Glucocorticosteroids for people with alcoholic hepatitis.

Science.gov (United States)

Pavlov, Chavdar S; Varganova, Daria L; Casazza, Giovanni; Tsochatzis, Emmanuel; Nikolova, Dimitrinka; Gluud, Christian

2017-11-02

Alcoholic hepatitis is a form of alcoholic liver disease, characterised by steatosis, necroinflammation, fibrosis, and potential complications to the liver disease. Typically, alcoholic hepatitis presents in people between 40 and 50 years of age. Alcoholic hepatitis can be resolved if people abstain from drinking, but the risk of death will depend on the severity of the liver damage and abstinence from alcohol. Glucocorticosteroids are used as anti-inflammatory drugs for people with alcoholic hepatitis. Glucocorticosteroids have been studied extensively in randomised clinical trials in order to assess their benefits and harms. However, the results have been contradictory. To assess the benefits and harms of glucocorticosteroids in people with alcoholic hepatitis. We identified trials through electronic searches in Cochrane Hepato-Biliary's (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, and Science Citation Index Expanded. We looked for ongoing or unpublished trials in clinical trials registers and pharmaceutical company sources. We also scanned reference lists of the studies retrieved. The last search was 20 October 2016. Randomised clinical trials assessing glucocorticosteroids versus placebo or no intervention in people with alcoholic hepatitis, irrespective of year, language of publication, or format. We considered trials with adult participants diagnosed with alcoholic hepatitis, which could have been established through clinical or biochemical diagnostic criteria or both. We defined alcoholic hepatitis as mild (Maddrey's score less than 32) and severe (Maddrey's score 32 or more). We allowed co-interventions in the trial groups, provided they were similar. We followed Cochrane and CHB methodology, performing the meta-analyses using Review Manager 5 and Trial Sequential Analysis. We presented the results of dichotomous outcomes as risk ratios (RR) and those of the continuous outcomes as mean difference (MD). We applied both the fixed

Current Management of Alcoholic Hepatitis and Future Therapies

Institute of Scientific and Technical Information of China (English)

Behnam Saberi; Alia S.Dadabhai; Yoon-Young Jang; Ahmet Gurakar; Esteban Mezey

2016-01-01

Alcohol is one of the most common etiologies of liver disease,and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States.It encompasses a spectrum of disease,including fatty liver disease,alcoholic hepatitis (AH),and alcoholic cirrhosis.AH can range from mild to severe disease,with severe disease being defined as:Discriminant Function (DF) ≥ 32,or Model for End-stage Liver Disease (MELD) ≥ 21,or presence of hepatic encephalopathy.Management of the mild disease consists mainly of abstinence and supportive care.Severe AH is associated with significant mortality.Currently,there is no ideal medical treatment for this condition.Besides alcohol cessation,corticosteroids have been used with conflicting results and are associated with an inherent risk of infection.Overall steroids have shown short term benefit when compared to placebo,but they have no obvious long term benefits.Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial.Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death.Currently,early stage trials are underway,mainly targeting novel pathways based on disease pathogenesis,including modulation of innate immune system,inhibition of gut-liver axis and cell death pathways,and activation of transcription factor farnesyl X receptor (FXR).Future treatment may lie in human induced pluripotent stem cell (iPSC)technology,which is currently under investigation for the study of pathogenesis,drug discovery,and stem cell transplantation.Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ Suppply.

[Management of severe alcoholic hepatitis].

Science.gov (United States)

Wieser, Verena; Tilg, Herbert

2014-01-01

Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNFα) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future.

Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

Science.gov (United States)

Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

2015-08-28

To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and

Hepatic folate metabolism in the chronic alcoholic monkey

International Nuclear Information System (INIS)

Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

1981-01-01

To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3 H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected

Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

DEFF Research Database (Denmark)

Kermanizadeh, Ali; Jacobsen, Nicklas R.; Roursgaard, Martin

2017-01-01

or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation......, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models...... is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked....

[Cinnamon rolls are not associated with admission for toxic or alcoholic hepatitis in a Danish liver referral centre].

Science.gov (United States)

Gr Ønbæk, Henning; Borre, Mette

2014-12-08

Cinnamon contains cumarin, which may be toxic to the liver. EU-regulations standardardize the amount of cinnamon in pastry including cinnamon rolls. The aim of the study was to investigate if cinnamon intake from pastry was associated with toxic or alcoholic hepatitis. We registered 58 patients with toxic hepatitis, 38 (66%) women and 20 (34%) men with a median age of 51 (range: 32-80) and 53 (range: 18-78) years, respectively. A total of 22 patients had primarily cholestasis and 36 had hepatitis biochemically. The duration of toxic liver disease from admission to normalization of liver enzymes was similar in the two groups (3.5 ± 3.5 vs 3.6 ± 3.5 months). Toxic hepatitis was most often caused by drugs e.g. NSAID (n = 15; 26%), antibiotics (n = 9; 16%), alternative medicine (n = 7; 12%) and Antabuse (n = 5; 9%). We registered eight patients admitted with severe alcoholic hepatitis, five men and three women, median age of 60 (range: 34-67) years. Alcoholic hepatitis was associated with high alcohol intake. None of the patients with toxic or alcoholic hepatitis reported of excessive intake of cinnamon rolls and there was no evidence of cinnamon added to alcohol of alternative medicine products. Intake of cinnamon from cinnamon rolls is not associated with admission for toxic or alcoholic hepatitis. However, for the diagnosis of toxic liver diseases including alcohol it is very important to have patient information regarding any new drugs, alternative medicine and alcohol intake. Further, other causes of liver diseases should be excluded. not relevant. not relevant.

Alcohol Consumption and Viral Hepatitis in Chronic Liver Disease in ...

African Journals Online (AJOL)

Background: Precise assessment of the risks and interactions of alcohol consumption and viral hepatitis in the aetiology of chronic liver disease [CLD] are not locally available. Methodology: 74 patients with CLD and 74 controls were evaluated for Hepatitis B and C infection [anti-HCV, HBsAg]. The type and amount of ...

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

Science.gov (United States)

Groebner, Jennifer L; Tuma, Pamela L

2015-09-18

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options.

Science.gov (United States)

Teschke, Rolf

2018-06-01

Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used. Areas covered: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH. Expert opinion: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.

Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

Directory of Open Access Journals (Sweden)

Dong-Hyung Noh

2014-03-01

Full Text Available Hepatitis C virus (HCV has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC in the majority of patients (70% to 80%. Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG, core wild-Tg mice (TG-K, mutant core 116-Tg mice (TG-116 and mutant core 99-Tg mice (TG-99 were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01. Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

Directory of Open Access Journals (Sweden)

Jennifer L. Groebner

2015-09-01

Full Text Available The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

Unusual Infections Complicating the Use of Steroids with Severe Alcoholic Hepatitis: Report of 2 Cases

Directory of Open Access Journals (Sweden)

Vitor Arantes

1995-01-01

Full Text Available Corticosteroid therapy for acute alcoholic hepatitis has been demonstrated to enhance survival in patients who are encephalopathic, and who do not have renal failure or gastrointestinal bleeding. However, the complications of steroid therapy in such patients have been less well documented. The authors report two patients with alcoholic liver disease who developed life-threatening infections after steroid therapy was started. The first patient initially developed diabetes followed by Fournier's gangrene of the perineum, and a lung abscess following septic emboli. The second patient had established alcoholic cirrhosis rather than alcoholic hepatitis. She developed a necrotic ulcer on the arm at the site of an intravenous line, which was infected with a rhizopus species. Despite surgical debridement the lesion progressed and contributed to her death. Treatment of alcoholic hepatitis with steroids is not innocuous, and physicians should be aware of the potential for life-threatening complications.

Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease.

Science.gov (United States)

Tarantino, Giovanni; Finelli, Carmine

2013-10-28

Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing's syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing's syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing's syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing's syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

Alcoholic liver disease patients’ perspective on coping and physical activity-oriented rehabilitation intervention after hepatic encephalopathy

DEFF Research Database (Denmark)

Mikkelsen, Maria Rudkjær; Hendriksen, Carsten; Schiødt, Frank

2016-01-01

Aim and objective: To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. Background: Patients who have experienced...... were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. Results: The significance...... of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients’ ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category ‘regain control...

A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P rats.

Directory of Open Access Journals (Sweden)

Jonathon D Klein

Full Text Available Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (∼ 7.43 g ethanol/kg/day in inbred alcohol-preferring (iP10a rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake.

A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.

Science.gov (United States)

Klein, Jonathon D; Sherrill, Jeremy B; Morello, Gabriella M; San Miguel, Phillip J; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M; Lumeng, Lawrence; Lossie, Amy C

2014-01-01

Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (∼ 7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake.

Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population.

Science.gov (United States)

Mankal, Pavan Kumar; Abed, Jean; Aristy, Jose David; Munot, Khushboo; Suneja, Upma; Engelson, Ellen S; Kotler, Donald P

2015-03-01

Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function

International Nuclear Information System (INIS)

Lieber, Charles S.; Leo, Maria Anna; Wang, Xiaolei; DeCarli, Leonore M.

2008-01-01

Chronic alcohol consumption affects the gene expression of a NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-γ coactivator1α (PGC-1α). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days. Alcohol increased hepatic mRNA expression of FoxO1 (p = 0.003) and p53 (p = 0.001) while corresponding protein levels remained unchanged. However phospho-FoxO1 and phospho-Akt (protein kinase) were both decreased by alcohol consumption (p = 0.04 and p = 0.02, respectively) while hepatic p53 was found hyperacetylated (p = 0.017). Furthermore, mitochondrial SIRT5 was reduced (p = 0.0025), and PGC-1α hyperacetylated (p = 0.027), establishing their role in protein modification. Thus, alcohol consumption disrupts nuclear-mitochondrial interactions by post-translation protein modifications, which contribute to alteration of mitochondrial biogenesis through the newly discovered reduction of SIRT5

Alcoholic hepatitis with negligible sup(99m)Tc uptake and transient elevation of serum alpha-fetoprotein

International Nuclear Information System (INIS)

Hoshino, Hirosuke; Okumura, Makoto; Shimizu, Masanori; Eimoto, Tadaaki

1981-01-01

A 35 year old male with typical alcoholic hepatitis presented almost negligible uptake of sup(99m)Tc on the liver scan. Electron microscopic findings disclosing decreased number of Kupffer cells and impaired blood flow in the sinusoids may elucidate extremely diminshed uptake of isotope by the liver. Transient elevation of serum α-fetoprotein up to 3200 ng/ml observed during the active stage may indicate a regeneration process of hepatic necrosis occurred following the acute alcoholic hepatitis. (author)

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

DEFF Research Database (Denmark)

Rambaldi, A; Jacobs, B P; Iaquinto, G

2005-01-01

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

DEFF Research Database (Denmark)

Rambaldi, A; Jacobs, B P; Gluud, C

2007-01-01

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

Hepatic Encephalopathy

Medline Plus

Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

Directory of Open Access Journals (Sweden)

Luciana P. Rodrigues

2010-01-01

Full Text Available AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group were studied. After the undernourishment period (4 weeks with or without alcohol, both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage (carnitine groups. No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P.05 was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

A Snapshot of the Hepatic Transcriptome: Ad Libitum Alcohol Intake Suppresses Expression of Cholesterol Synthesis Genes in Alcohol-Preferring (P) Rats

OpenAIRE

Klein, Jonathon D.; Sherrill, Jeremy B.; Morello, Gabriella M.; San Miguel, Phillip J.; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M.; Lumeng, Lawrence; Lossie, Amy C.

2014-01-01

Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcoh...

Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

Directory of Open Access Journals (Sweden)

Kostić Velimir

2006-01-01

Full Text Available Background/Aim. Hepatitis C virus infection (HCV is a complex disease, most commonly chronicle (80-85%. The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. Methods. The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. Results. The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection. Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients. There was a signficant difference between the two subgroups (p < 0.001 regarding the examined values γ-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. Conclusion. Based on the number of the examined patients (n = 15, we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

Hepatic Hazard Assessment of Silver Nanoparticle Exposure in Healthy and Chronically Alcohol Fed Mice

DEFF Research Database (Denmark)

Kermanizadeh, Ali; Jacobsen, Nicklas R.; Roursgaard, Martin

2017-01-01

effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ’s ability for recovery post-NP challenge...

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

BACKGROUND: The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic...... 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...... participants could be of any sex and ethnic origin, above 16 years old, hospitalised or managed as outpatients. We excluded participants with viral hepatitis, autoimmunity, metabolic diseases, and toxins. DATA COLLECTION AND ANALYSIS: We followed the guidelines in the draft Cochrane Handbook for Systematic...

Alcoholic Hepatitis

Science.gov (United States)

... yellow color. Confusion, drowsiness and slurred speech (hepatic encephalopathy). A damaged liver has trouble removing toxins from your body. The ... of toxins can damage your brain. Severe hepatic encephalopathy can result in ... of the liver frequently leads to liver failure. Kidney failure. A ...

Carcinoma hepatocelular, alcoholismo y virus de la hepatitis C Hepatocellular carcinoma, alcoholism and hepatitis C virus infection

Directory of Open Access Journals (Sweden)

John Jairo Orrego B.

1994-02-01

Full Text Available Presentamos el caso de un paciente de 64 años, con el antecedente de consumo excesivo de alcohol, quien consulta por dolor localizado en el cuadrante superior derecho, de varios meses de evolución. En la laparoscopia se aprecian cirrosis macronodular y una masa localizada en el lóbulo Izquierdo del hígado, previamente detectada por ecografía. El estudio histológico demostró un carcinoma hepatocelular. Los estudios metabólicos, Inmunológicos y sexológicos permitieron documentar solamente la asociación con anticuerpos contra el virus de la Hepatitis C.

We report on the case of a sixty-four year old man who drank alcohol chronically. For several months he had suffered pain in his right upper abdominal quadrant. At laparoscopy macronodular cirrhosis and a mass 10-calized on the left hepatic lobe were observed; the mass had previously been identified by ultrasound examination. Histologic examination of the lesion established the presence of a hepatocellular carcinoma. Metabolic, Immunologic and serologic studies documented only the association with antibodies to hepatitis C virus.

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.

Directory of Open Access Journals (Sweden)

Tommaso Stroffolini

Full Text Available The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV and hepatitis C virus (HCV on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation.Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis.Females were older than males (p<0.01 and less frequently showed HBV and alcoholic aetiology (p<0.01. In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01. An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56 exceeds the sum (4.14 of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake. No interaction is observed in male sex.The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.

Alcoholic liver disease patients' perspective of a coping and physical activity-oriented rehabilitation intervention after hepatic encephalopathy.

Science.gov (United States)

Mikkelsen, Maria Rudkjaer; Hendriksen, Carsten; Schiødt, Frank Vinholt; Rydahl-Hansen, Susan

2016-09-01

To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. Patients who have experienced alcohol-induced hepatic encephalopathy have reduced quality of life, multiple complications, and social problems, and rehabilitation opportunities for these patients are limited. A grounded theory study and an evaluation study of a controlled intervention study. Semi-structured interviews were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. The significance of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients' ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category 'regain control over the diseased body'. This is subdivided into three separate categories: 'the experience of being physically strong', 'togetherness' and 'self-control', and they impact each other and are mutually interdependent. Alcoholic liver disease patients described the strength of the rehabilitation as regaining control over the diseased body. Professionals and relatives of patients with alcoholic liver disease may need to focus on strengthening and preserving patients' control of their diseased body by facilitating the experience of togetherness, self-control and physical strength when interacting with and supporting patients with alcoholic liver disease. A coping and physical activity-oriented rehabilitation intervention may help alcoholic liver disease patients to regain control over their diseased body and give patients the experience

Hepatic Myelopathy in a Patient with Decompensated Alcoholic Cirrhosis and Portal Colopathy

Directory of Open Access Journals (Sweden)

Madhumita Premkumar

2012-01-01

Full Text Available Cirrhotic or hepatic myelopathy is a rare neurological complication of chronic liver disease usually seen in adults and presents as a progressive pure motor spastic paraparesis which is usually associated with overt liver failure and a surgical or spontaneous systemic portocaval shunt. We describe the development of progressive spastic paraparesis, in a patient with alcoholic cirrhosis with portal hypertension and portal colopathy who presented with the first episode of hepatic encephalopathy. The patient had not undergone any shunt procedure.

Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy--in interaction with professionals and relatives.

Science.gov (United States)

Mikkelsen, Maria Rudkjær; Hendriksen, Carsten; Schiødt, Frank Vinholt; Rydahl-Hansen, Susan

2015-12-01

To identify and describe conditions that limit or support patients, with alcoholic liver disease after surviving alcohol-induced hepatic encephalopathy, ability to cope with current and potential physical and psychosocial problems--in interaction with professionals and relatives--and to recommend appropriate interventions. Alcoholic liver disease patients surviving alcohol-induced hepatic encephalopathy have significantly impaired quality of life. Internationally, there is a lack of knowledge about the conditions that affect alcoholic liver disease patients' coping and rehabilitation. A grounded theory study. Semi-structured interviews, conducted with 11 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy. The interview guide was inspired by Richard S. Lazarus's theory of stress and coping. The elements that support or limit alcoholic liver disease patients' ability to cope with physical and psychosocial problems in interaction with professionals and relatives were represented by the core category 'Struggle for preservation of identity as a significant individual'. It was characterised by three categories, which are interrelated and impact upon each other: 'Acknowledgement', 'Struggle to maintain control' and 'Achieving a sense of security'. Alcoholic liver disease patients experience a struggle to preserve their identity as a significant individual. It can be assumed that professionals and relatives in their interaction with, and support of, patients should focus on strengthening and preserving patients' identity in the form of acknowledgement, helping alcoholic liver disease patients maintain self-control and providing a safety net so patients feel a sense of security. It can be assumed that professionals should support alcoholic liver disease patients' appraisal of, and coping with, physical and psychosocial problems based on acknowledgment, understanding and a sympathetic attitude. Professionals should proactively approach patients

Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

Science.gov (United States)

Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

2014-09-01

We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

Directory of Open Access Journals (Sweden)

Claudia Sanna

2016-05-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

Glucocorticoids are ineffective in alcoholic hepatitis

DEFF Research Database (Denmark)

Christensen, E; Gluud, C

1995-01-01

The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted...... logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its...... overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment...

[Prevalence of hepatitis C virus and excessive consumption of alcohol in a nonhospital worker population].

Science.gov (United States)

Prieto Domingo, J J; Carrión Bolaños, J A; Bandrés Moya, F

1997-12-01

The aim of the study was to know the prevalence of the hepatitis C virus (HCV) in a non hospital work population by ELISA 3.0 and PCR-Amplicor, as well as its relationship with excessive alcohol intake (more than 280 g/week in men and 168 g/week in women). A transversal seroepidemiologic study was carried out in 1,109 workers of the Empresa Nacional de Electricidad, S.A. (ENDESA). During the annual medical examinations (April 1993-October 1994) the amount of alcoholic beverages each worker had consumed over the 7 days prior to the medical examination was obtained by anamnesis together with a blood sample for different laboratory tests. Sixteen percent of the workers had had excessive alcohol intake. The prevalence of anti HCV antibodies in the study population was 2.4% being up to 4.6% in the workers declaring excessive alcohol consumption and 10.4% if they also presented an elevation in any of the transaminases. The prevalence of the potentially ineffective workers was 1.46%. The prevalence of anti C antibodies by ELISA 3.0 was greater than expected (2.4%) significantly increasing in the population group which declared excessive alcohol intake, thereby demonstrating the relationship between alcohol and hepatitis C.

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

Science.gov (United States)

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

2005-11-07

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. 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-mum thick sections 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. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal 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, Pmodel 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, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report.

Science.gov (United States)

Etxagibel, Aitziber; Julià, M Rosa; Brotons, Alvaro; Company, M Margarita; Dolz, Carlos

2008-01-28

Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

Science.gov (United States)

Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

2003-09-01

Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report

Directory of Open Access Journals (Sweden)

Etxagibel Aitziber

2008-01-01

Full Text Available Abstract Introduction Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. Case presentation We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Conclusion Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

Directory of Open Access Journals (Sweden)

Adeeba Ahmed

Full Text Available Non alcoholic fatty liver disease (NAFLD is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH and cirrhosis. The potential role of glucocorticoids (GC in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F from inactive cortisone (E (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR.In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone.In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa.Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may

A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

Science.gov (United States)

Ahmed, Adeeba; Rabbitt, Elizabeth; Brady, Theresa; Brown, Claire; Guest, Peter; Bujalska, Iwona J; Doig, Craig; Newsome, Philip N; Hubscher, Stefan; Elias, Elwyn; Adams, David H; Tomlinson, Jeremy W; Stewart, Paul M

2012-01-01

Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F) from inactive cortisone (E) (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1), or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR). In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may serve to

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

NARCIS (Netherlands)

Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

2009-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity

DEFF Research Database (Denmark)

Henriksen, Jens Henrik; Ring-Larsen, H; Christensen, N J

1987-01-01

clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3...

Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

International Nuclear Information System (INIS)

Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

2010-01-01

Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH - ) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH - and hepatic ADH-normal (ADH + ) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼ 1.5-fold greater in ADH - vs. ADH + deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH - deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

Clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in treatment of alcoholic hepatitis

Directory of Open Access Journals (Sweden)

JI Huichun

2014-10-01

Full Text Available ObjectiveTo investigate the clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in the treatment of alcoholic hepatitis. MethodsA total of 92 patients with alcoholic hepatitis who were admitted to our hospital from February 2011 to February 2014 were recruited in this study and randomly divided into two groups. The control group (n=46 was treated with conventional therapy combined with compound ammonium glycyrrhetate S. The test group (n=46 was treated with puerarin in addition to the regimen used in the control group. After 20 days of treatment, the levels of total bilirubin (TBil, alanine aminotransferase (ALT, aspartate aminotransferase (AST, glutamyl transpeptidase (GGT, albumin (Alb, Glasgow alcoholic hepatitis score (GAHS, and abdominal ultrasound were measured and compared with the results before the treatment in both groups. The clinical efficacy and adverse reactions in the two groups were also compared. ResultsAfter the treatment, the GAHSs and levels of TBil, ALT, AST, and GGT in the two groups were all significantly lower than those before the treatment (all P＜0.05. In the test group after the treatment, the levels of TBil (20.96±6.85 μmol/L, ALT (33.72±14.18 U/L, and AST (38.69±6.38 U/L were all significantly lower than those in the control group (all P＜0.05. The marked response rate, overall response rate, and rate of improvement in abdominal ultrasound in the test group were 63.04%, 93.48%, and 44.44%, respectively, all significantly higher than those in the control group (all P＜0.05. There was no significant difference in adverse reactions between the two groups (P＞0.05. ConclusionFor patients with alcoholic hepatitis, the combined therapy with puerarin and compound ammonium glycyrrhetate S can improve the treatment outcome and protect the liver function, and it has high safety and holds promise for clinical application.

SUPERIMPOSED MESH PLOTTING IN MCNP

Energy Technology Data Exchange (ETDEWEB)

J. HENDRICKS

2001-02-01

The capability to plot superimposed meshes has been added to MCNP{trademark}. MCNP4C featured a superimposed mesh weight window generator which enabled users to set up geometries without having to subdivide geometric cells for variance reduction. The variance reduction was performed with weight windows on a rectangular or cylindrical mesh superimposed over the physical geometry. Experience with the new capability was favorable but also indicated that a number of enhancements would be very beneficial, particularly a means of visualizing the mesh and its values. The mathematics for plotting the mesh and its values is described here along with a description of other upgrades.

Alcohol and Cirrhosis

Science.gov (United States)

... Alcohol and Cirrhosis Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans and the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting ...

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

OpenAIRE

Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

2017-01-01

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apo...

Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark.

Science.gov (United States)

Rex, Karsten Fleischer; Krarup, Henrik Bygum; Laurberg, Peter; Andersen, Stig

2016-01-01

Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (pbiochemistry. Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect of alcohol intake on AST. HBV infection was slightly associated with ALP but not with other liver biochemistry parameters.

Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease)

DEFF Research Database (Denmark)

Buzzetti, Elena; Kalafateli, Maria; Thorburn, Douglas

2017-01-01

of the various pharmacological interventions compared with each other or with placebo or no intervention. Data collection and analysis: Two review authors independently identified trials and independently extracted data. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CIs) using...... cirrhosis, liver transplantation. None of the trials reported health-related quality of life or incidence of hepatocellular carcinoma. Severe alcoholic hepatitis Of the trials on alcoholic hepatitis, 19 trials (2545 participants) included exclusively participants with severe alcoholic hepatitis (Maddrey...... and follow-up of one to two years in order to compare the benefits and harms of different treatments in people with alcoholic hepatitis. Randomised clinical trials should include health-related quality of life and report serious adverse events separately from adverse events. Future randomised clinical trials...

Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

Directory of Open Access Journals (Sweden)

Torsten Schröder

2016-04-01

Full Text Available Objective: Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH. However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH. Methods: To determine the effect of a well-defined mitochondrial dysfunction on liver physiology at baseline and during dietary challenge, C57BL/6J-mtFVB/N mice were employed. This conplastic inbred strain has been previously reported to exhibit decreased mitochondrial respiration likely linked to a non-synonymous gene variation (nt7778 G/T of the mitochondrial ATP synthase protein 8 (mt-ATP8. Results: At baseline conditions, C57BL/6J-mtFVB/N mice displayed hepatic mitochondrial dysfunction characterized by decreased ATP production and increased formation of reactive oxygen species (ROS. Moreover, genes affecting lipid metabolism were differentially expressed, hepatic triglyceride and cholesterol levels were changed in these animals, and various acyl-carnitines were altered, pointing towards an impaired mitochondrial carnitine shuttle. However, over a period of twelve months, no spontaneous hepatic steatosis or inflammation was observed. On the other hand, upon dietary challenge with either a methionine and choline deficient diet or a western-style diet, C57BL/6J-mtFVB/N mice developed aggravated steatohepatitis as characterized by lipid accumulation, ballooning of hepatocytes and infiltration of immune cells. Conclusions: We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary Biliary Cholangitis Primary Sclerosing Cholangitis What ... B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis ...

Anti-inflammatory function of ginsenoside Rg1 on alcoholic hepatitis through glucocorticoid receptor related nuclear factor-kappa B pathway.

Science.gov (United States)

Gao, Yan; Chu, Shifeng; Li, Jingwei; Li, Jianping; Zhang, Zhao; Xia, Congyuan; Heng, Yang; Zhang, Meijin; Hu, Jinfeng; Wei, Guining; Li, Yueting; Chen, Naihong

2015-09-15

Ginseng is the dried root of Panax ginseng C.A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Pharmacological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rg1 is the most pharmacological active one. Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms. C57BL/6 mice were given oral consumption of 6g/kg alcohol 1h after treated with Rg1 (10, 20 and 40mg/kg) or dexamethasone (1mg/kg) for 9 consecutive days. Biochemical analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. According to our data, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in alcohol-intoxicated mouse livers. In addition, changes of GR related NF-κB pathway, including phospho-IκB-α, were also modulated to normal levels. This study demonstrates that Rg1 might promote GR mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Superimposed lichen planus pigmentosus].

Science.gov (United States)

Monteagudo, Benigno; Suarez-Amor, Óscar; Cabanillas, Miguel; de Las Heras, Cristina; Álvarez, Juan Carlos

2014-05-16

Lichen planus pigmentosus is an uncommon variant of lichen planus that is characterized by the insidious onset of dark brown macules in sun-exposed areas and flexural folds. Superimposed linear lichen planus is an exceedingly rare disorder, but it has been found in both lichen planopilaris and lichen planus types. A 39-year-old woman is presented showing a segmental and linear lichen planus associated with non-segmental lesions meeting all criteria for the diagnosis of superimposed linear planus pigmentosus. The segmental lesions were always more pronounced.

Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.

Science.gov (United States)

Guo, Rui; Liong, Emily C; So, Kwok Fai; Fung, Man-Lung; Tipoe, George L

2015-04-01

Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD. We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing intrahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptor gamma expression levels; (ii) decreasing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro-inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

Electrical stimulation superimposed onto voluntary muscular contraction.

Science.gov (United States)

Paillard, Thierry; Noé, Frédéric; Passelergue, Philippe; Dupui, Philippe

2005-01-01

Electrical stimulation (ES) reverses the order of recruitment of motor units (MU) observed with voluntary muscular contraction (VOL) since under ES, large MU are recruited before small MU. The superimposition of ES onto VOL (superimposed technique: application of an electrical stimulus during a voluntary muscle action) can theoretically activate more motor units than VOL performed alone, which can engender an increase of the contraction force. Two superimposed techniques can be used: (i) the twitch interpolation technique (ITT), which consists of interjecting an electrical stimulus onto the muscle nerve; and (ii) the percutaneous superimposed electrical stimulation technique (PST), where the stimulation is applied to the muscle belly. These two superimposed techniques can be used to evaluate the ability to fully activate a muscle. They can thus be employed to distinguish the central or peripheral nature of fatigue after exhausting exercise. In general, whatever the technique employed, the superimposition of ES onto volitional exercise does not recruit more MU than VOL, except with eccentric actions. Nevertheless, the neuromuscular response associated with the use of the superimposed technique (ITT and PST) depends on the parameter of the superimposed current. The sex and the training level of the subjects can also modify the physiological impact of the superimposed technique. Although the motor control differs drastically between training with ES and VOL, the integration of the superimposed technique in training programmes with healthy subjects does not reveal significant benefits compared with programmes performed only with voluntary exercises. Nevertheless, in a therapeutic context, training programmes using ES superimposition compensate volume and muscle strength deficit with more efficiency than programmes using VOL or ES separately.

Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease.

Science.gov (United States)

Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2016-03-01

The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). A total of 186 patients were included 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, psteatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥ 90%, CAP cutoffs for the detection of ≥ S2 and ≥ S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.

Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

Science.gov (United States)

Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Sarfati, Gilles; Nubret, Esther; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Bergheim, Ina; Cynober, Luc; De-Bandt, Jean-Pascal

2016-02-01

Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition

DYNAMICS OF CLINICAL AND BIOCHEMICAL PARAMETERS AND FUNCTIONAL STATE OF THE AUTONOMIC NERVOUS SYSTEM IN PATIENTS WITH ACUTE HEPATITIS B WITH CHRONIC ALCOHOL USE IN HEPATOTOXIC DOSES

Directory of Open Access Journals (Sweden)

O. O. Furyk

2014-02-01

Full Text Available Relevance of hepatitis B due to the high incidence complexity of pathogenesis, ineffective treatment, severe consequences of the disease. Among combined lesions of the liver, special attention is paid to viral-alcoholic type. One of the mechanisms of chronic hepatitis of different etiology is violation of the functional activity of the autonomic nervous system. The aim of this work- to determine the dynamics of spectral indices of heart rate variability in patients with acute hepatitis B from chronic use of alcohol in hepatotoxic doses. Materials and methods. 133 patients with acute hepatitis B were under observation. Patients were divided into groups taking account the presence or absence of chronic use of alcohol in hepatotoxic doses and using the classification of alcohol consumption based on the frequency and dose of consumed alcohol. I group comprised 52 patients with chronic use of alcohol in the hepatotoxic doses, II group consisted of 81 patient without this factor. Heart rate variability was diagnosed using computer cardiointervalometry performed by electrocardiographic diagnostic system CardioLab-2000. 20 healthy individuals were in the control group. Results and discussion. Prodromal period in patients of the I group was longer (p0,05. However, only patients in group I had marked hemorrhagic manifestations (5,8 % and itching (7.7%. Average serum total bilirubin level was higher (p<0,05 in patients from the I group than in patients from II group. Functional state of autonomic nervous system in patients of both groups were decreased in acute period (vagotonia. Period of convalescence in patients from the I group was accompanied by more severe autonomic dysfunction in 33,6 % (p<0,05. Conclusions. 1. Acute hepatitis B in patients with chronic alcohol use in hepatotoxic doses is characterized by longer (p<0,05 prodrome, cholestatic (7,7% and hemorrhagic manifestations (5,8%, higher levels of hyperbilirubinemia (p<0,05, and during

Phospholipids as Biomarkers for Excessive Alcohol Use

Science.gov (United States)

2017-03-01

17. Zhou P, Ross RA, Pywell CM, Liangpunsakul S, Duffield GE. Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis ...liver disease, alcoholic hepatitis , and alcoholic pancreatitis) among returning veterans at the younger age (~31 years old), compared to previously...Fibrosis in Chronic Hepatitis C Patients: A Systemic Review and Meta- Analysis. J Clin Gastroenterol 2016;50:80-84. 7. Gough G, Heathers L, Puckett D

Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of Alcoholic Hepatitis.

Science.gov (United States)

Horvath, Bela; Allende, Daniela; Xie, Hao; Guirguis, John; Jeung, Jennifer; Lapinski, James; Patil, Deepa; McCullough, Arthur J; Dasarathy, Srinivasan; Liu, Xiuli

2017-09-01

Alcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH and the effect of this variability on the proposed AHHS categories. Hematoxylin-eosin- and trichrome-stained slides from 32 patients diagnosed with AH with liver biopsies within 1 month of presentation (2000 to 2015) were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated, and an AHHS category (mild, moderate, severe) was assigned. The Fleiss' kappa coefficient (κ) analysis was performed to determine the interobserver agreement. A slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathologic features of AH with κ value ranging from 0.20 (95% confidence interval (CI): 0.03 to 0.46, megamitochondria) to 0.52 [95% CI: 0.40 to 0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (κ = 0.33, 95% CI: 0.20 to 0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a κ value of 0.40 (95% CI: 0.22 to 0.60). In general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice. Copyright �

Relationship between adiponectin and hepatic fibrosis markers expressions as well as insulin resistance index in patients with non-alcoholic fatty liver disease

International Nuclear Information System (INIS)

Cui Jianhe; Pan Feng; Zhou Chuanwen; Ren Jianguo; Li Donghai

2009-01-01

Objective: To investigate the retationship between expressions of adiponectin and hepatic fibrosis markers as well as insulin resistance index in patients with non-alcoholic fatty liver disease. Methods: Serum adiponectin, type III pro-collagen (PCIII), hyaluronic acid (HA), type IV collagen (CIV), laminin levels (with ELISA) and insulin resistance index (IRI) (calculated from homeostasis model assessment) were determined in 46 patients with non-alcoholic fatty liver disease (NAFLD) and 46 controls. Results The serum adiponectin levels in patients with NAFLD were significantly lower than those in controls while the serum hepatic fibrosis markers (PCIII, HA, CIV, LN) levels and IRI were significantly higher than those in controls (P<0.05). IRI was significantly positively correlated with the hepatic fibrosis markers levels (P<0.05). Serum adiponectin levels were significantly negatively correlated with WHR, RMI, HOMA-IRI and levels of FRG, TG, FINS hepatic fibrosis markers (P<0.05 or P<0.01). Conclusion: Serum adiponectin levels were greatly reduced in patients with NAFLD, which might play important role in the increase of insulin resistance and development of hepatic fibrosis. (authors)

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

DEFF Research Database (Denmark)

Perry, Rachel J; Samuel, Varman T.; Petersen, Kitt Mia Falck

2014-01-01

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding...... of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol...... activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes....

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

Directory of Open Access Journals (Sweden)

Boix Loreto

2006-11-01

Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

Directory of Open Access Journals (Sweden)

Michiko Itoh

Full Text Available Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

Science.gov (United States)

McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

2017-07-07

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Hepatitis C and Incarceration

Science.gov (United States)

... Hepatitis Cdo to take care of their liver? People with Hepatitis C should not use alcohol or street drugs, as these can hurt the liver. Some other products can also hurt people with Hepatitis C, even if they appear to ...

Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1α in rats

International Nuclear Information System (INIS)

Lieber, Charles S.; Leo, Maria A.; Wang Xiaolei; DeCarli, Leonore M.

2008-01-01

The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-γ coactivator1α (PGC-1α) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1α mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1α, while the transcription factor PPAR-γ remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1α mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1α and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications

Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function.

Science.gov (United States)

Groebner, Jennifer L; Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

2014-12-01

Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to microtubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease.

Science.gov (United States)

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-27

To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) ( P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Pulmonary and intestinal permeabilities in alcoholic hepatic cirrhosis

International Nuclear Information System (INIS)

De Botton, S.; Huglo, B.; Canva-Delacambre, V.; Colombel, J.F.; Beauchat, V.; Ziegels, P.; Prangere, T.; Steinling, M.; Machandise, X.; Wallaert, B.

1997-01-01

The aim of this prospective study was to evaluate simultaneously the intestinal permeability (IP), usually normal, and the pulmonary permeability, (PP) rather rarely studied, in patients afflicted with hepatic cirrhosis of alcoholic (HCA) origin. Thirty five non-smoker patients, afflicted with HCA, proved by biopsy, without pulmonary pathology and with normal pulmonary scanography were subject to our investigation. The pre-graft hepatic examination contained also respiratory functional explorations as well as bronchi-alveolar clearance (BAC) explorations. After inhalation of the DTPA- 99m Tc aerosols, a 20 min dynamical study in posterior-front condition was achieved. After exponential matching on the activity/time curve of the right lung, the half life (T 1/2 in min) and the Residual Activity at 10 min (RA in %) were calculated. The PI were than estimated and on the basis of urinary activity of EDTA- 51 Cr obtained on 24 h and expressed in % of the uptake activity, according to the Bjarnasson's technique. The results were compared (significant non-parametric tests if p 1/2 and 87.1% ± 6.7 vs 92.8% ± 2.6 (p < 0.002) for RA. It is significantly correlated with the total number of cells (r = -0.379) and with the number of lymphocytes (r = 0.351) in the BAC. For the first time an enhanced PP was observed in HCA, correlated with the increase in the number of cells at BAC

Non-Alcoholic Fatty Liver Disease in HIV Infection.

Science.gov (United States)

Macías, Juan; Pineda, Juan A; Real, Luis M

2017-01-01

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

The Adverse Effects of Alcohol on Vitamin A Metabolism

Directory of Open Access Journals (Sweden)

William S. Blaner

2012-05-01

Full Text Available The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A, as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered.

Chronic hepatitis

African Journals Online (AJOL)

infection by four diagnostic systems: first generation and second generation. ELlSA, second generation recombinant immunoblot assay and nested polymerase chain reaction analysis. HepatoJogy 1992; 16: 300-305. 14. Van der Poel CL, ... Alpha-1-antitrypsin deficiency. Alcoholic hepatitis. Non-alcoholic steatohepatitis.

Alcoholic hepatitis.

Science.gov (United States)

Damgaard Sandahl, Thomas

2014-10-01

Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an

Clinical significance of measurement of hepatic volume by computed tomography

International Nuclear Information System (INIS)

Sato, Hiroyuki; Matsuda, Yoshiro; Takada, Akira

1984-01-01

Hepatic volumes were measured by computed tomography (CT) in 91 patients with chronic liver diseases. Mean hepatic volume in alcoholic liver disease was significantly larger than that in non-alcoholic liver disease. Hepatic volumes in the majority of decompensated liver cirrhosis were significantly smaller than those of compensated liver cirrhosis. In liver cirrhosis, significant correlations between hepatic volume and various hepatic tests which reflect the total functioning hepatic cell masses were found. Combinations of hepatic volume with ICG maximum removal rate and with serum cholinesterase activity were most useful for the assessment of prognosis in liver cirrhosis. These results indicated that estimation of hepatic volume by CT is useful for analysis of pathophysiology and prognosis of chronic liver diseases, and for diagnosis of alcoholic liver diseases. (author)

PHARMACOTHERAPY FOR ALCOHOL ADDICTION IN A PATIENT WITH ALCOHOLIC CIRRHOSIS AND MASSIVE UPPER GASTROINTESTINAL BLEED: A CASE STUDY

OpenAIRE

Young, Samantha; Wood, Evan; Ahamad, Keith

2015-01-01

Alcohol use causes a substantial burden of morbidity and mortality worldwide. The pharmacologic treatment of alcohol dependence has been increasingly studied and proven to improve outcomes in individuals with alcohol use disorder. However, the treatment of alcohol use disorder is often challenging in the context of patients with hepatic impairment as many medications to treat alcohol use disorder are hepatically metabolised or may cause liver toxicity in some instances. We present a case hist...

76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Science.gov (United States)

2011-03-28

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; RFA-AA-11-02 Alcohol Induced Metabolic and Hepatic...: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

Motor performance during and following acute alcohol intoxication in healthy non-alcoholic subjects

DEFF Research Database (Denmark)

Poulsen, Mette Buch; Jakobsen, Johannes Klitgaard; Andersen, Henning

2007-01-01

Chronic alcohol abuse has adverse effects on skeletal muscle, and reduced muscle strength is frequently seen in chronic alcoholics. In this study the acute effects of moderate alcohol intoxication on motor performance was evaluated in 19 non-alcoholic healthy subjects (10 women, 9 men......). A randomised double-blinded placebo controlled design was applied to subjects receiving alcohol in juice and pure juice at two separate test periods. Isokinetic and isometric muscle strength and endurance were determined before, during, 24 and 48 h after the ingestion of alcohol in juice and juice (placebo......). To detect a reduced activation of the central motor pathways superimposed external electrical stimulations during voluntary contractions were applied. Creatine kinase (CK) was measured to detect any alcohol-induced changes in sarcolemmal integrity. No change was seen in isokinetic as well as in isometric...

Liver Disease in the Alcoholic

OpenAIRE

Szilagyi, Andrew

1986-01-01

The problem of liver damage in alcoholic patients is widespread. This review discusses hepatic damage on the basis of a histologic classification of increasing severity. In the early stages, or with compensated cirrhosis, clinical and laboratory findings may not accurately reflect hepatic involvement. Furthermore, there exists a group of alcoholic patients in whom liver disease may be caused by factors other than alcohol. Nevertheless, in most patients with liver disease, certain biochemical ...

