer. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index/html).

  12. Progression of liver fibrosis in HIV/hepatitis C virus-coinfected individuals on antiretroviral therapy with early stages of liver fibrosis at baseline.

    Science.gov (United States)

    Sanmartín, R; Tor, J; Sanvisens, A; López, J J; Jou, A; Muga, R; Ojanguren, I; Barluenga, E; Videla, S; Planas, R; Clotet, B; Tural, C

    2014-04-01

    The aim of the study was to assess the progression of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients with no or mild-to-moderate fibrosis (stages F0-F2). Liver fibrosis was reassessed by transient elastometry (TE) between January 2009 and November 2011 in HIV/HCV-coinfected patients with stage F0-F2 fibrosis in a liver biopsy performed between January 1997 and December 2007. Patients with liver stiffness at the end of follow-up < 7.1 kPa were defined as nonprogressors, and those with values ≥ 9.5 kPa or who died from liver disease were defined as progressors. Cirrhosis was defined as a cut-off of 14.6 kPa. The follow-up period was the time between liver biopsy and TE. Cox regression models adjusted for age, gender and liver fibrosis stage at baseline were applied. The median follow-up time was 7.8 years [interquartile range (IQR) 5.5-10 years]. The study population comprised 162 patients [115 (71%) nonprogressors and 47 (29%) progressors; 19 patients (11.7%) had cirrhosis]. The median time from the diagnosis of HCV infection to the end of follow-up was 20 years (IQR 16.3-23.1 years). Three progressors died from liver disease (1.8%). The variables associated with a lower risk of progression were age ≤ 38 years (hazard ratio (HR) 0.32; 95% confidence interval (CI) 0.16-0.62; P = 0.001], having received interferon (HR 2.18; 95% CI 1.14-4.15; P = 0.017), being hepatitis B virus surface antigen (HBsAg) negative (HR 0.20; 95% CI 0.04-0.92; P = 0.039), and baseline F0-F1 (HR 0.43; 95% CI 0.28-0.86; P = 0.017). A high proportion of patients with stage F0-F2 fibrosis progress to advanced liver fibrosis. Advanced liver fibrosis must be included in the list of diseases associated with aging. Our results support the recommendation to offer HCV antiviral therapy to HIV/HCV-coinfected patients at early stages of liver fibrosis. © 2013 British HIV Association.

  13. 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

    PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying...

  14. Integration of VEGF and α-SMA Expression Improves the Prediction Accuracy of Fibrosis in Chronic Hepatitis C Liver Biopsy.

    Science.gov (United States)

    Elzamly, Shaimaa; Agina, Hala A; Elbalshy, Abd El-Latif; Abuhashim, Maha; Saad, Eman; Abd Elmageed, Zakaria Y

    2016-03-17

    The progression of fibrosis in chronic hepatitis C (CHC) is a multifactorial process. The high adverse effects and the cost of standard health care increase the demand to discover new predictors for the progression of fibrosis in CHC patients. Our study aims to establish the relation between the angiogenic marker [vascular endothelial growth factor (VEGF)] and activated hepatic stellate cells (HSCs) represented by the expression of α-smooth muscle actin (α-SMA) and whether these 2 markers can be used as predictors for the progression of fibrosis in patients with CHC. Histopathologic and immunohistochemical analyses were used for examining the morphology and the expression of VEGF and α-SMA in 60 CHC biopsies procured from CHC patients. Multivariate analysis was used to correlate the protein expression with staging and grading of liver fibrosis. Cutoff values of α-SMA and VEGF were determined by the receiver operating characteristics curve. There was a positive correlation between VEGF and HSCs expressing α-SMA (ρ=0.287, P=0.026) and both factors were correlated with the stage of fibrosis (PSMA (area under the curve=0.82, PSMA in CHC biopsies and together can be used as a predictor for the progression of fibrosis.

  15. MicroRNA-29a Alleviates Bile Duct Ligation Exacerbation of Hepatic Fibrosis in Mice through Epigenetic Control of Methyltransferases

    Directory of Open Access Journals (Sweden)

    Ya-Ling Yang

    2017-01-01

    Full Text Available MicroRNA-29 (miR-29 is found to modulate hepatic stellate cells’ (HSCs activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice and wild-type littermates were subjected to bile duct-ligation (BDL to develop cholestatic liver fibrosis. Primary HSCs were transfected with a miR-29a mimic and antisense inhibitor. Profibrogenic gene expression, histone methyltransferases and global genetic methylation were probed with real-time quantitative RT-PCR, immunohistochemical stain, Western blot and ELISA. Hepatic tissue in miR-29aTg mice displayed weak fibrotic matrix as evidenced by Sirius Red staining concomitant with low fibrotic matrix collagen 1α1 expression within affected tissues compared to the wild-type mice. miR-29a overexpression reduced the BDL exaggeration of methyltransferases, DNMT1, DNMT3b and SET domain containing 1A (SET1A expression. It also elevated phosphatase and tensin homolog deleted on chromosome 10 (PTEN signaling within liver tissue. In vitro, miR-29a mimic transfection lowered collagen 1α1, DNMT1, DNMT3b and SET1A expression in HSCs. Gain of miR-29a signaling resulted in DNA hypomethylation and high PTEN expression. This study shines a new light on miR-29a inhibition of methyltransferase, a protective effect to maintain the DNA hypomethylation state that decreases fibrogenic activities in HSC. These robust analyses also highlight the miR-29a regulation of epigenetic actions to ameliorate excessive fibrosis during cholestatic liver fibrosis development.

  16. MicroRNA-29a Alleviates Bile Duct Ligation Exacerbation of Hepatic Fibrosis in Mice through Epigenetic Control of Methyltransferases

    Science.gov (United States)

    Yang, Ya-Ling; Wang, Feng-Sheng; Li, Sung-Chou; Tiao, Mao-Meng; Huang, Ying-Hsien

    2017-01-01

    MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells’ (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis. Primary HSCs were transfected with a miR-29a mimic and antisense inhibitor. Profibrogenic gene expression, histone methyltransferases and global genetic methylation were probed with real-time quantitative RT-PCR, immunohistochemical stain, Western blot and ELISA. Hepatic tissue in miR-29aTg mice displayed weak fibrotic matrix as evidenced by Sirius Red staining concomitant with low fibrotic matrix collagen 1α1 expression within affected tissues compared to the wild-type mice. miR-29a overexpression reduced the BDL exaggeration of methyltransferases, DNMT1, DNMT3b and SET domain containing 1A (SET1A) expression. It also elevated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling within liver tissue. In vitro, miR-29a mimic transfection lowered collagen 1α1, DNMT1, DNMT3b and SET1A expression in HSCs. Gain of miR-29a signaling resulted in DNA hypomethylation and high PTEN expression. This study shines a new light on miR-29a inhibition of methyltransferase, a protective effect to maintain the DNA hypomethylation state that decreases fibrogenic activities in HSC. These robust analyses also highlight the miR-29a regulation of epigenetic actions to ameliorate excessive fibrosis during cholestatic liver fibrosis development. PMID:28106784

  17. Effects of gentiana scabra bage on expression of hepatic typeⅠ,Ⅱ collagen proteins inParagonimus skrjabini rats with liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Zhao-Xia Qu; Fang Li; Chao-Dong Ma; Jun Liu; Shu-De Li; Wen-Lin Wang

    2015-01-01

    Objective:To explore the effects of gentiana scabra bage on the expression of hepatic collagen proteins in Paragonimus skrjabinirats with liver fibrosis.Methods:Immunohistochemical technique was used to observe the changes of content of hepatic type Ⅰ, Ⅱ collagen proteins in Paragonimus skrjabinirats with liver fibrosis before and after the gentiana scabra bage treatmeat. Results:Comparing with the model group, changes of hepatic type Ⅰand type Ⅱ collagen proteins in gentiana scabra bage treated group were significantly weakened.Conclusions:Gentiana scabra bage treatment can reduce the content of hepatic type Ⅱ and typeⅠcollagen protein significantly in Paragonimus skrjabinirats with liver fibrosis, thereby, playing the role against hepatic fibrosis.

  18. Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Sporea, Ioan, E-mail: isporea@umft.ro [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Peck-Radosavljevic, Markus, E-mail: markus.peck@meduniwien.ac.at [Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Sirli, Roxana, E-mail: roxanasirli@gmail.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Tanaka, Hironori, E-mail: hironori@hyo-med.ac.jp [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Iijima, Hiroko, E-mail: hiroko.iijima@nifty.com [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Badea, Radu, E-mail: rbadea2003@yahoo.com [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Lupsor, Monica, E-mail: monica.lupsor@umfcluj.ro [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Fierbinteanu-Braticevici, Carmen, E-mail: cfierbinteanu@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Petrisor, Ana, E-mail: ana1petrisor@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Saito, Hidetsugu, E-mail: hidetsugusaito@gmail.com [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Ebinuma, Hirotoshi, E-mail: ebinuma@a5.keio.jp [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Friedrich-Rust, Mireen, E-mail: Mireen.Friedrich-Rust@kgu.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); Sarrazin, Christoph, E-mail: sarrazin@em.uni-frankfurt.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); and others

    2012-12-15

    Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. Patients and methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5–10 valid measurements, expressed in meters/second – m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6–10 valid measurements, expressed in kiloPascals – kPa). Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r = 0.654) was found between ARFI measurements and fibrosis (p < 0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 – cut-off > 1.19 m/s (AUROC = 0.779), F ≥ 2 – cut-off > 1.33 m/s (AUROC = 0.792), F ≥ 3 – cut-off > 1.43 m/s (AUROC = 0.829), F = 4 – cut-off > 1.55 m/s (AUROC = 0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r = 0.728 vs. 0.689, p = 0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p = 0.01) and fibrosis (F ≥ 1, METAVIR) (p = 0.01). Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

  19. A New Oleanolic Acid Derivative against CCl4-Induced Hepatic Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Hongjun Xiang

    2017-03-01

    Full Text Available A novel hepatoprotective oleanolic acid derivative, 3-oxours-oleana-9(11, 12-dien-28-oic acid (Oxy-Di-OA, has been reported. In previous studies, we found that Oxy-Di-OA presented the anti-HBV (Hepatitis B Virus activity (IC50 = 3.13 µg/mL. Remarkably, it is superior to lamivudine in the inhibition of the rebound of the viral replication rate. Furthermore, Oxy-Di-OA showed good performance of anti-HBV activity in vivo. Some studies showed that liver fibrosis may affiliate with HBV gene mutations. In addition, the anti-hepatic fibrosis activity of Oxy-Di-OA has not been studied. Therefore, we evaluated the protective effect of Oxy-Di-OA against carbon tetrachloride (CCl4-induced liver injury in rats. Daily intraperitoneally administration of Oxy-Di-OA prevented the development of CCl4-induced liver fibrosis, which was evidenced by histological study and immunohistochemical analysis. The entire experimental protocol lasted nine weeks. Oxy-Di-OA significantly suppressed the increases of plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT levels (p < 0.05. Furthermore, Oxy-Di-OA could prevent expression of transforming growth factor β1 (TGF-β1. It is worth noting that the high-dose group Oxy-Di-OA is superior to bifendate in elevating hepatic function. Compared to the model group, Oxy-Di-OA in the high-dose group and low-dose group can significantly reduce the liver and spleen indices (p < 0.05. The acute toxicity test showed that LD50 and a 95% confidence interval (CIs value of Oxy-Di-OA were 714.83 mg/kg and 639.73–798.73 mg/kg via intraperitoneal injection in mice, respectively. The LD50 value of Oxy-Di-OA exceeded 2000 mg/kg via gavage in mice. In addition, a simple and rapid high performance liquid chromatography-ultraviolet (HPLC-UV method was developed and validated to study the pharmacokinetic characteristics of the compound. After single-dose oral administration, time to reach peak concentration of Oxy-Di-OA (Cmax

  20. Effects of augmentation of liver regeneration recombinant plasmid on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Qing Li; Dian-Wu Liu; Li-Mei Zhang; Bing Zhu; Yu-Tong He; Yong-Hong Xiao

    2005-01-01

    AIM: To investigate the effects of eukaryotic expression of plasmid on augmentation of liver regeneration (ALR) in rat hepatic fibrosis and to explore their mechanisms. METHODS: Ten rats were randomly selected from 50Wistar rats as normal control group. The rest were administered intraperitoneally with porcine serum twice weekly. After 8 wk, they were randomly divided into:model control group, colchicine group (Col), first ALR group (ALR1), second ALR group (ALR2). Then colchicine ALR recombinant plasmid were used to treat them respectively. At the end of the 4th wk, rats were killed.Serum indicators were detected and histopathological changes were graded. Expression of type Ⅰ, Ⅲ, collagen and TIMP-1 were detected by immunohisto-chemistry and expression of TIMP-1 mRNA was detected by semiquantified RT-PCR.RESULTS: The histologic examination showed that the degree of the rat hepatic fibrosis in two ALR groups was lower than those in model control group. Compared with model group, ALR significantly reduced the serum levels of ALT,AST, HA, LN, PCⅢ and Ⅳ (P<0.05). Immunohistochemical staining showed that expression of type Ⅰ, Ⅲ, collagen and TIMP-1 in two ALR groups was ameliorated dramatically compared with model group (Ⅰ collagen: 6.94±1.42, 5.80±1.66and 10.83±3.58 in ALR1, ALR2 and model groups, respectively;Ⅲ collagen: 7.18±1.95, 4.50±1.67 and 10.25±2.61,respectively; TIMP-1: 0.39±0.05, 0.20±0.06 and 0.53±0.12,respectively, P<0.05 or P<0.01). The expression level of TIMP-1 mRNA in the liver tissues was markedly decreased in two ALR groups compared with model group (TIMP-1mRNA/β-actin: 0.89±0.08, 0.65±0.11 and 1.36±0.11 in ALR1, ALR2 and model groups respectively, P<0.01).CONCLUSION: ALR recombinant plasmid has beneficial effects on rat hepatic fibrosis by enhancing regeneration of injured liver cells and inhibiting TIMP-1 expressions.

  1. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Jian-Zhao Niu; Ji-Feng Wang; Yu Li; Xiao-Hua Tao

    2005-01-01

    AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension.METHODS: Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type Ⅳ collagen (CoⅣ) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-μm thick sectiors were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated,total protein was extracted and separated by SDS-PAGE.MMP-2 and TIMP-1 protein expression was estimated by Western blotting.RESULTS: The diameter (2.207 ± 0.096 vs 1.528 ± 0.054 mm, P<0.01) and pressure (11.014±0.395 vs 8.533±0.274 mmHg, P<0.01) of portal vein were significantly higher in model group than those in the control group. Plasma HA (129.97±16.10 vs 73.09±2.38 ng/mL, P<0.01), ColⅣ (210.49±4.36 vs 89.65±4.42 ng/mL, P<0.01) and LN (105.00±7.29 vs 55.70±4.32 ng/mL, P<0.01) were upregulated in model group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ.Immunohistochemical staining showed that ColⅣ protein level (0.130±0.007 vs 0.032±0.004, P<0.01) and LN protein level (0.152±0.005 vs 0.029±0.005, P<0.01)were up-regulated remarkably in model group. MMP-2 protein expression (2.306±1.089 vs 0.612±0.081,P<0.01) and TIMP-1 protein expression (3.015±1.364 vs 0.446±0.009, P<0

  2. Liver fibrosis diagnosis by blood test and elastography in chronic hepatitis C: agreement or combination?

    Science.gov (United States)

    Calès, P; Boursier, J; Lebigot, J; de Ledinghen, V; Aubé, C; Hubert, I; Oberti, F

    2017-04-01

    In chronic hepatitis C, the European Association for the Study of the Liver and the Asociacion Latinoamericana para el Estudio del Higado recommend performing transient elastography plus a blood test to diagnose significant fibrosis; test concordance confirms the diagnosis. To validate this rule and improve it by combining a blood test, FibroMeter (virus second generation, Echosens, Paris, France) and transient elastography (constitutive tests) into a single combined test, as suggested by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. A total of 1199 patients were included in an exploratory set (HCV, n = 679) or in two validation sets (HCV ± HIV, HBV, n = 520). Accuracy was mainly evaluated by correct diagnosis rate for severe fibrosis (pathological Metavir F ≥ 3, primary outcome) by classical test scores or a fibrosis classification, reflecting Metavir staging, as a function of test concordance. Score accuracy: there were no significant differences between the blood test (75.7%), elastography (79.1%) and the combined test (79.4%) (P = 0.066); the score accuracy of each test was significantly (P < 0.001) decreased in discordant vs. concordant tests. Classification accuracy: combined test accuracy (91.7%) was significantly (P < 0.001) increased vs. the blood test (84.1%) and elastography (88.2%); accuracy of each constitutive test was significantly (P < 0.001) decreased in discordant vs. concordant tests but not with combined test: 89.0 vs. 92.7% (P = 0.118). Multivariate analysis for accuracy showed an interaction between concordance and fibrosis level: in the 1% of patients with full classification discordance and severe fibrosis, non-invasive tests were unreliable. The advantage of combined test classification was confirmed in the validation sets. The concordance recommendation is validated. A combined test, expressed in classification instead of score, improves this rule and validates the

  3. Symposium 6: Young people, artificial nutrition and transitional care. The nutritional challenges of the young adult with cystic fibrosis: transition.

    LENUS (Irish Health Repository)

    Morton, Alison M

    2012-02-01

    Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120-150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

  4. Quantitative measurement of hepatic fibrosis with gadoxetic acid-enhanced magnetic resonance imaging in patients with chronic hepatitis B infection: A comparative study on aspartate aminotransferase to platelet ratio index and fibrosis-4 index

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Guy Mok; Kim, Youe Ree; Cho, Eun Young; Lee, Young Hwan; Yoon, Kwon Ha [Wonkwang University School of Medicine, Iksan (Korea, Republic of); Ryu, Jong Hyun; Kim, Tae Hoon [Imaging Science Research Center, Wonkwang University, Iksan (Korea, Republic of)

    2017-06-15

    To quantitatively measure hepatic fibrosis on gadoxetic acid-enhanced magnetic resonance (MR) in chronic hepatitis B (CHB) patients and identify the correlations with aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) values. This study on gadoxetic acid-enhanced 3T MR imaging included 81 patients with CHB infection. To quantitatively measure hepatic fibrosis, MR images were analyzed with an aim to identify inhomogeneous signal intensities calculated from a coefficient of variation (CV) map in the liver parenchyma. We also carried out a comparative analysis between APRI and FIB-4 based on metaregression results. The diagnostic performance of the CV map was evaluated using a receiver-operating characteristic (ROC) curve. In the MR images, the mean CV values in control, groups I, II, and III based on APRI were 4.08 ± 0.92, 4.24 ± 0.80, 5.64 ± 1.11, and 5.73 ± 1.28, respectively (p < 0.001). In CHB patients grouped by FIB-4, the mean CV values of groups A, B, and C were 4.22 ± 0.95, 5.40 ± 1.19, and 5.71 ± 1.17, respectively (p < 0.001). The mean CV values correlated well with APRI (r = 0.392, p < 0.001) and FIB-4 (r = 0.294, p < 0.001). In significant fibrosis group, ROC curve analysis yielded an area under the curve of 0.875 using APRI and 0.831 using FIB-4 in HB, respectively. Gadoxetic acid-enhanced MR imaging for calculating a CV map showed moderate correlation with APRI and FIB-4 values and could be employed to quantitatively measure hepatic fibrosis in patients with CHB.

  5. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J

    2015-01-01

    as potential biomarkers for clinically significant and advanced fibrosis. METHODS: Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C......BACKGROUND AND AIM: Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments.......75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88. CONCLUSION: The Pro-C3 protein fragment provided clinically relevant diagnostic accuracy...

  6. Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Miao Chen; Guang-Ji Wang; Yong Diao; Rui-An Xu; Hai-Tang Xie; Xin-Yan Li; Jian-Guo Sun

    2005-01-01

    AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosisin vitro and in vivo.METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-L, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected.RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ,, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group,the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0,458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L,respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13.CONCLUSION: All these results indicated that rAAV-INF-γhas potential effects for gene therapy of hepatic fibrosis,which could inhibit the progression of hepatic fibrosis.

  7. Radiation hepatology of the rat: Association of the production of prostacyclin with radiation-induced hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Geraci, J.P.; Mariano, M.S. [Univ. of Washington, Seattle, WA (United States)

    1996-01-01

    The hypothesis that hepatic fibrosis is preceded by inflammation and formation of prostanoids from arachidonic acid liberated from damaged cell membranes was investigated. Liver slices were prepared using a Krumdieck precision tissue slicer from sham-irradiated rats or from rats whose livers had been irradiated with 25 Gy {sup 137}Cs {gamma} rays in which injury was allowed to develop in vivo for 6 to 55 days. Unused portions of the liver were analyzed for hydroxyproline content to determine hepatic fibrosis. A unique organ culture system was used to incubate liver slices for 2 h. Secretion into the incubation medium of aspartate aminotransferase and 6-keto prostaglandin F{sub 1{alpha}} were measured to quantify damage to the hepatocyte membrane and production of prostacyclin, respectively. A threefold increase in the concentration of 6-keto prostaglandin F{sub 1{alpha}} in the medium was evident by 13 days after irradiation. This elevated concentration of 6-keto prostaglandin F{sub 1{alpha}} persisted for the remainder of the study and preceded fibrosis, as measured by liver hydroxyproline concentration, and hepatocyte membrane damage, as measured by release of aspartate aminotransferase into the incubation medium or plasma. We therefore suggest that, in the nonregenerating liver, damage and breakdown of nonparenchymal liver cell membrane is the principal source of 6-keto prostaglandin F1. These results are also compatible with the supposition that inflammation and release of arachidonic acid metabolites are one of the early biochemical events leading to hepatic fibrosis. How the release of arachidonic acid metabolites might initiate and sustain radiation-induced fibrosis is discussed. An explanation for the difference in liver fibrosis induced by chemicals and radiation is also presented. 30 refs., 5 figs.

  8. Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

    Science.gov (United States)

    Harris, Todd R.; Bettaieb, Ahmed; Kodani, Sean; Dong, Hua; Myers, Richard; Chiamvimonvat, Nipavan; Haj, Fawaz G.; Hammock, Bruce D.

    2015-01-01

    Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl4)-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl4-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl4-treated group relative to the control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl4-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl4, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. PMID:25827057

  9. Graptopetalum paraguayense ameliorates chemical-induced rat hepatic fibrosis in vivo and inactivates stellate cells and Kupffer cells in vitro.

    Directory of Open Access Journals (Sweden)

    Li-Jen Su

    Full Text Available BACKGROUND: Graptopetalum paraguayense (GP is a folk herbal medicine with hepatoprotective effects that is used in Taiwan. The aim of this study was to evaluate the hepatoprotective and antifibrotic effects of GP on experimental hepatic fibrosis in both dimethylnitrosamine (DMN- and carbon tetrachloride (CCl(4-induced liver injury rats. METHODS: Hepatic fibrosis-induced rats were fed with the methanolic extract of GP (MGP by oral administration every day. Immunohistochemistry, biochemical assays, and Western blot analysis were performed. The effects of MGP on the expression of fibrotic markers and cytokines in the primary cultured hepatic stellate cells (HSCs and Kupffer cells, respectively, were evaluated. RESULTS: Oral administration of MGP significantly alleviated DMN- or CCl(4-induced liver inflammation and fibrosis. High levels of alanine transaminase, aspartate transaminase, bilirubin, prothrombin activity and mortality rates also decreased in rats treated with MGP. There were significantly decreased hydroxyproline levels in therapeutic rats compared with those of the liver-damaged rats. Collagen I and alpha smooth muscle actin (α-SMA expression were all reduced by incubation with MGP in primary cultured rat HSCs. Furthermore, MGP induced apoptotic cell death in activated HSCs. MGP also suppressed lipopolysaccharide-stimulated rat Kupffer cell activation by decreasing nitric oxide, tumor necrosis factor-α and interleukin-6 production, and increasing interleukin-10 expression. CONCLUSIONS: The results show that the administration of MGP attenuated toxin-induced hepatic damage and fibrosis in vivo and inhibited HSC and Kupffer cell activation in vitro, suggesting that MGP might be a promising complementary or alternative therapeutic agent for liver inflammation and fibrosis.

  10. Diagnostic value of real-time tissue elastography for liver fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    ZHANG Guosheng

    2014-07-01

    Full Text Available ObjectiveTo investigate the diagnostic value of real-time tissue elastography (RTE in evaluating liver fibrosis in patients with chronic hepatitis B (CHB. MethodsEighty-six patients with CHB, who visited Beijing Tiantan Hospital and Beijing You′an Hospital from March to August, 2013, were grouped according to the pathological stages of liver fibrosis. They were examined by RTE, biochemical tests, and liver biopsy. Then, liver fibrosis index (LFI and aspartate aminotransferase-to-platelet ratio index (APRI were calculated. Comparison between groups was made by one-way analysis of variance, followed by LSD t-test for multiple comparisons. The correlation between LFI and pathological stage of liver fibrosis was analyzed by Spearman correlation test. The sensitivity and specificity of LFI for the diagnosis of liver fibrosis were calculated. Regarding S≥2 (significant liver fibrosis and S≥4 (early liver cirrhosis as the positive standards, the receiver operating characteristic (ROC curve was drawn and compared with APRI. ResultsLFI differed significantly across the groups (P=0.000, except the comparison between S0 and S1 (P=0.298. LFI was significantly correlated with pathological stage (r=0.831, P<0.001. The areas under the ROC curve of LFI in diagnosing significant liver fibrosis and early liver cirrhosis were 0873 (P<0.001 and 0.923 (P=0002, respectively; the diagnostic thresholds were 2.74 and 3.61, respectively; the sensitivity and specificity were 0.766/0.872 and 0.833/0.878, respectively. LFI was significantly superior to APRI. ConclusionRTE has high diagnostic values for significant liver fibrosis and early liver cirrhosis and is an important noninvasive diagnostic method for liver fibrosis in patients with CHB.

  11. The antiproliferative drug doxorubicin inhibits liver fibrosis in bile duct-ligated rats and can be selectively delivered to hepatic stellate cells in vivo

    NARCIS (Netherlands)

    Greupink, R; Bakker, HI; Bouma, W; Reker-Smit, C; Meijer, DKF; Beljaars, L; Poelstra, K

    Hepatic stellate cell (HSC) proliferation is a key event in liver fibrosis; therefore, pharmacological intervention with antiproliferative drugs may result in antifibrotic effects. In this article, the antiproliferative effect of three cytostatic drugs was tested in cultured rat HSC. Subsequently,

  12. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

    NARCIS (Netherlands)

    Doherty, D.; Parisi, M. A.; Finn, L. S.; Gunay-Aygun, M.; Al-Mateen, M.; Bates, D.; Clericuzio, C.; Demir, H.; Dorschner, M.; van Essen, A. J.; Gahl, W. A.; Gentile, M.; Gorden, N. T.; Hikida, A.; Knutzen, D.; Ozyurek, H.; Phelps, I.; Rosenthal, P.; Verloes, A.; Weigand, H.; Chance, P. F.; Dobyns, W. B.; Glass, I. A.

    2010-01-01

    Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spect

  13. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

    NARCIS (Netherlands)

    Doherty, D.; Parisi, M. A.; Finn, L. S.; Gunay-Aygun, M.; Al-Mateen, M.; Bates, D.; Clericuzio, C.; Demir, H.; Dorschner, M.; van Essen, A. J.; Gahl, W. A.; Gentile, M.; Gorden, N. T.; Hikida, A.; Knutzen, D.; Ozyurek, H.; Phelps, I.; Rosenthal, P.; Verloes, A.; Weigand, H.; Chance, P. F.; Dobyns, W. B.; Glass, I. A.

    Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a

  14. RELATIONSHIP OF THE MARKERS OF ENDOTHELIAL DYSFUNCTION AND FIBROSIS IN CHRONIC HEPATITIS AND CIRRHOSIS

    Directory of Open Access Journals (Sweden)

    V. V. Shchekotov

    2014-07-01

    Full Text Available The aim – assessing the relationship of markers of endothelial dysfunction and fibrosis (AF in patients with chronic viral hepatitis and liver cirrhosis (LC.Materials and methods. We examined 40 patients with chronic hepatitis C in the phase of reactivation. The second group included 15 patients with viral CP in stage of decompensation. Using the method of ELISA tests was studied evaluating the functional state of endothelium in the blood serum with a level of total nitrogen oxide (OA, endothelin-1 (ET-1, vascular-endothelial growth factor (VEFR. Evaluated the functional activity of Willebrand factor (WF, calculated the number of desquamated endothelial cells (DETS in blood plasma, determined the level of hyaluronic acid (HA in serum. Established diagnostic sensitivity (Qh, specificity (DS and efficiency (DE of laboratory parameters.Results. In chronic hepatitis (CH found an inverse significant relationship of HA and OA, and direct relationship with Civil ET-1, VEFR, WF, indicating the association of fibrosis with the severity of the damage of the endothelium. Patients with CKD also had a direct correlation between HA and ET-1,VEFR, PV. Ratio of aspartate and alanine aminotransferase (AST/ALT with hCG was associated with OA, ET-1, VEFR, DETS. In patients with CKD significant coefficient de Rytis nteractions with OA, ET-1, VEFR are found. At the point of separating the concentration of SC > 120.0 ng / ml for the diagnosis of CKD has Qh 92 %, FS –76 %, DE – 82 %. In evaluating the operating characteristics of the indicators of endothelial dysfunction capacity of tests to stratify CG and CP were installed, the sensitivity was 73–92 %, specificity – 50–96 %, and efficiency – 69–86 %.Conclusion. CG and CP demonstrated the relationship of indicators of endothelial dysfunction with markers OP – HA, AST/ALT. The results suggest that indicators of endothelial damage may serve as indirect markers of AF.

  15. Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism

    Science.gov (United States)

    Liu, Yu-Kan; Shen, Wei

    2003-01-01

    AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl4-plus ethanol-induced hepatic fibrogenesis in experimental rats. METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl4 and ethanol solution at the beginning of the experiment to induce hepatic fibrosis. The CS group was also treated with CS 10 days after the beginning of CCl4 and ethanol administration. All control groups were given corresponding placebo at the same time. At the end of the 9th week, rats in each group were humanely sacrificed. Blood and tissue specimens were taken. Biochemical, radioimmunological, immunohistochemical and molecular biological examinations were used to determine the level change of ALT, AST, HA, LN content in serum and TGFβ1, PDGF, collagen I and III expression in tissue at either protein or mRNA level or both of them. RESULTS: As compared with the model control group, serum ALT, AST, HA, and LN content levels were markedly dropped in CS group (86.0 ± 34.4 vs 224.3 ± 178.9, 146.7 ± 60.2 vs 272.6 ± 130.1, 202.0 ± 79.3 vs 316.5 ± 94.1 and 50.4 ± 3.0 vs 59.7 ± 9.8, respectively, P 0.05). CONCLUSION: Cordyceps sinensis could inhibit hepatic fibrogenesis derived from chronic liver injury, retard the development of cirrhosis, and notably ameliorate the liver function. Its possible mechanism involves inhibiting TGFβ1 expression, and thereby, down regulating PDGF expression, preventing HSC activation and deposition of procollagen I and III. PMID:12632512

  16. Aspartate aminotransferase-to-platelet ratio index for fibrosis and cirrhosis prediction in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Roberto Gomes da Silva Junior

    2008-02-01

    Full Text Available In chronic hepatitis C (CHC, liver biopsy is the gold standard method for assessing liver histology, however it is invasive and can have complications. Non-invasive markers have been proposed and aspartate aminotransferase (AST-to-platelet ratio index (APRI has been shown as an easy and inexpensive marker of liver fibrosis. This study evaluated the diagnostic performance of APRI for significant fibrosis and cirrhosis prediction in CHC patients. This study included treatment-naive CHC patients who had undergone liver biopsy from January 2000 to August 2006. All histological slides were reviewed according to the METAVIR system. APRI was calculated based on laboratory results performed within four months from the biopsy. Twenty-eight (56% patients had significant fibrosis (F2-F4 and 13 (26% had cirrhosis (F4. The area under ROC curves of APRI for predicting significant fibrosis and cirrhosis were 0.92 (0.83-1.00 and 0.92 (0.85-1.00, respectively. Using cut-off values recommended by prior studies, significant fibrosis could be identified, in accordance with liver biopsy, in 44% and cirrhosis in 66% of patients. APRI could identify significant fibrosis and cirrhosis at a high degree of accuracy in studied patients.

  17. Aspartate aminotransferase-to-platelet ratio index for fibrosis and cirrhosis prediction in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Roberto Gomes da Silva Junior

    Full Text Available In chronic hepatitis C (CHC, liver biopsy is the gold standard method for assessing liver histology, however it is invasive and can have complications. Non-invasive markers have been proposed and aspartate aminotransferase (AST-to-platelet ratio index (APRI has been shown as an easy and inexpensive marker of liver fibrosis. This study evaluated the diagnostic performance of APRI for significant fibrosis and cirrhosis prediction in CHC patients. This study included treatment-naive CHC patients who had undergone liver biopsy from January 2000 to August 2006. All histological slides were reviewed according to the METAVIR system. APRI was calculated based on laboratory results performed within four months from the biopsy. Twenty-eight (56% patients had significant fibrosis (F2-F4 and 13 (26% had cirrhosis (F4. The area under ROC curves of APRI for predicting significant fibrosis and cirrhosis were 0.92 (0.83-1.00 and 0.92 (0.85-1.00, respectively. Using cut-off values recommended by prior studies, significant fibrosis could be identified, in accordance with liver biopsy, in 44% and cirrhosis in 66% of patients. APRI could identify significant fibrosis and cirrhosis at a high degree of accuracy in studied patients.

  18. Response to hepatitis A and B vaccine alone or in combination in patients with chronic hepatitis C virus and advanced fibrosis.

    Science.gov (United States)

    Kramer, Erik Seth; Hofmann, Charlotte; Smith, Paula G; Shiffman, Mitchell L; Sterling, Richard K

    2009-09-01

    Patients with advanced fibrosis are at increased risk of severe outcomes if they develop acute infection with hepatitis A (HAV) or hepatitis B (HBV) viruses. There are no data on the efficacy of combined HAV/HBV vaccination in patients with advanced fibrosis. Our aim was to evaluate the response to the HAV and HBV vaccine alone or in combination for patients with chronic hepatitis C (HCV) and advanced fibrosis and to evaluate the impact of administering the vaccine while patients were receiving peginterferon for treatment of chronic HCV. In this prospective study of patients with advanced fibrosis (Ishak 3-6), those without serologic evidence of prior exposure were vaccinated with either Havrix HAV, Engerix( HBV, or the TWINRIX HAV/HBV combination vaccine as appropriate, and response was defined as the development of anti-HAV or anti-HBV surface antibodies. Of the 162 eligible patients, the prevalence of prior exposure to HAV and HBV was 30 and 18%, respectively. Of the 84 patients vaccinated, 38% received Havrix, 14% Engerix, and 48% TWINRIX. The response to the HAV vaccine was 75% in those receiving Havrix compared to 78% receiving TWINRIX. In contrast, the response to HBV vaccination was 42% in patients receiving Engerix compared to 60% in those vaccinated with TWINRIX (difference 18.3%; OR 0.29; 95% CI: 0.57-7.79). The presence of diabetes was the only risk factor identified for reduced HBV response (P = 0.01). Responses to both HAV and HBV vaccines when administered alone or in combination were lower than expected in patients with HCV and advanced fibrosis, especially in those with diabetes. The observation that the decline in HBV vaccine response was somewhat lower when this was administered alone as opposed to the combination A/B vaccine suggests that the administration of a combination vaccine may enhance the vaccination response to HBV.

  19. Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl4-induced hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Da-Hee Jeong; Gi-Ppeum Lee; Won-Il Jeong; Sun-Hee Do; Hai-Jie Yang; Dong-Wei Yuan; Ho-Yong Park; Kyu-Jong Kim; Kyu-Shik Jeong

    2005-01-01

    AIM: Silymarin is a potent antioxidant, antiinflammatory and anti-fibrogenic agent in the liver, which is mediated by alteration of hepatic Kupffer cell function, lipid peroxidation, and collagen production. Especially, in hepatic fibrogenesis, mast cells are expressed in chronic inflammatory conditions, and promote fibroblast growth and stimulate production of the extracellular matrix by hepatic stellate cells.METHODS: We examined the inhibitory mechanism of silymarin on CCl4-induced hepatic cirrhosis in rats. At 4, 8,and 12 wk, liver tissues were examined histopathologically for fibrotic changes produced by silymarin treatment.RESULTS: In the silymarin with CCl4-treated group,increase of hepatic stellate cells and TGF-β1 production were lower than in the CCl4-treated group at early stages.Additionally, at the late fibrogenic stage, expressions of TGF-β1 were weaker and especially not expressed in hepatocytes located in peripheral areas. Moreover, the number of mast cell in portal areas gradually increased and was dependent on the fibrogenic stage, but those of CCl4+silymarin-treated group decreased significantly.CONCLUSION: Anti-fibrotic and antiinflammatory effects of silymarin were associated with activation of hepatic stellate cells through the expression of TGF-β1 and stabilization of mast cells. These results suggest that silymarin prevent hepatic fibrosis through suppression of inflammation and hypoxia in the hepatic fibrogenesis.

  20. Modulation of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis by olmesartan and omega-3.

    Science.gov (United States)

    Shaaban, Ahmed A; Shaker, Mohamed E; Zalata, Khaled R; El-kashef, Hassan A; Ibrahim, Tarek M

    2014-01-25

    This study was designed to investigate the potential effects of omega-3, olmesartan and their combination on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received subcutaneous injections of CCl4 twice weekly for 12weeks, as well as daily oral treatments of olmesartan (1 and 3mg/kg), omega-3 (75 and 150mg/kg) and their combination during the last 4weeks of intoxication. Our results indicated that omega-3 and, to a lesser extent, olmesartan dose-dependently blunted CCl4-induced necroinflammation scoring and elevation of liver injury parameters in serum. Besides, omega-3 and, to a lesser extent, olmesartan treatments in a dose dependent manner attenuated CCl4-induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both omega-3 and olmesartan were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing α-smooth muscle actin (α-SMA) expression in the liver; (3) inhibiting the proliferation and chemotaxis of HSCs, as evidenced by downregulating platelet-derived growth factor receptors-β (PDGFR-β) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting the secretion of transforming growth factor-β1 (TGF-β1). Unexpectedly, when olmesartan was co-administered with omega-3, it interfered with the hepatoprotective and anti-fibrotic activities of omega-3. In conclusion, this study introduces the first evidence regarding the pronounced anti-fibrotic activity of omega-3 and suggests that it may be beneficial in the treatment of hepatic fibrosis in humans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Evolutionary-driven support vector machines for determining the degree of liver fibrosis in chronic hepatitis C.

    Science.gov (United States)

    Stoean, Ruxandra; Stoean, Catalin; Lupsor, Monica; Stefanescu, Horia; Badea, Radu

    2011-01-01

    Hepatic fibrosis, the principal pointer to the development of a liver disease within chronic hepatitis C, can be measured through several stages. The correct evaluation of its degree, based on recent different non-invasive procedures, is of current major concern. The latest methodology for assessing it is the Fibroscan and the effect of its employment is impressive. However, the complex interaction between its stiffness indicator and the other biochemical and clinical examinations towards a respective degree of liver fibrosis is hard to be manually discovered. In this respect, the novel, well-performing evolutionary-powered support vector machines are proposed towards an automated learning of the relationship between medical attributes and fibrosis levels. The traditional support vector machines have been an often choice for addressing hepatic fibrosis, while the evolutionary option has been validated on many real-world tasks and proven flexibility and good performance. The evolutionary approach is simple and direct, resulting from the hybridization of the learning component within support vector machines and the optimization engine of evolutionary algorithms. It discovers the optimal coefficients of surfaces that separate instances of distinct classes. Apart from a detached manner of establishing the fibrosis degree for new cases, a resulting formula also offers insight upon the correspondence between the medical factors and the respective outcome. What is more, a feature selection genetic algorithm can be further embedded into the method structure, in order to dynamically concentrate search only on the most relevant attributes. The data set refers 722 patients with chronic hepatitis C infection and 24 indicators. The five possible degrees of fibrosis range from F0 (no fibrosis) to F4 (cirrhosis). Since the standard support vector machines are among the most frequently used methods in recent artificial intelligence studies for hepatic fibrosis staging, the

  2. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Wai-Kay Seto

    Full Text Available OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5% HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥ 7 or fibrosis score ≥ 3. There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women and patients with a normal ALT but exceeding the Prati criteria (p = 0.024. Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively. HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively. An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345 and -negative (p = 0.544 disease. There was no significant difference in fibrosis staging among ALT 1-2 × upper limit of normal (ULN and > × 2 ULN for both HBeAg-positive (p = 0.098 and -negative (p = 0.838 disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.

  3. Serum NX-DCP as a New Noninvasive Model to Predict Significant Liver Fibrosis in Chronic Hepatitis C.

    Science.gov (United States)

    Saito, Masaya; Yano, Yoshihiko; Hirano, Hirotaka; Momose, Kenji; Yoshida, Masaru; Azuma, Takeshi

    2015-02-01

    Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.

  4. The study of the effect of adefovir on the liver function and fibrosis state for patients with hepatitis B cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Nian-Xia Sun

    2016-01-01

    Objective:To explore the effect of adefovir on liver function and fibrosis index, HBV-DNA, portal vein diameter and the thickness of spleen for patients with hepatitis B cirrhosis. Methods: A total of 102 cases of hepatitis Bcirrhosisin thedepartment of our hospital from April 2013 to November 2015 were chosen. According to the admission of the order number, the odd number was as the control group, and the even number was as the observation group, 51 cases in each group. The two groups of patients were given with conventional liver treatment, on the basis of the treatment, the control group was treated with lamivudine, the observation group was taken with oral adefovir dipivoxil tablets therapy, and the treatment period was six months. The changes of liver function, liver fibrosis, serum HBV-DNA level, portal vein diameter, thickness variation spleen for the two groups before and after treatment were taken for statistical analysis.Results: The alanine aminotransferase (ALT) and total bilirubin (TBIL), serum albumin (ALB), prothrombin activity (PTA) of liver function before treatment were without significant differences. The hepatic fibrosis hyaluronidase (HA), laminin (LN),Type IV collagen (IV-C) and type III procollagen (PCIII) were compared, there were no statistical differences; serum HBV-DNA and portal vein diameter, thickness of spleen had no significant difference. Compared after treatment, the ALT and TBIL in the observation group were significantly decreased compared with the control group, ALB, PTA were significantly increased, the differences were significant. The HA, LN, IV-C of fibrosis markers and PCIII in the observation group were lower compared with control group, the differences were with statistical significance. The serum HBV-DNA negative rate in the observation group was significantly higher than the control group, there were significant differences. The portal vein diameter, thickness of spleen in the observation group after treatment were

  5. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    OpenAIRE

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Marina B Klein

    2015-01-01

    Background.  Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamiv...

  6. Diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B: a meta-analysis of diagnostic test.

    Science.gov (United States)

    Yin, Zhi; Zou, Jin; Li, Qiongxuan; Chen, Lizhang

    2017-01-02

    This study is aimed at evaluating the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B through a meta-analysis of diagnostic test. We conducted a comprehensive search in the Pubmed, Embase, Web of Science, and Chinese National Knowledge Infrastructure before October 31, 2016. Stata 14.0 software was used for calculation and statistical analyses. We used the sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CIs) to evaluate the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B. Twenty-six studies were included in the final analyses, with a total of 8274 individuals. The pooled parameters are calculated from all studies: sensitivity of 0.69 (95%CI:0.63-0.75), specificity of 0.81 (95%CI: 0.73-0.87), PLR of 3.63 (95%CI:2.66-4.94), NLR of 0.38 (95%CI:0.32-0.44), DOR of 9.57 (95%CI: 6.67-13.74), and area under the curve (AUC) of 0.80 (95%CI: 0.76-0.83). We also conducted subgroup based on the range of cut-off values. Results from subgroup analysis showed that cut-off was the source of heterogeneity in the present study. The sensitivity and specificity of cut-off>2 were 0.69 and 0.95 with the AUC of 0.90 (95%CI: 0.87-0.92). The overall diagnostic value of FIB-4 is not very high for liver fibrosis in patients with hepatitis B. However, the diagnostic value is affected by the cut-off value. FIB-4 has relatively high diagnostic value for detecting liver fibrosis in patients with hepatitis B when the diagnostic threshold value is more than 2.0.

  7. Coefficient of Variance as Quality Criterion for Evaluation of Advanced Hepatic Fibrosis Using 2D Shear-Wave Elastography.

    Science.gov (United States)

    Lim, Sanghyeok; Kim, Seung Hyun; Kim, Yongsoo; Cho, Young Seo; Kim, Tae Yeob; Jeong, Woo Kyoung; Sohn, Joo Hyun

    2017-08-14

    To compare the diagnostic performance for advanced hepatic fibrosis measured by 2D shear-wave elastography (SWE), using either the coefficient of variance (CV) or the interquartile range divided by the median value (IQR/M) as quality criteria. In this retrospective study, from January 2011 to December 2013, 96 patients, who underwent both liver stiffness measurement by 2D SWE and liver biopsy for hepatic fibrosis grading, were enrolled. The diagnostic performances of the CV and the IQR/M were analyzed using receiver operating characteristic curves with areas under the curves (AUCs) and were compared by Fisher's Z test, based on matching the cutoff points in an interactive dot diagram. All P values less than 0.05 were considered significant. When using the cutoff value IQR/M of 0.21, the matched cutoff point of CV was 20%. When a cutoff value of CV of 20% was used, the diagnostic performance for advanced hepatic fibrosis ( ≥ F3 grade) with CV of less than 20% was better than that in the group with CV greater than or equal to 20% (AUC 0.967 versus 0.786, z statistic = 2.23, P = .025), whereas when the matched cutoff value IQR/M of 0.21 showed no difference (AUC 0.918 versus 0.927, z statistic = -0.178, P = .859). The validity of liver stiffness measurements made by 2D SWE for assessing advanced hepatic fibrosis may be judged using CVs, and when the CV is less than 20% it can be considered "more reliable" than using IQR/M of less than 0.21. © 2017 by the American Institute of Ultrasound in Medicine.

  8. Soluble CD163 and mannose receptor associate with chronic hepatitis B activity and fibrosis and decline with treatment.