A new index for differential diagnosis between mild hepatic lesions associated with chronic alcoholism (steatosis, steatofibrosis) and severe alcoholic liver disease (cirrhosis) by a combination of an aminopyrine breath test and a colloid hepatosplenic scintigraphy

International Nuclear Information System (INIS)

Urbain, D.; Jeghers, O.; Lenaers, A.; Wanet, P.; Abramovici, J.; Preux, C.

1984-01-01

The severity of liver disease is related not only to the degree of hepatocellular lesions but also to the hemodynamic changes created by extensive fibrosis. Theoretically, the combination of two tests providing information on these two aspects should allow a better identification of patients with severe alcoholic liver disease. In the present work our new functional index clearly improves the ability in differentiating mild alcoholic hepatic lesions from alcoholic cirrhosis. (orig.)

IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

DEFF Research Database (Denmark)

Parlesak, Alexandr; Schäfer, C.; Bode, C.

2002-01-01

Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

Science.gov (United States)

Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

2017-02-01

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

Directory of Open Access Journals (Sweden)

Wei Zhong

2015-10-01

Full Text Available Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation.

Statistical properties of superimposed stationary spike trains.

Science.gov (United States)

Deger, Moritz; Helias, Moritz; Boucsein, Clemens; Rotter, Stefan

2012-06-01

The Poisson process is an often employed model for the activity of neuronal populations. It is known, though, that superpositions of realistic, non- Poisson spike trains are not in general Poisson processes, not even for large numbers of superimposed processes. Here we construct superimposed spike trains from intracellular in vivo recordings from rat neocortex neurons and compare their statistics to specific point process models. The constructed superimposed spike trains reveal strong deviations from the Poisson model. We find that superpositions of model spike trains that take the effective refractoriness of the neurons into account yield a much better description. A minimal model of this kind is the Poisson process with dead-time (PPD). For this process, and for superpositions thereof, we obtain analytical expressions for some second-order statistical quantities-like the count variability, inter-spike interval (ISI) variability and ISI correlations-and demonstrate the match with the in vivo data. We conclude that effective refractoriness is the key property that shapes the statistical properties of the superposition spike trains. We present new, efficient algorithms to generate superpositions of PPDs and of gamma processes that can be used to provide more realistic background input in simulations of networks of spiking neurons. Using these generators, we show in simulations that neurons which receive superimposed spike trains as input are highly sensitive for the statistical effects induced by neuronal refractoriness.

Evaluation of portal hypertension: a comparison of the use of liver perfusion CT with wedge hepatic venous pressure and hepatic

International Nuclear Information System (INIS)

Chung, Dong Jin; Kim, Young Joong; Park, Yong Sung; Lee, Tae Hee; Kim, Chong Soo; Kang, Heung Keun

2008-01-01

We compared the hepatic perfusion indices obtained using hepatic perfusion CT with the wedge hepatic venous pressure (WHVP) and hepatic venous pressure gradient (HVPG) to determine the efficacy of the use of liver perfusion CT for the evaluation of portal hypertension. Thirty-five patients with liver cirrhosis underwent hepatic vein catheterization to measure WHVP and HVPG and underwent a liver perfusion CT examination. Arterial perfusion, portal perfusion, total perfusion and the hepatic perfusion index (HPI) were calculated by the methods described by Miles and Blomlely. The overall correlation coefficients (r) between the perfusion indices and WHVP and HVPG were calculated. An additional correlation coefficient of 23 alcoholic cirrhosis patients was calculated. Using Blomley's equation, HPI had a positive correlation with WHVP (r = .471; ρ < .05) and HVPG (r = .482; ρ < .05). For the alcoholic liver cirrhosis patients, HPI had a higher positive correlation with WHVP (r = .500; ρ < .05) and HVPG (r = .539; ρ < .05) than for the non-alcoholic cirrhosis patients. There was no statistical difference between the use of Miles' equation and Blomley's equation for the evaluation of portal hypertension. This preliminary study showed that HPI positively correlated with WHVP and HVPG, especially in alcoholic cirrhosis patients. Liver perfusion CT may be useful in the evaluation of portal hypertension

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

OpenAIRE

Borini, Paulo; Guimarães, Romeu Cardoso

1999-01-01

Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.

Science.gov (United States)

Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

2017-08-21

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

Optical stress investigations of notched bars with superimposed types of loads

International Nuclear Information System (INIS)

Richard, H.A.; Theis, W.

1982-01-01

Starting from the notch effect for various types of load, notch stresses are determined by optical methods for superimposed tensile and shearing stress and for superimposed tensile and bending stress. The superimposed stresses are induced by a device developed at the Technical Mechanics Department of Kaiserslautern University; only tensile stress needs to be applied to this testing device. The investigations have shown that in notched bars subject to superimposed tensile and shearing stress, stress increases will be higher than the maximum values of the two types of stress. For superimposed tensile and bending stress, notches on the outer side of the test piece and eccentric notches on the inner side may lead to a considerable stress increase. However, the stress distribution can be improved by an optimum arrangement of notches. (orig.) [de

[Electroencephalography in delirium superimposed on dementia].

Science.gov (United States)

Hanemaaijer, Judith I; Wijnen, Viona J M; van Gool, W A

2017-09-01

Recognizing delirium superimposed on pre-existing cognitive impairment or dementia, 'delirium superimposed on dementia' (DSD), is challenging because signs of delirium might be interpreted as symptoms of pre-existing cognitive dysfunction.In this paper, we review the literature on the role of electrencephalography (EEG) in the differential diagnosis of delirium, dementia and DSD.Conventional EEG, applying twenty to thirty electrodes, taking thirty minutes registration, is not feasible in psychogeriatric patients. Recent studies suggest that it is possible to reliably detect delirium using only a limited number of EEG electrodes for a short period of time.With this, use of EEG in the detection of delirium in patients with cognitive impairment or clinically manifest dementia could be possible.

DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease.

Science.gov (United States)

Chen, Hanqing; Shen, Feng; Sherban, Alex; Nocon, Allison; Li, Yu; Wang, Hua; Xu, Ming-Jiang; Rui, Xianliang; Han, Jinyan; Jiang, Bingbing; Lee, Donghwan; Li, Na; Keyhani-Nejad, Farnaz; Fan, Jian-Gao; Liu, Feng; Kamat, Amrita; Musi, Nicolas; Guarente, Leonard; Pacher, Pal; Gao, Bin; Zang, Mengwei

2018-02-19

Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects of the DEP domain-containing mTOR-interacting protein (DEPTOR) and the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) in the liver of chronic-plus-binge ethanol-fed mice and in the liver of patients with ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on-chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation of the lipogenic regulator lipin 1 and prevented alcohol-mediated inhibition of fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the ability of alcohol to up-regulate lipogenesis, to down-regulate fatty acid oxidation, and to induce steatogenic phenotypes. Chronic-plus-binge ethanol feeding led to activation of SREBP-1 and lipin 1 through S6K1-dependent and independent mechanisms. Furthermore, hepatocyte-specific deletion of SIRT1 disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic fatty liver, inflammation, and liver injury in mice. The dysregulation of SIRT1

Evaluation of portal hypertension: a comparison of the use of liver perfusion CT with wedge hepatic venous pressure and hepatic

Energy Technology Data Exchange (ETDEWEB)

Chung, Dong Jin; Kim, Young Joong; Park, Yong Sung; Lee, Tae Hee [University of Konyang College of Medicine, Daejeon (Korea, Republic of); Kim, Chong Soo; Kang, Heung Keun [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2008-09-15

We compared the hepatic perfusion indices obtained using hepatic perfusion CT with the wedge hepatic venous pressure (WHVP) and hepatic venous pressure gradient (HVPG) to determine the efficacy of the use of liver perfusion CT for the evaluation of portal hypertension. Thirty-five patients with liver cirrhosis underwent hepatic vein catheterization to measure WHVP and HVPG and underwent a liver perfusion CT examination. Arterial perfusion, portal perfusion, total perfusion and the hepatic perfusion index (HPI) were calculated by the methods described by Miles and Blomlely. The overall correlation coefficients (r) between the perfusion indices and WHVP and HVPG were calculated. An additional correlation coefficient of 23 alcoholic cirrhosis patients was calculated. Using Blomley's equation, HPI had a positive correlation with WHVP (r = .471; {rho} < .05) and HVPG (r = .482; {rho} < .05). For the alcoholic liver cirrhosis patients, HPI had a higher positive correlation with WHVP (r = .500; {rho} < .05) and HVPG (r = .539; {rho} < .05) than for the non-alcoholic cirrhosis patients. There was no statistical difference between the use of Miles' equation and Blomley's equation for the evaluation of portal hypertension. This preliminary study showed that HPI positively correlated with WHVP and HVPG, especially in alcoholic cirrhosis patients. Liver perfusion CT may be useful in the evaluation of portal hypertension.

Characterization of an alcoholic hepatic steatosis model induced by ethanol and high-fat diet in rats

Directory of Open Access Journals (Sweden)

Carlos Eduardo Alves de Souza

2015-06-01

Full Text Available Alcoholic liver disease is characterized by a wide spectrum of liver damage, which increases when ethanol is associated with high-fat diets (HFD. This work aimed to establish a model of alcoholic hepatic steatosis (AHS by using a combination of 10% ethanol and sunflower seeds as the source of HFD. Male rats received water or 10% ethanol and regular chow diet and/or HFD, which consisted of sunflower seeds. The food consumption, liquid intake and body weight of the rats were monitored for 30 days. After this period, blood was collected for biochemical evaluation, and liver samples were collected for histological, mitochondrial enzyme activity and oxidative stress analyses. Our results indicated that the combination of 10% ethanol and HFD induced micro- and macrosteatosis and hepatocyte tumefaction, decreased the levels of reduced glutathione and glutathione S-transferase activity and increased the level of lipoperoxidation and superoxide dismutase activity. The mitochondrial oxidation of NADH and succinate were partially inhibited. Complexes I and II were the main inhibition sites. Hepatic steatosis was successfully induced after 4 weeks of the diet, and the liver function was modified. The combination of 10% ethanol and sunflower seeds as an HFD produced an inexpensive model to study AHS in rats.

Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis.

Directory of Open Access Journals (Sweden)

Rie Ibusuki

Full Text Available Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1.Transgenic (TG mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro.After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro.HNP-1 secreted by neutrophils may exacerbate alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2 expression and an increase in miR-34a-5p expression.

Diagnosis of alcohol misuse and alcoholic liver disease among ...

African Journals Online (AJOL)

Alcohol related hepatocellular liver injury was assessed using aspartate aminotransferase, and alanine aminotransferase levels. A combination of CAGE score ≥2 and De Ritis ratio ≥2 defined alcoholic liver disease (ALD). Human Immunodeficiency Virus (HIV), and viral hepatitis B and C serologies were evaluated in all ...

Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

Directory of Open Access Journals (Sweden)

Sarah M. DeNucci

2010-01-01

Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

Adapting a computer-delivered brief alcohol intervention for veterans with Hepatitis C.

Science.gov (United States)

Cucciare, Michael A; Jamison, Andrea L; Combs, Ann S; Joshi, Gauri; Cheung, Ramsey C; Rongey, Catherine; Huggins, Joe; Humphreys, Keith

2017-12-01

This study adapted an existing computer-delivered brief alcohol intervention (cBAI) for use in Veterans with the hepatitis C virus (HCV) and examined its acceptability and feasibility in this patient population. A four-stage model consisting of initial pilot testing, qualitative interviews with key stakeholders, development of a beta version of the cBAI, and usability testing was used to achieve the study objectives. In-depth interviews gathered feedback for modifying the cBAI, including adding HCV-related content such as the health effects of alcohol on liver functioning, immune system functioning, and management of HCV, a preference for concepts to be displayed through "newer looking" graphics, and limiting the use of text to convey key concepts. Results from usability testing indicated that the modified cBAI was acceptable and feasible for use in this patient population. The development model used in this study is effective for gathering actionable feedback that can inform the development of a cBAI and can result in the development of an acceptable and feasible intervention for use in this population. Findings also have implications for developing computer-delivered interventions targeting behavior change more broadly.

Hepatic Encephalopathy

Medline Plus

Full Text Available ... to continue to work to my full capacity? Will I be able to drive? Patient Stories Angie M. Caregiver for Brother Charles DiAngelo Hepatic Encephalopathy Jason Dedmon Alcohol-related Cirrhosis ...

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

Science.gov (United States)

Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

Directory of Open Access Journals (Sweden)

Songtao Li

Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0 T MR spectroscopy

International Nuclear Information System (INIS)

Werven, J.R. van; Schreuder, T.C.M.A.; Nederveen, A.J.; Lavini, C.; Jansen, P.L.M.; Stoker, J.

2010-01-01

Rationale and objective: Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ( 1 H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was to assess hepatic UFA in patients with NAFLD using 1 H MRS. Materials and methods: We included 26 consecutive patients with deranged liver enzymes, with and without type 2 diabetes mellitus (DM2), suspected for NAFLD. Liver function and metabolic parameters were assessed. 1 H MRS measurements were performed at 3.0 T. From the 1 H MR spectra two ratios were calculated: ratio 1 (UFA); unsaturated fatty acid peak vs. reference water peak and ratio 2 (HTGC); total fatty acid peak vs. reference water peak. Results: Twenty-six patients were included. In these patients hepatic UFA (ratio 1) correlated with AST/ALT ratio (r = -0.46, p = 0.02), glucose levels (r = 0.46, p = 0.018), HOMA-IR (r = 0.59, p = 0.004) and HTGC (r = 0.81, p 1 H MRS. 1 H MRS determined hepatic UFA correlate with clinical and metabolic parameters associated with NAFLD. Hepatic UFA are increased in patients with DM2. This study provides evidence for the use of non-invasive 1 H MRS to assess hepatic UFA in vivo.

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

Science.gov (United States)

Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-10

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females ( p disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness ( p = 0.044). Tea consumption had no effect ( p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

A case of alcoholic hepatitis demonstrating focal fatty infiltration of the liver on computed tomography

International Nuclear Information System (INIS)

Uesaka, Toshihiro; Kato, Masayoshi; Nagai, Tadayuki; Kametani, Tomio; Horigami, Tateyuki; Takimoto, Hiroaki; Tanino, Mikio

1985-01-01

Focal fatty infiltration of the liver is a newly recognized entity that may be confused with primary neoplasm or tumor metastasis on computed tomography. We report a 31-year-old woman with a history of chronic alcoholism. Physical examination revealed jaundice, marked hepatomegaly and ascites. Laboratory studies revealed mild elevation of bilirubin, AlP, GOT, γ-GTP and marked leukocytosis. Abdominal CT showed a large area of decreased density in the right lobe. The radionuclide scan demonstrated the area of diminished activity located in the central portion of the right lobe. Ultrasonography demonstrated high echoic mass shadows in the right lobe. The rapid disappearance of the low density area on CT was recognized. The liver biopsy specimen revealed fatty metamorphosis, alcoholic hyaline bodies, pericellular fibrosis and mild lobular disorganization. Focal fatty infiltration can mimic focal hepatic lesions and repeat CT scans are useful in diagnosis. (author)

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis Bile duct disease such as Primary Biliary Cirrhosis (PBC) ... spleen (splenomegaly) Stone-like particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver ...

Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling.

Science.gov (United States)

Lin, Chao-Jen; Chiu, Chun-Ching; Chen, Yi-Chen; Chen, Mu-Lin; Hsu, Tsai-Ching; Tzang, Bor-Show

2015-12-01

Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

Controlled acceleration of superimposed Bessel beams

CSIR Research Space (South Africa)

Dudley, Angela L

2013-06-01

Full Text Available spatial light modulator (SLM) to create superimposed, non-canonical, higher-order Bessel beams and a CCD camera to investigate the propagation of the resulting field. It is already known that the intensity profile of the resulting field experiences...

Hepatic and erythrocytic glutathione peroxidase activity in liver diseases.

Science.gov (United States)

Cordero, R; Ortiz, A; Hernández, R; López, V; Gómez, M M; Mena, P

1996-09-01

Hepatic and erythrocytic glutathione peroxidase activity, together with malondialdehyde levels, were determined as indicators of peroxidation in 83 patients from whom liver biopsies had been taken for diagnostic purposes. On histological study, the patients were classified into groups as minimal changes (including normal liver), steatosis, alcoholic hepatitis, hepatic cirrhosis, light to moderately active chronic hepatitis, and severe chronic active hepatitis. The glutathione peroxidase activity in erythrocytes showed no significant changes in any liver disease group. In the hepatic study, an increased activity was observed in steatosis with respect to the minimal changes group, this increased activity induced by the toxic agent in the initial stages of the alcoholic hepatic disease declining as the hepatic damage progressed. There was a negative correlation between the levels of hepatic malondialdehyde and hepatic glutathione peroxidase in subjects with minimal changes. This suggested the existence of an oxidative equilibrium in this group. This equilibrium is broken in the liver disease groups as was manifest in a positive correlation between malondialdehyde and glutathione peroxidase activity.

Selective attention in vision: recognition memory for superimposed line drawings.

Science.gov (United States)

Goldstein, E B; Fink, S I

1981-10-01

These experiments show that observers can selectively attend to one of two stationary superimposed pictures. If superimposed line drawings are presented to observers who are told to attend to one line drawing in the pair and to ignore the other line drawing in the pair, then a subsequent recognition test in which the pictures are presently singly, the attended picture in each pair is recognized much more frequently than the unattended picture in each pair. This selective recognition occurs both with large (11 degrees-22 degrees) displays in which observers are free to make eye movements during a 3-sec exposure and with small (1 degree) displays in which observers are instructed to fixate steadily on a point during a 1-sec exposure. The results of the steady fixation experiments show that in the absence of eye movements, attention to one of two superimposed stimuli can cause an observer to remember the attended image and not to remember the other, clearly visible, unattended image in a superimposed pair.

Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection

Directory of Open Access Journals (Sweden)

Won Gil Chung

2012-06-01

Full Text Available Background/AimsThe aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV therapy in chronic hepatitis B (CHB patients.MethodsThe medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI values and Alcohol Use Disorders Identification Test (AUDIT scores were obtained at 6 months after the initiation of ETV (0.5 mg daily treatment.ResultsA BMI of 25 kg/m2 or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3% were obese and 17 (19.3% were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT normalization, and hepatitis B virus (HBV-DNA negativity (<300 copies/mL at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033.ConclusionsObesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.

Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

Directory of Open Access Journals (Sweden)

Godwin Sokpor

2012-05-01

Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

Hepatic Encephalopathy

Medline Plus

Full Text Available ... damages your liver over many years – such as long-term alcohol abuse or chronic hepatitis – can cause ... treated. It’s important to continue treatment for as long as necessary to keep HE from coming back. ...

Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review.

Science.gov (United States)

Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M

2016-07-21

To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "non-alcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents. Prescribed exercise in subjects with NAFLD reduces IHTG independent of

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

DEFF Research Database (Denmark)

Schytte, S; Hansen, M; Møller, S

1999-01-01

40-65, palcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney......The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP....... It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired...

Infantile osteopetrosis with superimposed rickets.

Science.gov (United States)

Gonen, Korcan Aysun; Yazici, Zeynep; Gokalp, Gokhan; Ucar, Ayse Kalyoncu

2013-01-01

Rickets is a complication of infantile osteopetrosis and pre-treatment recognition of this complication is important. To describe four children with infantile osteopetrosis complicated by rickets (osteopetrorickets) and review the relevant literature. Retrospective chart analysis of four infants with osteopetrorickets and a systematic review of the relevant literature. We saw five children with infantile osteopetrosis, of whom four had superimposed rickets, for a period of 12 years. The review of the literature (including the current four children), yielded 20 children with infantile osteopetrorickets. The children ranged in age from 2 months to 12 months. In all children, hepatosplenomegaly was found. Sixteen (80%) children had visual impairments and eight (40%) children had hearing impairments. Serum calcium-phosphorus product was less than 30 in 18 children (90%). Twelve children (60%) were hypocalcemic and 18 (90%) were hypophosphatemic. In all children, the radiological examination demonstrated diffuse bony sclerosis and metaphyseal splaying and fraying of long bones. Five children (25%) had pathological fracture of extremities and 15 (75%) had rachitic rosary. Rickets as a complication to infantile osteopetrosis is not uncommon. Skeletal roentgenograms are of critical importance in the diagnosis of both osteopetrosis and superimposed rickets.