    Science.gov (United States)

    Laursen, Tea Lund; Wong, Grace Lai-Hung; Kazankov, Konstantin; Sandahl, Thomas; Møller, Holger Jon; Hamilton-Dutoit, Stephen; George, Jacob; Chan, Henry Lik-Yuen; Grønbaek, Henning

    2017-06-15

    Liver macrophages are activated in chronic hepatitis B virus (CHB) infection and play a pivotal role in hepatic inflammation and fibrosis. However, their role during anti-viral treatment is unclear. The soluble (s) macrophage activation markers, sCD163 and mannose receptor (sMR), are released during liver damage and their serum levels reflect liver disease severity and portal hypertension. We aimed to investigate associations between sCD163 and sMR and histopathological activity and fibrosis, and changes in sCD163, sMR and hepatic CD163-expression following anti-viral treatment in CHB patients. We assessed Ishak histological necroinflammatory activity and fibrosis scores in liver biopsies from 254 CHB patients, and serially in 71 patients before and after nucleoside-analogue treatment. Liver CD163-expression was semi-quantitatively determined by immunohistochemistry and serum sCD163 and sMR measured by ELISA. Before treatment, the mean levels of sCD163 and sMR were 3.57 (SD 1.72) mg L(-1) and 0.35 (0.12) mg L(-1) . sCD163 and sMR increased with histological inflammatory activity (sCD163: r=0.46, pCD163-expression (p=0.0002). The macrophage activation markers sCD163 and sMR were associated with activity and fibrosis in liver biopsies from CHB patients. Both serum markers decreased with anti-viral treatment, along with decreased hepatic CD163 expression. This article is protected by copyright. All rights reserved.

  9. Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to investigate the effect of paeoniflorin (PAE)on hepatic fibrosis of mice with Schistosomiasis japonica in vivo and in vitro,a model of hepatic fibrosis caused by schistosomiasis was established in mice infected with cercariae of Schistosomajaponicum.Then,PAE was orally administered before and after praziquantel treatment and both therapeutics were given simultaneously at different time points after the infection.The concentration of serum hyaluronic acid(HA)was determined by radioimmunoassay(RIA).Hepatic granuloma and fibrosis were evaluated via HE and Masson staining.The expression of s-smooth muscle actin(α-SMA),transforming growth factor 131(TGF-β1)and collagen I(Col Ⅰ)protein was detected by immunohistochemistry.The effect of soluble egg antigen(SEA)and PAE on the production of TGF-131 from mouse peritoneal macrophages (PMφs)was investigated by RT-PCR,Western blotting and ELISA.The effect of TGF-β1 in optimum macrophage-conditioned medium(OPMCM)on the proliferation of hepatic stellate cells(HSCs)and collagen secretion from HSCs with anti-TGF-β1 antibody was explored by MTT assay and ELISA.The results show that PAE could significantly reduce the concentration of serum HA,the size of egg granuloma,the severity of hepatic fibrosis and the expression of α-SMA,TGF-β1 and Col I protein in the pre-treatment group.However,in sim-or post-treatment group,PAE did not have any significant therapeutic effect.TGF-β1 could be secreted from PMφs stimulated by SEA.Meanwhile,the production of TGF-β1 from PMφs could be depressed significantly by PAE in a concentration-dependent manner.TGF-β1 could promote the proliferation of HSCs and the secretion of collagens.In a word,PAE can prevent hepatic granuloma and fibrosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-β1 from PMφs,the proliferation and activation of HSCs and the secretion of collagens from HSCs.

  10. In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis.

    Science.gov (United States)

    Rezvani, Milad; Español-Suñer, Regina; Malato, Yann; Dumont, Laure; Grimm, Andrew A; Kienle, Eike; Bindman, Julia G; Wiedtke, Ellen; Hsu, Bernadette Y; Naqvi, Syed J; Schwabe, Robert F; Corvera, Carlos U; Grimm, Dirk; Willenbring, Holger

    2016-06-02

    Liver fibrosis, a form of scarring, develops in chronic liver diseases when hepatocyte regeneration cannot compensate for hepatocyte death. Initially, collagen produced by myofibroblasts (MFs) functions to maintain the integrity of the liver, but excessive collagen accumulation suppresses residual hepatocyte function, leading to liver failure. As a strategy to generate new hepatocytes and limit collagen deposition in the chronically injured liver, we developed in vivo reprogramming of MFs into hepatocytes using adeno-associated virus (AAV) vectors expressing hepatic transcription factors. We first identified the AAV6 capsid as effective in transducing MFs in a mouse model of liver fibrosis. We then showed in lineage-tracing mice that AAV6 vector-mediated in vivo hepatic reprogramming of MFs generates hepatocytes that replicate function and proliferation of primary hepatocytes, and reduces liver fibrosis. Because AAV vectors are already used for liver-directed human gene therapy, our strategy has potential for clinical translation into a therapy for liver fibrosis.

  11. HuR contributes to Hepatic Stellate Cell activation and liver fibrosis

    Science.gov (United States)

    Woodhoo, A.; Iruarrizaga-Lejarreta, M.; Beraza, N.; García-Rodríguez, J.L.; Embade, N.; Fernández-Ramos, D.; Matinez-Lopez, N.; Gutiérrez, Virginia; Arteta, B.; Caballeria, J.; Lu, S.C.; Mato, J.M.; Varela-Rey, M.; Martinez-Chantar, M.L.

    2012-01-01

    RNA-binding proteins (RBPs) play a major role in control of mRNA turnover and translation rates. We examined the role of the RBP human antigen R (HuR) during cholestatic liver injury and hepatic stellate cells (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and α-SMA (α-smooth muscle actin) expression. HuR expression increased in activated HSC from BDL mice and during HSC activation in vitro, and HuR silencing markedly reduced HSC activation. HuR regulated platelet-derived growth factor (PDGF)-induced proliferation and migration, and controlled expression of several mRNAs involved in these processes (Actin, MMP9, Cyclin D1 and B1). These functions of HuR were linked to its abundance and cytoplasmic localisation, controlled by PDGF, via ERK and PI3K activation, and ERK-LKB1 activation respectively. More importantly, we identified the tumor suppressor LKB1 as a novel downstream target of PDGF-induced ERK activation in HSC. HuR also controlled transforming growth factor beta (TGF-β-induced profibrogenic actions by regulating expression of TGF-β, α-SMA, and p21. This was likely due to an increased cytoplasmic localisation of HuR, controlled by TGF-β-induced p38 MAPK activation. Finally, we found that HuR and LKB1 (Ser428) levels were highly expressed in activated HSC in human cirrhotic samples. Conclusion: Our results show that HuR is important for pathogenesis of liver fibrosis development in the cholestatic injury model, for HSC activation, and for the response of activated HSC to PDGF and TGF-β. PMID:22576182

  12. Hepatic fibrosis in patients with chronic hepatitis C assessed by transient elastography: implications for determining the efficacy of antiviral therapy Evaluación de la fibrosis hepática en pacientes con hepatopatía crónica C mediante elastografía transitoria: implicaciones para determinar la eficacia del tratamiento antiviral

    Directory of Open Access Journals (Sweden)

    J. Mendoza

    2010-07-01

    Full Text Available Background: the efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC is well established; moreover, it is able to arrest or even reverse liver fibrosis. Aims: to analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE in patients who underwent a sustained virological response (SVR during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients. Material and methods: after hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE. Results: of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3 in two and mild fibrosis (stage 1 in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88% patients, whereas in the non-responder it improved in only 4 (25% (p < 0.05. The difference between development of severe fibrosis (F ≥ 3 in responders and non-responders was not significant (p = 0.23, possibly due to the small sample size. Conclusions: regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a

  13. Expression of scavenger receptor‐AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis

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    Labonte, Adam C.; Sung, Sun‐Sang J.; Jennelle, Lucas T.; Dandekar, Aditya P.

    2016-01-01

    The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood. In this report, we demonstrate that expression of C‐type lectin receptor scavenger receptor‐AI (SR‐AI) is crucial for promoting M2‐like Mϕ activation and polarization during hepatic inflammation. Liver Mϕ uniquely up‐regulated SR‐AI during hepatotropic viral infection and displayed increased expression of alternative Mϕ activation markers, such as YM‐1, arginase‐1, and interleukin‐10 by activation of mer receptor tyrosine kinase associated with inhibition of mammalian target of rapamycin. Expression of these molecules was reduced on Mϕ obtained from livers of infected mice deficient for the gene encoding SR‐AI (msr1). Furthermore, in vitro studies using an SR‐AI‐deficient Mϕ cell line revealed impeded M2 polarization and decreased phagocytic capacity. Direct stimulation with virus was sufficient to activate M2 gene expression in the wild‐type (WT) cell line, but not in the knockdown cell line. Importantly, tissue damage and fibrosis were exacerbated in SR‐AI–/– mice following hepatic infection and adoptive transfer of WT bone‐marrow–derived Mϕ conferred protection against fibrosis in these mice. Conclusion: SR‐AI expression on liver Mϕ promotes recovery from infection‐induced tissue damage by mediating a switch to a proresolving Mϕ polarization state. (Hepatology 2017;65:32‐43). PMID:27770558

  14. MiR-21 simultaneously regulates ERK1 signaling in HSC activation and hepatocyte EMT in hepatic fibrosis.

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    Juan Zhao

    Full Text Available BACKGROUND: MicroRNA-21 (miR-21 plays an important role in the pathogenesis and progression of liver fibrosis. Here, we determined the serum and hepatic content of miR-21 in patients with liver cirrhosis and rats with dimethylnitrosamine-induced hepatic cirrhosis and examined the effects of miR-21 on SPRY2 and HNF4α in modulating ERK1 signaling in hepatic stellate cells (HSCs and epithelial-mesenchymal transition (EMT of hepatocytes. METHODS: Quantitative RT-PCR was used to determine miR-21 and the expression of SPRY2, HNF4α and other genes. Immunoblotting assay was carried out to examine the expression of relevant proteins. Luciferase reporter assay was performed to assess the effects of miR-21 on its predicted target genes SPRY2 and HNF4α. Primary HSCs and hepatocytes were treated with miR-21 mimics/inhibitors or appropriate adenoviral vectors to examine the relation between miR-21 and SPRY2 or HNF4α. RESULTS: The serum and hepatic content of miR-21 was significantly higher in cirrhotic patients and rats. SPRY2 and HNF4α mRNA levels were markedly lower in the cirrhotic liver. MiR-21 overexpression was associated with enhanced ERK1 signaling and EMT in liver fibrosis. Luciferase assay revealed suppressed SPRY2 and HNF4α expression by miR-21. Ectopic miR-21 stimulated ERK1 signaling in HSCs and induced hepatocyte EMT by targeting SPRY2 or HNF4α. Downregulating miR-21 suppressed ERK1 signaling, inhibited HSC activation, and blocked EMT in TGFβ1-treated hepatocytes. CONCLUSIONS: MiR-21 modulates ERK1 signaling and EMT in liver fibrosis by regulating SPRY2 and HNF4α expression. MiR-21 may serve as a potentially biomarker as well as intervention target for hepatic cirrhosis.

  15. Immunological status does not influence hepatitis c virus or liver fibrosis in HIV-hepatitis C virus-coinfected patients.

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    Collazos, Julio; Cartón, José Antonio; Asensi, Víctor

    2011-04-01

    The possible effects on liver fibrosis and HCV viral load of the immunological status of HIV-HCV-coinfected patients are unclear. A cohort of HIV-HCV-coinfected patients was divided according to the current CD4 counts into poor (≤200/μl, n = 117) or good (≥500/μl, n = 441) immunological status. The groups were compared for diverse HCV- and fibrosis-related parameters. Fibrosis was evaluated by transient elastometry and other noninvasive indexes. Many variables were significantly associated with the immunological status in univariate analyses, including fibrosis parameters. However, in multivariate analyses current immunological status or nadir CD4 were not associated with HCV viral load (p = 0.8 and p = 0.3, respectively), liver fibrosis at the time of evaluation (p = 0.9 for both), or fibrosis progression over time (p = 0.98 and p = 0.8, respectively). The factors independently associated with significant fibrosis, advanced fibrosis, and cirrhosis, as compared with minimal or no fibrosis, were alcohol abuse [OR 3.57 (95% CI 1.43-8.85), p = 0.006; OR 10.10 (3.75-27.03), p Immunological status did not associate with any fibrosis stage (significant fibrosis, p = 0.7; advanced fibrosis, p = 0.4; and cirrhosis p = 0.9). The current or past immunological status of HIV-HCV-coinfected patients does not seem to have any significant influence on HCV viral load or on the development of liver fibrosis when adjusting for important covariates.

  16. Ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on the stage of liver fibrosis: the first pediatric study.

    Science.gov (United States)

    Sobaniec-Lotowska, Maria Elzbieta Sobaniec-Lotowska; Lotowska, Joanna Maria; Lebensztejn, Dariusz Marek

    2007-06-07

    To investigate the ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on their location in areas of collagen fibroplasia. Morphological investigations were conducted on biopsy material obtained from 40 children, aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells, the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells, i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

  17. Ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on the stage of liver fibrosis: The first pediatric study

    Institute of Scientific and Technical Information of China (English)

    Maria Elzbieta Sobaniec-Lotowska; Joanna Maria Lotowska; Dariusz Marek Lebensztejn

    2007-01-01

    AIM: To investigate the ultrastructure of oval ceils in children with chronic hepatitis B, with special emphasis on their location in areas of collagen fibroplasia.METHODS: Morphological investigations were conducted on biopsy material obtained from 40 children,aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis.RESULTS: Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells, the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells, i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells.CONCLUSION: We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

  18. Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

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    Costa Luciano Bello

    2002-01-01

    Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

  19. Presentation of an infant with nutritional deficiency dermatitis as the initial manifestation of cystic fibrosis

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    Stojković Anđelka

    2013-01-01

    Full Text Available Introduction. Cystic fibrosis (CF is a multisystemic autosomal recessive disease most frequently recognized by characteristic respiratory and/or digestive manifestations. Exceptionally rare, as is the case with the infant we are presenting, the initial sign of the disease can be nutritional deficiency dermatitis (NDD. Case Outline. A three-month-old male infant of young and healthy non-consanguineous parents, born at term after the first uneventful pregnancy, was hospitalized due to atopic dermatitis (AD-like skin changes, failure to thrive and normochromic anemia (Hb 60 g/L. As exclusively breast-fed, failure to thrive was attributed to hypogalactia and skin changes to nutritional allergy, so that, besides exclusion of cow’s milk protein and other highly allergenic foods in mother’s diet, hypoallergenic milk formula was added to the child’s diet. However, dietetic measures were without effect, and the child was re-hospitalized at age 4.5 months, this time in the condition of severe malnutrition with hypoproteinemic edemas, extensive dermatitis, moderate hepatosplenomegaly and recurrent normochromic anemia (Hb 57 g/L. After plasma-free erythrocyte transfusion, correction of hypoalbuminemia and two-week parenteral and semi-elementary nutrition resulted in gradual recovery of the child, also including the resolution of skin changes. Having in mind the clinical course of the disease, as well as the response to applied therapeutic measures, CF was suspected as the cause of the child’s problems, which was also confirmed by a high level of sweat chlorine (92 mmol/L and DNA analysis (∆F508/∆F508. Conclusion. Our experience indicates that NDD, as the initial manifestation of CF, should be also kept in mind in differential diagnosis of the infant’s AD-like changes.

  20. Clinical Observation of the Effect of Xuesaitong Soft Capsule (血塞通软胶囊)on Post-hepatitis Fibrosis

    Institute of Scientific and Technical Information of China (English)

    DENG Yin-quan; FAN Xiao-fen; Li You-di

    2005-01-01

    Objective:To study the effect of Xuesaitong soft capsule (血塞软胶囊, XST) on liver fibrosis criteria in patients with post-hepatitis fibrosis. Methods: Sixty-four patients with such fibrosis were randomly divided into the treated group and control group. They were treated with XST and Dahuang Zheter treatment. Results: The levels of serum procollagen Ⅲ, hyaluronic acid, collagen Ⅳ, laminin in the two groups were significantly lower (P<0.01) than those before treatment. The differences between the two groups were insignificant (P>0.05). Conclusion: XST could recover liver dysfunction and had anti-liver fibrosis function.

  1. Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

    2015-05-26

    Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Hepatic arteriolo-portal venular shunting guarantees maintenance of nutritional microvascular supply in hepatic arterial buffer response of rat livers.

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    Richter, S; Vollmar, B; Mücke, I; Post, S; Menger, M D

    2001-02-15

    To elucidate the hepatic microvascular response upon the hepatic arterial buffer response (HABR), we analysed blood flow (ultrasonic flowprobes) of the hepatic artery (HA) and portal vein (PV), microcirculation (intravital microscopy), and tissue oxygenation (polarography) in anaesthetized Sprague-Dawley rats and re-evaluated the role of adenosine in mediating the HABR by using 8-phenyltheophylline as a competitive antagonist. 2. Upon restriction of PV blood flow to 11 +/- 3 % of baseline values, HA blood flow increased by a factor of 1.77 (P portal venules (TPVs) decreased to only 66 % (P portal venular shunting. As a consequence, red blood cell velocity and volumetric blood flow in sinusoids were found to be reduced to only 66-68 % compared with baseline (P oxygen delivery, despite the marked reduction of total liver blood flow. Further, hepatic arteriolo-portal venular shunting guaranteed homogeneity of nutritive blood flow upon HABR, as given by an unchanged intra-acinar coefficient of variance of sinusoidal perfusion. 4. Pretreatment of animals with the adenosine antagonist 8-phenyltheophylline completely blocked the hepatic arterial buffer response with the consequence of decreased tissue oxygenation and increased heterogeneity of sinusoidal perfusion. 5. In conclusion, hepatic microhaemodynamics, in particular unchanged diameters of THAs, TPVs and sinusoids, during HABR indicate that reduction in resistance to HA flow is located upstream and functions via hepatic arteriolo-portal venular shunts resulting in equal distribution of microvascular blood flow and oxygen delivery under conditions of restricted PV blood supply.

  3. Is portal vein cavernous transformation a component of congenital hepatic fibrosis?

    Institute of Scientific and Technical Information of China (English)

    Ozlem Yonem; Yusuf Bayraktar

    2007-01-01

    Congenital hepatic fibrosis (CHF) is an autosomal recessive disorder that belongs to the family of fibropolycystic liver diseases. This family includes a spectrum of disorders which are usually found in combination with each other and are usually inherited.Clinically fibropolycystic diseases have three effects being present in different proportions, those of a space occupying lesion, of portal hypertension and of cholangitis. In most patients, the first manifestations of CHF are signs and symptoms related to portal hypertension such as splenomegaly and varices. Portal hypertension in these patients has been attributed to the hypoplasia or compression of the portal vein radicles in the fibrous bands. Cavernous transformation of the portal vein (CTPV) is a relatively rare condition resulting from extrahepatic portal vein obstruction with recanalization or collateral vein formation to bypass the obstruction. It has been found that patients with CHF having an accompanying CTPV have relatively large splenomegaly and suffers more frequent episodes of bleeding from esophageal varices. We believe that CTPV is a congenital component of CHF and also one of the important causative factors of portal hypertension in these patients.

  4. Modulation of IKKβ/NF-κB and TGF-β1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice

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    Rong-Qi Wang

    2015-04-01

    Conclusion: FZHY-containing therapies prevented nutritional steatohepatitis and fibrosis through modulating the expression of factors associated with the IKKβ/NF-κB and TGF-β1/Smad signaling pathways and oxidative stress related genes.

  5. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis.

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    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.

  6. Hepatocyte expression of minichromosome maintenance protein-2 predicts fibrosis progression after transplantation for chronic hepatitis C virus: a pilot study.

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    Marshall, Aileen; Rushbrook, Simon; Morris, Lesley S; Scott, Ian S; Vowler, Sarah L; Davies, Susan E; Coleman, Nicholas; Alexander, Graeme

    2005-04-01

    Although graft infection with hepatitis C virus (HCV) occurs in virtually all patients transplanted for HCV-related liver disease, the outcome ranges from minimal disease to the rapid development of cirrhosis. Induction of hepatocyte cell cycle entry followed by inhibition of cell cycle progression has been proposed as a potential mechanism whereby HCV may cause hepatocyte dysfunction and may promote fibrogenesis. The aim of this study was to assess whether early hepatocyte cell cycle entry might predict subsequent fibrosis progression in patients with graft HCV infection after liver transplantation. Liver biopsies from 21 liver transplant recipients diagnostic of graft HCV infection but before development of significant fibrosis were studied. Patients were classed as nonprogressors, intermediate progressors, or rapid progressors according to the rate of fibrosis progression calculated from the most recent biopsy. Minichromosome maintenance protein 2 (Mcm-2), a highly sensitive and specific marker of cell cycle entry, and cyclin-dependent kinase inhibitor p21 were detected by immunohistochemistry. Hepatocyte Mcm-2 expression increased significantly according to rate of fibrosis. For nonprogressors, the median percentage of positive hepatocytes was 5.3% (range, 0.92%-11.2%) compared with 20.7% (4.6%-43.7%) in intermediate progressors and 23.7% (11.6%-55.2%) in rapid progressors (P = 0.002). By contrast, there was no evidence of a difference in hepatocyte p21 expression. Median values and ranges were 3.4% (range, 1.1%-30%), 13.3% (range, 1.4%-42.3%), and 11.8% (range, 7.6%-52.3%) for nonprogressors, intermediate progressors, and rapid progressors, respectively (P = 0.11). In conclusion, hepatocyte cell cycle entry may be important in the pathogenesis of posttransplant HCV hepatitis. Early assessment of hepatocyte Mcm-2 expression could help identify patients at high risk for progressive fibrosis before it occurs.

  7. Deregulation of energy metabolism promotes antifibrotic effects in human hepatic stellate cells and prevents liver fibrosis in a mouse model.

    Science.gov (United States)

    Karthikeyan, Swathi; Potter, James J; Geschwind, Jean-Francois; Sur, Surojit; Hamilton, James P; Vogelstein, Bert; Kinzler, Kenneth W; Mezey, Esteban; Ganapathy-Kanniappan, Shanmugasundaram

    2016-01-15

    Liver fibrosis and cirrhosis result from uncontrolled secretion and accumulation of extracellular matrix (ECM) proteins by hepatic stellate cells (HSCs) that are activated by liver injury and inflammation. Despite the progress in understanding the biology liver fibrogenesis and the identification of potential targets for treating fibrosis, development of an effective therapy remains elusive. Since an uninterrupted supply of intracellular energy is critical for the activated-HSCs to maintain constant synthesis and secretion of ECM, we hypothesized that interfering with energy metabolism could affect ECM secretion. Here we report that a sublethal dose of the energy blocker, 3-bromopyruvate (3-BrPA) facilitates phenotypic alteration of activated LX-2 (a human hepatic stellate cell line), into a less-active form. This treatment-dependent reversal of activated-LX2 cells was evidenced by a reduction in α-smooth muscle actin (α-SMA) and collagen secretion, and an increase in activity of matrix metalloproteases. Mechanistically, 3-BrPA-dependent antifibrotic effects involved down-regulation of the mitochondrial metabolic enzyme, ATP5E, and up-regulation of glycolysis, as evident by elevated levels of lactate dehydrogenase, lactate production and its transporter, MCT4. Finally, the antifibrotic effects of 3-BrPA were validated in vivo in a mouse model of carbon tetrachloride-induced liver fibrosis. Results from histopathology & histochemical staining for collagen and α-SMA substantiated that 3-BrPA promotes antifibrotic effects in vivo. Taken together, our data indicate that sublethal, metronomic treatment with 3-BrPA blocks the progression of liver fibrosis suggesting its potential as a novel therapeutic for treating liver fibrosis.

  8. IkB kinase-beta inhibitor attenuates hepatic fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Jue Wei; Min Shi; Wei Qi Wu; Ting Wang; Na Wang; Jia-Li Ma; Yu-Gang Wang

    2011-01-01

    AIM: To investigate the anti-fibrosis effect of IκkB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin- 6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κkB (NF-κkB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear translocation translocation of NF-κkB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05).CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver

  9. Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats

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    Cheng-Jeng Tai

    2016-02-01

    Full Text Available Background: Advanced glycation end products (AGEs signal through the receptor for AGE (RAGE, which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30% with ethanol (10%. Male Wistar rats (4 weeks of age were randomly divided into four groups (n = 6: (1 control (basal diet; (2 HFD (30% + ethanol (10% (HFD/ethanol; (3 HFD/ethanol + AESN (100 mg/kg, oral administration; and (4 HFD/ethanol + pioglitazone (10 mg/kg, oral administration and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα, PPARγ co-activator (PGC-1α, carbohydrate response element-binding protein (ChREBP, acetyl-CoA carboxylase (ACC, and fatty acid synthase (FAS mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

  10. Effects of the combined administration of entecavir and adefovir dipivoxil to improve hepatic fibrosis in hepatitis B patients with interferon resistance.

    Science.gov (United States)

    Sun, Yuqiu; Wu, Keqin; Shen, Fei; Qiu, Ling; Chen, Binhe; Yu, Lijun; Chang, Shuzhen

    2017-09-08

    To observe the effect of the combined administration of entecavir and adefovir dipivoxil to improve hepatic fibrosis in hepatitis B patients with interferon resistance. This study comprised 90 hepatitis B patients with hepatic fibrosis and interferon (IFN) resistance who were admitted in the hospital's department of infectious disease for diagnosis and treatment between January 2013 and September 2015. They were randomly divided into two groups in accordance with the random number table: (1) the combination treatment group (n = 45), and (2) the entecavir group (n = 45). They were observed for any variations in the indexes of liver function and fibrosis, as well as the Model for end-stage liver disease (MELD) scores, before and after treatment. After treatment, the levels of the indexes in both groups (the combination treatment group vs. the entecavir group) were as follows: bilirubin (67.5±7.7 vs. 82.4±13.5 μmol/L); International Normalized Ratio (INR) (1.21±0.8 vs. 1.14±0.7); creatinine (147.3±12.4 vs. 287.4±21.6 mg/dl); GGT (67.4±23.2 vs. 88.4±23.7 U/L); and ALT (63.4±40.8 vs. 96.5±23.5 U/L). In comparison of the indexes of hepatic fibrosis between the two groups, we found the following differences: PCIII (67.5±7.7 vs. 82.4±13.5 μg/L); IV-C (61.3±18.7 vs. 74.5±17.9 μg/L); HA (147.3±12.4 vs. 87.4±31.6 μg/L); and LN (88.7±13.2 vs 102.5±23.4 μg/L). The results showed that the differences in comparison of the indexes before and after the treatment were statistically significant (p < 0.05). After treatment, the MELD score of patients in the combination treatment group was significantly lower than that in the entecavir group (18.7±3.2 vs. 22.5±3.4), with a statistically significant difference (p < 0.05). In the chronic hepatitis B patients with interferon resistance, the combined administration of entecavir and adefovir dipivoxil can significantly improve liver function, hepatic fibrosis and MELD scores. The results highlight the need to

  11. Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Todd R. [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Bettaieb, Ahmed [Department of Nutrition, University of California, Davis, CA 95616 (United States); Kodani, Sean; Dong, Hua [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Myers, Richard; Chiamvimonvat, Nipavan [Department of Internal Medicine: Cardiovascular, University of California, Davis, CA 95616 (United States); Haj, Fawaz G. [Department of Nutrition, University of California, Davis, CA 95616 (United States); Department of Internal Medicine: Endocrinology, Diabetes and Metabolism, University of California, Davis, CA 95616 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States)

    2015-07-15

    Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl{sub 4})-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl{sub 4}-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl{sub 4}-treated group relative to the Control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl{sub 4}-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-(4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy)-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl{sub 4}, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. - Highlights: • We administer an inhibitor of sEH in a CCl4 murine model. • sEH inhibition reduces liver collagen deposition and pro-fibrotic gene expression. • sEH inhibition induces MMP-1a activity.

  12. Interleukin-28 and hepatitis C virus genotype-4: Treatment-induced clearance and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Moutaz Derbala; Nasser Rizk; Fatima Shebl; Saad Alkaabi; Nazeeh Eldweik; Anil John; Manik Sharma

    2012-01-01

    AIM:To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men (89.6%),with a median age of 47 years,inter-quartile range (40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger (x2 =4.91,P =0.027),and less likely to have fibrosis (x2=15.54,P < 0.0001),or inflammation (x2 =7.58,P =0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender (P =0.466),pretreatment viral load (P =0.600),inflammation (P =0.435),or fibrosis (P =0.291).The frequencies of IL28B rs12979860genotypes were TT (14.8%),CT (49.0%),and CC (36.2%).Compared to rs12979860 genotype TT,aORs (95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92 (2.09-16.76),respectively]; CT genotype,[5.15 (1.80-14.78) and 2.48 (0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%,respectively) than individuals who had ETR or SVR (47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR =5

  13. Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients.

    Science.gov (United States)

    Zayed, Rania A; Omran, Dalia; Mokhtar, Doha A; Zakaria, Zinab; Ezzat, Sameera; Soliman, Mohamed A; Mobarak, Lamiaa; El-Sweesy, Hossam; Emam, Ghada

    2017-01-16

    Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls. Genotyping of TLR-3 (_7 C/A [rs3775296]), TLR-3 (c.1377C/T [rs3775290]) and TLR-9 (1237T/C [rs5743836]) were done by polymerase chain reaction restriction fragment length polymorphism technique. Frequency of polymorphic genotypes in TLR-3 (_7 C/A), TLR-3 (c.1377C/T) and TLR-9 (1237T/C) were not significantly different between studied HCV-positive patients and controls with P values 0.121, 0.112, and 0.683, respectively. TLR-3 c.1377 T-allele was associated with advanced stage of hepatic fibrosis (P = 0.003).

  14. Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis

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    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.

  15. Hepatic and Splenic Acoustic Radiation Force Impulse Shear Wave Velocity Elastography in Children with Liver Disease Associated with Cystic Fibrosis

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    Teresa Cañas

    2015-01-01

    Full Text Available Background. Liver disease associated with cystic fibrosis (CFLD is the second cause of mortality in these patients. The diagnosis is difficult because none of the available tests are specific enough. Noninvasive elastographic techniques have been proven to be useful to diagnose hepatic fibrosis. Acoustic radiation force impulse (ARFI imaging is an elastography imaging system. The purpose of the work was to study the utility of liver and spleen ARFI Imaging in the detection of CFLD. Method. 72 patients with cystic fibrosis (CF were studied and received ARFI imaging in the liver and in the spleen. SWV values were compared with the values of 60 healthy controls. Results. Comparing the SWV values of CFLD with the control healthy group, values in the right lobe were higher in patients with CFLD. We found a SWV RHL cut-off value to detect CFLD of 1.27 m/s with a sensitivity of 56.5% and a specificity of 90.5%. CF patients were found to have higher SWC spleen values than the control group. Conclusions. ARFI shear wave elastography in the right hepatic lobe is a noninvasive technique useful to detect CFLD in our sample of patients. Splenic SWV values are higher in CF patients, without any clinical consequence.

  16. Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus–coinfected Women

    Science.gov (United States)

    Kelly, Erin M.; Dodge, Jennifer L.; Sarkar, Monika; French, Audrey L.; Tien, Phyllis C.; Glesby, Marshall J.; Golub, Elizabeth T.; Augenbraun, Michael; Plankey, Michael; Peters, Marion G.

    2016-01-01

    Background. Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS). Methods. Liver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression. Results. Among 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6–17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88–2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02–1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02–1.85], P = .04), CD4+ count (risk per 100-cell increase: HR, 0.90 [95% CI, .86–.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05–1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02–1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4+ count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92–1.10], P = .83). Conclusions. In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women. PMID:27225241

  17. 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.

  18. TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver.

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    Susanne Nicole Weber

    Full Text Available The development of hepatocellular carcinoma (HCC is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN, with HCC formation depending amongst others on interleukin (IL 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver. The aim of this study was to investigate DEN-induced liver injury in TLR4-deficient mice with biliary fibrosis.ABCB4-deficient mice on the FVB/NJ genetic background were crossed to two distinct genetic backgrounds (TLR4-sufficient C3H/HeN and TLR4-deficient C3H/HeJ for more than 10 generations. The two congenic knockout and the two corresponding wild-type mouse lines were treated with a single dose of DEN for 48 hours. Phenotypic differences were assessed by measuring hepatic collagen contents, inflammatory markers (ALT, CRP, IL6 as well as hepatic apoptosis (TUNEL and proliferation (Ki67 rates.Hepatic collagen accumulation is significantly reduced in ABCB4-/-:TLR4-/-double-deficient mice. After DEN challenge, apoptosis, proliferation and inflammatory markers are decreased in TLR4-deficient in comparison to TLR4-sufficient mice. When combining ABCB4 and TLR4 deficiency with DEN treatment, hepatic IL6 expression and proliferation rates are lowest in fibrotic livers from the double-deficient line. Consistent with these effects, selective digestive tract decontamination in ABCB4-/- mice also led to reduced tumor size and number after DEN.This study demonstrates that liver injury upon DEN challenge

  19. Relationship between body balance, lung function, nutritional status and functional capacity in adults with cystic fibrosis

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    Jennifer T. S. Penafortes

    2013-10-01

    Full Text Available BACKGROUND: Cystic fibrosis (CF is a hereditary condition in which lung disease affects all patients. In addition to pulmonary involvement, the multisystemic components of CF cause significant physical limitations. However, the impact of lung function on balance control in CF has not been studied. OBJECTIVE: To assess body balance in adults with CF and to test its possible associations with lung function, nutritional status, and functional capacity. METHOD: This was a cross-sectional study in which 14 adults with CF underwent pulmonary function testing (spirometry, body plethysmography, and carbon monoxide diffusing capacity (DLco, respiratory muscle strength, 6-min walking distance (6MWD, Berg balance scale (BBS, nutritional analysis (body mass index and bioelectrical impedance, and stabilometry. Body balance was quantified using stabilometry; all participants performed the following two trials: opened base, eyes open (OBEO; closed base, eyes closed (CBEC. RESULTS: In stabilometry, the median for the lateral range and anterior-posterior range in the CBEC trial was 0.10 (0.08-0.11 and 0.13 (0.11-0.22, respectively (p<0.05. The maximal inspiratory pressure (MIP correlated inversely with the lateral standard deviation (ρ=–0.61; p<0.05 as the DLco correlated positively with the anterior-posterior range (ρ=0.54; p<0.05. There were significant relationships between body composition indexes and almost all stabilometric variables measured. There were no relationships of the BBS and 6MWD with the stabilometric variables. CONCLUSIONS: In adults with CF, imbalance occurs mainly in the anterior-posterior direction and is especially associated with body composition.

  20. Soporte alimentario y nutricional en niños con fibrosis quística Nutritional support in children presenting with cystic fibrosis

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    Aida Esplugas Montoya

    2011-03-01

    Full Text Available INTRODUCCIÓN. La fibrosis quística es una enfermedad que se manifiesta en las vías respiratorias, el páncreas y el tracto intestinal. El control nutricional es un aspecto decisivo en el tratamiento de la enfermedad. El objetivo del estudio fue caracterizar un grupo de pacientes que se encontraban en fases de soporte y rehabilitación nutricional. MÉTODOS. Se realizó un estudio prospectivo con 7 pacientes menores de 18 años, que ingresaron para su tratamiento en la unidad especializada en fibrosis quística del Hospital Pediátrico Universitario «William Soler» (La Habana. Se realizaron mediciones antropométricas al ingreso y al egreso, y se clasificó a los niños en desnutrido, de bajo peso y de peso normal. Los valores fueron comparados con las tablas de crecimiento y desarrollo de la población cubana. RESULTADOS. A 3 pacientes se les aplicó una intervención de soporte nutricional y 4 pacientes fueron tratados además con nutrición enteral suplementaria. En la evaluación nutricional se encontró que la distribución porcentual calórica que aportaron los alimentos fue de un 12 % para las proteínas, 37 % para las grasas y 51 % para los carbohidratos. La energía que aportaron los alimentos consumidos ascendió a 4 360 kcal, 134,27 g de proteínas, 177,51 g de grasas y 558,20 g de carbohidratos. CONCLUSIONES. Al aumentar la densidad calórica de los alimentos y aplicar nutrición enteral a los pacientes se obtuvo un incremento de la ganancia ponderal y mejoró el estado nutricional.INTRODUCTION. Cystic fibrosis is a disease of airways, pancreas and intestinal tract. The nutritional control is a decisive feature in treatment of disease. The objective of present paper was to characterize a group of patients in nutritional support and rehabilitation phases. METHODS. A prospective study was conducted in 7 patients aged under 18 admitted for treatment in the cystic fibrosis specialized unit or the "William Soler" University Children

  1. Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.

    Science.gov (United States)

    Tawara, Seiichi; Tatsumi, Tomohide; Iio, Sadaharu; Kobayashi, Ichizou; Shigekawa, Minoru; Hikita, Hayato; Sakamori, Ryotaro; Hiramatsu, Naoki; Miyoshi, Eiji; Takehara, Tetsuo

    2016-01-01

    Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2). In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3). In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB4) index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.

  2. Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C.

    Science.gov (United States)

    Kazankov, Konstantin; Barrera, Francisco; Møller, Holger Jon; Bibby, Bo Martin; Vilstrup, Hendrik; George, Jacob; Grønbaek, Henning

    2014-08-01

    Macrophages are involved in inflammation and liver fibrosis and soluble (s)CD163 is a specific marker of activated macrophages. We investigated associations between sCD163 and biochemical and histological parameters of inflammatory activity and fibrosis in 551 patients with chronic hepatitis C virus (HCV) and 203 patients with chronic hepatitis B virus (HBV) before antiviral treatment. Scheuer histological scores of activity and fibrosis were obtained. Clinical, biochemical, and metabolic parameters were recorded. We measured sCD163 by enzyme-linked immunosorbent assay (ELISA). Soluble CD163 was higher in patients with HCV compared to HBV (3.6 [interquartile range (IQR) 2.5-5.4] versus 2.4 [IQR 1.8-3.6] mg/L, P CD163-HCV-FS and CD163-HBV-FS, which showed areas under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI: 0.74-0.83) and 0.71 (95% CI: 0.62-0.79), respectively, for significant fibrosis. Compared to existing fibrosis scores, CD163-HCV-FS was significantly superior to the aspartate aminotransferase (AST) to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis, but CD163-HBV-FS was not. sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-HCV-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with HCV infection. © 2014 by the American Association for the Study of Liver Diseases.

  3. Effects of total glucosides of peony on immunological hepatic fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Hua Wang; Wei Wei; Ni-Ping Wang; Cheng-Yi Wu; Shang-Xue Yan; Li Yue; Ling-Ling Zhang; Shu-Yun Xu

    2005-01-01

    AIM: To study the effects of total glucosides of peony (TGP) on immunological hepatic fibrosis induced by human albumin in rats.METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into: Normal group, model group, TGP (60 and 120 mg/kg) treatment groups and colchicines (0.1 mg/kg) treatment group. On the day before the rats were killed, those in TGP or colchicine groups received TGP or colchicine as above from the first day of tail vein injection of human albumin. The rats in normal and model groups were only administered with the same volume of vehicle. At the end of the 16th wk, rats in each group were killed. Blood and tissue specimens were taken. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were measured by biochemical methods. Serum procollagen type Ⅲ (PC Ⅲ) and laminin (LN) were determined by radioimmunoassay. Liver collagen level was determined by measuring hydroxyproline content in fresh liver samples. Hepatic tissue sections were stained with hematoxylin-eosin and examined under a light microscope.RESULTS: Histological results showed that TGP improved the human albumin-induced alterations in the liver structure, alleviated lobular necrosis and significantly lowered collagen content. The antifibrotic effect of TGP was also confirmed by decreased serum content of LN and PCⅢ in TGP-treated group. Moreover, the treatment with TGP effectively reduced the hydroxyproline contentin liver homogenates. However, the level of ALT and AST increased in fibrotic rat but had no significance compared with normal control, whereas the ratio of A/G decreased without significance. TGP had no effect on level of ALT, AST and the ratio of A/G. Furthermore, TGP treatment significantly blocked the increase in MDA and NO, associated with a partial elevation in liver total antioxidant capacity including

  4. Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

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    Luis Jesuino de Oliveira Andrade

    2011-02-01

    Full Text Available Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV. In this work, we report the association between the presence of smooth muscle antibodies (SMA and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05. The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

  5. Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers.

    Science.gov (United States)

    Andrade, Luis Jesuino de Oliveira; Melo, Paulo Roberto Santana de; Atta, Ajax Mercês; Atta, Maria Luiza Brito de Sousa; Jesus, Larissa Santana de; Sousa, Gabriel Menezes de; Silva, Carolina Alves Costa; Paraná, Raymundo

    2011-01-01

    Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

  6. The Role of Ultrasound Imaging in the Definition of the Stage of Liver Fibrosis in Patients with Chronic Hepatitis C

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    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.

  7. 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

  8. New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples

    Institute of Scientific and Technical Information of China (English)

    Thomas G(o)bel; Sonja Vorderwülbecke; Katarzyna Hauck; Holger Fey; Dieter H(a)ussinger; Andreas Erhardt

    2006-01-01

    AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV).METHODS: Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-Ⅱ c; Ciphergen Biosystems) after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks.RESULTS: A 4 peptide/protein multimarker panel (7486,12843, 44293 and 53598 Da) correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples (AUROC 0.943). Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosisusing a 5 peptide/protein multimarker pattern (2873,6646, 7775, 10525 and 67867 Da) with a specificity of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APRI score and alfa-fetopotein (AFP) improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-Ⅰ.CONCLJSION: SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Most probably a combination of different serum markers will help to identify liver cirrhosis and early

  9. Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.

    Science.gov (United States)

    Younossi, Zobair M; Stepanova, Maria; Afdhal, Nezam; Kowdley, Kris V; Zeuzem, Stefan; Henry, Linda; Hunt, Sharon L; Marcellin, Patrick

    2015-08-01

    New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir. Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies. There were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0-1 scale p0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to -0.056 in comparison with none-to-mild fibrosis, pwork productivity after viral clearance was not related to the stage of fibrosis (all p>0.05). Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  10. Anti-hepatic fibrosis effects of a novel turtle shell decoction by inhibiting hepatic stellate cell proliferation and blocking TGF-β1/Smad signaling pathway in rats.

    Science.gov (United States)

    Bai, Ganping; Yan, Guohe; Wang, Guojian; Wan, Ping; Zhang, Ronghua

    2016-11-01

    Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear. In the present study, we first improved the original formula of TSP to produce a novel turtle shell decoction (NTSD) with less toxicity and easier accessible materials. In a carbon tetrachloride (CCl4)-induced HF rat model, we observed that NTSD and TSP had similar effects on the improvement of liver functions in rats, including a decrease in serum alanine amino transferase (ALT) and aspartate amino transferase (AST) serum concentrations and increased albumin content in addition to a marked attenuation of CCl4-induced liver damage and fibrosis. NTSD containing rat serum inhibited rat liver stellate cell line HSC-T6 cell proliferation and induced cell apoptosis in vitro. Moreover, the NTSD treatment significantly decreased the transforming growth factor beta 1 (TGF-β1) and Smad3 gene expression and increased inhibitory Smad7 gene expression in liver tissues of HF rats, suggesting that NTSD inhibited the ECM expression of HSC by downregulating the TGF-β1/Smad signaling pathway. The results of our rat model study revealed that NTSD showed good in vitro and in vivo anti-HF effects via proliferation inhibition and the induction of apoptosis of HSCs and blocked the TGF-β1/Smad signaling pathway.

  11. P0525 : N-Acetylated alpha smooth muscle actin levels are increased in hepatic fibrosis but decreased in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Nielsen, M.J.; Nielsen, Signe Holm; Hansen, N.U.B.

    2015-01-01

    Alpha Smooth Muscle Actin (a-SMA) is upregulated together with extracellular matrix (ECM) during activation of Hepatic Stellate Cells (HSCs) in fibrosis. Histone deacetylase (HDAC) remove acetylations and regulate the expression of genes, which is associated with cancers. There is a close...... relationship between cirrhosis and hepatocellular carcinoma (HCC), and markers enabling identification of patients in risk of developing HCC with cirrhosis is a major unmet clinical need. We developed an ELISA for the assessment of acetylated a-SMA (Aca- SMA) in serum. The objective was to investigate...

  12. Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    Yu-Kan Liu; Wei Shen

    2003-01-01

    AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl4-plus ethanolinduced hepatic fibrogenesis in experimental rats.METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl4 and ethanol solution at the beginning of the experiment to induce hepatic fibrosis. The CS group was also treated with CS 10 days after the beginning of CCl4 and ethanol administration. All control groups were given corresponding placebo at the same time. At the end of the 9th week, rats in each group were humanely sacrificed. Blood and tissue specimens were taken.Biochemical, radioimmunological, immunohistochemical and molecular biological examinations were used to determine the level change of ALT, AST, HA, LN content in serum and TGFβ1, PDGF, collagen Ⅰ and Ⅲ expression in tissue at either protein or mRNA level or both of them.RESULTS: As compared with the model control group,serum ALr, AST, HA, and LN content levels were markedly dropped in CS group (86.0±34.4 vs224.3±178.9, 146.7±60.2vs272.6±130.1, 202.0±79.3 vs316.5±94.1 and 50.4±3.0vs 59.7±9.8, respectively, P<0.05). Tissue expression of TGFβ1 and its mRNA, collagen I mRNA were also markedly decreased (0.2±0.14 vs1.73±1.40, 1.68±0.47 vs3.17±1.17,1.10±0.84 vs 2.64±1.40, respectively, P<0.05). More dramatical drop could be seen in PDGF expression (0.87±0.43vs1.91±0.74, P<0.01). Although there was no statistical significance, it was still strongly suggested that collagen Ⅲ mRNA expression was also decreased in CS group as compared with model control group (0.36±0.27 vs0.95±0.65,P=0.0615). In this experiment, no significant change could be found in PDGF mRNA expression between two groups (0.35±0.34 vs 0.70±0.46, P>0.05).CONCLUSION: Cordyceps sinensis could inhibit hepatic fibrogenesis derived from chronic liver injury, retard the development of cirrhosis, and

  13. The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

    Directory of Open Access Journals (Sweden)

    Natália Picelli

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.METHODS:Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23 and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13. Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression.RESULTS:There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems.CONCLUSION:The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

  14. Clinical effect of Dahuang Zhechong capsules combined with entecavir in treatment of chronic hepatitis B patients with liver fibrosis

    Directory of Open Access Journals (Sweden)

    XIE Yongcai

    2016-08-01

    Full Text Available jectiveTo investigate the clinical effect of Dahuang Zhechong capsules combined with entecavir in the treatment of chronic hepatitis B (CHB patients with liver fibrosis. MethodsA total of 100 CHB patients with liver fibrosis who visited or were hospitalized in Shenzhen Hospital of Peking University from October 2014 to January 2016 were enrolled and randomly divided into Western medicine group and combined treatment group, with 50 patients in each group. The patients in the Western medicine group were given entecavir, and those in the combined treatment group were given Dahuang Zhechong capsules in addition to entecavir. The course of the treatment was 48 weeks. The changes in liver function, HBV DNA load, four serum parameters of liver fibrosis, liver stiffness, and aspartate aminotransferase-to-platelet ratio index (APRI/FibroIndex were observed in both groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsBoth groups showed significant reductions in serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and HBV DNA load after 48 weeks of treatment (all P<0.05. After treatment, the four serum parameters of liver fibrosis all returned to normal after treatment, and the serum levels of hyaluronic acid, type Ⅲ precollagen, and type IV collagen showed significant differences between the two groups (all P<005, and the portal vein diameter, thickness of the spleen, liver stiffness and APRI/FibroIndex also showed significant differences between the two groups (both P<0.05. The combined treatment group had a significantly higher overall response rate than the Western medicine group (920% vs 720%, χ2=6.775, P=0009. ConclusionDahuang Zhechong capsules combined with entecavir have a better effect in the treatment of CHB patients with liver fibrosis compared with entecavir alone.