Dynamic and static strain gauge using superimposed fiber Bragg gratings

International Nuclear Information System (INIS)

Ma, Y C; Yang, Y H; Yang, M W; Li, J M; Tang, J; Liang, T

2012-01-01

This paper demonstrates a simple and fast interrogation method for the dynamic and/or static strain gauge using a reflection spectrum from two superimposed fiber Bragg gratings (FBGs). The superimposed FBGs are designed to decrease nonequidistant space of generated a sensing pulse train in a time domain during dynamic strain gauge. By combining centroid finding with smooth filtering methods, both the interrogation speed and accuracy are improved. A four times increase in the interrogation speed of dynamic strain, by generating a 2 kHz optical sensing pulse train from a 500 Hz scanning frequency, is demonstrated experimentally. The interrogation uncertainty and total harmonic distortion characterization of superimposed FBGs are tested and less than 4 pm standard deviation is obtained. (paper)

Paroxysmal Nocturnal Hemoglobinuria Superimposed with Preeclampsia

Directory of Open Access Journals (Sweden)

Mann-Ling Chen

2006-09-01

Conclusion: The most frequent causes of PNH-related fetomaternal morbidity and mortality are hemolysis and thrombosis. The situation becomes even more complicated when PNH is superimposed with preeclampsia. Appropriate clinical surveillance, awareness of the potential risks of hemolysis and thrombosis, as well as evaluation of fetal wellbeing are essential.

Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0 T MR spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Werven, J.R. van, E-mail: j.r.vanwerven@amc.uva.n [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Schreuder, T.C.M.A. [Department of Gastroenterology and Hepatology, VU Medical Center, Amsterdam (Netherlands); Nederveen, A.J.; Lavini, C. [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Jansen, P.L.M. [AMC Liver Center/Department of Hepatology, Academic Medical Center, Amsterdam (Netherlands); Stoker, J. [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

2010-08-15

Rationale and objective: Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ({sup 1}H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was to assess hepatic UFA in patients with NAFLD using {sup 1}H MRS. Materials and methods: We included 26 consecutive patients with deranged liver enzymes, with and without type 2 diabetes mellitus (DM2), suspected for NAFLD. Liver function and metabolic parameters were assessed. {sup 1}H MRS measurements were performed at 3.0 T. From the {sup 1}H MR spectra two ratios were calculated: ratio 1 (UFA); unsaturated fatty acid peak vs. reference water peak and ratio 2 (HTGC); total fatty acid peak vs. reference water peak. Results: Twenty-six patients were included. In these patients hepatic UFA (ratio 1) correlated with AST/ALT ratio (r = -0.46, p = 0.02), glucose levels (r = 0.46, p = 0.018), HOMA-IR (r = 0.59, p = 0.004) and HTGC (r = 0.81, p < 0.001). In diabetic patients (n = 12) hepatic UFA correlated with alkaline phosphatase levels (r = 0.72, p = 0.01), HOMA-IR (r = 0.73, p = 0.01) and HTGC (r = 0.83, p = 0.002). Compared to non-diabetic patients with NAFLD, hepatic UFA levels were increased in patients with DM2 and NAFLD (0.032 vs. 0.014, p = 0.03). Conclusion: Hepatic UFA can be assessed with {sup 1}H MRS. {sup 1}H MRS determined hepatic UFA correlate with clinical and metabolic parameters associated with NAFLD. Hepatic UFA are increased in patients with DM2. This study provides evidence for the use of non-invasive {sup 1}H MRS to assess hepatic UFA in vivo.

Tools to Detect Delirium Superimposed on Dementia: A Systematic Review

Science.gov (United States)

Morandi, Alessandro; McCurley, Jessica; Vasilevskis, Eduard E.; Fick, Donna M.; Bellelli, Giuseppe; Lee, Patricia; Jackson, James C.; Shenkin, Susan D.; Trabucchi, Marco; Schnelle, John; Inouye, Sharon K.; Ely, Wesley E.; MacLullich, Alasdair

2012-01-01

Background Delirium commonly occurs in patients with dementia. Though several tools for detecting delirium exist, it is unclear which are valid in patients with delirium superimposed on dementia. Objectives Identify valid tools to diagnose delirium superimposed on dementia Design We performed a systematic review of studies of delirium tools, which explicitly included patients with dementia. Setting In-hospital patients Participants Studies were included if delirium assessment tools were validated against standard criteria, and the presence of dementia was assessed according to standard criteria that used validated instruments. Measurements PubMed, Embase, and Web of Science databases were searched for articles in English published between January 1960 and January 2012. Results Nine studies fulfilled the selection criteria. Of the total of 1569 patients, 401 had dementia, and 50 had delirium superimposed on dementia. Six delirium tools were evaluated. One studyusing the Confusion Assessment Method (CAM) with 85% patients with dementia showed a high specificity (96–100%) and moderate sensitivity (77%).Two intensive care unit studies that used the CAM for the Intensive Care Unit (CAM-ICU) ICU reported 100% sensitivity and specificity for delirium among 23 dementia patients. One study using electroencephalography reported a sensitivity of 67% and a specificity of 91% among a population with 100% prevalence of dementia. No studies examined potential effects of dementia severity or subtype upon diagnostic accuracy. Conclusions The evidence base on tools for detection of delirium superimposed on dementia is limited, although some existing tools show promise. Further studies of existing or refined tools with larger samples and more detailed characterization of dementia are now required to address the identification of delirium superimposed on dementia. PMID:23039270

Hepatic fat quantification using the two-point Dixon method and fat color maps based on non-alcoholic fatty liver disease activity score.

Science.gov (United States)

Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu

2017-04-01

The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2  = 0.90 and R 2  = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.

Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease.

Science.gov (United States)

Tang, Y; Bian, Z; Zhao, L; Liu, Y; Liang, S; Wang, Q; Han, X; Peng, Y; Chen, X; Shen, L; Qiu, D; Li, Z; Ma, X

2011-11-01

Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (T(regs)) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose T(reg)-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17(+) cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and T(regs) should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for

[The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

Science.gov (United States)

Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

2015-02-25

In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

DEFF Research Database (Denmark)

Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan

2011-01-01

Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but th......Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH...

[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

Science.gov (United States)

Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

2012-08-01

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic Cochrane Hepato-Biliary Group review with meta-analyses of randomized clinical trials

DEFF Research Database (Denmark)

Rambaldi, Andrea; Jacobs, Bradly P; Iaquinto, Gaetano

2005-01-01

Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and/or hepatitis B and/or C liver diseases....

The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity

Directory of Open Access Journals (Sweden)

Natalie M. Zahr

2018-03-01

Full Text Available As successfully treated individuals with Human Immunodeficiency Virus (HIV-infected age, cognitive and health challenges of normal aging ensue, burdened by HIV, treatment side effects, and high prevalence comorbidities, notably, Alcohol Use Disorders (AUD and Hepatitis C virus (HCV infection. In 2013, people over 55 years old accounted for 26% of the estimated number of people living with HIV (~1.2 million. The aging brain is increasingly vulnerable to endogenous and exogenous insult which, coupled with HIV infection and comorbid risk factors, can lead to additive or synergistic effects on cognitive and motor function. This paper reviews the literature on neuropsychological and in vivo Magnetic Resonance Imaging (MRI evaluation of the aging HIV brain, while also considering the effects of comorbidity for AUD and HCV.

Current management of non-alcoholic fatty liver disease

OpenAIRE

LISBOA, QUELSON COELHO; COSTA, SILVIA MARINHO FEROLLA; COUTO, CLÁUDIA ALVES

2016-01-01

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic infla...

Predicting short-term mortality and long-term survival for hospitalized US patients with alcoholic hepatitis.

Science.gov (United States)

Cuthbert, Jennifer A; Arslanlar, Sami; Yepuri, Jay; Montrose, Marc; Ahn, Chul W; Shah, Jessica P

2014-07-01

No study has evaluated current scoring systems for their accuracy in predicting short and long-term outcome of alcoholic hepatitis in a US population. We reviewed electronic records for patients with alcoholic liver disease (ALD) admitted to Parkland Memorial Hospital between January 2002 and August 2005. Data and outcomes for 148 of 1,761 admissions meeting pre-defined criteria were collected. The discriminant function (DF) was revised (INRdf) to account for changes in prothrombin time reagents that could potentially affect identification of risk using the previous DF threshold of >32. Admission and theoretical peak scores were calculated by use of the Model for End-stage Liver Disease (MELD). Analysis models compared five different scoring systems. INRdf was closely correlated with the old DF (r (2) = 0.95). Multivariate analysis of the data showed that survival for 28 days was significantly associated with a scoring system using a combination of age, bilirubin, coagulation status, and creatinine (p short-term mortality (p 50 % mortality at four weeks and >80 % mortality at six months without specific treatment.

Silage alcohols in dairy cow nutrition

DEFF Research Database (Denmark)

Raun, Birgitte Marie Løvendahl

Corn silages with high propanol concentrations has been suspected to cause reduced feed intake and health problems for dairy cows in the post-pattum transition period. With the increasing use of hetero fermentative inoculants to support corn silage fermentation it is likely that silage concentrat......Corn silages with high propanol concentrations has been suspected to cause reduced feed intake and health problems for dairy cows in the post-pattum transition period. With the increasing use of hetero fermentative inoculants to support corn silage fermentation it is likely that silage...... of alcohols will lead to high alcohol concentrations in peripheral bood for a considerable period. Increased hepatic NEFA uptake in the postpartum transition period may result in even further decreased hepatic capacity for alcohol metabolism making post-partum transition cows especially vulnerable to high...... alcohol intakes. In order to evaluate the impact of alcohol fermentation in corn silages on dairy cow performance, the main purpose of this thesis was first to investigate the concentrations and composition of alcohols in typical field corn silages, and second to study how transition and lactating dairy...

Interaction of paracetamol in chronic alcoholic patients. Importance for odontologists.

Science.gov (United States)

Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio

2008-04-01

For social, cultural and historical motives alcohol (ethanol or isopenthanol) is considered to be just a beverage rather than a liquor. However, from a pharmatherapeutic point of view alcohol is a depressor of the central nervous system. The effects of alcohol consumption can range from raised loquacity to drunkenness, loss of consciousness and death as a result of insufficient respiration. Probably the most frequent pharmacological interaction is the combination of alcohol with other depressors of the central nervous system which increases the depression even further. Some medicaments which more frequently produce an interaction are antihistamines, analgesics, antidepressants and medicaments for coughs, common cold and influenza. Paracetamol or acetaminophen is an analgesic medicament similar to acetylsalicylic acid lacking anticoagulatory properties and gastric irritation. However, its major drawback is hepatic toxicity as a result of a toxic metabolite produced in the liver by cytochrome P-450, principally cytochrome CYP2E1, which is detoxified under normal conditions by hepatic glutathione. Ethanol is also detoxified by CYP2E1, which is an inducer of ethanol such that chronic ingestion increases the level of this enzyme. When the ingestion of alcohol is stopped, CYP2E1 is greatly increased and only metabolises the paracetamol giving rise to high quantities of hepatotoxic metabolites so that the hepatic glutathione is unable to detoxify resulting in irreversible hepatic damage. Therefore for odontologists it is important that in chronic alcoholic patients the consumption of alcohol should not be suspended on prescribing paracetamol.

Infecções bacterianas pioram o prognóstico da hepatite alcoólica Alcoholic hepatitis: bad prognosis due to concomitant bacterial infections

Directory of Open Access Journals (Sweden)

Edna Strauss

2004-06-01

Full Text Available As infecções bacterianas cursam com altos índices de morbilidade e mortalidade na cirrose hepática. O objetivo do nosso trabalho foi avaliar se também na hepatite alcoólica as infecções bacterianas são fatores de mau prognóstico. Na avaliação retrospectiva de 681 pacientes hospitalizados em um único centro, por período de 6 anos, foram bem documentados 52 (7,5% casos de hepatite alcoólica, sendo 73,1% com biópsia hepática para análise histopatológica e os restantes por diagnóstico clínico-bioquímico. Houve predomínio do sexo masculino (relação 3,3:1,0, com idade média de 40 anos e ingestão média de etanol puro de 193g/dia por mais de 3 anos. As principais complicações foram: encefalopatia hepática (n=5, insuficiência renal (n=4 e hemorragia digestiva alta (n=3. Houve infecção bacteriana em 11 (21,1% pacientes, sendo pulmonar (n=5, peritonite bacteriana espontânea (PBE (n=2, urinária (n=3 e dermatológica (n=1. Óbito precoce, durante o período de internação ocorreu em 8 (15,4% casos e a análise comparativa entre eles e os sobreviventes mostrou serem fatores de mau prognóstico a presença de encefalopatia hepática (p=0,012, bilirrubinas > 20mg% (p=0,012 e associação com infecções graves (pulmonar/PBE, com p=0,004. Em conclusão, demonstramos que as infecções bacterianas são fatores de mau prognóstico na hepatite alcoólica. Recomendamos, portanto, que a profilaxia com antibióticos que se faz durante hemorragia digestiva alta na cirrose e em casos de insuficiência hepática fulminante, seja estendida para a hepatite alcoólica, em sua forma grave, com finalidade de evitar infecções bacterianas e mortalidade precoce.Bacterial infections increase morbidity and mortality in cirrhosis. Our aim was to investigate whether in alcoholic hepatitis the development of bacterial infections was also a poor prognostic factor. In the retrospective evaluation of 681 hospitalized patients with liver disease

Proteins Differentially Expressed in the Pancreas of Hepatic Alcohol Dehydrogenase-Deficient Deer Mice Fed Ethanol For 3 Months.

Science.gov (United States)

Bhopale, Kamlesh K; Amer, Samir M; Kaphalia, Lata; Soman, Kizhake V; Wiktorowicz, John E; Shakeel Ansari, Ghulam A; Kaphalia, Bhupendra S

2017-07-01

The aim of this study was to identify differentially expressed proteins in the pancreatic tissue of hepatic alcohol dehydrogenase-deficient deer mice fed ethanol to understand metabolic basis and mechanism of alcoholic chronic pancreatitis. Mice were fed liquid diet containing 3.5 g% ethanol daily for 3 months, and differentially expressed pancreatic proteins were identified by protein separation using 2-dimensional gel electrophoresis and identification by mass spectrometry. Nineteen differentially expressed proteins were identified by applying criteria established for protein identification in proteomics. An increased abundance was found for ribosome-binding protein 1, 60S ribosomal protein L31-like isoform 1, histone 4, calcium, and adenosine triphosphate (ATP) binding proteins and the proteins involved in antiapoptotic processes and endoplasmic reticulum function, stress, and/or homeostasis. Low abundance was found for endoA cytokeratin, 40S ribosomal protein SA, amylase 2b isoform precursor, serum albumin, and ATP synthase subunit β and the proteins involved in cell motility, structure, and conformation. Chronic ethanol feeding in alcohol dehydrogenase-deficient deer mice differentially expresses pancreatic functional and structural proteins, which can be used to develop biomarker(s) of alcoholic chronic pancreatitis, particularly amylase 2b precursor, and 60 kDa heat shock protein and those involved in ATP synthesis and blood osmotic pressure.

Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice.

Science.gov (United States)

Iracheta-Vellve, Arvin; Petrasek, Jan; Gyogyosi, Benedek; Bala, Shashi; Csak, Timea; Kodys, Karen; Szabo, Gyongyi

2017-07-01

Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. In this study, we tested IL-1 receptor antagonist to block IL-1 signalling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH. We observed that inhibition of IL-1 signalling decreased liver inflammation and neutrophil infiltration, and resulted in enhanced regeneration of hepatocytes and increased rate of recovery from liver injury in AH. Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Roux-en Y gastric bypass results in long-term remission of hepatocyte apoptosis and hepatic histological features of non-alcoholic steatohepatitis

Directory of Open Access Journals (Sweden)

Anne-Sophie Schneck

2016-08-01

Full Text Available The long-term effects of bariatric surgery on non alcoholic steatohepatitis (NASH, focusing on liver injury and hepatocyte apoptosis,are not well established. We here performed a longitudinal study with paired liver biopsies of 9 morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m2 with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB surgery. LRYGB surgery was associated with significant weight loss (median BMI loss –13.7 [–16.4; –9.5] kg/m2, improved hepatic steatosis in all patients (55.5% with total resolution, and resolution of hepatic inflammation and hepatocyte ballooning in 100% and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase 3levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.

Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

Science.gov (United States)

Schneck, Anne-Sophie; Anty, Rodolphe; Patouraux, Stéphanie; Bonnafous, Stéphanie; Rousseau, Déborah; Lebeaupin, Cynthia; Bailly-Maitre, Beatrice; Sans, Arnaud; Tran, Albert; Gugenheim, Jean; Iannelli, Antonio; Gual, Philippe

2016-01-01

The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m(2)) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss -13.7 [-16.4; -9.5] kg/m(2)), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

Science.gov (United States)

Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

2016-10-01

Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

Superimposed disturbance in the ionosphere triggered by spacecraft launches in China

OpenAIRE

L. M. He; L. X. Wu; L. X. Wu; S. J. Liu; S. N. Liu

2015-01-01

Using GPS dual-frequency observations collected by continuously operating GPS tracking stations in China, superimposed disturbances caused by the integrated action of spacecraft's physical effect and chemical effect on ionosphere during the launches of the spacecrafts Tiangong-1 and Shenzhou-8 in China were firstly determined. The results show that the superimposed disturbance was composed of remarkable ionospheric waves and significant ionospheric depletion emerged after bo...

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

Science.gov (United States)

Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

2017-01-01

This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

Experience of Using Mineral Water in the Treatment of Patients with Chronic Viral Hepatitis C with Concomitant Non-Alcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

N.V. Dragomyretska

2016-02-01

Full Text Available The paper proved the feasibility of a course of mineral water intake (in double dosing regimen in combination treatment of patients with chronic viral hepatitis C and concomitant non-alcoholic fatty liver disease in order to improve the clinical course of the underlying disease and comorbidity, to restore the functional state of the liver, to reduce insulin resistance.

Comparative genetics of alcoholism in the Kenyan populations ...

African Journals Online (AJOL)

Hepatic alcohol dehydrogenase and aldehyde dehydrogenase are major enzymes in the metabolism of exogenous ethanol. These enzymes are polymorphic and are involved in alcohol drinking and risk of alcoholism in some world populations. Three hundred and seventy one samples of hair root lyzates from five Kenyan ...

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: assessment of non-invasive indices predicting hepatic steatosis and fibrosis.

Science.gov (United States)

Polyzos, Stergios A; Goulis, Dimitrios G; Kountouras, Jannis; Mintziori, Gesthimani; Chatzis, Panagiotis; Papadakis, Efstathios; Katsikis, Ilias; Panidis, Dimitrios

2014-01-01

Insulin resistance contributes to the pathogenesis of both polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). The main aim of the present study was the evaluation of non-invasive indices of hepatic steatosis and fibrosis in PCOS women with or without metabolic syndrome (MetS). In this cross-sectional study, three non-invasive indices for hepatic steatosis [NAFLD liver fat score, lipid accumulation product (LAP) and hepatic steatosis index (HIS)] and four for fibrosis [FIB-4, aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), body mass index (BMI)-Age-Alanine aminotransferase (ALT)-Triglycerides (BAAT) and BMI AST/ALT Ratio Diabetes (BARD)] were calculated in 314 PCOS women (77 with, 237 without MetS) and 78 controls. All steatosis indices were significantly higher in the PCOS than the control group (NAFLD liver fat score: -0.139 ± 0.117 vs. -0.976 ± 0.159, psteatosis indices were significantly higher in PCOS women with than without MetS (NAFLD liver fat score: 1.874 ± 0.258 vs. -0.793 ± 0.099, phepatic steatosis were significantly higher in PCOS, especially in the presence of MetS, whereas indices of hepatic fibrosis yielded controversial results. Further studies are warranted to evaluate the long-term outcomes of hepatic steatosis and fibrosis indices in PCOS women.

Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

Science.gov (United States)

Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

2016-08-01

Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil

Directory of Open Access Journals (Sweden)

Alessandra Carvalho Goulart

Full Text Available CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT. We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI and the hepatic steatosis index (HSI. RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83 than CT. CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Science.gov (United States)

Goulart, Alessandra Carvalho; Oliveira, Ilka Regina Souza de; Alencar, Airlane Pereira; Santos, Maira Solange Camara dos; Santos, Itamar Souza; Martines, Brenda Margatho Ramos; Meireles, Danilo Peron; Martines, João Augusto dos Santos; Misciagna, Giovanni; Benseñor, Isabela Martins; Lotufo, Paulo Andrade

2015-01-01

Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI). Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT. The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

liver cirrhosis from autoimmune hepatitis in a nigerian woman

African Journals Online (AJOL)

Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with ... chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in .... effects.2,5,9 We opted for the Budesonide/AZA therapy because ...

Acetaldehyde Adducts in Alcoholic Liver Disease

Directory of Open Access Journals (Sweden)

Mashiko Setshedi

2010-01-01

Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

Superimpose of images by appending two simple video amplifier circuits to color television

International Nuclear Information System (INIS)

Kojima, Kazuhiko; Hiraki, Tatsunosuke; Koshida, Kichiro; Maekawa, Ryuichi; Hisada, Kinichi.

1979-01-01

Images are very useful to obtain diagnostic informations in medical fields. Also by superimposing two or three images obtained from the same patient, various informations, for example a degree of overlapping and anatomical land mark, which can not be found in only one image, can be often found. In this paper characteristics of our trial color television system for the purpose of superimposing x-ray images and/or radionuclide images are described. This color television system superimposing two images in each different color consists of two monochromatic vidicon cameras and 20 inches conventional color television in which only two simple video amplifier circuits are added. Signals from vidicon cameras are amplified about 40 dB and are directly applied to cathode terminals of color CRT in the television. This system is very simple and economical color displays, and enhance a degree of overlapping and displacement between images. As one of typical clinical applications, pancreas images were superimposed in color by this method. As a result, size and position of pancreas was enhanced. Also x-ray image and radionuclide image were superimposed to find exactly the position of tumors. Furthermore this system was very useful for color display of multinuclides scintigraphy. (author)

Superimpose of images by appending two simple video amplifier circuits to color television

Energy Technology Data Exchange (ETDEWEB)

Kojima, K; Hiraki, T; Koshida, K; Maekawa, R [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K

1979-09-01

Images are very useful to obtain diagnostic informations in medical fields. Also by superimposing two or three images obtained from the same patient, various informations, for example a degree of overlapping and anatomical land mark, which can not be found in only one image, can be often found. In this paper characteristics of our trial color television system for the purpose of superimposing x-ray images and/or radionuclide images are described. This color television system superimposing two images in each different color consists of two monochromatic vidicon cameras and 20 inches conventional color television in which only two simple video amplifier circuits are added. Signals from vidicon cameras are amplified about 40 dB and are directly applied to cathode terminals of color CRT in the television. This system is very simple and economical color displays, and enhance a degree of overlapping and displacement between images. As one of typical clinical applications, pancreas images were superimposed in color by this method. As a result, size and position of pancreas was enhanced. Also x-ray image and radionuclide image were superimposed to find exactly the position of tumors. Furthermore this system was very useful for color display of multinuclides scintigraphy.

Effect of severity of steatosis as assessed ultrasonographically on hepatic vascular indices in non-alcoholic fatty liver disease.

Science.gov (United States)

Mohammadi, Afshin; Ghasemi-rad, Mohammad; Zahedi, Hengameh; Toldi, Gergely; Alinia, Tahereh

2011-09-01

Early monitoring of non-alcoholic fatty liver disease (NAFLD) progression in obese patients is important to avoid the development of complications associated with fatty infiltration. of this study was to investigate the relationship between the degrees of fatty infiltration and reduced vascular compliance in NAFLD patients in the three main hepatic vessels. Two hundred and fourty subjects were enrolled in the study. They were divided into 4 groups: 60 controls, 60 grade 1 NAFLD patients, 60 grade 2 NAFLD patients and 60 grade 3 NAFLD patients. After US confirmation of the presence and grade of NAFLD, the peak and mean portal vein velocity (PPVV and MPVV, respectively), the hepatic artery resistance index (HARI), and the phasicity of the hepatic vein were measured. The PPVV was 19.6 +/- 2.4 cm/sec in patients with grade 1 fatty liver, 17.6 +/- 1.2 cm/sec in grade 2 and 15.4 +/- 1.1 cm/sec in grade 3. The MPVV was 16.6 +/- 2.4 cm/sec in patients with grade 1 fatty liver, 16.6 +/- 2.9 cm/sec in grade 2 and 12.7 +/- 0.7 cm/sec in grade 3. The HARI was 0.75 in patients with grade 1 fatty liver, 0.68 in grade 2 and 0.64 in grade 3. There was an inverse relationship between PPVV, MPVV and HARI and different grades of fatty liver in patients (p = 0.001 for PPVV (Figure 7) and HARI, p = 0.006 for MPVV. The values of the investigated liver blood flow parameters were inversely correlated with the fatty infiltration grading. Fatty infiltration can severely influence hepatic blood flow, pointing attention to the importance of early diagnosis and the need for hepatic vessel flow abnormalities characterization in the NAFLD population.

Acute hepatic encephalopathy with diffuse cortical lesions

Energy Technology Data Exchange (ETDEWEB)

Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

2001-07-01

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

Acute hepatic encephalopathy with diffuse cortical lesions

International Nuclear Information System (INIS)

Arnold, S.M.; Spreer, J.; Schumacher, M.; Els, T.

2001-01-01

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

Bee's honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-NLRP3 inflammasome pathway.

Science.gov (United States)

Xiao, Jia; Liu, Yingxia; Xing, Feiyue; Leung, Tung Ming; Liong, Emily C; Tipoe, George L

2016-06-01

We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models. NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH.

If You Have Chronic Hepatitis B Virus (HBV) Infection

Science.gov (United States)

... globulin (HBIG) and started on the hepatitis B vaccine series within 12 hours of birth to prevent your baby from getting HBV infec- tion.  Avoid alcoholic beverages. Alcohol can damage your liver. HBV infection People can get HBV ...

A dual-wavelength tunable laser with superimposed fiber Bragg gratings

International Nuclear Information System (INIS)

Álvarez-Tamayo, R I; Durán-Sánchez, M; Pottiez, O; Ibarra-Escamilla, B; Kuzin, E A; Cruz, J L; Andrés, M V

2013-01-01

We report a dual-wavelength tunable fiber laser. The cavity is formed by two superimposed fiber Bragg gratings (FBGs) and a temperature tunable high-birefringence fiber optical loop mirror (FOLM). FBGs with wavelengths of 1548.5 and 1538.5 nm were printed in the same section of a fiber using two different masks. The superimposed FBGs were placed on a mechanical mount that allows stretch or compression of the FBGs. As a result of the FBG strain both lines are shifted simultaneously. Dual-wavelength generation requires a fine adjustment of the cavity loss for both wavelengths. (paper)

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

Science.gov (United States)

Lettéron, P; Duchatelle, V; Berson, A; Fromenty, B; Fisch, C; Degott, C; Benhamou, J P; Pessayre, D

1993-01-01

Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID:8472992

Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

Science.gov (United States)

Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

2015-01-01

Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

[Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

Science.gov (United States)

Lebedev, S P

1982-01-01

Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

COMPLICATIONS OF ALCOHOLIC LIVER DISEASE AND DIAGNOSTIC MARKERS

Directory of Open Access Journals (Sweden)

Milena Ilić

2011-12-01

Full Text Available Alcoholism is one of the leading diseases affecting people’s health and immunity worldwide. Nearly 30 thousand people in the USA die from chronic liver damage. The liver is the central organ in the metabolism of alcohol. Alcohol is primarily a hepatotoxic agent. Hepatotoxicity of alcohol is clinically manifested by the development of alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis. It is characterized by appropriate symptomatology, depending on the degree of liver damage. Excessive use of alcohol for a long period of time, along with malnutrition, genetic and ethnic predisposition, leads to alcoholic cirrhosis and the development of its complications. Portal hypertension damages other organs and organ systems, causing hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy, spontaneous bacterial peritonitis, etc. For these reasons, alcoholism reduction is given priority, as well as reduction of morbidity and mortality of people with alcoholic chronic liver damage. Therefore, early diagnosis of alcohol abuse is necessary, as well as timely diagnosis of different degrees of alcoholic liver damage. The diagnosis of chronic alcoholic liver damage is set on the basis of confirmed data of alcohol consumption; liver function test (serum markers aminotransferase, gammaglutamyl transferase, prothrombin time, serum bilirubin and albumin level; serum markers of liver fibrosis. Fibrosis markers are directly involved in sedimentation and dissolution of extracellular matrix, i.e. in the process of fibrogenesis and fibrinolysis of liver tissues. They include markers and enzymes of metabolism, as well as cytokines and chemokines.

Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing

Science.gov (United States)

Zhou, Can‐Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao‐Bing; Li, Guo‐Qiang; Song, Jie; Xu, Tian‐Ying; Li, Zhi‐Yong; Guan, Yun‐Feng

2016-01-01

Abstract Background and Purpose Ageing is an important risk factor of non‐alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD+), a ubiquitous coenzyme, links ageing with NAFLD. Experimental Approach Hepatic concentrations of NAD+, protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD+ biosynthesis, were compared in middle‐aged and aged mice or patients. The influences of NAD+ decline on the steatosis and steatohepatitis were evaluated in wild‐type and H247A dominant‐negative, enzymically‐inactive NAMPT transgenic mice (DN‐NAMPT) given normal or high‐fat diet (HFD). Key Results Hepatic NAD+ level decreased in aged mice and humans. NAMPT‐controlled NAD+ salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle‐age DN‐NAMPT mice displayed systemic NAD+ reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro‐inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α‐SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus‐mediated SIRT1 overexpression only partially rescued these phenotypes. Conclusions and Implications These results provide the first evidence that ageing‐associated NAD+ deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD+ substrates may be a promising therapeutic strategy to prevent and treat NAFLD. PMID:27174364

Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver disease.

Science.gov (United States)

Chaudhury, Chloe S; Purdy, Julia B; Liu, Chia-Ying; Morse, Caryn G; Stanley, Takara L; Kleiner, David; Hadigan, Colleen

2018-05-01

Non-alcoholic fatty liver disease is common in human immunodeficiency virus, but there are no approved therapies. The aim of this open-label proof-of-concept study was to determine the effect of the mineralocorticoid receptor antagonist eplerenone on hepatic fat in human immunodeficiency virus-infected patients with hepatic fat ≥5% by magnetic resonance spectroscopy. Five subjects received eplerenone (25 mg daily × 1 week followed by 50 mg daily × 23 weeks). Laboratory tests were done at each visit, and the primary endpoint, change in hepatic fat content, was determined by MRI spectroscopy at baseline and week 24. The study was stopped early after observing unexpected significant increases in hepatic fat at week 24 (mean increase 13.0 ± 7.3%, P = .02). The increases in steatosis were accompanied by a tendency for transaminase values to decrease (alanine aminotransferase mean change -14 ± 16 IU/L, P = .14). There were no consistent changes in other metabolic parameters or blood pressure. Repeat assessment of hepatic steatosis 1-2 months after stopping study medication revealed improvements in steatosis towards baseline values. The unexpected observation of increased hepatic steatosis with the administration of eplerenone led to early termination of the investigation. While limited because of the small number of participants and the open-label design, this study provides data to suggest that mineralocorticoid receptor antagonism with eplerenone may not be an effective approach to treat hepatic steatosis in human immunodeficiency virus or the general population. Additional research is needed to determine the pathophysiological mechanism behind these unanticipated observations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo.

Science.gov (United States)

Gonçalves, Patricia Lofego; Zago-Gomes, Maria da Penha; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

2013-01-01

To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2 ± 12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1 %), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1 %), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (pAlcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

Directory of Open Access Journals (Sweden)

Banasch M

2012-06-01

Full Text Available Abstract Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD, increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%. cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36. The area under the ROC curve (AUROC for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1. Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial function in non-alcoholic fatty liver disease.

Epidemiology Of Alcoholic Liver Disease

Directory of Open Access Journals (Sweden)

А.Г. Мартынова

2009-12-01

Full Text Available One of the main factors of chronic liver disease is alcohol. The level of alcoholic liver disease incidence and cirrhosis mortality has increased considerably in the recent years in many countries. The risk of development and disease progression are determined by the effect of endogenous and exogenous factors: "drinking mode", female gender, heredity and genetic predisposition, obesity, concomitant viral hepatitis

Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease

DEFF Research Database (Denmark)

Pavlov, Chavdar S; Casazza, Giovanni; Semenistaia, Marianna

2016-01-01

, but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk...... with alcoholic liver disease; however, besides the difficulties of finding a suitable liver transplant organ, there are many other factors that may influence a person's survival.Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound...... Handbook for Systematic Reviews of Diagnostic Test Accuracy. MAIN RESULTS: The review included two studies that provided numerical data regarding alcoholic cirrhosis in 205 men and women with alcoholic liver disease. Although there were no applicability concerns in terms of participant selection, index...

Hipoinsulinemia em alcoolistas com hepatopatia mínima Hypoinsulinemia in alcoholics with minimal hepatopaty

Directory of Open Access Journals (Sweden)

M.M. das Neves

2000-03-01

Full Text Available OBJETIVO: Em alcoolistas portadores de lesões hepáticas mínimas avaliar os níveis de glicose e insulina séricas após estímulo com glicose intravenosa. MÉTODOS: Em oito etilistas, portadores de alterações hepáticas mínimas, caracteriza por biópsia hepática, e em 26 controles sadios não-alcoólicos, foram estudados os níveis glicêmicos e insulinêmicos (RIE nos tempos 1, 3, 5, e 10 minutos após estímulo com glicose intravenosa (0.5g/Kg de peso. RESULTADOS: As médias da insulina sérica dos tempos 1, 3 minutos e resposta integrada total (RIT-10min após estímulo foram menores no grupo alcoolista em relação ao controle (p The chronic pancreatitis (CP may evolve with low insulin levels and develop clinical picture of diabetes mellitus. Low seric levels of insulin and C peptide after stimulus has also been described in asymptomatic alcoholics even with normal glicemic curves. It is known that the chronic alcoholism is the main etiological factor of CP and hepatic diseases, and that the insulin produced by the pancreas is metabolized mainly by the liver. High levels of periferic insulin are described in hepatic cirrhosis due to decrease of hepatic metabolization alone or associated to increase of periferic resistence. AIM: In alcoholics with minimal hepatic lesions to evaluate the seric insulin and glucose levels after stimulus with intravenous glucose. METHODS: In 8 alcoholic patients with minimal hepatic lesions characterized by hepatic biopsy, and 26 non-alcoholics, healthy controls, it was studied the serum glucose and insulin levels in basal time, 1, 3, 5, and 10 minutes after stimulus with intravenous glucose (0.5 g/kg. RESULTS: The insulin means in time 1, 3 minutes and total integrated response after stimulus were lower (p < 0.05 in alcoholic group than in control, even with normal glucose curves. CONCLUSION: Alcoholics with minimal hepatic lesions showed low seric insulin levels after glucose stimulus, similar to former

Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

Science.gov (United States)

Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N; Cooper, Sara; Malik, Shahid; Behari, Jaideep

2014-01-01

While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Severe AAH is characterized by a distinct metabolic phenotype spanning

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

International Nuclear Information System (INIS)

Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

2014-01-01

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

Energy Technology Data Exchange (ETDEWEB)

Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

2014-01-03

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

Directory of Open Access Journals (Sweden)

Hui eHan

2013-10-01

Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

Biochemical studies of effects of alcohol consumption on fat and carbohydrate metabolism in rats fed different levels of proteins

International Nuclear Information System (INIS)

Shalan, M.G.M.

1996-01-01

Alcohol, ethanol and ethyl alcohol are synonymously used during the present dissertation. Alcohol probably was among the first psychoactive substances to be used by man (Winger et al., 1992). Ethanol is mainly oxidized to acetaldehyde in the liver (Ugarte and Peresa, 1978) by alcohol dehydrogenase (ADH). Alcohol is associated with many metabolic disorders inside the body (Thayer and Rubin, 1979; Forsander and Poso, 1988; Poso and Hirsimaki, 1991; Bernal, et al., 1992). The nutritional factors which received little attention have an important role in alcoholic metabolizing alterations. Morphologically and biochemically, an increase in hepatic lipid was demonstrated when ethanol was given either as a supplement or as an iso caloric substitute for carbohydrate together with an otherwise nutritionally adequate diet. Low-protein diets have been shown to diminish hepatic alcohol dehydrogenase (ADH) levels in rats and to slow down the metabolism of ethanol considerably (Wilson et al., 1986). Hepatic steatosis was produced, even with a high-protein, vitamin-supplemented diet and was accompanied by major ultrastructural liver changes and by elevations of hepatic transaminases in blood (Lieber et al., 1963 and 1965 and Lane and Lieber, 1966). If dietary fat was reduced from 35 to 25% of total calories, hepatic triglyceride accumulation greatly decreased (Lieber and DeCarli, 970)

Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage.

Science.gov (United States)

Di Costanzo, Alessia; D'Erasmo, Laura; Polimeni, Licia; Baratta, Francesco; Coletta, Paola; Di Martino, Michele; Loffredo, Lorenzo; Perri, Ludovica; Ceci, Fabrizio; Montali, Anna; Girelli, Gabriella; De Masi, Bruna; Angeloni, Antonio; Catalano, Carlo; Maranghi, Marianna; Del Ben, Maria; Angelico, Francesco; Arca, Marcello

2017-02-01

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Carotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects. Compared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p hepatic steatosis), the median CIMT in group M (0.84 [0.70-0.95] mm) was significantly greater than that in group G (0.66 [0.55-0.74] mm; p < 0.001), which was similar to that in controls (0.70 [0.64-0.81] mm). Results were similar in the subgroup evaluated using MRS/MRI. Excess liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Applications of magnetic resonance spectroscopy for noninvasive assessment of hepatic steatosis

OpenAIRE

van Werven, J.R.

2011-01-01

MR spectroscopy is a noninvasive technique to quantify hepatic steatosis. MR spectroscopy provides information about the chemical composition of tissues in a spectrum. Hepatic steatosis is characterized by accumulation of fat in the liver. The prevalence of hepatic steatosis is increasing due to its relation with obesity and insulin resistance in non-alcoholic fatty liver disease. This thesis describes the applications of MR spectroscopy (primarily on 3T) for noninvasive assessment of hepatic...

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

International Nuclear Information System (INIS)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

2016-01-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

Directory of Open Access Journals (Sweden)

Borini Paulo

1999-01-01

Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

Science.gov (United States)

Williams, Roger; Alexander, Graeme; Armstrong, Iain; Baker, Alastair; Bhala, Neeraj; Camps-Walsh, Ginny; Cramp, Matthew E; de Lusignan, Simon; Day, Natalie; Dhawan, Anil; Dillon, John; Drummond, Colin; Dyson, Jessica; Foster, Graham; Gilmore, Ian; Hudson, Mark; Kelly, Deirdre; Langford, Andrew; McDougall, Neil; Meier, Petra; Moriarty, Kieran; Newsome, Philip; O'Grady, John; Pryke, Rachel; Rolfe, Liz; Rice, Peter; Rutter, Harry; Sheron, Nick; Taylor, Alison; Thompson, Jeremy; Thorburn, Douglas; Verne, Julia; Wass, John; Yeoman, Andrew

2018-03-17

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on

Modelling snow ice and superimposed ice on landfast sea ice in Kongsfjorden, Svalbard

Directory of Open Access Journals (Sweden)

Caixin Wang

2015-08-01

Full Text Available Snow ice and superimposed ice formation on landfast sea ice in a Svalbard fjord, Kongsfjorden, was investigated with a high-resolution thermodynamic snow and sea-ice model, applying meteorological weather station data as external forcing. The model shows that sea-ice formation occurs both at the ice bottom and at the snow/ice interface. Modelling results indicated that the total snow ice and superimposed ice, which formed at the snow/ice interface, was about 14 cm during the simulation period, accounting for about 15% of the total ice mass and 35% of the total ice growth. Introducing a time-dependent snow density improved the modelled results, and a time-dependent oceanic heat flux parameterization yielded reasonable ice growth at the ice bottom. Model results suggest that weather conditions, in particular air temperature and precipitation, as well as snow thermal properties and surface albedo are the most critical factors for the development of snow ice and superimposed ice in Kongsfjorden. While both warming air and higher precipitation led to increased snow ice and superimposed ice forming in Kongsfjorden in the model runs, the processes were more sensitive to precipitation than to air temperature.

Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

Science.gov (United States)

Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

2016-05-01

We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Numerical Simulation of Damage during Forging with Superimposed Hydrostatic Pressure by Active Media

International Nuclear Information System (INIS)

Behrens, B.-A.; Hagen, T.; Roehr, S.; Sidhu, K. B.

2007-01-01

The effective reduction of energy consumption and a reasonable treatment of resources can be achieved by minimizing a component's weight using lightweight metals. In this context, aluminum alloys play a major role. Due to their material-sided restricted formability, the mentioned aluminum materials are difficult to form. The plasticity of a material is ascertained by its maximum forming limit. It is attained, when the deformation causes mechanical damage within the material. Damage of that sort is reached more rapidly, the greater the tensile strength rate in relation to total tension rate. A promising approach of handling these low ductile, high-strength aluminum alloys within a forming process, is forming with a synchronized superposition of comprehensive stress by active media such as by controlling oil pressure. The influence of superimposed hydrostatic pressure on the flow stress was analyzed as well as the formability for different procedures at different hydrostatic pressures and temperature levels. It was observed that flow stress is independent of superimposed hydrostatic pressure. Neither the superimposed pressure has an influence on the plastic deformation, nor does a pressure dependent material hardening due to increasing hydrostatic pressure take place. The formability increases with rising hydrostatic pressure. The relative gain at room temperature and increase of the superimposed pressure from 0 to 600 bar for tested materials was at least 140 % and max. 220 %. Therefore in this paper, based on these experimental observations, it is the intended to develop a numerical simulation in order to predict ductile damage that occurs in the bulk forging process with superimposed hydrostatic pressure based Lemaitre's damage model

Alcohol and retinoids

DEFF Research Database (Denmark)

Crabb, D.W.; Pinairs, J.; Hasanadka, R.

2001-01-01

, M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and beta-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K. Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver...