  15. A New Metabolism-Related Index Correlates with the Degree of Liver Fibrosis in Hepatitis C Virus-Positive Patients

    Directory of Open Access Journals (Sweden)

    Hirayuki Enomoto

    2015-01-01

    Full Text Available Background. Only a few biomarkers based on metabolic parameters for evaluating liver fibrosis have been reported. The aim of this study was to investigate the relevance of an index obtained from three metabolic variables (glycated albumin: GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio: BTR to the degree of liver fibrosis in hepatitis C virus virus- (HCV- positive patients. Methods. A total of 394 HCV-positive patients were assessed based on the values of a new index (GA/HbA1c/BTR. The index findings were used to investigate the relationship with the degree of liver fibrosis. Results. The new index showed an association with the stage of fibrosis (METAVIR scores: F0-1: 0.42 ± 0.10, F2: 0.48 ± 0.15, F3: 0.56 ± 0.22, and F4: 0.71 ± 0.30. The index was negatively correlated with three variables of liver function: the prothrombin time percentage (P<0.0001, albumin level (P<0.0001, and cholinesterase level (P<0.0001. The new index showed a higher correlation related to liver function than FIB-4 and the APRI did. In addition, the index showed a higher AUROC value than that of FIB-4 and the APRI for prediction of liver cirrhosis. Conclusion. The new metabolism-related index, GA/HbA1c/BTR value, is shown to relate to the degree of liver fibrosis in HCV-positive patients.

  16. Evaluación nutricional dietética en pacientes afectos de fibrosis quística Dietetic nutritional assessment in patients with cystic fibrosis

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    Aida E. Esplugas Montoya

    2008-09-01

    Full Text Available INTRODUCCIÓN. La fibrosis quística es una enfermedad hereditaria de transmisión autosómica recesiva, que afecta a las células epiteliales exocrinas, y los órganos más afectados son el páncreas y los pulmones. La esteatorrea es la más importante manifestación clínica y afecta al estado nutritivo, al desarrollo y a la absorción de micronutrientes y vitaminas liposolubles. Mantener un estado nutricional adecuado es un aspecto decisivo en el tratamiento de estos pacientes. El objetivo de este trabajo fue caracterizar el estado nutricional dietético de niños que se encuentran en situaciones de riesgo nutricional. MÉTODOS. Se realizó un estudio descriptivo con un grupo de pacientes afectos de fibrosis quística. El universo comprendió 17 pacientes que recibieron atención médica y seguimiento en el Hospital Pediátrico Docente "William Soler". RESULTADOS. En la encuesta se encontró que la distribución porcentual calórica que aportaron los alimentos consumidos por los pacientes fue del 12 % para las proteínas, del 33 % para las grasas y del 55 % para los carbohidratos. La energía que aportaron los alimentos consumidos ascendió a 3400 kcal, con un intervalo mínimo de 1703 kcal y máximo de 6180 kcal. Para las proteínas el consumo fue de 101 g, con un rango de 49 a 207 g; para las grasas fue de 128 g, con rango de 60 g a 270 g y para los carbohidratos, 457 g con intervalo mínimo de 243 g e intervalo máximo de 704 g. CONCLUSIONES. La evaluación dietética de un niño puede predecir la alteración de su estado nutricional antes de la alteración bioquímica y mucho antes de que se hagan evidentes los signos clínicos de deficiencia.INTRODUCTION: Cystic fibrosis is a hereditary disease of recessive autosomal transmission, affecting the exocrine epithelial cells. The most affected organs are pancreas and lungs. Steatorrhea is the most significant clinical manifestation affecting the nutritional status, development and the

  17. Association between noninvasive fibrosis markers and cardio-vascular organ damage among adults with hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Giorgio Sesti

    Full Text Available Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS, is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT, and left ventricular mass index (LVMI. In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP, fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1 levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12-13.87 as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH (OR 3.55, 95% CI 1.22-10.34 as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors.

  18. Performance of the AST to Platelet Ratio Index (APRI) as a Noninvasive Marker of Fibrosis in Pediatric Patients with Chronic Viral Hepatitis

    OpenAIRE

    2010-01-01

    We investigated the performance of AST to platelet ratio index (APRI) as a non-invasive marker of fibrosis and cirrhosis in children with chronic viral hepatitis. All patients 0–20 years old with chronic hepatitis B or C seen at a tertiary medical center from 1992–2008 were identified. 36 patients were evaluated with 48 biopsy results. The areas under the ROC curve were 0.71 for fibrosis and 0.52 for cirrhosis. When examining subgroups, the APRI performed better in older patients and in those...

  19. Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Chang-Feng; Dong; Jia; Xiao; Ling-Bo; Shan; Han-Ying; Li; Yong-Jia; Xiong; Gui-Lin; Yang; Jing; Liu; Si-Min; Yao; Sha-Xi; Li; Xiao-Hua; Le; Jing; Yuan; Bo-Ping; Zhou; George; L; Tipoe; Ying-Xia; Liu

    2016-01-01

    AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

  20. [Dynamic expression profile of HBsAg according to hepatic parenchyma cells' volume at different liver fibrosis stages in the immune clearance phase].

    Science.gov (United States)

    Wu, Zhe-bin; Cao, Hong; Liu, Ting; Wu, Ze-qian; Ke, Wei-min; Gao, Zhi-liang

    2012-10-01

    The aim of this study was to determine the dynamic expression profile of hepatitis B surface antigen (HBsAg) according to hepatic parenchyma cells' volume at different stages of liver fibrosis during the immune clearance phase. Eighty-nine patients with HBeAg-positive chronic hepatitis B (CHB) in the immune clearance stage were recruited for study. Each patient's serum HBsAg levels were detected by electrochemiluminescence. The serum HBsAg levels were apportioned according to hepatic parenchyma cells' volume at liver fibrosis stages 1, 2, 3, and 4 and compared by ANOVA. The unapportioned serum HBsAg levels (IU/mL) at liver fibrosis stages 1 (227.2+/-237.7), 2 (211.0+/-131.4), 3(300.1+/-144.6), and 4 (278.7+/-148.8) were not significantly different (all comparisons, P range: 0.061 to 0.759). However, when the serum HBsAg levels were apportioned by the same hepatic parenchyma cells' volume at liver fibrosis stages 1 (343.9+/-359.8), 2 (336.4+/-209.5), 3 (508.7+/-245.1), and 4 (525.2+/-274.8), the levels were significantly different (all comparisons, F = 3.045 and P = 0.033; stage 1 vs. 3, P = 0.041; stage 1 vs. 4, P = 0.046; stage 2 vs. 3, P = 0.028; stage 2 vs. 4, P = 0.034). During the immune clearance phase of chronic hepatitis B, increased HBsAg expression is associated with increased hepatic parenchyma cells' volume and progressive liver fibrosis stage.

  1. Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in chronic hepatitis C genotype 1 infection.

    Science.gov (United States)

    Kitson, Matthew T; George, Jacob; Dore, Gregory J; Leung, Reynold; Button, Peter; McCaughan, Geoffrey W; Grawford, Darrell H G; Siebert, William; Weltman, Martin D; Cheng, Wendy S C; Roberts, Stuart K

    2014-01-01

    Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86–17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14–0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00–1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.

  2. Assessment of Liver Fibrosis with Diffusion-Weighted Magnetic Resonance Imaging Using Different b-values in Chronic Viral Hepatitis.

    Science.gov (United States)

    Kocakoc, Ercan; Bakan, Ayse Ahsen; Poyrazoglu, Orhan Kursat; Dagli, Adile Ferda; Gul, Yeliz; Cicekci, Mehtap; Bahcecioglu, Ibrahim Halil

    2015-01-01

    To examine the effectiveness of apparent diffusion coefficient (ADC) values and to compare the reliability of different b-values in detecting and identifying significant liver fibrosis. There were 44 patients with chronic viral hepatitis (CVH) in the study group and 30 healthy participants in the control group. Diffusion-weighted magnetic resonance imaging (DWI) was performed before the liver biopsy in patients with CVH. The values of ADC were measured with 3 different b-values (100, 600, 1,000 s/mm2). In addition, liver fibrosis was classified using the modified Ishak scoring system. Liver fibrosis stages and ADC values were compared using areas under the receiver-operating characteristic (ROC) curve. The study group's mean ADC value was not statistically significantly different from the control group's mean ADC value at b = 100 s/mm2 (3.69 ± 0.5 × 10-3 vs. 3.7 ± 0.3 × 10-3 mm2/s) and b = 600 s/mm2 (2.40 ± 0.3 × 10-3 vs. 2.5 ± 0.5 × 10-3 mm2/s). However, the study group's mean ADC value (0.99 ± 0.3 × 10-3 mm2/s) was significantly lower than that of the control group (1.2 ± 0.1 × 10-3 mm2/s) at b = 1,000 s/mm2. With b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s for the diagnosis of liver fibrosis, the mean area under the ROC curve was 0.702 ± 0.07 (p = 0.0015). For b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s to diagnose significant liver fibrosis (Ishak score = 3), the mean area under the ROC curve was 0.759 ± 0.07 (p = 0.0001). Measurement of ADC values by DWI was effective in detecting liver fibrosis and accurately identifying significant liver fibrosis when a b-value of 1,000 s/mm2 was used. © 2015 S. Karger AG, Basel.

  3. Restoring homeostasis of CD4⁺ T cells in hepatitis-B-virus-related liver fibrosis.

    Science.gov (United States)

    Cheng, Li-Sha; Liu, Yun; Jiang, Wei

    2015-10-14

    Immune-mediated liver injury is widely seen during hepatitis B virus (HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis (HBVLF), occurring as a result of HBV-induced chronic hepatitis, is a reversible, intermediate stage of chronic hepatitis B (CHB) and liver cirrhosis. Therefore, defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently, the homeostasis of CD4(+) T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms, in this review, we systematically retrospect the impacts of different CD4(+) T-cell subsets on CHB and HBVLF. We emphasize CD4(+) T-cell homeostasis and the important balance between regulatory T (Treg) and T helper 17 (Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin (IL)-17, IL-22, IL-21, IL-23, IL-10, IL-35 and IL-33, as well as surface molecules such as programmed cell death protein 1, cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4(+) T cells in CHB and HBVLF.

  4. Murine junctional adhesion molecules JAM-B and JAM-C mediate endothelial and stellate cell interactions during hepatic fibrosis.

    Science.gov (United States)

    Hintermann, Edith; Bayer, Monika; Ehser, Janine; Aurrand-Lions, Michel; Pfeilschifter, Josef M; Imhof, Beat A; Christen, Urs

    2016-07-03

    Classical junctional adhesion molecules JAM-A, JAM-B and JAM-C influence vascular permeability, cell polarity as well as leukocyte recruitment and immigration into inflamed tissue. As the vasculature becomes remodelled in chronically injured, fibrotic livers we aimed to determine distribution and role of junctional adhesion molecules during this pathological process. Therefore, livers of naïve or carbon tetrachloride-treated mice were analyzed by immunohistochemistry to localize all 3 classical junctional adhesion molecules. Hepatic stellate cells and endothelial cells were isolated and subjected to immunocytochemistry and flow cytometry to determine localization and functionality of JAM-B and JAM-C. Cells were further used to perform contractility and migration assays and to study endothelial tubulogenesis and pericytic coverage by hepatic stellate cells. We found that in healthy tissue, JAM-A was ubiquitously expressed whereas JAM-B and JAM-C were restricted to the vasculature. During fibrosis, JAM-B and JAM-C levels increased in endothelial cells and JAM-C was de novo generated in myofibroblastic hepatic stellate cells. Soluble JAM-C blocked contractility but increased motility in hepatic stellate cells. Furthermore, soluble JAM-C reduced endothelial tubulogenesis and endothelial cell/stellate cell interaction. Thus, during liver fibrogenesis, JAM-B and JAM-C expression increase on the vascular endothelium. More importantly, JAM-C appears on myofibroblastic hepatic stellate cells linking them as pericytes to JAM-B positive endothelial cells. This JAM-B/JAM-C mediated interaction between endothelial cells and stellate cells stabilizes vessel walls and may control the sinusoidal diameter. Increased hepatic stellate cell contraction mediated by JAM-C/JAM-C interaction may cause intrahepatic vasoconstriction, which is a major complication in liver cirrhosis.

  5. Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Roberto Catanzaro; Michele Milazzo; Silvia Arona; Chiara Sapienza; Dario Vasta

    2013-01-01

    BACKGROUND: The  prognosis  and  clinical  management  of patients  with  chronic  liver  diseases  are  closely  related  to  the severity  of  liver  fibrosis.  Liver  biopsy  is  considered  the  gold standard  for  the  staging  of  liver  fibrosis.  However,  it  is  an invasive  test  sometimes  related  to  complications.  This  study aimed to assess the diagnostic value of enhanced liver fibrosis (ELF)  test  to  predict  liver  fibrosis  in  patients  with  chronic hepatitis C. METHODS: This study included 162 patients with liver disease and  67  healthy  controls.  Hyaluronic  acid,  tissue  inhibitor of  matrix  metalloproteinase  type  1,  and  amino-terminal propeptide  type  III  procollagen  were  measured  by  enzyme-linked immunosorbent assay with the ELF test ADVIA Centaur ® (Siemens  Healthcare  Diagnostics  Inc.).  Fibrosis  stage  was determined using the Metavir scoring system. RESULTS: In our study, for the diagnosis of significant fibrosis (Metavir  F≥2)  a  cut-off  value  >7.72  provides  a  sensitivity  of 93.0% and a specificity of 83.0%. The areas under the receiver operator  characteristic  curve,  sensitivity,  specificity,  and positive and negative predictive values were 0.94, 93.3%, 81.0%, 93.3%,  and  81.0%,  respectively  (P9.3  provides  a sensitivity of 93.0% and a specificity of 86.0%. The areas under the receiver operator characteristic curve, sensitivity, specificity, and  positive  and  negative  predictive  values  were  0.94,  79.1%, 90.8%, 75.6%, and 92.3%, respectively (P CONCLUSIONS: The  ELF  test  is

  6. Excess body weight, liver steatosis, and early fibrosis progression due to hepatitis C recurrence after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Pierluigi Toniutto; Carlo Fabris; Claudio Avellini; Rosalba Minisini; Davide Bitetto; Elisabetta Rossi; Carlo Smirne; Mario Pirisi

    2005-01-01

    AIM: To investigate how weight gain after OLT affects the speed of fibrosis progression (SFP) during recurrent hepatitis C virus (HCV) infection of the graft.METHODS: Ninety consecutive patients (63 males,median age 53 years; 55 with HCV-related liver disease),transplanted at a single institution, were studied. All were followed for at least 2 years after OLT and had at least one follow-up graft biopsy, performed not earlier than 1 year after the transplant operation. For each biopsy, a single,experienced pathologist gave an estimate of both the staging according to Ishak and the degree of hepatic steatosis.The SFP was quantified in fibrosis units/month (FU/mo).The lipid metabolism status of patients was summarized by the plasma triglycerides/cholesterol (T/C) ratio. Body mass index (BMI) was measured before OLT, and 1 and 2 years after it.RESULTS: In the HCV positive group, the highest SFP was observed in the first post-OLT year. At that time point,a SFP ≤0.100 FU/mo was observed more frequently among recipients who had received their graft from a young donor and had a pre-transplant BMI value >26.0 kg/m2. At completion of the first post-transplant year, a BMI value >26.5 kg/m2 was associated with a T/C ratio ≤1. The proportion of patients with SFP >0.100 FU/mo descended in the following order: female recipients with a high T/C ratio, male recipients with high T/C ratio, and recipients of either gender with low T/C ratio. Hepatic steatosis was observed more frequently in recipients who, in the first post-transplant year, had increased their BMI ≥1.5 kg/m2 in comparison to the pre-transplant value. Hepatic steatosis was inversely associated with the staging score.CONCLUSION: Among HCV positive recipients, excessweight gain post-OLT does not represent a factor favoring early liver fibrosis development and might even be protective against it.

  7. Artificial neural network aided non-invasive grading evaluation of hepatic fibrosis by duplex ultrasonography

    National Research Council Canada - National Science Library

    Zhang, Li; Li, Qiao-Ying; Duan, Yun-You; Yan, Guo-Zhen; Yang, Yi-Lin; Yang, Rui-Jing

    2012-01-01

    Artificial neural networks (ANNs) are widely studied for evaluating diseases. This paper discusses the intelligence mode of an ANN in grading the diagnosis of liver fibrosis by duplex ultrasonogaphy...

  8. Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid–PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Yu-Nong Chen

    2016-12-01

    Full Text Available In this study, we developed curcumin-encapsulated hyaluronic acid–polylactide nanoparticles (CEHPNPs to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA were crosslinked by adipic acid dihydrazide (ADH. The synthesis of HA–PLA was monitored by Fourier-transform infrared (FTIR and Nuclear Magnetic Resonance (NMR. The average particle size was approximately 60–70 nm as determined by dynamic light scattering (DLS and scanning electron microscope (SEM. Zeta potential was around −30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC50 (inhibitory concentration at 50% value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.

  9. Nutritional status is associated with health-related quality of life in children with cystic fibrosis aged 9-19 years.

    Science.gov (United States)

    Shoff, Suzanne M; Tluczek, Audrey; Laxova, Anita; Farrell, Philip M; Lai, HuiChuan J

    2013-12-01

    The impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF). Associations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9-19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ). Associations between height z-score (HtZ), BMI z-score (BMIZ) and seven CFQ dimensions were evaluated. Mean values of at least 80 were observed for all CFQ dimensions except respiratory symptoms and treatment burden. Treatment burden was significantly worse in patients with meconium ileus (57) compared to pancreatic insufficient (65) and sufficient (78) subjects, pnutritional status was associated with increased HRQOL scores. Early diagnosis through newborn screening and improved nutrition provides an opportunity to enhance quality of life and body image perception. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  10. 3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human Adipose-Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Xuan Zhang

    2016-01-01

    Full Text Available Three-dimensional (3D cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells (MSCs. However, the action mechanisms of 3D MSCs vary greatly and are far from being thoroughly investigated. In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose-derived MSCs for hepatic fibrosis. Our results showed that 3D culture enhanced the expression of antifibrotic factors by MSCs, including insulin growth factor 1 (IGF-1, interleukin-6 (IL-6, and hepatocyte growth factor (HGF. In vitro studies indicated conditioned medium of 3D cultured MSCs protected hepatocytes from cell injury and apoptosis more effectively compared with 2D cultured cells. More importantly, when transplanted into model mice with hepatic fibrosis, 3D spheroids of MSCs were more beneficial in ameliorating hepatic fibrosis and improving liver function than 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs and might be promising for treatment of hepatic fibrosis.

  11. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  12. A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells.

    Science.gov (United States)

    Wu, Li-Mei; Wu, Xing-Xin; Sun, Yang; Kong, Xiang-Wen; Zhang, Yi-Hua; Xu, Qiang

    2008-03-01

    Regulation on the function of the hepatic stellate cells (HSCs) is one of the proposed therapeutic approaches to liver fibrosis. In the present study, we examined the in vitro and in vivo effects of CPU-II2, a novel synthetic oleanolic acid (OLA) derivative with nitrate, on hepatic fibrosis. This compound alleviated CCl4-induced hepatic fibrosis in mice with a decrease in hepatic hydroxyproline (Hyp) content and histological changes. CPU-II2 also attenuated the mRNA expression of alpha-smooth muscle actin (alpha-SMA) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) induced by CCl4 in mice and reduced both mRNA and protein levels of alpha-SMA in HSC-T6 cells. Interestingly, CPU-II2 did not affect the survival of HSC-T6 cells but decreased the expression of procollagen-alpha1 (I) in HSC-T6 cells through down-regulating the phosphorylation of p38 MAPK. CPU-II2 attenuates the development of liver fibrosis rather by regulating the function of HSCs through p38 MAPK pathway than by damaging the stellate cells.

  13. Homing in on the hepatic scar: recent advances in cell-specific targeting of liver fibrosis [version 1; referees: 3 approved

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    Ross Dobie

    2016-07-01

    Full Text Available Despite the high prevalence of liver disease globally, there are currently no approved anti-fibrotic therapies to treat patients with liver fibrosis. A major goal in anti-fibrotic therapy is the development of drug delivery systems that allow direct targeting of the major pro-scarring cell populations within the liver (hepatic myofibroblasts whilst not perturbing the homeostatic functions of other mesenchymal cell types present within both the liver and other organ systems. In this review we will outline some of the recent advances in our understanding of myofibroblast biology, discussing both the origin of myofibroblasts and possible myofibroblast fates during hepatic fibrosis progression and resolution. We will then discuss the various strategies currently being employed to increase the precision with which we deliver potential anti-fibrotic therapies to patients with liver fibrosis.

  14. Effect of antioxidant therapy on hepatic fibrosis and liver iron concentrations in β-thalassemia major patients.

    Science.gov (United States)

    Elalfy, Mohsen S; Adly, Amira A M; Attia, Atef A M; Ibrahim, Fatma A; Mohammed, Amer S; Sayed, Abdelbasset M

    2013-01-01

    To assess the effects of combined vitamin therapy on oxidant-antioxidant hepatic status and hemoglobin (Hb) derivatives on β-thalassemia major (β-TM), a prospective study of 60 β-TM patients aged 4 to 17 years, was conducted. Thirty-nine patients with initial low serum vitamins E, C and A, were treated with oral combined vitamins for 1 year compared to 21 patients with normal vitamin levels. Serum transaminases, serum ferritin, hepatic fibroscan elastography (TE) and magnetic resonance imaging R2* (MRI R2*) for liver iron concentration (LIC), were assessed before and after 6 and 12 months of therapy. Antioxidant capacity was assessed by levels of reduced glutathione (GSH), malondialdehyde (MDA), catalase, superoxide dismutase and GSH enzymes. The studied vitamins, reduced GSH and Hb levels were significantly elevated and paralleled by progressive decline in MDA and ferritin during therapy (p 12 kPa) at baseline compared to 20.5% after therapy (p >0.05), although LIC values were significantly decreased (p <0.001). Combined vitamin therapy improves the antioxidant/oxidant balance, LIC and hepatic fibrosis in young β-TM patients.

  15. Clinical Effect of Low Dose Tetraiodothyronine in Hepatic Fibrosis Activity on Compensated Cirrhosis with T3 Degraded%小剂量甲状腺素对低T_3代偿期肝硬化的影响

    Institute of Scientific and Technical Information of China (English)

    陈洁

    2009-01-01

    目的 探讨代偿期肝硬化甲状腺激素水平的变化及小剂量甲状腺素对低T_3代偿期肝硬化患者肝纤维化的影响.方法 60名伴有T_3降低的代偿期肝硬化患者,随机分为两组,给予相同的保肝、营养支持治疗,治疗组另加左旋甲状腺素片25 mg/d,连续1个月,观察两组临床疗效、肝功能及肝纤维化指标的变化.结果 治疗组同对照组临床疗效无差异,治疗组血清AST、ALT、血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PC-Ⅲ)、Ⅳ型胶原(C-Ⅳ)水平低于对照组,ALB无变化,A/G比值高于对照组.结论 外源性甲状腺素对T_3代偿期肝硬化患者能减轻肝纤维化的发展.%Objectives To investigate change of Tetraiodothyronine(TH)in serum on compensated cirrhosis with T_3 degraded and observe the effect of TH in hepatic fibrosis activity.Methods Sixty patients were randomly divided into experimental group and control group.The patients in experimental group and control group received same treatment,including protecting hepatic function and nutritional support.TH were taken to experimental group with 25 mg/d for a month.clinical effect were estimated,Hepatic function and hepatic fibrosis activity were measured in serum on all patients when the treatment was over.Results In comparison with control group,the levels of AST、ALT、HA、LN、PC-Ⅲand C-Ⅳin serum were lower,the level of ALB Was indiscriminate,and proportionality of A/G was higher in cirrhosis.Clinical effect was same in two groups.Conclusion The level of TH in serum was decreasing in compensation cirrhosis,and additional TH can decrease hepatic fibrosis activity,but can not improve clinical effect in short.

  16. Hepatic stellate cell-targeted delivery of hepatocyte growth factor transgene via bile duct infusion enhances its expression at fibrotic foci to regress dimethylnitrosamine-induced liver fibrosis.

    Science.gov (United States)

    Narmada, Balakrishnan Chakrapani; Kang, Yuzhan; Venkatraman, Lakshmi; Peng, Qiwen; Sakban, Rashidah Binte; Nugraha, Bramasta; Jiang, Xuan; Bunte, Ralph M; So, Peter T C; Tucker-Kellogg, Lisa; Mao, Hai-Quan; Yu, Hanry

    2013-05-01

    Liver fibrosis generates fibrotic foci with abundant activated hepatic stellate cells and excessive collagen deposition juxtaposed with healthy regions. Targeted delivery of antifibrotic therapeutics to hepatic stellate cells (HSCs) might improve treatment outcomes and reduce adverse effects on healthy tissue. We delivered the hepatocyte growth factor (HGF) gene specifically to activated hepatic stellate cells in fibrotic liver using vitamin A-coupled liposomes by retrograde intrabiliary infusion to bypass capillarized hepatic sinusoids. The antifibrotic effects of DsRed2-HGF vector encapsulated within vitamin A-coupled liposomes were validated by decreases in fibrotic markers in vitro. Fibrotic cultures transfected with the targeted transgene showed a significant decrease in fibrotic markers such as transforming growth factor-β1. In rats, dimethylnitrosamine-induced liver fibrosis is manifested by an increase in collagen deposition and severe defenestration of sinusoidal endothelial cells. The HSC-targeted transgene, administered via retrograde intrabiliary infusion in fibrotic rats, successfully reduced liver fibrosis markers alpha-smooth muscle actin and collagen, accompanied by an increase in the expression of DsRed2-HGF near the fibrotic foci. Thus, targeted delivery of HGF gene to hepatic stellate cells increased the transgene expression at the fibrotic foci and strongly enhanced its antifibrotic effects.

  17. Didymin Alleviates Hepatic Fibrosis Through Inhibiting ERK and PI3K/Akt Pathways via Regulation of Raf Kinase Inhibitor Protein

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    Xing Lin

    2016-12-01

    Full Text Available Background: Didymin has been reported to have anti-cancer potential. However, the effect of didymin on liver fibrosis remains illdefined. Methods: Hepatic fibrosis was induced by CCl4 in rats. The effects of didymin on liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminases activities and collagen-related indicators levels were determined by commercially available kits. Moreover, the effects of didymin on hepatic stellate cell apoptosis and cell cycle were analyzed by flow cytometry. Mitochondrial membrane potential was detected by using rhodamine-123 dye. The expression of Raf kinase inhibitor protein (RKIP and the phosphorylation of the ERK/MAPK and PI3K/Akt pathways were assessed by Western blot. Results: Didymin significantly ameliorated chronic liver injury and collagen deposition. It strongly inhibited hepatic stellate cells proliferation, induced apoptosis and caused cell cycle arrest in G2/M phase. Moreover, didymin notably attenuated mitochondrial membrane potential, accompanied by release of cytochrome C. Didymin significantly inhibited the ERK/MAPK and PI3K/Akt pathways. The effects of didymin on the collagen accumulation in rats and on the biological behaviors of hepatic stellate cells were largely abolished by the specific RKIP inhibitor locostatin. Conclusion: Didymin alleviates hepatic fibrosis by inhibiting ERK/MAPK and PI3K/Akt pathways via regulation of RKIP expression.

  18. Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.

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    Tian Lan

    Full Text Available Reactive oxygen species (ROS produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX play a key role in liver injury and fibrosis. Previous studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared. HSCs are the primary myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation. Mice were treated with carbon tetrachloride (CCl4 to induce liver fibrosis. Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4 deficiency are approximately equally effective in preventing liver injury in the mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as inflammatory and proliferative genes induced by lipopolysaccharide (LPS, platelet-derived growth factor (PDGF, or sonic hedgehog (Shh in primary mouse HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for 5 days. Finally, NOX1 and NOX4 protein levels were increased in human livers with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling mediates the pathogenesis of liver fibrosis, including the direct activation of HSC.

  19. Peroxiredoxin 2: a potential biomarker for early diagnosis of Hepatitis B Virus related liver fibrosis identified by proteomic analysis of the plasma

    Directory of Open Access Journals (Sweden)

    Wang Haijian

    2010-10-01

    Full Text Available Abstract Background Liver fibrosis is a middle stage in the course of chronic Hepatitis B virus (HBV infection, which will develop into cirrhosis and eventually hepatocellular carcinoma (HCC if not treated at the early stage. Considering the limitations and patients' reluctance to undergo liver biopsy, a reliable, noninvasive diagnostic system to predict and assess treatment and prognosis of liver fibrosis is needed. The aim of this study was to identify biomarkers for early diagnosis of HBV related liver fibrosis. Method Plasma samples from 7 healthy volunteers and 27 HBV infected patients with different stages of fibrosis were selected for 2-DIGE proteomic screening. One-way ANOVA analysis was used to assess differences in protein expression among all groups. The alteration was further confirmed by western blotting. Plasma levels of 25 serological variables in 42 healthy volunteers and 68 patients were measured to establish a decision tree for the detection of various stages fibrosis. Result The up-regulated proteins along with fibrosis progress included fibrinogen, collagen, macroglobulin, hemopexin, antitrypsin, prealbumin and thioredoxin peroxidase. The down-regulated proteins included haptoglobin, serotransferrin, CD5 antigen like protein, clusterin, apolipoprotein and leucine-rich alpha-2-glycoprotein. For the discrimination of milder stage fibrosis, the area under curve for Prx II was the highest. Four variables (PT, Pre, HA and Prx II were selected from the 25 variables to construct the decision tree. In a training group, the correct prediction percentage for normal control, milder fibrosis, significant fibrosis and early cirrhosis was 100%, 88.9%, 95.2% and 100%, respectively, with an overall correct percent of 95.9%. Conclusion This study showed that 2-D DIGE-based proteomic analysis of the plasma was helpful in screening for new plasma biomarkers for liver disease. The significant up-expression of Prx II could be used in the early

  20. Insulin resistance as a non-invasive method for the assessment of fibrosis in patients with hepatitis C: a comparative study of biochemical methods La resistencia a la insulina en la valoración no invasiva de la fibrosis en pacientes con hepatitis C: Estudio comparativo de métodos bioquímicos

    Directory of Open Access Journals (Sweden)

    M. Romera

    2006-03-01

    Full Text Available Introduction: insulin resistance (IR promotes the progression of fibrosis and diminishes response to treatment in patients with hepatitis C. Recently, Sydney's index (includes IR has been proposed as a non-invasive method for the prediction of fibrosis. Objective: to assess the usefulness of Sydney's index for the prediction of advanced fibrosis (F3-F4 or absence of significant fibrosis (F0-F1 in patients with chronic hepatitis C. Patients and methods: we included 131 patients suffering from chronic hepatitis C. Mean age was 40 ± 11, 78 men and 53 women. Fibrosis stage was (F0-F1 69 patients, F2: 40, and advanced (F3-F4 in 22 patients. We measured baseline AST, ALT, GGT, platelet, cholesterol, alcohol, and IR (HOMA - IR levels. Sydney, Forns' and APRI indexes were calculated. Results: the area under the curve for the diagnosis of absence of significant fibrosis in each method was: Sydney: 0.80, Forns: 0.71, APRI: 0.70; p = ns. Moreover, the diagnostic capacity of advanced fibrosis was: Sydney: 0.88, Forns: 0.83, APRI: 0.82; p = ns. The predictive negative value of significant fibrosis was 74, 72, and 67%, respectively. Due to the presence of intermediate values, the indexes were not applicable to 36, 44 and 43% of patients respectively. Conclusions: the incorporation of insulin resistance among biochemical non-invasive methods slightly improves the yield of other indexes. Nevertheless, results are suboptimal, and more than one third of patients might not be correctly classified.Introducción: la resistencia a la insulina (RI promueve la progresión de la fibrosis y disminuye la respuesta al tratamiento en pacientes con hepatitis C. Recientemente, se ha propuesto el índice de Sidney como método no invasivo de predicción de la fibrosis que incluye la RI. Objetivo: valorar la utilidad del índice de Sidney en la predicción de fibrosis avanzada (F3-F4 o ausencia de fibrosis significativa (F0-F1 en pacientes con hepatitis C. Pacientes y m

  1. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC e da imunodeficiência humana (VHC/HIV tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC. Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são poss

  2. Cultured Mycelium Cordyceps sinensis allevi¬ates CCl4-induced liver inflammation and fibrosis in mice by activating hepatic natural killer cells.

    Science.gov (United States)

    Peng, Yuan; Huang, Kai; Shen, Li; Tao, Yan-yan; Liu, Cheng-hai

    2016-02-01

    Recent evidence shows that cultured mycelium Cordyceps sinensis (CMCS) effectively protects against liver fibrosis in mice. Here, we investigated whether the anti-fibrotic action of CMCS was related to its regulation of the activity of hepatic natural killer (NK) cells in CCl4-treated mice. C57BL/6 mice were injected with 10% CCl4 (2 mL/kg, ip) 3 times per week for 4 weeks, and received CMCS (120 mg·kg(-1)·d(-1), ig) during this period. In another part of experiments, the mice were also injected with an NK cell-deleting antibody ASGM-1 (20 μg, ip) 5 times in the first 3 weeks. After the mice were sacrificed, serum liver function, and liver inflammation, hydroxyproline content and collagen deposition were assessed. The numbers of hepatic NK cells and expression of NKG2D (activation receptor of NK cells) on isolated liver lymphocytes were analyzed using flow cytometry. Desmin expression and cell apoptosis in liver tissues were studied using desmin staining and TUNEL assay, respectively. The levels of α-SMA, TGF-β, RAE-1δ and RAE-1ε in liver tissues were determined by RT-qPCR. In CCl4-treated mice, CMCS administration significantly improved liver function, attenuated liver inflammation and fibrosis, and increased the numbers of hepatic NK cells and expression level of NKG2D on hepatic NK cells. Furthermore, CMCS administration significantly decreased desmin expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Injection with NK cell-deleting ASGM-1 not only diminished the numbers of hepatic NK cells, but also greatly accelerated liver inflammation and fibrosis in CCl4-treated mice. In CCl4-treated mice with NK cell depletion, CMCS administration decelerated the rate of liver fibrosis development, and mildly upregulated the numbers of hepatic NK cells but without changing NKG2D expression. CMCS alleviates CCl4-induced liver inflammation and fibrosis via promoting activation of hepatic NK cells. CMCS partially reverses ASGM

  3. [Correlation of liver stiffness measured by FibroTouch and FibroScan with Ishak fibrosis score in patients with chronic hepatitis B].

    Science.gov (United States)

    Chen, G F; Ping, J; Gu, H T; Zhao, Z M; Zhou, Y; Xing, F; Tao, Y Y; Mu, Y P; Liu, P; Liu, C H

    2017-02-20

    Objective: To investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B. Methods: A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis. Results: There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and

  4. Anti-hepatitis C virus seropositivity is not associated with metabolic syndrome irrespective of age, gender and fibrosis.

    Science.gov (United States)

    Cheng, Yuan-Lung; Wang, Yuan-Chen; Lan, Keng-Hsin; Huo, Teh-Ia; Huang, Yi-Hsiang; Su, Chien-Wei; Lin, Han-Chieh; Lee, Fa-Yauh; Wu, Jaw-Ching; Lee, Shou-Dong

    2015-01-01

    Although many studies have tried to clarify the association between hepatitis C virus (HCV) infection and metabolic syndrome, few studies have comprehensively assessed their relationship stratified by different demographic characteristics. We aimed to investigate the correlation between metabolic syndrome and anti-HCV seropositivity in Taiwan. This study enrolled consecutive subjects who had received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Metabolic syndrome was diagnosed according to the criteria defined by the International Diabetes Federation Task Force on Epidemiology and Prevention. Among the 30616 subjects enrolled in this study, the prevalence of positive anti-HCV serology was 2.7%, and 28.8% were diagnosed with metabolic syndrome. By multivariate analysis, metabolic syndrome was associated with higher body mass index, older age, male sex, a higher level of alanine aminotransferase, gamma-glutamyltransferase, platelet count and the presence of fatty liver whereas anti-HCV seropositivity was not an independent variable for metabolic syndrome. Further stratifying the subjects by age and sex, and there was still no significant difference in HCV status between those with and without metabolic syndrome. Moreover, the stage of liver fibrosis represented by aspartate aminotransferase to platelet ratio index was also not correlated with metabolic syndrome in the subjects with anti-HCV seropositivity. In conclusion, although subjects with anti-HCV seropositivity had higher fasting glucose levels and lower cholesterol and triglyceride levels compared to those with negative anti-HCV test, anti-HCV seropositivity was not associated with metabolic syndrome based on the current diagnostic criteria irrespective of age, gender and the stage of hepatic fibrosis.

  5. Efficacy of HGF carried by ultrasound microbubble-cationic nano-liposomes complex for treating hepatic fibrosis in a bile duct ligation rat model, and its relationship with the diffusion-weighted MRI parameters.

    Science.gov (United States)

    Zhang, Shou-hong; Wen, Kun-ming; Wu, Wei; Li, Wen-yan; Zhao, Jian-nong

    2013-12-01

    Hepatic fibrosis is a major consequence of liver aggression. Finding novel ways for counteracting this damaging process, and for evaluating fibrosis with a non-invasive imaging approach, represent important therapeutic and diagnostic challenges. Hepatocyte growth factor (HGF) is an anti-fibrosis cell growth factor that induces apoptosis in activated hepatic stellate cells, reduces excessive collagen deposition, and stimulates hepatocyte regeneration. Thus, using HGF in gene therapy against liver fibrosis is an attractive approach. The aims of the present study were: (i) to explore the efficacy of treating liver fibrosis using HGF expression vector carried by a novel ultrasound microbubble delivery system; (ii) to explore the diagnostic interest of diffusion-weighted MRI (DWI-MRI) in evaluating liver fibrosis. We established a rat model of hepatic fibrosis. The rats were administered HGF linked to novel ultrasound micro-bubbles. Progression of hepatic fibrosis was evaluated by histopathology, hydroxyproline content, and DWI-MRI to determine the apparent diffusion coefficient (ADC). Our targeted gene therapy produced a significant anti-fibrosis effect, as shown by liver histology and significant reduction of hydroxyproline content. Moreover, using DWI-MRI, the b value (diffusion gradient factor) was equal to 300s/mm(2), and the ADC values significantly decreased as the severity of hepatic fibrosis increased. Using this methodology, F0-F2 could be distinguished from F3 and F4 (Pmicrobubble-cationic nano-liposome complex for gene delivery. The data indicate that, this approach is efficient to counteract the fibrosis process. DWI-MRI appears a promising imaging technique for evaluating liver fibrosis.

  6. Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.

    Science.gov (United States)

    Chen, Pengguo; Li, Jie; Huo, Yan; Lu, Jin; Wan, Lili; Li, Bin; Gan, Run; Guo, Cheng

    2015-01-01

    Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-β stimulated HSCs compared with control group. After NR4A2 knockdown α-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.

  7. A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P. [University Hospital Giessen, Department of Pediatric Radiology, Giessen (Germany); Naehrlich, Lutz [University Hospital Giessen, Department of Pediatrics, Giessen (Germany); Harth, Sebastian; Krombach, Gabriele A. [University Hospital Giessen, Department of Radiology, Giessen (Germany)

    2013-03-15

    Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

  8. Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data

    Science.gov (United States)

    Dadabhai, Alia S; Saberi, Behnam; Lobner, Katie; Shinohara, Russell T; Mullin, Gerard E

    2017-01-01

    AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. METHODS Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis. PMID:28261385

  9. Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B: A cross-sectional study of diagnostic accuracy.

    Science.gov (United States)

    Wei, Xinhuan; Wei, Hongshan; Lin, Wei; Hu, Zhongjie; Zhang, Jing

    2017-05-01

    Cell death markers, M65 and M30, have been suggested to be sensitive markers of liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic hepatitis C. Our aim was to investigate whether these markers were useful in diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were controls. The blood samples were collected from CHB patients within 1 week before or after liver biopsy. According to METAVIR score system, liver inflammation was graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in parallel with the grades of liver inflammation. M65, not M30, increased significantly in patients with severe inflammation and normal alanine aminotransferase. M65 is one of the independent predictors of severe liver inflammation (≥A2). The levels of M65 and M30 levels significantly increased in parallel with the degree of inflammation in F1 patients, whereas they showed no statistical difference between different stages of fibrosis in A1 patients.Serum M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not M30, is valuable in the grading of liver fibrosis.

  10. Serum concentration of transforming growth factor (TGF)-beta 1 does not predict advanced liver fibrosis in children with chronic hepatitis B.

    Science.gov (United States)

    Lebensztejn, Dariusz Marek; Sobaniec-Lotowska, Maria; Kaczmarski, Maciej; Werpachowska, Irena; Sienkiewicz, Jerzy

    2004-01-01

    The aim of the study was to evaluate if measurement of TGF-beta1 has clinical usefulness as a marker of liver fibrosis using ROC analysis and to assess its serum concentration during IFN alpha treatment. Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig and Ishak et al. before and 12 months after the end of IFN alpha treatment of 30 children with chronic hepatitis B. TGF-beta1 was measured by means of the quantitative sandwich enzyme immunoassay technique using recombinant human TGF-beta soluble receptor type II as a solid phase pre-coated onto a microplate (R&D System Inc., Minneapolis, USA). There was no significant correlation between serum TGF-beta1 level and the stage of liver fibrosis. However TGF-beta1 levels in patients before IFN alpha therapy were significantly higher than in controls. IFN alpha treatment did not improve histological fibrosis during 18 months of observation and it did not cause any significant changes in serum TGF-beta1 levels although there was a tendency to decrease its level during therapy and follow-up. Serum concentration of TGF-beta1 does not predict advanced liver fibrosis in children with chronic hepatitis B.

  11. NUTRITIONAL STATUS AND DIETARY INTAKE IN NON-CIRRHOTIC ADULT CHRONIC HEPATITIS C PATIENTS

    Directory of Open Access Journals (Sweden)

    Catarina B A GOTTSCHALL

    2015-09-01

    Full Text Available BackgroundThe hepatitis C virus is one of the main causes of liver disease worldwide and may develop nutritional deficiencies.ObjectiveThe objective of this study was to assess and compare different nutritional status methods of adult patients with chronic hepatitis C virus, and to describe inadequacies in dietary intake.MethodsA cross-sectional study was conducted with adult outpatients with hepatitis C virus at a Brazilian hospital. Nutritional assessment included the 24-hour dietary recall, anthropometry (body weight, height, body mass index, triceps skinfold, mid-upper arm circumference, mid-arm muscle circumference, mid-upper arm muscle area, adductor policis muscle, Subjective Global Assessment, Royal Free Hospital Global Assessment and handgrip strength.ResultsA total of 94 outpatients (ages 30 to 76 years, was included, 46 were men. The prevalence of malnutrition as measured by the different methods was 6.4% (body mass index; 60.6% (handgrip strength, and 53.2% (Royal Free Hospital Global Assessment. There was correlation between mid-upper arm circumference and mid-arm muscle circumference (r=0.821, mid-upper arm circumference and triceps skinfold (r=0.575 and mid-upper arm circumference and mid-upper arm muscle area (r=0.781. Energy and protein intakes were below recommended levels in 49 (52.1% and 44 (46.8% of patients, respectively. Inadequate calcium, potassium, zinc and vitamin C intakes occurred in 92.6%, 97.9%, 63.8% and 60.6% of patients. There was an association between dietary energy and protein intake with Royal Free Hospital Global Assessment (P<0.001 and a tendency for them to be associated with handgrip strength (P=0.076 and P=0.054.ConclusionMalnutrition is frequently in hepatitis C virus patients. They have high prevalence of inadequate energy, protein and micronutrients intake, even in the absence of cirrhosis.

  12. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Nutrition Clinical Trials Primary Sclerosing Cholangitis Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  13. Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model.

    Science.gov (United States)

    Thomas, Reju George; Moon, Myeong Ju; Kim, Jo Heon; Lee, Jae Hyuk; Jeong, Yong Yeon

    2015-01-01

    Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.

  14. Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats

    Institute of Scientific and Technical Information of China (English)

    Guang-Fu Xu; Peng-Tao Li; Xin-Yue Wang; Xu Jia; De-Lu Tian; Liang-Duo Jiang; Jin-Xiang Yang

    2004-01-01

    AIM: To determine the dynamic changes in the expression of matrix metalloproteinases (MMPs) and the endogenous tissue inhibitors of MMPs inhibitors (TIMPs) during hepatic fibrosis induced by alcohol.METHODS: Male Sprague-Dawley rats were randomly divided into normal, 4 d, 2 wk, 4 wk, 9 wkand 11 wk groups, and the model rats were fed with a mixture of alcohol by gastric infusion at the designed time, respectively, then decollated and their livers were harvested for the examination of MMP2, MMP-3, MMP-9, MMP-13, TIMP-1 and TIMP-2 by immunohistochemistry, zymograghy and Westem blotting, respectively.RESULTS: Normal rats had moderate expression of MMP-2,which was decreased in the model rats except in the 11 wk group, where MMP-2 expression slightly increased. MMP-3had the similar changing pattern to MMP-2 despite weaker expression. MMP-9 expression decreased in the 4 d and 2 wk groups, rose in the 4 wk group, decreased again in the 9 wk group and returned to normal levels in the 11 wk group.MMP-13 expression decreased in the 4 d and 2 wk groups,and returned to normal levels in the 4 wk, 9 wk and 11 wk groups. TIMP-1 expression decreased in the 4 d and 2 wk groups, but sharply increased in the 4 wk group and sustained at a high level even after modeling was stopped for 2 wk. In normal rats TIMP-2 expression was strong. However, it decreased as soon as modeling began, and then gradually rose, but remained to a level lower than that in normal rats even after modeling was stopped for 2 wk.CONCLUSION: MMP-2 may not always expresses at a high level during hepatic fibrosis. MMP-13 and MMP-3 are acutely affected by TIMP-1. In this model TIMP-1 is the most powerful factor imposed on capillarization and peri-sinusoidal fibrosis. TIMP-2 is the most effective regulator on the metabolism of type IV collagen located in the basement of sinus.