Effects of Clostridium difficile infection in patients with alcoholic hepatitis.

Science.gov (United States)

Sundaram, Vinay; May, Folasade P; Manne, Vignan; Saab, Sammy

2014-10-01

Infection increases mortality in patients with alcoholic hepatitis (AH). Little is known about the association between Clostridium difficile infection (CDI) and AH. We examined the prevalence and effects of CDI in patients with AH, compared with those of other infections. We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2008 through 2011. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with AH. We used multivariable logistic regression to determine risk factors that affect mortality, negative binomial regression to evaluate the effects of CDI on predicted length of stay (LOS), and Poisson regression to determine the effects of CDI on predicted hospital charges. Chi-square and Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital charges associated with CDI with those associated with urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP). Of 10,939 patients with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.75; P = .04), a longer predicted LOS (10.63 vs 5.75 d; P effects appear similar to those for UTI and SBP. We propose further studies to determine the cost effectiveness of screening for CDI among patients with AH. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Alcoholic Liver Disease and Malnutrition

OpenAIRE

McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

2011-01-01

Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepat...

Acute Pancreatitis in acute viral hepatitis

Directory of Open Access Journals (Sweden)

S K.C.

2011-03-01

Full Text Available Introduction: The association of acute viral hepatitis and acute pancreatitis is well described. This study was conducted to find out the frequency of pancreatic involvement in acute viral hepatitis in the Nepalese population. Methods: Consecutive patients of acute viral hepatitis presenting with severe abdominal pain between January 2005 and April 2010 were studied. Patients with history of significant alcohol consumption and gall stones were excluded. Acute viral hepatitis was diagnosed by clinical examination, liver function test, ultrasound examination and confirmed by viral serology. Pancreatitis was diagnosed by clinical presentation, biochemistry, ultrasound examination and CT scan. Results: Severe abdominal pain was present in 38 of 382 serologically-confirmed acute viral hepatitis patients. Twenty five patients were diagnosed to have acute pancreatitis. The pancreatitis was mild in 14 and severe in 11 patients. The etiology of pancreatitis was hepatitis E virus in 18 and hepatitis A virus in 7 patients. Two patients died of complications secondary to shock. The remaining patients recovered from both pancreatitis and hepatitis on conservative treatment. Conclusions: Acute pancreatitis occurred in 6.5 % of patients with acute viral hepatitis. Cholelithiasis and gastric ulcers are the other causes of severe abdominal pain. The majority of the patients recover with conservative management. Keywords: acute viral hepatitis, acute pancreatitis, pain abdomen, hepatitis E, hepatitis A, endemic zone

Alcohol and atherosclerosis

Directory of Open Access Journals (Sweden)

DA LUZ PROTASIO L.

2001-01-01

Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

Directory of Open Access Journals (Sweden)

He Peiyuan

2017-01-01

Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

Science.gov (United States)

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

Directory of Open Access Journals (Sweden)

Lijun Hao

2015-01-01

Full Text Available We investigated the effects of Hericium erinaceus (HEM on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT level, aspartate aminotransaminase (AST level, Maleic dialdehyde (MDA level, hepatic total antioxidant status (TAOS, and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P<0.05 decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Acrolein Is a Pathogenic Mediator of Alcoholic Liver Disease and the Scavenger Hydralazine Is Protective in MiceSummary

Directory of Open Access Journals (Sweden)

Wei-Yang Chen

2016-09-01

Full Text Available Background & Aims: Alcoholic liver disease (ALD remains a major cause of morbidity and mortality, with no Food and Drug Administration–approved therapy. Chronic alcohol consumption causes a pro-oxidant environment and increases hepatic lipid peroxidation, with acrolein being the most reactive/toxic by-product. This study investigated the pathogenic role of acrolein in hepatic endoplasmic reticulum (ER stress, steatosis, and injury in experimental ALD, and tested acrolein elimination/scavenging (using hydralazine as a potential therapy in ALD. Methods: In vitro (rat hepatoma H4IIEC cells and in vivo (chronic+binge alcohol feeding in C57Bl/6 mice models were used to examine alcohol-induced acrolein accumulation and consequent hepatic ER stress, apoptosis, and injury. In addition, the potential protective effects of the acrolein scavenger, hydralazine, were examined both in vitro and in vivo. Results: Alcohol consumption/metabolism resulted in hepatic accumulation of acrolein-protein adducts, by up-regulation of cytochrome P4502E1 and alcohol dehydrogenase, and down-regulation of glutathione-s-transferase-P, which metabolizes/detoxifies acrolein. Alcohol-induced acrolein adduct accumulation led to hepatic ER stress, proapoptotic signaling, steatosis, apoptosis, and liver injury; however, ER-protective/adaptive responses were not induced. Notably, direct exposure to acrolein in vitro mimicked the in vivo effects of alcohol, indicating that acrolein mediates the adverse effects of alcohol. Importantly, hydralazine, a known acrolein scavenger, protected against alcohol-induced ER stress and liver injury, both in vitro and in mice. Conclusions: Our study shows the following: (1 alcohol consumption triggers pathologic ER stress without ER adaptation/protection; (2 alcohol-induced acrolein is a potential therapeutic target and pathogenic mediator of hepatic ER stress, cell death, and injury; and (3 removal/clearance of

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

Energy Technology Data Exchange (ETDEWEB)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

2016-11-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

Original Article Studies on Prevalence and Risk Factors for Hepatitis ...

African Journals Online (AJOL)

2011-12-20

Dec 20, 2011 ... Risk factors such as blood transfusion was 32.0% among male ... females. Unfortunately, the prevalence of HBV appears high among the studied ... form of both acute and chronic viral hepatitis ... of expression for this disease, at this phase the .... Alcohol consumption .... Hepatitis B virus Infection in China.

A case of acute hepatitis following mad honey ingestion

Directory of Open Access Journals (Sweden)

Fatma Sari Dogan

2015-12-01

Full Text Available Acute hepatitis is characterized by liver inflammation and liver cell necrosis. The most frequently observed underlying cause thereof is viruses, but various other causes, such as alcohol, medication, or toxins may also lead thereto.In this paper, a case of acute hepatitis presenting with bradycardia, hypotension, and a prominent increase in liver enzymes following mad honey ingestion is discussed. Since there are only few cases of acute hepatitis following mad honey ingestion in the literature, we want to present this subject matter. Keywords: Mad honey poisoning, Mad honey intoxication, Bradycardia, Hypotension, Acute hepatitis

Serum YKL-40 is increased in patients with hepatic fibrosis

DEFF Research Database (Denmark)

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

2000-01-01

BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds...... 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/l......) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p

Isolation of Mallory bodies and an attempt to demonstrate cell mediated immunity to Mallory body isolate in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Hardt, F; Aldershvile, J

1981-01-01

Mallory bodies were isolated from necropsy livers from patients with alcoholic hepatitis with and without cirrhosis with a Ficoll viscosity barrier. The purity of Mallory bodies in the isolate varied between 70 and 90%, estimated by counting Mallory bodies and non-Mallory body structures in haema...... was found between controls and patients with alcoholic hepatitis, alcoholic steatosis, alcoholic cirrhosis and miscellaneous liver diseases.......Mallory bodies were isolated from necropsy livers from patients with alcoholic hepatitis with and without cirrhosis with a Ficoll viscosity barrier. The purity of Mallory bodies in the isolate varied between 70 and 90%, estimated by counting Mallory bodies and non-Mallory body structures...

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

Energy Technology Data Exchange (ETDEWEB)

Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

2014-06-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

International Nuclear Information System (INIS)

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

2014-01-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice

NARCIS (Netherlands)

Wouters, Kristiaan; van Bilsen, Marc; van Gorp, Patrick J.; Bieghs, Veerle; Luetjohann, Dieter; Kerksiek, Anja; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

2010-01-01

Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response

DEFF Research Database (Denmark)

Hallager, Sofie; Ladelund, Steen; Christensen, Peer Brehm

2017-01-01

Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained......, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted...... elevated in patients with alcohol overuse after SVR. Conclusion: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients...

Antilipogenic and Anti-Inflammatory Activities of Codonopsis lanceolata in Mice Hepatic Tissues after Chronic Ethanol Feeding

Directory of Open Access Journals (Sweden)

Areum Cha

2012-01-01

Full Text Available This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v, providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR- mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.

Ductular reaction or hepatic reparative complex: immunohistochemical features in liver cirrhosis in patients with chronic hepatitis

Directory of Open Access Journals (Sweden)

V. A. Tumanskiy

2018-04-01

Full Text Available Until recently, a discussion about the mechanisms of development and the biological role of the ductular reaction, which develops in patients with chronic liver diseases continues among hepatologists and pathomorphologists. Purpose of the study. To characterize the pathomorphological features and significance of the ductular response in liver cirrhosis in patients with chronic non-alcoholic, alcoholic and viral hepatitis in hepatobioptats with the use of immunohistochemical (IHC techniques. Material and methods of investigation. Histological, histochemical and IHC study of the ductular liver reaction in liver biopsies of 52 patients aged 24 to 66 years with cirrhosis of the liver on the background of non-alcoholic steatohepatitis (13 patients, and alcoholic steatohepatitis (13 patients and on the background of chronic viral hepatitis C (10 patients, 26–47 years, as well as those suffering from severe biliostasis (8 patients and focal nodular liver hyperplasia (8 patients. Results. The ductular reaction can be detected in the active phase with maximum manifestations in patients with liver cirrhosis on the background of chronic hepatitis, it may have an average or weak degree of severity; in a significant number of patients, the effects of the ductular reaction of the liver are revealed. Cellular chains and groups of cells with the immunophenotype of the progenitor cells of the liver appear in the active phase of the ductular reaction at the periphery of the hepatic lobules in the projection of the Goering canals, in the fibrotically altered portal tracts, in the subcapsular zone of the liver and in the thickened fibrosis septa (c-kit CD117+, CD34+, CD56+ CK7-, CK19-, Hepar- without presence of figures of mitosis or increased level of expression of Кі-67 in them. In small ductules localized in the projection of the Goering canals, single cells with the expression of c-kit CD 117+, CD44 Std./HCAM+, CD34+, CD56+, expressing the markers of

Imaging of hepatic steatosis and fatty sparing

Energy Technology Data Exchange (ETDEWEB)

Karcaaltincaba, Musturay [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)]. E-mail: musturayk@yahoo.com; Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)

2007-01-15

Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing.

Imaging of hepatic steatosis and fatty sparing

International Nuclear Information System (INIS)

Karcaaltincaba, Musturay; Akhan, Okan

2007-01-01

Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing

Physicochemical analog for modeling superimposed and coded memories

Science.gov (United States)

Ensanian, Minas

1992-07-01

The mammalian brain is distinguished by a life-time of memories being stored within the same general region of physicochemical space, and having two extraordinary features. First, memories to varying degrees are superimposed, as well as coded. Second, instantaneous recall of past events can often be affected by relatively simple, and seemingly unrelated sensory clues. For the purposes of attempting to mathematically model such complex behavior, and for gaining additional insights, it would be highly advantageous to be able to simulate or mimic similar behavior in a nonbiological entity where some analogical parameters of interest can reasonably be controlled. It has recently been discovered that in nonlinear accumulative metal fatigue memories (related to mechanical deformation) can be superimposed and coded in the crystal lattice, and that memory, that is, the total number of stress cycles can be recalled (determined) by scanning not the surfaces but the `edges' of the objects. The new scanning technique known as electrotopography (ETG) now makes the state space modeling of metallic networks possible. The author provides an overview of the new field and outlines the areas that are of immediate interest to the science of artificial neural networks.

Additive non-uniform random sampling in superimposed fiber Bragg grating strain gauge

Science.gov (United States)

Ma, Y. C.; Liu, H. Y.; Yan, S. B.; Yang, Y. H.; Yang, M. W.; Li, J. M.; Tang, J.

2013-05-01

This paper demonstrates an additive non-uniform random sampling and interrogation method for dynamic and/or static strain gauge using a reflection spectrum from two superimposed fiber Bragg gratings (FBGs). The superimposed FBGs are designed to generate non-equidistant space of a sensing pulse train in the time domain during dynamic strain gauge. By combining centroid finding with smooth filtering methods, both the interrogation speed and accuracy are improved. A 1.9 kHz dynamic strain is measured by generating an additive non-uniform randomly distributed 2 kHz optical sensing pulse train from a mean 500 Hz triangular periodically changing scanning frequency.

Valencia's Palau d'En Bou. Superimposed architectures.

Directory of Open Access Journals (Sweden)

Rafael Soler Verdú

1997-09-01

Full Text Available The restoration of the Palau díen Bou is a sample of the complexity that arises when practising an intervention on a building with indefinite superimposed architectures, in other words, an accumulation of interventions from different periods and in different styles, but difficult to understand in its original condition. Architect Rafael Soler describes his reading and interpretation of the building during the initial study and the solutions recommended by research that were applied during the restoration stage

Liver scintigraphic features associated with alcoholism

International Nuclear Information System (INIS)

Drum, D.E.; Beard, J.O.

1978-01-01

The relationships between scintigraphic features and clinical alcoholism were studied by review of 2406 liver scintiphotos. Two distinct patterns were significantly associated with alcoholism: heterogeneous distribution of radiocolloid in the liver, and jointly increased uptake of tracer by the spleen and vertebral bone marrow. A total of 13 overall patterns were found to distinguish, with considerable reliability, alcoholics from all other patients. This finding reflects the frequency with which alcohol abuse is associated with hepatic dysfunction in hospital patients. These observations indicate an important role for the nuclear medicine physician in detection of alcoholism among patients referred for liver-spleen imaging, and they form a basis for comparison with the diagnostic efficacy of other methods of evaluating diffuse liver diseases

Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.

Directory of Open Access Journals (Sweden)

Raimundo Fernandes de Araújo Júnior

Full Text Available To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV in rats with ethanol-induced liver injury.Liver injury was induced by gavage administration of alcohol (7 g/kg for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL-1β, IL-10, and tumor necrosis factor (TNF-α level as well as for myeloperoxidase (MPO activity and malonyldialdehyde (MDA and glutathione (GSH levels. Serum aspartate aminotransferase (AST activity and liver triglyceride (TG levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2, receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL, suppressor of cytokine signalling (SOCS1, the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1, intercellular adhesion molecule 1 (ICAM-1, superoxide dismutase (SOD-1, and glutathione peroxidase (GPx-1 expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.CARV treatment (5 mg/kg during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01, ALT (p < 0.01, TG (p < 0.001, MPO (p < 0.001, MDA (p < 0.05, and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05, and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001 and GSH (p < 0.05, compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05, while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05 and decreasing expression of IL-1β and NF-κB (both, p < 0.05. Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI, procollagen

Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

OpenAIRE

Silveira, Luciano Alves Matias da; Torquato, Bianca Gonçalves Silva; Oliveira, Mariana Silva; Juliano, Guilherme Ribeiro; Oliveira, Lívia Ferreira; Cavellani, Camila Lourencini; Ramalho, Luciana Santos; Espindula, Ana Paula; Teixeira, Vicente de Paula Antunes; Ferraz, Mara Lúcia Fonseca

2017-01-01

Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals ...

The Impact of Host Metabolic Factors on Treatment Outcome in Chronic Hepatitis C

Directory of Open Access Journals (Sweden)

Savvidou Savvoula

2012-01-01

Full Text Available Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P=0.003 and histological evidence of advanced fibrosis (P<0.001. Older age (OR 2.51, P=0.002, genotype (OR 3.28, P<0.001, cirrhosis (OR 4.23, P=0.005, and hepatic steatosis (OR 2.48, P=0.001 were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related.

Additive non-uniform random sampling in superimposed fiber Bragg grating strain gauge

International Nuclear Information System (INIS)

Ma, Y C; Liu, H Y; Yan, S B; Li, J M; Tang, J; Yang, Y H; Yang, M W

2013-01-01

This paper demonstrates an additive non-uniform random sampling and interrogation method for dynamic and/or static strain gauge using a reflection spectrum from two superimposed fiber Bragg gratings (FBGs). The superimposed FBGs are designed to generate non-equidistant space of a sensing pulse train in the time domain during dynamic strain gauge. By combining centroid finding with smooth filtering methods, both the interrogation speed and accuracy are improved. A 1.9 kHz dynamic strain is measured by generating an additive non-uniform randomly distributed 2 kHz optical sensing pulse train from a mean 500 Hz triangular periodically changing scanning frequency. (paper)

Correlation of hepatic 18F-fluorodeoxyglucose uptake with fatty liver

International Nuclear Information System (INIS)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

2006-01-01

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 ± 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), γ -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and γ -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration

Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.

Science.gov (United States)

Estep, J Michael; Baranova, Ancha; Hossain, Noreen; Elariny, Hazem; Ankrah, Kathy; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

2009-05-01

White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients. We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes. Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM. Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.

LPSF/GQ-02 inhibits the development of hepatic steatosis and inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD).

Science.gov (United States)

Soares e Silva, Amanda Karolina; de Oliveira Cipriano Torres, Dilênia; dos Santos Gomes, Fabiana Oliveira; dos Santos Silva, Bruna; Lima Ribeiro, Edlene; Costa Oliveira, Amanda; dos Santos, Laise Aline Martins; de Lima, Maria do Carmo Alves; Pitta, Ivan da Rocha; Peixoto, Christina Alves

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3-HFD+pioglitazone; 4-HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on

Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

Science.gov (United States)

Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

2016-02-01

Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

[Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners].

Science.gov (United States)

Bouma, M; van Geldrop, W J; Numans, M E; Wiersma, Tj; Goudswaard, A N

2008-12-06

The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.

Effects of Loaded Squat Exercise with and without Application of Superimposed EMS on Physical Performance

Directory of Open Access Journals (Sweden)

Nicolas Wirtz, Christoph Zinner, Ulrike Doermann, Heinz Kleinoeder, Joachim Mester

2016-03-01

Full Text Available The aim of the present study was to investigate the effects of a multiple set squat exercise training intervention with superimposed electromyostimulation (EMS on strength and power, sprint and jump performance. Twenty athletes from different disciplines participated and were divided into two groups: strength training (S or strength training with superimposed EMS (S+E. Both groups completed the same training program twice a week over a six week period consisting of four sets of the 10 repetition maximum of back squats. Additionally, the S+E group had EMS superimposed to the squat exercise with simultaneous stimulation of leg and trunk muscles. EMS intensity was adjusted to 70% of individual pain threshold to ensure dynamic movement. Strength and power of different muscle groups, sprint, and vertical jump performance were assessed one week before (pre, one week after (post and three weeks (re following the training period. Both groups showed improvements in leg press strength and power, countermovement and squat jump performance and pendulum sprint (p < 0.05, with no changes for linear sprint. Differences between groups were only evident at the leg curl machine with greater improvements for the S+E group (p < 0.05. Common squat exercise training and squat exercise with superimposed EMS improves maximum strength and power, as well as jumping abilities in athletes from different disciplines. The greater improvements in strength performance of leg curl muscles caused by superimposed EMS with improvements in strength of antagonistic hamstrings in the S+E group are suggesting the potential of EMS to unloaded (antagonistic muscle groups.

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan.

Science.gov (United States)

Deng, J F; Wang, J D; Shih, T S; Lan, F L

1987-01-01

Three workers from a color printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure and pulmonary edema. An investigation was subsequently conducted at the plant to determine the etiology of the outbreak and the prevalence of liver disease among the remaining workers. Comprehensive medical evaluations were conducted, which included physical examinations, liver function tests, and serological screening for hepatitis. Seventeen of 25 workers from the plant had abnormal liver function tests 10 days after the outbreak, and a significant association was found between the presence of abnormal liver function tests and a history of recently having worked inside any of three rooms in which an interconnecting air conditioning system had been installed to cool the printing machines. After further investigation, it was determined that the incident occurred following inadvertent use of carbon tetrachloride to clean a pump in the printing machine. A simulation of the pump cleaning operation revealed ambient air levels of carbon tetrachloride of 300-500 ppm. Ultimately, it was concluded that the outbreak was in all likelihood due to the combined use of carbon tetrachloride and isopropyl alcohol in the cleaning operation. This outbreak underscores the importance of adopting appropriate industrial hygiene measures in a rapidly industrializing nation such as Taiwan.

Additional ion bombardment in PVD processes generated by a superimposed pulse bias voltage

International Nuclear Information System (INIS)

Olbrich, W.; Kampschulte, G.

1993-01-01

The superimposed pulse bias voltage is a tool to apply an additional ion bombardment during deposition in physical vapour deposition (PVD) processes. It is generated by the combination of a d.c. ground voltage and a higher d.c. pulse voltage. Using a superimposed pulse bias voltage in ion-assisted PVD processes effects an additional all-around ion bombardment on the surface with ions of higher energy. Both metal and reactive or inert-gas ions are accelerated to the surface. The basic principles and important characteristics of this newly developed process such as ion fluxes or deposition rates are shown. Because of pulsing the high voltage, the deposition temperature does not increase much. The adhesion, structure, morphology and internal stresses are influenced by these additional ion impacts. The columnar growth of the deposited films could be suppressed by using the superimposed pulse bias voltage without increasing the deposition temperature. Different metallizations (Cr and Cu) produced by arc and sputter ion plating are investigated. Carbon-fibre-reinforced epoxy are coated with PVD copper films for further treatment in electrochemical processes. (orig.)

Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

Science.gov (United States)

Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

2015-01-01

Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.

Identification of igneous rocks in a superimposed basin through integrated interpretation dominantly based on magnetic data

Science.gov (United States)

LI, S.

2017-12-01

Identification of igneous rocks in the basin environment is of great significance to the exploration for hydrocarbon reservoirs hosted in igneous rocks. Magnetic methods are often used to alleviate the difficulties faced by seismic imaging in basins with thick cover and complicated superimposed structures. We present a case study on identification of igneous rocks in a superimposed basin through integrated interpretation based on magnetic and other geophysical data sets. The study area is located in the deepest depression with sedimentary cover of 14,000 m in Huanghua basin, which is a Cenozoic basin superimposed on a residual pre-Cenozoic basin above the North China craton. Cenozoic and Mesozoic igneous rocks that are dominantly intermediate-basic volcanic and intrusive rocks are widespread at depth in the basin. Drilling and seismic data reveal some volcanic units and intrusive rocks in Cenozoic stratum at depths of about 4,000 m. The question remains to identify the lateral extent of igneous rocks in large depth and adjacent areas. In order to tackle the difficulties for interpretation of magnetic data arisen from weak magnetic anomaly and remanent magnetization of igneous rocks buried deep in the superimposed basin, we use the preferential continuation approach to extract the anomaly and magnetic amplitude inversion to image the 3D magnetic units. The resultant distribution of effective susceptibility not only correlates well with the locations of Cenozoic igneous rocks known previously through drilling and seismic imaging, but also identifies the larger scale distribution of Mesozoic igneous rocks at greater depth in the west of the basin. The integrated interpretation results dominantly based on magnetic data shows that the above strategy is effective for identification of igneous rocks deep buried in the superimposed basin. Keywords: Identification of igneous rocks; Superimposed basin; Magnetic data

Curcumin influences hepatic expression patterns of matrix metalloproteinases in liver toxicity.

Science.gov (United States)

Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Menon, Venugopal Padmanabhan

2004-07-01

Hepatic fibrosis is a result of an imbalance between enhanced matrix synthesis and diminished breakdown of connective tissue proteins, the net result of which is increased deposition of Extra Cellular Matrix. In this concept Matrix Metalloproteinases play an important role because their activity is largely responsible for extra cellular matrix breakdown. In the present study we have tested the influence of curcumin, the active principle of turmeric, on matrix metalloproteinase expression during alcohol and thermally oxidised sunflower oil induced liver toxicity. Male albino Wistar rats were used for the study. The matrix metalloproteinase expressions were found to be increased significantly in alcohol as well as thermally oxidised sunflower oil groups and on treatment with curcumin there was a significant decrease. In alcohol + thermally oxidised sunflower oil group, we found a significant decrease in matrix metalloproteinase activities. Administration of curcumin significantly improved their activities. From the results obtained, we could conclude that curcumin influences the hepatic matrix metalloproteinases and effectively protects liver against alcohol and delta PUFA induced toxicity.

The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.

Directory of Open Access Journals (Sweden)

Hans Dieter Nischalke

Full Text Available BACKGROUND: An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409 has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC. METHODS: We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. RESULTS: PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001 increased in alcoholic cirrhosis with (53.7% and without HCC (36.2% but was not different between healthy controls (22.9% and patients with cirrhosis (25.3%; p = 0.545 and HCC (30.2%; p = 0.071 due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR 16.8 versus healthy controls; 95% confidence interval (CI 6.68-42.43, p<0.001. Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013 as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006. CONCLUSION: The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that

Consumption of Coprinus comatus polysaccharide extract causes recovery of alcoholic liver damage in rats

NARCIS (Netherlands)

Ozalp, F.O.; Canbek, M.; Yamac, M.; Kanbak, G.; Griensven, van L.J.L.D.; Uyanoglu, M.; Senturk, H.; Karlkava, K.; Oglakci, A.

2014-01-01

Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been

Clinical Profile of Alcoholic Liver Disease in a Tertiary Care Centre and its Correlation with Type, Amount and Duration of Alcohol Consumption.

Science.gov (United States)

Nand, Nitya; Malhotra, Parveen; Dhoot, Dipesh Kumar

2015-06-01

Alcoholic liver disease (ALD) is a major cause of mortality and morbidity worldwide. Various studies show contradictory results about the role of amount, type and duration of alcohol exposure in determining the risk to develop ALD with ethnic variations in susceptibility to develop ALD and South Asians are shown to be more prone to develop ALD. This study was carried out to evaluate clinical profile of ALD in Indian population and to find out the correlation of disease severity and outcome with alcohol intake. 201 patients of ALD were evaluated to correlate their clinical complications, biochemical parameters, prognostic markers (Discriminant function [DF] score, Model for end-stage liver disease [MELD] score and Child-Pugh score) and in-hospital mortality with their alcohol intake data in form of type, amount and duration of alcohol intake. Hepatic encephalopathy, neutrophil to lymphocyte ratio (NLR) and all three prognostic scores showed a dose-dependent relation with the amount of alcohol intake (p < 0.05). However, the mortality rate didn't show a significant relation with amount. Further the type of alcohol intake didn't show any relation with disease severity; however, the duration of alcohol intake showed a positive relation with mortality rate. NLR emerged as a useful bedside marker of disease severity which correlates well with all prognostic markers (p < 0.05 for NLR's Spearman correlation with DF score and Child-Pugh Score), more so with MELD score (p < 0.0001); and complications like hepatic encephalopathy and hepato-renal syndrome. NLR also correlated with mortality rate but it was not statistically significant.

Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

Energy Technology Data Exchange (ETDEWEB)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

2006-10-15

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

Superimposed disturbance in the ionosphere triggered by spacecraft launches in China

Science.gov (United States)

He, L. M.; Wu, L. X.; Liu, S. J.; Liu, S. N.

2015-11-01

Using GPS dual-frequency observations collected by continuously operating GPS tracking stations in China, superimposed disturbances caused by the integrated action of spacecraft's physical effect and chemical effect on ionosphere during the launches of the spacecrafts Tiangong-1 and Shenzhou-8 in China were firstly determined. The results show that the superimposed disturbance was composed of remarkable ionospheric waves and significant ionospheric depletion emerged after both launches. Meanwhile, we found for the first time that the ionospheric waves were made up of two periods of wave by wavelet analysis. The first period of ∼ 4 min shows one event in the near stations and two sub-events in the few far stations. The second period of ∼ 9 min shows only one event in all the observed stations. Finally, the time characteristics for ionospheric waves and depletions were examined.

Superimposed disturbance in the ionosphere triggered by spacecraft launches in China

Directory of Open Access Journals (Sweden)

L. M. He

2015-11-01

Full Text Available Using GPS dual-frequency observations collected by continuously operating GPS tracking stations in China, superimposed disturbances caused by the integrated action of spacecraft's physical effect and chemical effect on ionosphere during the launches of the spacecrafts Tiangong-1 and Shenzhou-8 in China were firstly determined. The results show that the superimposed disturbance was composed of remarkable ionospheric waves and significant ionospheric depletion emerged after both launches. Meanwhile, we found for the first time that the ionospheric waves were made up of two periods of wave by wavelet analysis. The first period of ∼ 4 min shows one event in the near stations and two sub-events in the few far stations. The second period of ∼ 9 min shows only one event in all the observed stations. Finally, the time characteristics for ionospheric waves and depletions were examined.

Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice Models

Directory of Open Access Journals (Sweden)

Qin Yi

2018-03-01

Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD, which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD-induced obesity (DIO mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT, glucose tolerance test (GTT, and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.

Continuous intravenous flumazenil infusion in a patient with chlordiazepoxide toxicity and hepatic encephalopathy

Directory of Open Access Journals (Sweden)

Moh′d Al-Halawani

2015-01-01

Full Text Available Flumazenil, a benzodiazepine receptor antagonist, is the drug of choice for the diagnosis and treatment of benzodiazepine overdose. We are presenting a patient with chronic alcoholism and alcoholic liver disease, who came with alcohol withdrawal symptoms and treated chlordiazepoxide. Subsequently he developed a prolonged change in mental status that required treatment for benzodiazepine overdose and hepatic encephalopathy with flumazenil infusion for 28 days.

Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study

DEFF Research Database (Denmark)

Jepsen, Peter; Ott, Peter; Andersen, Per Kragh

2010-01-01

The clinical course of alcoholic cirrhosis, a condition with a high mortality, has not been well described. We examined prevalence, risk, chronology, and mortality associated with three complications of cirrhosis: ascites, variceal bleeding, and hepatic encephalopathy. We followed a population......-risks methods. At diagnosis of alcoholic cirrhosis, 24% of patients had no complications, 55% had ascites alone, 6% had variceal bleeding alone, 4% had ascites and variceal bleeding, and 11% had hepatic encephalopathy. One-year mortality was 17% among patients with no initial complications, 20% following...... variceal bleeding alone, 29% following ascites alone, 49% following ascites and variceal bleeding (from the onset of the later of the two complications), and 64% following hepatic encephalopathy. Five-year mortality ranged from 58% to 85%. The risk of complications was about 25% after 1 year and 50% after...

Selective Attention in Vision: Recognition Memory for Superimposed Line Drawings.

Science.gov (United States)

Goldstein, E. Bruce; Fink, Susan I.

1981-01-01

Four experiments show that observers can selectively attend to one of two stationary superimposed pictures. Selective recognition occurred with large displays in which observers were free to make eye movements during a 3-sec exposure and with small displays in which observers were instructed to fixate steadily on a point. (Author/RD)

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

Directory of Open Access Journals (Sweden)

Tong Zhou

2017-01-01

Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

Science.gov (United States)

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

Science.gov (United States)

Pérez-Martínez, Laura; Pérez-Matute, Patricia; Aguilera-Lizarraga, Javier; Rubio-Mediavilla, Susana; Narro, Judit; Recio, Emma; Ochoa-Callejero, Laura; Oteo, José-Antonio; Blanco, José-Ramón

2014-07-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

Science.gov (United States)

Sim, Mi-Ok; Lee, Hae-In; Ham, Ju Ri; Seo, Kwon-Il; Kim, Myung-Joo

2015-01-01

BACKGROUND/OBJECTIVES Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS Chronic alcohol intake significantly increased serum tumor necrosis factor-α (TNF-α) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-α gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system. PMID:26244074

Mass spectrometry characterization of circulating human serum albumin microheterogeneity in patients with alcoholic hepatitis.

Science.gov (United States)

Naldi, Marina; Baldassarre, Maurizio; Domenicali, Marco; Giannone, Ferdinando Antonino; Bossi, Matteo; Montomoli, Jonathan; Sandahl, Thomas Damgaard; Glavind, Emilie; Vilstrup, Hendrik; Caraceni, Paolo; Bertucci, Carlo

2016-04-15

Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature fluctuations superimposed on background temperature change

International Nuclear Information System (INIS)

Otto, James; Roberts, J.A.

2016-01-01

Proxy data allows the temperature of the Earth to be mapped over long periods of time. In this work the temperature fluctuations for over 200 proxy data sets were examined and from this set 50 sets were analyzed to test for periodic and quasi-periodic fluctuations in the data sets. Temperature reconstructions over 4 different time scales were analyzed to see if patterns emerged. Data were put into four time intervals; 4,000 years, 14,000 years, 1,000,000 years, and 3,000,000 years and analyzed with a goal to understanding periodic and quasi-periodic patterns in global temperature change superimposed on a “background” average temperature change. Quasi-periodic signatures were identified that predate the Industrial Revolution, during much of which direct data on temperature are not available. These data indicate that Earth temperatures have undergone a number of periodic and quasi-periodic intervals that contain both global warming and global cooling cycles. The fluctuations are superimposed on a background of temperature change that has a declining slope during the two periods, pre-ice age and post ice age with a transition about 12,000 BCE. The data are divided into “events” that span the time periods 3,000,000 BCE to “0” CE, 1,000,000 BCE to “0” CE, 12,000 BCE to 2,000 CE and 2,000 BCE to 2,000 CE. An equation using a quasi-periodic (frequency modulated sine waves) patterns was developed to analyze the date sets for quasi-periodic patterns. “Periodicities” which show reasonable agreement with the predictions of Milankovitch and other investigators were found in the data sets.

Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro.

Directory of Open Access Journals (Sweden)

Wei Gao

Full Text Available Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets

Relaxin-3 receptor (RXFP3 signalling mediates stress-related alcohol preference in mice.

Directory of Open Access Journals (Sweden)

Andrew W Walker

Full Text Available Stressful life events are causally linked with alcohol use disorders (AUDs, providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3 prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT and Rxfp3 knockout (KO (C57/B6JRXFP3TM1/DGen littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

Abnormal Metabolite in Alcoholic Subjects,

Science.gov (United States)

1982-01-01

this study included alcoholic hepatitis or cirrhosis of the liver in 29. of the alcoholic subjects; diabetes mellitus in 8 and Korsakoff’s syndrome in 6...evidence of -7- Korsakoff’s syndrome and the presence or absence of 2,3-butanediol. There was, however, a suggestive correlation with independently...Gamma GT 193, SGPT 29 b 0 0.023 0.05 51a F.B. 22 M 28 0.029 0.14 b 0 ɘ.01 0.12 77 J.N.S. 52 M 0 0.027 0.11 57 JJ.S 45 m 4. 0.25 .35 Korsakoff ’s

Variables predicting elevated portal pressure in alcoholic liver disease. Results of a multivariate analysis

DEFF Research Database (Denmark)

Krogsgaard, K; Christensen, E; Gluud, C

1987-01-01

In 46 alcoholic patients the association of wedged-to-free hepatic-vein pressure with other variables (clinical, histologic, hemodynamic, and liver function data) was studied by means of multiple regression analysis, taking the wedged-to-free hepatic-vein pressure as the dependent variable. Four ...

Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

Directory of Open Access Journals (Sweden)

Ryan J Mailloux

Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD.

Science.gov (United States)

Permutt, Z; Le, T-A; Peterson, M R; Seki, E; Brenner, D A; Sirlin, C; Loomba, R

2012-07-01

Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T(2)* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD). To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis. A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system. The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r(2) = 0.56, P hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P steatosis grade (1.4 vs. 2.2, P steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease. © 2012 Blackwell Publishing Ltd.

Fibroblast growth factor-21 and omentin-1 hepatic mRNA expression and serum levels in morbidly obese women with non-alcoholic fatty liver disease.

Science.gov (United States)

Waluga, M; Kukla, M; Zorniak, M; Kajor, M; Liszka, L; Dyaczynski, M; Kowalski, G; Zadlo, D; Waluga, E; Olczyk, P; Buldak, R J; Berdowska, A; Hartleb, M

2017-06-01

Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays. The FGF21 serum level was significantly higher in patients with a greater extent of steatosis (grade 2 and 3) compared to those without or with mild steatosis (grade 0 and 1) (P = 0.049). Receiver Operating Characteristic analysis, however, showed poor discriminant power for the FGF21 serum levels in differentiating between more and less extensive steatosis with an AUC = 0.666. There was a tendency towards higher levels of hepatic FGF21 mRNA in patients with lobular inflammation and fibrosis and towards lower levels in the case of hepatocyte ballooning and steatosis. There was a positive mutual correlation between hepatic FGF21 and omentin-1 mRNA levels (r = 0.78; P hepatic omentin-1 mRNA levels showed a tendency to be lower in patients with advanced steatosis and hepatocyte ballooning. In conclusion, our study, which focused on hepatic FGF21 and omentin-1 mRNA expression, confirmed marked expression of both molecules in the liver of morbidly obese patients with NAFLD. More extensive steatosis was associated with evident changes in the serum FGF21 concentration in morbidly obese women with NAFLD, but the difference did not reach statistical significance. The vast amount of fat, both visceral and subcutaneous, in severely obese patients may be the additional source and influence

Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury.

Science.gov (United States)

Xu, Jiesi; Xu, Yang; Li, Yuanyuan; Jadhav, Kavita; You, Min; Yin, Liya; Zhang, Yanqiao

2016-04-14

The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4α (HNF4α) and CES1 were markedly reduced in patients with alcoholic steatohepatitis. Alcohol repressed both HNF4α and CES1 expression in primary hepatocytes. HNF4α regulated CES1 expression by directly binding to the proximal promoter of CES1. Global inactivation of CES1 aggravated alcohol- or MCD diet-induced liver inflammation and liver injury, likely as a result of increased production of acetaldehyde and reactive oxygen species and mitochondrial dysfunctions. Knockdown of hepatic CES1 exacerbated ethanol-induced steatohepatitis. These data indicate that CES1 plays a crucial role in protection against alcohol- or MCD diet-induced liver injury.

Focal hepatic steatosis: ultrasound and CT scan features may mimick carcinoma of the liver

International Nuclear Information System (INIS)

Monnin, J.L.; Blanc, F.; Guiry, P.; Bruel, J.M.; Monnin, E.; Ciurana, A.J.

1988-01-01

Ultrasound and CT scan features of focal hepatic steatosis (FHS) may closely resemble those of primary or secondary malignant hepatic tumors. Three cases of FHS in chronic alcoholics are reported. In two cases, the area of steatosis was hyperechogenic upon ultrasonography. In all three patients, CT scan demonstrated a hypodense image, with poor enhancement following opacification and no mass effect. Diagnosis of FHS was ascertained upon hepatic biopsy under CT scan guidance in all three patients [fr

Validation of coding algorithms for the identification of patients hospitalized for alcoholic hepatitis using administrative data.

Science.gov (United States)

Pang, Jack X Q; Ross, Erin; Borman, Meredith A; Zimmer, Scott; Kaplan, Gilaad G; Heitman, Steven J; Swain, Mark G; Burak, Kelly W; Quan, Hude; Myers, Robert P

2015-09-11

Epidemiologic studies of alcoholic hepatitis (AH) have been hindered by the lack of a validated International Classification of Disease (ICD) coding algorithm for use with administrative data. Our objective was to validate coding algorithms for AH using a hospitalization database. The Hospital Discharge Abstract Database (DAD) was used to identify consecutive adults (≥18 years) hospitalized in the Calgary region with a diagnosis code for AH (ICD-10, K70.1) between 01/2008 and 08/2012. Medical records were reviewed to confirm the diagnosis of AH, defined as a history of heavy alcohol consumption, elevated AST and/or ALT (34 μmol/L, and elevated INR. Subgroup analyses were performed according to the diagnosis field in which the code was recorded (primary vs. secondary) and AH severity. Algorithms that incorporated ICD-10 codes for cirrhosis and its complications were also examined. Of 228 potential AH cases, 122 patients had confirmed AH, corresponding to a positive predictive value (PPV) of 54% (95% CI 47-60%). PPV improved when AH was the primary versus a secondary diagnosis (67% vs. 21%; P codes for ascites (PPV 75%; 95% CI 63-86%), cirrhosis (PPV 60%; 47-73%), and gastrointestinal hemorrhage (PPV 62%; 51-73%) had improved performance, however, the prevalence of these diagnoses in confirmed AH cases was low (29-39%). In conclusion the low PPV of the diagnosis code for AH suggests that caution is necessary if this hospitalization database is used in large-scale epidemiologic studies of this condition.

The benefits of exercise for patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Keating, Shelley E; George, Jacob; Johnson, Nathan A

2015-01-01

As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.

Hepatic cholesterol ester hydrolase in human liver disease.

Science.gov (United States)

Simon, J B; Poon, R W

1978-09-01

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

Regulator of G protein signaling 6 is a critical mediator of both reward-related behavioral and pathological responses to alcohol.

Science.gov (United States)

Stewart, Adele; Maity, Biswanath; Anderegg, Simon P; Allamargot, Chantal; Yang, Jianqi; Fisher, Rory A

2015-02-17

Alcohol is the most commonly abused drug worldwide, and chronic alcohol consumption is a major etiological factor in the development of multiple pathological sequelae, including alcoholic cardiomyopathy and hepatic cirrhosis. Here, we identify regulator of G protein signaling 6 (RGS6) as a critical regulator of both alcohol-seeking behaviors and the associated cardiac and hepatic morbidities through two mechanistically divergent signaling actions. RGS6(-/-) mice consume less alcohol when given free access and are less susceptible to alcohol-induced reward and withdrawal. Antagonism of GABA(B) receptors or dopamine D2 receptors partially reversed the reduction in alcohol consumption in RGS6(-/-) animals. Strikingly, dopamine transporter inhibition completely restored alcohol seeking in mice lacking RGS6. RGS6 deficiency was associated with alterations in the expression of genes controlling dopamine (DA) homeostasis and a reduction in DA levels in the striatum. Taken together, these data implicate RGS6 as an essential regulator of DA bioavailability. RGS6 deficiency also provided dramatic protection against cardiac hypertrophy and fibrosis, hepatic steatosis, and gastrointestinal barrier dysfunction and endotoxemia when mice were forced to consume alcohol. Although RGS proteins canonically function as G-protein regulators, RGS6-dependent, alcohol-mediated toxicity in the heart, liver, and gastrointestinal tract involves the ability of RGS6 to promote reactive oxygen species-dependent apoptosis, an action independent of its G-protein regulatory capacity. We propose that inhibition of RGS6 might represent a viable means to reduce alcohol cravings and withdrawal in human patients, while simultaneously protecting the heart and liver from further damage upon relapse.