  15. Assessment of nutritional status in adult patients with cystic fibrosis: whole-body bioimpedance vs body mass index, skinfolds, and leg-to-leg bioimpedance

    NARCIS (Netherlands)

    Hollander, F.M.; Roos, de N.M.; Vries, de J.H.M.; Berkhout, van F.T.

    2005-01-01

    Objective: To investigate whether body mass index (BMI) or body fat percentage estimated from BMI, skinfolds, or leg-to-leg bioimpedance are good indicators of nutritional status in adult patients with cystic fibrosis. Body fat percentage measured by whole-body bioimpedance was used as the reference

  16. Self-reported use of vitamins and other nutritional supplements in adult patients with cystic fibrosis. Is daily practice in concordance with recommendations?

    NARCIS (Netherlands)

    Hollander, F.M.; Roos, de N.M.; Dopheide, J.

    2010-01-01

    Background: In cystic fibrosis (CF), prophylactic supplementation of the fat-soluble vitamins A, D, E, and K is recommended. Limited data is available describing vitamin prescription adherence by adult patients. The aim of this study was to assess the use of prescribed vitamins and other nutritional

  17. Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations.

    Science.gov (United States)

    Li, Li; Somerset, Shawn

    2016-08-01

    An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression.

  18. 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.

  19. Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis

    Science.gov (United States)

    FAN, HUI-NING; CHEN, NI-WEI; SHEN, WEI-LIN; ZHAO, XIANG-YUN; ZHANG, JING

    2015-01-01

    The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL-propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine-γ-lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription-quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P<0.05). Conversely, the expression levels of ALB were significantly lower in the PAG group, as compared with the model group. In addition, the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with

  20. Effects of insulin-like growth factor binding protein-related protein 1 in mice with hepatic fibrosis induced by thioacetamide

    Institute of Scientific and Technical Information of China (English)

    LIU Li-xin; ZHANG Hai-yan; ZHANG Qian-qian; GUO Xiao-hong

    2010-01-01

    Background Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) can activate hepatic stellate cells and increase extracellular matrix (ECM) in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study.Methods Intraperitoneal injection of thioacetamide (TAA) is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, α-smooth muscle actin (α-SMA) and ECM in liver tissues, and the expression of transforming growth factor-β1 (TGF-β1) and Smad3. Data were statistically analyzed using one-way analysis of variance (ANOVA), the SNK-q test for inter-group differences.Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased (P <0.01), and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group (P <0.01). The expression of hepatic IGFBPrP1, α-SMA, TGF-β1, Smad3, collagen I and fibronectin (FN) was significantly up-regulated in the TAA5w group (P <0.01). Anti-IGFBPrP1 treatment reversed these changes (P <0.01).Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM (namely, collagen I and FN). The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.

  1. Effects of drug serum of anti-fibrosis I herbal compound on calcium in hepatic stellate cell and its molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    Yong-Hong Xiao; Dian-Wu Liu; Qing Li

    2005-01-01

    AIM: To investigate the effects of anti-fibrosis I herbal compound on intracellular Ca2+ in activated hepatic stellate cell (HSC) and to try to survey its molecular mechanism in treatment and prevention of hepatic fibrosis and portal hypertension.METHODS: The activated HSC line was plated on small glass cover slips in 24 wells culture dishes at a density of 5x106/mL, and incubated in RPMI-1640 media for 24 h.After the cells were loaded with Fluo-3/AM, intracellular Ca2+ was measured with laser scanning confocal microscopy (LSCM). The dynamic changes of intracellular Ca2+,stimulated by carbon tetrachloride, TGF-β1 antibody and the drug serum of anti-fibrosis I herbal compound and under orthogonal design were determined by LSCM. The effect of anti-fibrosis I herbal compound on intracellular Ca2+ was observed before and after the addition of TGF-β1antibody.RESULTS: The intracellular Ca2+ were significantly different in different dosage of carbon tetrachloride anti-fibrosis Iformula drug serum, TGF-β1 antibody and different turn of these substance, but their interval time between CCl4and TGF-β1 antibody, CCl4 and anti-fibrosis I drug serum had no influence on intracellular Ca2+. The result showed intracellular Ca2+ wasn't significantly different between rat serum without anti-fibrosis I and untreated group.After carbon tetrachloride stimulation, intracellular Ca2+ of activated HSC increased significantly when the dosage of CCl4 from 5 to 15 mmol/L, however, decreased significantly after stimulation by 5-20 μg/mL TGF-β1antibody or 5-20 mL/L drug serum. Moreover, before and after the addition of TGF-β1 antibody, intracellular Ca2+was significantly different. These results suggested that the molecular mechanism was independent of blocking TGF-β1 effects.CONCLUSION: Anti-fibrosis I herbal compound may treat hepatic fibrosis and decrease portal hypertension by inhibiting activated HSC contractility through decrease of intracellular Ca2+.

  2. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study.

    Science.gov (United States)

    Ferraioli, Giovanna; Tinelli, Carmine; Dal Bello, Barbara; Zicchetti, Mabel; Filice, Gaetano; Filice, Carlo

    2012-12-01

    Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. Copyright © 2012 American Association for the Study of Liver Diseases.

  3. Involvement of 90-kuD ribosomal S6 kinase in collagen type Ⅰ expression in rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Miao-Fang Yang; Jun Xie; Xiao-Yi Gu; Xiao-Hua Zhang; Andrew K Davey; Shuang-Jie Zhang; Ji-Ping Wang; Ren-Min Zhu

    2009-01-01

    AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type Ⅰ expression during the development of hepatic fibrosis in vivo and in vitro. METHODS: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type Ⅰ were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type Ⅰ in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type Ⅰ promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 μg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was overexpressed in activated HSCs and had a significant positive correlation with collagen type Ⅰ levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type Ⅰ was downregulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type Ⅰ promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line ( P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type Ⅰ through initiating the proliferation of HSCs.

  4. Evaluación de la fibrosis hepática en la hepatitis crónica por virus C mediante la aplicación prospectiva del Sabadell's NIHCED score: Sabadell's Non Invasive, Hepatitis C Related-Cirrhosis Early Detection Score Prospective evaluation of liver fibrosis in chronic viral hepatitis C infection using the Sabadell NIHCED: non-invasive hepatitis C related cirrhosis early detection index

    Directory of Open Access Journals (Sweden)

    G. Bejarano

    2009-05-01

    Full Text Available Introducción: la hepatitis crónica por VHC cursa de forma asintomática desarrollando cirrosis hepática y sus complicaciones en un 20-40% de los casos. En estudios previos se ha demostrado que la fibrosis avanzada es un factor pronóstico fundamental. El método gold standard para la valoración del grado de fibrosis es la biopsia hepática. Nuestro grupo ha validado un índice predictivo, el NIHCED (Sabadell's Non Invasive, Hepatitis C related-Cirrosis Early Detection Score, basado en datos demográficos, analíticos y ecográficos para determinar la presencia de cirrosis. Objetivo: nuestro objetivo es el de evaluar si el NIHCED predice la presencia de fibrosis avanzada en los pacientes con hepatitis crónica por virus C. Material y métodos: estudio prospectivo donde se incluyeron pacientes con hepatitis crónica por VHC. Se les realizó una biopsia hepática y el NIHCED. El grado de fibrosis se correlacionó con el valor del NIHCED mediante curva de ROC y el coeficiente de correlación de Spearman. Resultados: se incluyeron un total de 321 pacientes (ratio hombre/mujer 1,27 con una edad media de 48 ± 14 años. La biopsia hepática mostró que 131 (30,5% no tenían fibrosis o era expansión portal, mientras que 190 (69,5% tenían fibrosis avanzada o cirrosis. Para un punto de corte de 6 puntos, la sensibilidad fue del 72%, especificidad del 76,3%, VPP del 81%, VPN del 63,7% y una precisión diagnóstica del 72,5%, con un área bajo la curva fue de 0,787 y un coeficiente de correlación de Spearman de r = 0,65. Conclusiones: el NIHCED predice la presencia de fibrosis avanzada en un elevado porcentaje de pacientes sin necesidad de realizar biopsia hepática.Introduction: liver disease resulting from chronic hepatitis C virus (HCV infection follows an asymptomatic course towards cirrhosis and its complications in 20-40% of cases. Earlier studies demonstrated that advanced fibrosis is a prognostic factor. The "gold standard" for the evaluation

  5. Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis

    DEFF Research Database (Denmark)

    Görtzen, Jan; Schierwagen, Robert; Bierwolf, Jeanette

    2015-01-01

    . This study investigated the interaction of c-SRC and RhoA under different matrix stiffness conditions. METHODS: Liver fibrosis was induced in rats using bile duct ligation (BDL), thioacetamide (TAA) or carbon tetrachloride (CCl4) models. mRNA levels of albumin, PDGF-R, RHOA, COL1A1, and αSMA were analyzed....... RESULTS: Transcription of albumin and RhoA was decreased, whereas transcription and activation of c-SRC was increased in hepatocytes cultured on 12 kPa compared to 1 kPa gels. LX2 cells cultured on 12 kPa gels showed upregulation of RHOA, COL1A1, and αSMA mRNA levels. Inhibition of c-SRC by PP2 in LX2...... cells led to an increase in COL1A1 and αSMA most prominently in 12 kPa gels. In LX2 cells with RhoA overexpression, c-SRC inhibition by PP2 failed to improve fibrosis. RhoA expression was significantly elevated in human and experimental liver fibrosis, while c-SRC was inactivated. CONCLUSIONS...

  6. Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-β/Smad activity

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigated if paclitaxel can attenuate hepatic fi brosis in rat hepatic stellate cells (RHSCs). METHODS: RHSCs were cultured in vitro and randomly assigned to four groups: normal control group (treated only with Dulbecco's Modified Eagle's Medium), Taxol group (200 nmol/L paclitaxel was added to the cell culture), transforming growth factor (TGF)-β group (5 ng/mL recombinant human TGF-β1 was added to the cell culture), and TGF-β + Taxol group. TGF-β signaling cascade and status of various extracel...

  7. Endoscopically placed nasogastrojejunal feeding tubes: a safe route for enteral nutrition in patients with hepatic encephalopathy.

    Science.gov (United States)

    Lee, Steven S; Mathiasen, Ronald A; Lipkin, Craig A; Colquhoun, Steven D; Margulies, Daniel R

    2002-02-01

    Patients with hepatic encephalopathy are at particular risk for aspiration when given oral or gastric feedings. An ideal strategy might combine distal enteral feeding with proximal gastric decompression, which is offered by a nasogastrojejunal (NGJ) feeding tube. One objective was to determine the efficacy and safety of endoscopically placed NGJ feeding tubes in patients with hepatic encephalopathy. Charts of patients who underwent NGJ tube placements between April 1997 and January 2000 were retrospectively reviewed. Two endoscopic techniques ("push" and "pull") were used. Eighteen patients (nine male and nine female) underwent 32 procedures. Twelve patients had undergone liver transplantation, four had decompensated cirrhosis, and two had fulminant hepatic failure. Twenty procedures used the push technique and 12 required the pull technique. The insertion time was shorter for the push technique compared with the pull technique (21.8 vs 39.6 min, P < 0.05). Enteral feedings were begun at an average of 5.2 hours after tube placement. The tubes remained in place for an average of 13.9 days. Complications related to the NGJ tubes included self-removal in eight, tube clogging in five, proximal migration in four, and intraduodenal migration of the gastric port in one. No aspiration episodes occurred. We conclude that NGJ feeding tubes may be placed endoscopically as a bedside procedure for patients with hepatic encephalopathy and provide a safe, efficacious, and rapid route for enteral nutrition in these patients.

  8. NUTRITIONAL STATUS IS ASSOCIATED WITH HEALTH-RELATED QUALITY OF LIFE IN CHILDREN WITH CYSTIC FIBROSIS AGED 9–19 YEARS

    Science.gov (United States)

    Shoff, Suzanne M.; Tluczek, Audrey; Laxova, Anita; Farrell, Philip M.; Lai, HuiChuan J.

    2013-01-01

    Background The impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF). Methods Associations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9–19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ). Associations between height z-score (HtZ), BMI z-score (BMIZ) and seven CFQ dimensions were evaluated. Results Mean values of at least 80 were observed for all CFQ dimensions except respiratory symptoms and treatment burden. Treatment burden was significantly worse in patients with meconium ileus (57) compared to pancreatic insufficient (65) and sufficient (78) subjects, pnutritional status was associated with increased HRQOL scores. Early diagnosis through newborn screening and improved nutrition provides an opportunity to enhance quality of life and body image perception. PMID:23410621

  9. Research on zinc blood levels and nutritional status in adolescents with autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    Thalita Cremonesi Pereira

    2011-03-01

    Full Text Available CONTEXT: Zinc deficiency in children and adolescents impairs their growing, development and immune system. OBJECTIVE: To verify the existence of plasma and leukocyte zinc deficiency in adolescents with autoimmune hepatitis. METHODS: The study comprised 23 patients with autoimmune hepatitis, aged 10-18 years, assisted at the Ambulatory Service of Pediatric Hepatology of the University of Campinas Teaching Hospital, Campinas, SP, Brazil, and adolescents with ages compatible with the patients' ages comprised the control group. Sample of blood in both groups was collected for the analyses of plasma zinc and leukocyte zinc by atomic absorption spectrophotometry, beyond the nutritional status was evaluated in each adolescent. The following statistical tests were used: Mann-Whitney, Spearman's correlation and interclass concordance analysis. RESULTS:The significance level adopted was 5%. The average zinc level in plasma in patients was 71.91 ± 11.79 µg/dL and, in the control group, it was 80.74 ± 10.92 µg/dL, showing a significant difference (P = 0.04. The leukocyte zinc level in patients was 222.33 ± 166.13 pmol/10(6 cells and, in the control group, it was 226.64 ± 217.81 pmol/10(6 cells; there was no statistical significance between them (P = 0.45. CONCLUSION:The evaluation of the nutritional status showed that eutrophy is prevalent in patients, and they presented a higher body fat value than the control group, with a significant difference. More research is needed with adolescents with autoimmune hepatitis regarding levels of essential micronutrients, such as zinc, because a good nutritional status can improve the prognostic of liver disease.

  10. Hepatitis C virus induced miR200c down modulates FAP-1, a negative regulator of Src signaling and promotes hepatic fibrosis.

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    Sabarinathan Ramachandran

    Full Text Available Hepatitis C virus (HCV induced liver disease is the leading indication for liver transplantation (LTx. Reinfection and accelerated development of fibrosis is a universal phenomenon following LTx. The molecular events that lead to fibrosis following HCV infection still remains poorly defined. In this study, we determined microRNA (miRNA and mRNA expression profiles in livers from chronic HCV patients and normals using microarrays. Using Genego software and pathway finder we performed an interactive analysis to identify target genes that are modulated by miRNAs. 22 miRNAs were up regulated (>2 fold and 35 miRNAs were down regulated (>2fold compared to controls. Liver from HCV patients demonstrated increased expression of 306 genes (>3 fold and reduced expression of 133 genes (>3 fold. Combinatorial analysis of the networks modulated by the miRNAs identified regulation of the phospholipase C pathway (miR200c, miR20b, and miR31through cellular proto-oncogene tyrosine-protein kinase Src (cSrc, response to growth factors and hormones (miR141, miR107 and miR200c through peroxisome proliferator-activated receptor alpha and extracellular-signal-regulated kinases, and regulation of cellular proliferation (miR20b, miR10b, and miR141 through cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 p21. Real time PCR (RT-PCR validation of the miRNA in HCV infected livers demonstrated a 3.3 ±0.9 fold increase in miR200c. In vitro transfection of fibroblasts with miR200c resulted in a 2.2 fold reduction in expression of tyrosine-protein phosphatase non-receptor type 13 or FAS associated phosphatase 1 (FAP-1 and 2.3 fold increase in expression of cSrc. miR200c transfection resulted in significant increases in expression of collagen and fibroblast growth factor (2.8 and 3.4 fold, p<0.05. Therefore, we propose that HCV induced increased expression of miR200c can down modulate the expression of FAP1, a critical regulator of Src and MAP kinase pathway that

  11. Significance of the balance between regulatory T (Treg and T helper 17 (Th17 cells during hepatitis B virus related liver fibrosis.

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    Jing Li

    Full Text Available BACKGROUND: Hepatitis B virus-related liver fibrosis (HBV-LF always progresses from inflammation to fibrosis. However, the relationship between these two pathological conditions is not fully understood. Here, it is postulated that the balance between regulatory T (Treg cells and T helper 17 (Th17 cells as an indicator of inflammation may predict fibrosis progression of HBV-LF. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies and phenotypes of peripheral Treg and Th17 cells of seventy-seven HBeAg-positive chronic hepatitis B (CHB patients who underwent liver biopsies and thirty healthy controls were determined by flow cytometry. In the periphery of CHB patients, both Treg and Th17 frequencies were significantly increased and correlated, and a lower Treg/Th17 ratio always indicated more liver injury and fibrosis progression. To investigate exact effects of Treg and Th17 cells during HBV-LF, a series of in vitro experiments were performed using purified CD4(+, CD4(+CD25(+, or CD4(+CD25(- cells from the periphery, primary human hepatic stellate cells (HSCs isolated from healthy liver specimens, human recombinant interleukin (IL-17 cytokine, anti-IL-17 antibody and HBcAg. In response to HBcAg, CD4(+CD25(+ cells significantly inhibited cell proliferation and cytokine production (especially IL-17 and IL-22 by CD4(+CD25(- cells in cell-contact and dose-dependent manners. In addition, CD4(+ cells from CHB patients, compared to those from HC subjects, dramatically promoted proliferation and activation of human HSCs. Moreover, in a dramatically dose-dependent manner, CD4(+CD25(+ cells from CHB patients inhibited, whereas recombinant IL-17 response promoted the proliferation and activation of HSCs. Finally, in vivo evidence about effects of Treg/Th17 balance during liver fibrosis was obtained in concanavalin A-induced mouse fibrosis models via depletion of CD25(+ or IL-17(+ cells, and it's observed that CD25 depletion promoted, whereas IL-17 depletion

  12. [A clinical constelation in disuse: vitiligo, mastocytosis of the bone marrow, circulating heparinoid, chronic leg ulcer, hypoalbuminemia, ulcerative colitis and hepatic fibrosis].

    Science.gov (United States)

    Goihman Yahr, M; Goldstein, C; González, Y; Aranzazu, N; Convit, J; Acevedo Gallegos, F; Grases, P

    1977-01-01

    We report an unusual case. Our patient had vitiligo, ulcerative colitis, hepatic fibrosis, hypoalbuminemia, bone marrow mastocytosis, a circulating heparinoid and chronic leg ulcers. The relationship between some of the components of this constellation seems logical. This is the case with bone marrow mastocytosis and circulating heparinoid. Also, between hypoalbuminemia and colitis and liver disfunction. On the other hand, the relationship between other features does not seem clear in the light of current knowledge.

  13. Role of LncRNA-activated by transforming growth factor beta in the progression of hepatitis C virus-related liver fibrosis.

    Science.gov (United States)

    Fu, Na; Niu, Xuemin; Wang, Yang; Du, Huijuan; Wang, Baoyu; Du, Jinghua; Li, Ya; Wang, Rongqi; Zhang, Yuguo; Zhao, Suxian; Sun, Dianxing; Qiao, Liang; Nan, Yuemin

    2016-08-01

    Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages. Furthermore, increased expression level of LncRNA-ATB was also present in activated hepatic stellate cells (HSCs), and knockdown of LncRNA-ATB inhibited the expression of alpha-smooth muscle actin (α-SMA) and alpha-1 type I collagen (Col1A1). LncRNA-ATB was found to share the common miRNA responsive element of miR-425-5p with TGF-β type II receptor (TGF-βRII) and SMAD2. Ectopic expression of LncRNA-ATB in HSCs could upregulate the protein expression of TGF-βRII and SMAD2 by inhibiting the endogenous miR-425-5p. Moreover, overexpression of miR-425-5p could partly abrogate the expression of TGF-βRII and SMAD2 induced by LncRNA-ATB. Hence, we conclude that LncRNA-ATB promotes HCV-induced liver fibrogenesis by activating HSCs and increasing collagen I production through competitively binding to miR-425-5p. LncRNA-ATB may be a novel diagnostic biomarker and a potential therapeutic target for HCV-related hepatic fibrosis.

  14. Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis.

    Science.gov (United States)

    Fan, Hui-Ning; Chen, Ni-Wei; Shen, Wei-Lin; Zhao, Xiang-Yun; Zhang, Jing

    2015-09-01

    The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)‑induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL‑propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine‑γ‑lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription‑quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (PAGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with the model group (PAGTR1, which may be associated with the delayed progression of hepatic fibrosis.

  15. Digestive, hepatic, and nutritional manifestations in Latin American children with HIV/AIDS.

    Science.gov (United States)

    Velasco-Benítez, Carlos Alberto

    2008-08-01

    The HIV/AIDS infection is increasing in Latin America and the Caribbean regions, according to the World Health Organization (WHO). In Latin America, most cases are in Brasil, Mexico, and Colombia. Some causes of the HIV/AIDS infection in Latin America are poverty, limitations on the access to antiretroviral drugs, poor response from governmental and health authorities, migration, and scantiness of research resources. In the pediatric population, perinatal transmission is the main contact mechanism. Several digestive, hepatic, and nutritional manifestations allow the classification of HIV infection in children, according to the Centers for Disease Control and Prevention. Improvement in knowledge of the epidemiology, pathogenesis, physiopathology; and management of HIV enteropathy and on nutritional care practices of infected HIV children is recommended.

  16. Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    DENG Zi-yu; LI Jun; JIN Yong; CHEN Xiao-liang; Lü Xiong-wen

    2009-01-01

    Background Recent studies have suggested that p38 mitogen-activated protein kinases (MAPK) signalling pathway plays an important role in hepatic fibrosis. This study explored the antifibrotic effect of oxymatrine on tetrachloromethane induced liver fibrosis in rats and its modulation on the p38 MAPK signalling pathway. Methods One hundred and twenty healthy male Sprague-Dawley rats were randomly assigned to six groups: normal (n=20), induced fibrosis (n=20), colchicine (n=20) and three treatment groups of oxymatrine (n=20x3). We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type Ⅳ(CIV), procollagen Ⅲ(PCIII) and hydroxyproline (Hyp), α-smooth muscle actin (α-SMA) and phosphor-p38 (pp38).Results The relative indicators of changes in histopathology, HA, LN, CIV, PCIli, Hyp, α-SMA and pp38 were raised significantly in the induced fibrosis group (P <0.01 vs normal group). The semiquantitative hepatic fibrosis staging scores of middle dose group and high dose group were decreased (P <0.05 and P <0.01 respectively vs the induced fibrosis group), as was the average area of collagen in rats' liver, the concentrations of serum HA, LN, CIV, PCIII and liver tissue homogenate Hyp. The gene expression of a-SMA mRNA was considerably decreased in the treated animals, as was the protein espression of pp38 protein. Conclusions Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats in ways which relate to modulating the fibrogenic signal transduction via p38 MAPK signalling pathway.

  17. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    Science.gov (United States)

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B.

    2016-01-01

    Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%). Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. PMID:26400998

  18. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons.

    Science.gov (United States)

    Brunet, Laurence; Moodie, Erica E M; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B; Cohen, Jeff; Conway, Brian; Cooper, Curtis; Côté, Pierre; Cox, Joseph; Gill, John; Haider, Shariq; Sadr, Aida; Johnston, Lynn; Hull, Mark; Montaner, Julio; Moodie, Erica; Pick, Neora; Rachlis, Anita; Rouleau, Danielle; Sandre, Roger; Tyndall, Joseph Mark; Vachon, Marie-Louise; Sanche, Steve; Skinner, Stewart; Wong, David

    2016-01-15

    Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%). Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. Gypsophila elegans isoorientin attenuates CCl₄-induced hepatic fibrosis in rats via modulation of NF-κB and TGF-β1/Smad signaling pathways.

    Science.gov (United States)

    Lin, Xing; Chen, Yongxin; Lv, Shujuan; Tan, Shimei; Zhang, Shijun; Huang, Renbin; Zhuo, Lang; Liang, Shuang; Lu, Zhongpeng; Huang, Quanfang

    2015-09-01

    The hepatoprotective effect of Gypsophila elegans isoorientin (GEI) was evaluated using a hepatic fibrosis model induced by CCl4 in rats. The results revealed that GEI significantly prevented CCl4-induced liver injury and fibrosis, as evidenced by the attenuation of histopathological changes, the decrease in serum aminotransferase, and the inhibition of collagen accumulation. GEI strongly inhibited lipid peroxidation and recruited anti-oxidative defense system. Moreover, GEI alleviated pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 via inhibiting nuclear factor-κB (NF-κB) activation. In addition, GEI down-regulated the phosphorylation of Smad2/3 and up-regulated the level of hepatic Smad7, thereby inhibiting TGFβ1/Smad signaling pathway. In conclusion, our findings indicate that GEI can inhibit CCl4-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of NF-κB and TGF-β1/Smad signaling pathways.

  20. 24-Week Exposure to Oxidized Tyrosine Induces Hepatic Fibrosis Involving Activation of the MAPK/TGF-β1 Signaling Pathway in Sprague-Dawley Rats Model

    Directory of Open Access Journals (Sweden)

    Zhuqing Leslie Li

    2016-01-01

    Full Text Available Scope. Oxidized tyrosine (O-Tyr has been widely detected in many consumer protein products. O-Tyr products such as dityrosine (Dityr and 3-nitrotyrosine (3-NT are universal biomarkers of protein oxidation and have been demonstrated to be associated with metabolic disorders in biological system. Evaluation of potential intracorporal effects of dietary O-Tyr is important since the mechanism of biological impacts induced by oral oxidized protein products (OPPs is still limited although we have proved that some dietary OPPs would induce oxidative injury to liver and kidney. Methods and Results. The present study aimed to investigate the dose-dependent hepatic injury caused by oral O-Tyr in rats. 24-week feeding of O-Tyr enhanced aspartate aminotransferase (AST and alanine aminotransferase (ALT activities, increased total bilirubin (TBiL content, and led to oxidative damage in rats liver. Besides, O-Tyr distinctly increased the phosphorylation of p38 and ERK2 MAPKs and enhanced fibrosis-related TGF-β1 and Smad2/3 levels. Higher extracellular matrix (ECM indexes (ICTP, PIIINP and histological examination (HE and Masson staining also supported dose-dependent hepatic fibrosis caused by O-Tyr. Conclusion. These findings reveal that O-Tyr may induce oxidative damage and hepatic fibrosis via MAPK/TGF-β1 signaling pathway, in which ROS together with malondialdehyde (MDA and OPPs act as the pivotal mediators.

  1. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review.

    Science.gov (United States)

    Stallings, Virginia A; Stark, Lori J; Robinson, Karen A; Feranchak, Andrew P; Quinton, Hebe

    2008-05-01

    The Cystic Fibrosis Foundation established a process of systematic review of evidence to inform the development of clinical care guidelines and encourage evidence-based practice. The Subcommittee on Growth and Nutrition reviewed the evidence in two areas: energy intake and dosing for pancreatic enzyme replacement therapy. Evidence-based recommendations are presented here. Also, an ad hoc working group conducted a review of the literature and performed new analyses using the Cystic Fibrosis Foundation Patient Registry to update the recommendations for growth and weight-status monitoring. These Registry data-based recommendations are presented.

  2. Vitamin D status does not predict sustained virologic response or fibrosis stage in chronic hepatitis C genotype 1 infection.

    Science.gov (United States)

    Kitson, Matthew T; Dore, Gregory J; George, Jacob; Button, Peter; McCaughan, Geoffrey W; Crawford, Darrell H G; Sievert, William; Weltman, Martin D; Cheng, Wendy S; Roberts, Stuart K

    2013-03-01

    The relationship between vitamin D status and response to antiviral therapy and liver histology in hepatitis C virus genotype 1 (HCV-1) infection remains unclear, with studies to date yielding inconsistent results and failing to use reference assay methodology. We therefore analyzed pre-treatment 25-hydroxyvitamin D [25(OH)D] level, using reference liquid chromatography-tandem mass spectrometry methodology, in a cohort of treatment-naïve patients with HCV-1 to evaluate the association between vitamin D status, virologic response, and liver histology. 274 patients, with pre-treatment liver biopsy and up to 48 weeks of pegylated interferon alfa-2a plus ribavirin therapy, were tested for serum 25(OH)D level. Predictors of sustained virologic response (SVR), and variables associated with fibrosis stage, activity grade and 25(OH)D status were identified using multivariate analysis. Mean 25(OH)D level was 79.6 nmol/L, with a prevalence of 25(OH)D <75 nmol/L and <50 nmol/L of 48% and 16%, respectively. Season, race and geographic latitude were independent predictors of 25(OH)D status, while vitamin D deficiency was more prevalent in those with high activity grade (21% vs. 11%; p=0.03). Mean 25(OH)D level was lower (76.6 vs. 84.7 nmol/L; p=0.03) and 25(OH)D <75 nmol/L more prevalent (53% vs. 40%; p=0.03) in patients with an SVR, but no association between 25(OH)D status and SVR was found in multivariate analysis. Mean 25(OH)D level did not vary between fibrosis stage or activity grade. Baseline 25(OH)D level is not independently associated with SVR or fibrosis stage in HCV-1, but vitamin D deficiency is associated with high activity grade. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Analysis of the effects of xanthohumol on hepatic homeostasis, inflammation, fibrosis and cancerogenesis

    OpenAIRE

    Dorn, Christoph Michael

    2009-01-01

    Xanthohumol is the major prenylated chalcone found in hops, and it has been shown to exhibit various biological effects. However, xanthohumol effects on liver cells or in liver diseases, respectively, are widely unknown. In the present work, first the effects of xanthohumol on hepatic stellate cells (HSC), the central mediators of liver fibrogenesis, were analyzed. Xanthohumol inhibited the activation of primary human HSC and induces apoptosis in activated HSC in vitro in a dose dependent ...

  4. Vaccine induced Hepatitis A and B protection in children at risk for cystic fibrosis associated liver disease.

    Science.gov (United States)

    Shapiro, Adam J; Esther, Charles R; Leigh, Margaret W; Dellon, Elisabeth P

    2013-01-30

    Hepatitis A (HAV) and Hepatitis B (HBV) infections can cause serious morbidity in patients with liver disease, including cystic fibrosis associated liver disease (CFALD). HAV and HBV vaccinations are recommended in CFALD, and maintenance of detectable antibody levels is also recommended with chronic liver disease. A better understanding of factors predicting low HAV and HBV antibodies may help physicians improve protection from these viruses in CFALD patients. We examined HAV and HBV vaccine protection in children at risk for CFALD. Clinical and vaccine histories were reviewed, and HAV and HBV antibody titers measured. Those with no vaccination history or low HAV or HBV titers received primary or booster vaccinations, and responses were measured. Thirty-four of 308 children were at risk for CFALD per project criteria. Ten had previous HAV vaccination, of which 90% had positive anti-HAV antibodies. Thirty-three of 34 had previously received primary HBV vaccination (most in infancy), but only 12 (35%) had adequate anti-HBs levels (≥10mIU/mL). Children with adequate anti-HBs levels were older at first HBV vaccine (median 2.3 vs. 0.1 years, p<0.01), and at final HBV vaccine (median 4.0 vs. 0.8 years, p=0.01). Fourteen of 19 (74%) responded to HBV boosters. Z-scores for BMI at HBV booster were significantly lower in booster non-responders (p=0.04). Children at increased risk of CFALD have inadequate HAV and HBV antibody levels, and HBV antibody protection can be enhanced through vaccine boosters. HBV antibody titers should be assessed in CFALD patients with a history of vaccination, particularly in those who received HBV vaccines in infancy or who are malnourished. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Protective effect of isoorientin-2″-O-α-L-arabinopyranosyl isolated from Gypsophila elegans on alcohol induced hepatic fibrosis in rats.

    Science.gov (United States)

    Huang, Quan Fang; Zhang, Shi Jun; Zheng, Li; Liao, Ming; He, Min; Huang, RenBin; Zhuo, Lang; Lin, Xing

    2012-06-01

    Alcohol abuse is one of the major causes of liver fibrosis, which shows a sharply increasing trend worldwide, yet effective therapeutic options for advanced alcohol fibrosis are limited. Recently we investigated the effect of anti-fibrosis by isoorientin-2″-O-α-L-arabinopyranosyl (IOA) isolated from Gypsophila elegans. During the experiment, the model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. Analysis at the end of 24-week experiments showed that IOA could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, IOA could effectively inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that IOA was able to markedly reduce lipid peroxidation, recruit the anti-oxidative defense system, and induce HSC apoptosis by down-regulating bcl-2 mRNA, as well as inhibit the expression of α-smooth muscle actin and transforming growth factor β1 proteins. In short, our results showed that IOA is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model, which should be developed as a new drug to treat liver fibrosis and even cirrhosis.

  6. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia.

    Science.gov (United States)

    Sira, Mostafa M; Behairy, Behairy E; Abd-Elaziz, Azza M; Abd Elnaby, Sameh A; Eltahan, Ehab E

    2014-01-01

    Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2 ± 30.78 pg/mL versus 37.21 ± 5.39 pg/mL; P = 0.021). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P = 0.015, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P = 0.071). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.

  7. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4 in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia

    Directory of Open Access Journals (Sweden)

    Mostafa M. Sira

    2014-01-01

    Full Text Available Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4 and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2±30.78 pg/mL versus 37.21±5.39 pg/mL; P=0.021. ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P=0.015, 0.961, and 0.389, resp., whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P=0.071. In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.

  8. Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

    Science.gov (United States)

    Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

    2012-04-01

    Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.

  9. Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

    Science.gov (United States)

    Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

    2015-11-01

    Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis

  10. Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Fujun [Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai, 201508 (China); Zheng, Jianjian [Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai, 201508 (China); Dong, Peihong [Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China); Li, Guojun [Department of Hepatology, Ningbo Yinzhou Second Hospital, Ningbo, 315000 (China); Lu, Zhongqiu [Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China); Guo, Chuanyong; Liu, Zhanju [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai, 200072 (China); Fan, Xiaoming, E-mail: ktsqdph@163.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai, 201508 (China)

    2015-08-07

    In this study, we aimed at assessing a role of Alu-mediated p21 transcriptional regulator (APTR) in hepatofibrogenesis. APTR was upregulated in fibrotic liver samples and activated hepatic stellate cells (HSCs). Knockdown of APTR inhibited the activation of HSCs in vitro and mitigated the accumulation of collagen in vivo. Importantly, APTR silencing could abrogate TGF-β{sub 1}-induced upregulation of α-SMA in HSCs. In addition, inhibition of cell cycle and cell proliferation by APTR knockdown was attenuated by p21 siRNA1 in primary HSCs. Finally, serum APTR levels were increased in patients with liver cirrhosis, indicating a potential biomarker for liver cirrhosis. Collectively, evidence is proposed for a new biological role of APTR in hepatofibrogenesis. - Highlights: • APTR is upregulated in fibrotic liver tissues and activated HSCs. • APTR silencing inhibits HSC activation and the progression of liver fibrosis. • Antifibrotic effect of APTR silencing is achieved by increasing p21.

  11. Staging of Hepatic Fibrosis: Comparison of Magnetic Resonance Elastography and Shear Wave Elastography in the Same Individuals

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jeong Hee [Department of Radiology, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Woo, Hyun Sik; Yu, Mi Hye; Joo, Ijin; Lee, Eun Sun; Sohn, Ji Young [Department of Radiology, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lee, Kyung Boon [Department of Pathology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Han, Joon Koo; Choi, Byung Ihn [Department of Radiology, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2013-07-01

    To cross-validate liver stiffness (LS) measured on shear wave elastography (SWE) and on magnetic resonance elastography (MRE) in the same individuals. We included 94 liver transplantation (LT) recipients and 114 liver donors who underwent either MRE or SWE before surgery or biopsy. We determined the technical success rates and the incidence of unreliable LS measurements (LSM) of SWE and MRE. Among the 69 patients who underwent both MRE and SWE, the median and coefficient of variation (CV) of the LSM from each examination were compared and correlated. Areas under the receiver operating characteristic curve in both examinations were calculated in order to exclude the presence of hepatic fibrosis (HF). The technical success rates of MRE and SWE were 96.4% and 92.2%, respectively (p = 0.17), and all of the technical failures occurred in LT recipients. SWE showed 13.1% unreliable LSM, whereas MRE showed no such case (p < 0.05). There was moderate correlation in the LSM in both examinations (r = 0.67). SWE showed a significantly larger median LSM and CV than MRE. Both examinations showed similar diagnostic performance for excluding HF (Az; 0.989, 1.000, respectively). MRE and SWE show moderate correlation in their LSMs, although SWE shows higher incidence of unreliable LSMs in cirrhotic liver.

  12. High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262)

    Science.gov (United States)

    Lacombe, Karine; Duong Thi, Huong; Pham Thi Hanh, Phuc; Truong Thi Xuan, Lien; Chu Thi, Nga; Luong Que, Anh; Vu Hai, Vinh; Nagot, Nicolas; Tuaillon, Edouard; Dominguez, Stéphanie; Lemoine, Maud

    2016-01-01

    Rationale and Aims Screening and treatment for chronic hepatitis C are very limited in Vietnam and clinical data on HCV-related liver disease in HIV-coinfected people are almost inexistent. This study aimed to assess the severity of liver fibrosis and its risk factors in HIV-HCV coinfected patients in Haiphong, Northern Vietnam. Methods A cross-sectional study was conducted at a HIV outpatient clinic. Consecutive HIV treated adults with positive HCV serology completed a standardised epidemiological questionnaire and had a comprehensive liver assessment including hepatic elastography (Fibroscan®, Echosens). Results From February to March 2014, 104 HIV-HCV coinfected patients receiving antiretroviral therapy (ART) were prospectively enrolled (99 males, median age: 35.8 (32.7–39.6) years, median CD4 count: 504 (361–624) /mm3. Of them, 93 (89.4%) had detectable HCV RNA (median 6.19 (4.95–6.83 Log10 IU/mL). Patients were mainly infected with genotypes 1a/1b (69%) and genotypes 6a/6e (26%). Forty-three patients (41.3%) had fibrosis ≥F2 including 24 patients (23.1%) with extensive fibrosis (F3) and/or cirrhosis (F4). In univariate analysis, excessive alcohol consumption, estimated time duration from HCV infection, nevirapine and lopinavir-based ARV regimen and CD4 nadir were associated factors of extensive fibrosis/cirrhosis. Alcohol abuse was the only independent factor of extensive fibrosis in multivariate analysis. Using Fibroscan® as a gold standard, the high thresholds of AST-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4) had very good performances for the diagnosis of extensive fibrosis/cirrhosis (Se: 90 and 100%, Sp:84 and 81%, AUROCs = 0.93, 95%CI: 0.86–0.99 and 0.96 (0.92–0.99), respectively). Conclusion In this study, nearly 25% of HIV-HCV coinfected patients successfully treated with ART have extensive fibrosis or cirrhosis, and therefore require urgently HCV treatment. PMID:27148964

  13. Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?

    Energy Technology Data Exchange (ETDEWEB)

    Duran, Rafael, E-mail: rafael.duran@chuv.ch [Centre Hospitalier Universitaire Vaudois, University of Lausanne, Diagnostic and Interventional Radiology, Lausanne (Switzerland); Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Ronot, Maxime, E-mail: Maxime.ronot@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); University Paris Diderot, Sorbonne Paris Cité, INSERM U773, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3 Paris (France); Di Renzo, Sara, E-mail: Direnzo.sara@gmail.com [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Gregoli, Bettina, E-mail: Bettinagregoli@yahoo.it [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Van Beers, Bernard E., E-mail: Bernard.van-beers@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Vilgrain, Valérie, E-mail: Valerie.vilgrain@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); University Paris Diderot, Sorbonne Paris Cité, INSERM U773, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3 Paris (France)

    2015-05-15

    Highlights: • Hemangiomas were similar in patients with or without chronic liver disease on MRI. • Decrease in size & number of hemangiomas could start before the onset of cirrhosis. • T2 shine-through effect was less frequently observed in cirrhosis. - Abstract: Purpose: To compare qualitative and quantitative magnetic resonance (MR) imaging characteristics of hepatic hemangiomas in patients with normal, fibrotic and cirrhotic livers. Materials and methods: Retrospective, institutional review board approved study (waiver of informed consent). Eighty-nine consecutive patients with 231 hepatic hemangiomas who underwent liver MR imaging for lesion characterization were included. Lesions were classified into three groups according to the patients’ liver condition: no underlying liver disease (group 1), fibrosis (group 2) and cirrhosis (group 3). Qualitative and quantitative characteristics (number, size, signal intensities on T1-, T2-, and DW MR images, T2 shine-through effect, enhancement patterns (classical, rapidly filling, delayed filling), and ADC values) were compared. Results: There were 160 (69%), 45 (20%), and 26 (11%) hemangiomas in groups 1, 2 and 3, respectively. Lesions were larger in patients with normal liver (group 1 vs. groups 2 and 3; P = .009). No difference was found between the groups on T2-weighted images (fat-suppressed fast spin-echo (P = .82) and single-shot (P = .25)) and in enhancement patterns (P = .56). Mean ADC values of hemangiomas were similar between groups 1, 2 and 3 (2.11 ± .52 × 10{sup −3} mm{sup 2}/s, 2.1 ± .53 × 10{sup −3} mm{sup 2}/s and 2.14 ± .44 × 10{sup −3} mm{sup 2}/s, P = 87, respectively). T2 shine-through effect was less frequently observed in cirrhosis (P = .02). Conclusion: MR imaging characteristics of hepatic hemangioma were similar in patients with normal compared to fibrotic and cirrhotic livers. Smaller lesion size was observed with liver disease and less T2 shine-through effect was seen in

  14. Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression

    Directory of Open Access Journals (Sweden)

    Busch Michael P

    2007-12-01

    Full Text Available Abstract Background Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates. Methods We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use. Results Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before. Conclusion In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.

  15. 干扰素γ治疗肝和肺纤维化%Interferon gamma for the treatment of hepatic and pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    童葵塘

    2009-01-01

    实验室、动物试验和临床研究表明,干扰素γ(Interferon gamma,IFN-γ)对肝和肺纤维化有抑制作用.国内外学者报告用IFN-γ治疗各种原因引起的肝纤维化有效,临床症状明显改善,肝纤维化程度明显减轻.IFN-γ治疗特发性肺纤维化的初步结果显示,治疗后各种生物学指标有所改善,临床效果各家报道不一,多数学者认为IFN-γ治疗能降低病死率,对病情轻到中度的患者效果较好,用药时间应在1年以上.%Animal experiments and clinical studies show the inhibiting effect of IFN-γ on hepatic and pulmonary fibrosis.Numerous research evidence suggests that IFN-γ is an effective therapy for hepatic fibrosis in improving clinical symptoms,and relieving hepatic fibrosis.Preliminary study results of IFN-γ for the treatment of idiopathic pulmonary fibrosis (IPF) show that various biomarkers are improved after IFN-γ therapy,and the case mortality is lowered.The therapeutic efficacy of IFN-γ has been demonstrated to be better in mild and moderate patients with LPF.The duration of IFN-β therapy should be more than one year.

  16. Seguimento nutricional de pacientes com fibrose cística: papel do aconselhamento nutricional Nutritional follow-up of cystic fibrosis patients: the role of nutrition education

    Directory of Open Access Journals (Sweden)

    Fabíola V. Adde

    2004-12-01

    possibilitou melhora na aderência ao uso de enzimas pancreáticas e de suplementos nutricionais e no estado nutricional, principalmente nos pacientes de baixa idade.OBJECTIVE: To evaluate the nutritional status of a group of cystic fibrosis patients and establish the role of nutrition education addressed to them in a comparative study before and after intervention. METHODS: All cystic fibrosis patients in regular follow-up in the pulmonology clinic of Instituto da Criança during 1996-99 were prospectively monitored for 3.5 years. Measurements of weight, height, mid upper arm circumference, skinfolds and calculations of weight/age, height/age, weight/height, mid upper arm circumference and triceps z scores, percentage of ideal weight for height, percentage of body fat, check of the use of enzymes with meals and of the use of nutritional supplements were performed at four points in time: initial (I, 7 (II, 13 (III and 43 (IV months after the first evaluation. Nutritional counseling was given both verbally and in writing (booklet to all patients. RESULTS: Seventy-four patients, 38F/36M, age range 6 months to 18.4 years were evaluated. At study entry the anthropometric data showed: percentage of ideal weight for height = 94±13, percentage of body fat = 15±7.1, z scores for weight/age = -1.13±1.3, z scores for height/age = -0.94±1.2, z scores for weight/height = -0.69±1.1, z scores for mid upper arm circumference = -1.35±1.3, triceps z scores = -0.74±0.9. Compliance with enzyme therapy and use of high-calorie supplements improved during the study period. There was a significant increase in weight/height and triceps z scores and percentage of body fat throughout the study period. After stratifying patients into three age groups the anthropometric improvement was only significant among children under 5 years of age. CONCLUSIONS: Mild malnutrition was present in this group of cystic fibrosis patients. The nutrition education led to an improvement in compliance with enzyme

  17. Final Results of the Telaprevir Access Program: FibroScan Values Predict Safety and Efficacy in Hepatitis C Patients with Advanced Fibrosis or Cirrhosis

    Science.gov (United States)

    Lepida, Antonia; Colombo, Massimo; Fernandez, Inmaculada; Abdurakhmanov, Djamal; Abrao Ferreira, Paulo; Strasser, Simone I.; Urbanek, Petr; Mangia, Alessandra; Calleja, José L.; Iraqi, Wafae; DeMasi, Ralph; Lonjon-Domanec, Isabelle

    2015-01-01

    Background Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intention-to-treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. Trial Registration ClinicalTrials.gov NCT01508286 PMID:26398503