Superimposed chirped pulse parameter estimation based on the extended Kalman filter (EKF)

CSIR Research Space (South Africa)

Olivier, JC

2009-05-01

Full Text Available An extended Kalman filter (EKF) is proposed to estimate the frequencies and chirp rate of multiple superimposed chirped pulses. The estimation problem is a difficult one, where maximum likelyhood methods are very complex especially if more than two...

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

NARCIS (Netherlands)

Li, Jieyi; Chanda, Dipanjan; van Gorp, Patrick J.; Jeurissen, Mike L. J.; Houben, Tom; Walenbergh, Sofie M. A.; Debets, Jacques; Oligschlaeger, Yvonne; Gijbels, Marion J. J.; Neumann, Dietbert; Shiri-Sverdlov, Ronit

2016-01-01

Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)-a serum

Chronic hypertension and the risk for adverse pregnancy outcome after superimposed pre-eclampsia.

Science.gov (United States)

Vanek, M; Sheiner, E; Levy, A; Mazor, M

2004-07-01

To determine the risk factors and pregnancy outcome of patients with chronic hypertension during pregnancy after controlling for superimposed preeclampsia. A comparison of all singleton term (>36 weeks) deliveries occurring between 1988 and 1999, with and without chronic hypertension, was performed. Stratified analyses, using the Mantel-Haenszel technique, and a multiple logistic regression model were performed to control for confounders. Chronic hypertension complicated 1.6% (n=1807) of all deliveries included in the study (n=113156). Using a multivariable analysis, the following factors were found to be independently associated with chronic hypertension: maternal age >40 years (OR=3.1; 95% CI 2.7-3.6), diabetes mellitus (OR=3.6; 95% CI 3.3-4.1), recurrent abortions (OR=1.5; 95% CI 1.3-1.8), infertility treatment (OR=2.9; 95% CI 2.3-3.7), and previous cesarean delivery (CD; OR=1.8 CI 1.6-2.0). After adjustment for superimposed preeclampsia, using the Mantel-Haenszel technique, pregnancies complicated with chronic hypertension had higher rates of CD (OR=2.7; 95% CI 2.4-3.0), intra uterine growth restriction (OR=1.7; 95% CI 1.3-2.2), perinatal mortality (OR=1.6; 95% CI 1.01-2.6) and post-partum hemorrhage (OR=2.2; 95% CI 1.4-3.7). Chronic hypertension is associated with adverse pregnancy outcome, regardless of superimposed preeclampsia.

Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.

Science.gov (United States)

Niriella, Madunil Anuk; Kobbegala, Vipuli Jayendra; Karalliyadda, Hasnatha Nuwan; Ranawaka, Chamila Kumara; de Silva, Arjuna Priyadarshin; Dassanayake, Anuradha Supun; de Silva, Hithanadura Janaka

2017-07-21

As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.

Science.gov (United States)

Machado, Mariana V; Oliveira, António G; Cortez-Pinto, Helena

2011-09-01

Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta-analysis to evaluate HS prevalence and risk factors, in HBV infection. Standard guidelines for performance of meta-analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random-effects model and DerSimonian-Laid method. Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45-0.67], P SMD 2.17, 95%CI [1.23, 3.11], P SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10-2.15], P = 0.011) and negatively with HBV DNA (SMD -74.12, 95%CI [-82.93, -65.31], P infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Ethanol metabolism by alcohol dehydrogenase or cytochrome P450 2E1 differentially impairs hepatic protein trafficking and growth hormone signaling.

Science.gov (United States)

Doody, Erin E; Groebner, Jennifer L; Walker, Jetta R; Frizol, Brittnee M; Tuma, Dean J; Fernandez, David J; Tuma, Pamela L

2017-12-01

The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P 450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion, and nuclear translocation and that the defects are likely mediated by acetaldehyde. However, the roles of CYP2E1-generated metabolites and ROS in microtubule acetylation and these alcohol-induced impairments have not been examined. To determine if CYP2E1-mediated alcohol metabolism is required for enhanced acetylation and the trafficking defects, we coincubated cells with ethanol and diallyl sulfide (DAS; a CYP2E1 inhibitor) or N -acetyl cysteine (NAC; an antioxidant). Both agents failed to prevent microtubule hyperacetylation in ethanol-treated cells and also failed to prevent impaired secretion or clathrin-mediated endocytosis. Somewhat surprisingly, both DAS and NAC prevented impaired STAT5B nuclear translocation. Further examination of microtubule-independent steps of the pathway revealed that Jak2/STAT5B activation by growth hormone was prevented by DAS and NAC. These results were confirmed in ethanol-exposed HepG2 cells expressing only ADH or CYP2E1. Using quantitative RT-PCR, we further determined that ethanol exposure led to blunted growth hormone-mediated gene expression. In conclusion, we determined that alcohol-induced microtubule acetylation and associated defects in microtubule-dependent trafficking are mediated by ADH metabolism whereas impaired microtubule-independent Jak2/STAT5B activation is mediated by CYP2E1 activity. NEW & NOTEWORTHY Impaired growth hormone-mediated signaling is observed in ethanol

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

2015-03-01

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

Inaccessibility of alcohol-induced cirrhosis of the liver to radiopharmaceutical methods of investigation

International Nuclear Information System (INIS)

Roh, T.G.

1983-01-01

Three cases of chronic alcohol abuse are described where the scintigrams recorded completely failed to visualise the hepatic structures. The female patients included in the study abused alcohol over a period of several years and the quantities consumed were far above the dose generally believed to cause cirrhosis in women. All of them displayed signs of advanced cirrhosis of the liver like portal hypertension, icterus, coagulation disorders, hepatic encephalopathy, etc. and the disease eventually led to the death of the patients. Hepatic scintiscanning was performed using Au198, Hg197, Tc99m sulfur colloid, Tc99m antimonial colloid as well as rose bengal iodine 131 tagged isotope; one patient was additionally subjected to radionuclide examination of the abdominal cavity. The causes of the described phenomenon still remain obscure. Damage to the reticuloendothelial system appears to be one of the predominant factors in the etiology of the disease. (TRV) [de

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome*

Science.gov (United States)

Libby, Andrew E.; Bales, Elise; Orlicky, David J.; McManaman, James L.

2016-01-01

Perilipin-2 (PLIN2) is a constitutively associated cytoplasmic lipid droplet coat protein that has been implicated in fatty liver formation in non-alcoholic fatty liver disease. Mice with or without whole-body deletion of perilipin-2 (Plin2-null) were fed either Western or control diets for 30 weeks. Perilipin-2 deletion prevents obesity and insulin resistance in Western diet-fed mice and dramatically reduces hepatic triglyceride and cholesterol levels in mice fed Western or control diets. Gene and protein expression studies reveal that PLIN2 deletion suppressed SREBP-1 and SREBP-2 target genes involved in de novo lipogenesis and cholesterol biosynthetic pathways in livers of mice on either diet. GC-MS lipidomics demonstrate that this reduction correlated with profound alterations in the hepatic lipidome with significant reductions in both desaturation and elongation of hepatic neutral lipid species. To examine the possibility that lipidomic actions of PLIN2 deletion contribute to suppression of SREBP activation, we isolated endoplasmic reticulum membrane fractions from long-term Western diet-fed wild type (WT) and Plin2-null mice. Lipidomic analyses reveal that endoplasmic reticulum membranes from Plin2-null mice are markedly enriched in ω-3 and ω-6 long-chain polyunsaturated fatty acids, which others have shown inhibit SREBP activation and de novo lipogenesis. Our results identify PLIN2 as a determinant of global changes in the hepatic lipidome and suggest the hypothesis that these actions contribute to SREBP-regulated de novo lipogenesis involved in non-alcoholic fatty liver disease. PMID:27679530

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome.

Science.gov (United States)

Libby, Andrew E; Bales, Elise; Orlicky, David J; McManaman, James L

2016-11-11

Perilipin-2 (PLIN2) is a constitutively associated cytoplasmic lipid droplet coat protein that has been implicated in fatty liver formation in non-alcoholic fatty liver disease. Mice with or without whole-body deletion of perilipin-2 (Plin2-null) were fed either Western or control diets for 30 weeks. Perilipin-2 deletion prevents obesity and insulin resistance in Western diet-fed mice and dramatically reduces hepatic triglyceride and cholesterol levels in mice fed Western or control diets. Gene and protein expression studies reveal that PLIN2 deletion suppressed SREBP-1 and SREBP-2 target genes involved in de novo lipogenesis and cholesterol biosynthetic pathways in livers of mice on either diet. GC-MS lipidomics demonstrate that this reduction correlated with profound alterations in the hepatic lipidome with significant reductions in both desaturation and elongation of hepatic neutral lipid species. To examine the possibility that lipidomic actions of PLIN2 deletion contribute to suppression of SREBP activation, we isolated endoplasmic reticulum membrane fractions from long-term Western diet-fed wild type (WT) and Plin2-null mice. Lipidomic analyses reveal that endoplasmic reticulum membranes from Plin2-null mice are markedly enriched in ω-3 and ω-6 long-chain polyunsaturated fatty acids, which others have shown inhibit SREBP activation and de novo lipogenesis. Our results identify PLIN2 as a determinant of global changes in the hepatic lipidome and suggest the hypothesis that these actions contribute to SREBP-regulated de novo lipogenesis involved in non-alcoholic fatty liver disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Non-invasive means of measuring hepatic fat content.

Science.gov (United States)

Mehta, Sanjeev-R; Thomas, E-Louise; Bell, Jimmy-D; Johnston, Desmond-G; Taylor-Robinson, Simon-D

2008-06-14

Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo (1)H MRS is a fast, safe, non-invasive method for the quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions.

Monkey alcohol tissue research resource: banking tissues for alcohol research.

Science.gov (United States)

Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

2014-07-01

An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better

Extract of Citrus maxima (pummelo) leaves improve hepatoprotective activity in Wistar rats submitted to the induction of non-alcoholic hepatic steatosis.

Science.gov (United States)

Feksa, Denise Lima; Coelho, Ritiéle Pinto; Aparecida da Costa Güllich, Angélica; Dal Ponte, Emanuelle S; da Costa Escobar Piccoli, Jacqueline; Manfredini, Vanusa

2018-02-01

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection—Liver: The “Musketeer” in the Spotlight

Science.gov (United States)

Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

2016-01-01

The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved. PMID:27005620

Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection—Liver: The “Musketeer” in the Spotlight

Directory of Open Access Journals (Sweden)

Stefano Ballestri

2016-03-01

Full Text Available The pathogenesis of type 2 diabetes (T2D involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR, which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD encompasses a spectrum of fatty (simple steatosis and steatohepatitis and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

Energy Technology Data Exchange (ETDEWEB)

Xu, Wenxuan; Lu, Chunfeng; Yao, Lu; Zhang, Feng; Shao, Jiangjuan [Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China); Zheng, Shizhong, E-mail: nytws@163.com [Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China); Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province (China)

2017-01-15

Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

International Nuclear Information System (INIS)

Xu, Wenxuan; Lu, Chunfeng; Yao, Lu; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

2017-01-01

Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.

Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease

NARCIS (Netherlands)

ter Horst, Kasper W.; Serlie, Mireille J.

2017-01-01

Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be

Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations

Energy Technology Data Exchange (ETDEWEB)

Chavan, Ajay [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Klinikum Oldenburg, Department of Radiology and Nuclear Medicine, Oldenburg (Germany); Caselitz, Martin; Wagner, Siegfried; Manns, Michael [Hannover Medical School, Department of Gastroenterology and Hepatology, Hannover (Germany); Gratz, Karl-Friedrich [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Lotz, Joachim; Kirchhoff, Timm; Galanski, Michael [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Piso, Plinio [Hannover Medical School, Department of Abdominal and Transplantation Surgery, Hannover (Germany)

2004-11-01

At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10-136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly (P<0.001) from 12.57{+-}3.27 l/min pre-treatment to 8.36{+-}2.60 l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE. (orig.)

Addressing liver fibrosis with Liposomes targeted to hepatic stellate cells

NARCIS (Netherlands)

Adrian, Joanna E.; Poelstra, Klaas; Kamps, Jan A. A. M.

2007-01-01

Liver fibrosis is a chronic disease that results from hepatitis B and C infections, alcohol abuse or metabolic and genetic disorders. Ultimately, progression of fibrosis leads to cirrhosis, a stage of the disease characterized by failure of the normal liver functions. Currently, the treatment of

Alcohol and Mortality: Combining Self-Reported (AUDIT-C) and Biomarker Detected (PEth) Alcohol Measures Among HIV Infected and Uninfected.

Science.gov (United States)

Eyawo, Oghenowede; McGinnis, Kathleen A; Justice, Amy C; Fiellin, David A; Hahn, Judith A; Williams, Emily C; Gordon, Adam J; Marshall, Brandon D L; Kraemer, Kevin L; Crystal, Stephen; Gaither, Julie R; Edelman, E Jennifer; Bryant, Kendall J; Tate, Janet P

2018-02-01

Unhealthy alcohol use may be particularly detrimental among individuals living with HIV and/or hepatitis C virus (HCV), and is often under-reported. Direct biomarkers of alcohol exposure may facilitate improved detection of alcohol use. We evaluated the association of alcohol exposure determined by both self-report [Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and a direct biomarker [phosphatidylethanol (PEth)], with mortality among HIV-infected and HIV-uninfected in the Veterans Aging Cohort Study-Biomarker Cohort. We considered PEth AUDIT-C scores [0, 1-3/1-2 (men/women), 4-7/3-7 (men/women), 8-12] and PEth (AUDIT-C = 0 (abstinence). Of these, 15% (149/1015) had PEth ≥8 suggesting recent alcohol exposure. Among those with AUDIT-C = 0, HCV+ individuals were more likely to have PEth ≥8. After controlling for age, sex, race, HIV, HCV, and HIV viral suppression, those with AUDIT-C = 0 but PEth ≥8 had the highest risk of mortality (adjusted hazard ratio 2.15, 95% confidence interval: 1.40 to 3.29). PEth in addition to self-report may improve detection of alcohol use in clinical settings, particularly among those at increased risk of harm from alcohol use. Individuals infected with HCV were more likely to under-report alcohol use.

Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition

International Nuclear Information System (INIS)

Kim, Seok-Joo; Lee, Sun-Mee

2012-01-01

Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was intraperitoneally administered 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver. -- Highlights: ► Baicalin attenuates hepatic I/R-induced inflammation in alcoholic fatty liver. ► Baicalin downregulates TLR4, MyD88 expression during I/R in alcoholic fatty liver. ► Baicalin attenuates NF-κB nuclear translocation during I/R in alcoholic fatty liver.

Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts

NARCIS (Netherlands)

Van Den Bossche, Lindsay; Schoonenberg, Vivien A.C.; Burgener, Iwan A.; Penning, Louis C.; Schrall, Ingrid M.; Kruitwagen, Hedwig S.; Van Wolferen, Monique E.; Grinwis, Guy C.M.; Kummeling, Anne; Rothuizen, Jan; Van Velzen, Jeroen F.; Stathonikos, Nikolas; Molenaar, Martijn R.; Helms, Bernd J.; Brouwers, Jos F.H.M.; Spee, Bart; Van Steenbeek, Frank G.

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in

Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

Directory of Open Access Journals (Sweden)

Atrayee Banerjee

Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

Modulation of hepatic steatosis by dietary fatty acids

Science.gov (United States)

Ferramosca, Alessandra; Zara, Vincenzo

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the “case” of olive oil, since several studies have often provided different and⁄or conflicting results in animal models. PMID:24587652

Modulation of hepatic steatosis by dietary fatty acids.

Science.gov (United States)

Ferramosca, Alessandra; Zara, Vincenzo

2014-02-21

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the "case" of olive oil, since several studies have often provided different and/or conflicting results in animal models.

Controlled attenuation parameter using the FibroScan® XL probe for quantification of hepatic steatosis for non-alcoholic fatty liver disease in an Asian population.

Science.gov (United States)

Chan, Wah-Kheong; Nik Mustapha, Nik Raihan; Wong, Grace Lai-Hung; Wong, Vincent Wai-Sun; Mahadeva, Sanjiv

2017-02-01

The FibroScan® XL probe reduces failure of liver stiffness measurement (LSM) and unreliable results in obese patients. The objective of this article is to evaluate the accuracy of controlled attenuation parameter (CAP) obtained using the XL probe for the estimation of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). Adult NAFLD patients with a liver biopsy within six months were included and were examined with the FibroScan® M and XL probes. Histopathological findings were reported according to the Non-Alcoholic Steatohepatitis Clinical Research Network Scoring System. Participants who did not have fatty liver on ultrasonography were recruited as controls. A total of 57 NAFLD patients and 22 controls were included. The mean age of the NAFLD patients and controls was 50.1 ± 10.4 years and 20.2 ± 1.3 years, respectively ( p  = 0.000). The mean body mass index was 30.2 ± 5.0 kg per m 2 and 20.5 ± 2.4 kg per m 2 , respectively ( p  = 0.000). The distribution of steatosis grades were: S0, 29%; S1, 17%; S2, 35%; S3, 19%. The AUROC for estimation of steatosis grade ≥ S1, S2 and S3 was 0.94, 0.80 and 0.69, respectively, using the M probe, and 0.97, 0.81 and 0.67, respectively, using the XL probe. CAP obtained using the XL probe had similar accuracy as the M probe for the estimation of hepatic steatosis in NAFLD patients.

The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.

Science.gov (United States)

Ryan, Marno C; Itsiopoulos, Catherine; Thodis, Tania; Ward, Glenn; Trost, Nicholas; Hofferberth, Sophie; O'Dea, Kerin; Desmond, Paul V; Johnson, Nathan A; Wilson, Andrew M

2013-07-01

Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Advances in the pathogenesis of non alcoholic fatty liver disease].

Science.gov (United States)

Pár, Alajos; Pár, Gabriella

2017-06-01

Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury

DEFF Research Database (Denmark)

Junge, Jette; Horn, T; Christoffersen, P

1988-01-01

The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular...... localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis....... It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

A window of opportunity: declining rates of hepatitis B virus infection among injection drug users in Rio de Janeiro, and prospects for targeted hepatitis B vaccination.

Science.gov (United States)

Oliveira, Sabrina A N; Hacker, Mariana A; Oliveira, M Lourdes A; Yoshida, Clara F T; Telles, Paulo R; Bastos, Francisco I

2005-01-01

To measure hepatitis B virus (HBV) infection rates among injection drug users in Rio de Janeiro, Brazil, and to report their knowledge of and attitudes toward hepatitis and HBV vaccination. 609 injection drug users recruited in Rio de Janeiro between 1999 and 2001 answered a questionnaire and were tested for hepatitis B and other blood-borne infections. Questions covered sociodemographic information, alcohol and illicit drug consumption, drug injection and sexual practices, medical history, and knowledge about HIV, AIDS and viral hepatitis. The prevalence of HBV infection was 27.1%, with 3.4% of the sample positive for HbsAg (active infection) and 0.8% positive for anti-HBs (indicating previous HBV vaccination). Most interviewees (81.3%) were aware of at least one form of viral hepatitis and received information from many different sources. In agreement with laboratory findings, 96.7% of the interviewees stated they had never been vaccinated against hepatitis B, but almost all unvaccinated interviewees (97.8%) said they would volunteer to be vaccinated if HBV vaccination were available. Few of the injection drug users surveyed had ever been vaccinated against HBV. Although most were aware of the risks posed by viral hepatitis, this awareness seldom translated into consistent behavioral change. The participants' willingness to be vaccinated against HBV suggests that the implementation of vaccination for this population may help decrease rates of hepatitis B infection.

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

DEFF Research Database (Denmark)

Dela, Flemming; Mikines, K J; Larsen, J J

1999-01-01

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle tra...

Experimental Hepatic Carcinogenesis: Oxidative Stress and Natural Antioxidants

Directory of Open Access Journals (Sweden)

Velid Unsal

2017-08-01

Full Text Available Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C. Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons. 2-AAF is the inducer of DEN, and it is involved in tumour formation in the bladder and liver. Reactive Oxygen species (ROS; carbohydrates, lipids, DNA and enzymes, such as affect all important structures. Additionally, an excessive amount of ROS is highly toxic to cells. Antioxidants are protects against ROS, toxic substances, carcinogens. This review focuses on the literature on studies of Hepatic Carcinogenesis, oxidative stress and antioxidant therapy.

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

Science.gov (United States)

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in

Spatial mapping of multi-year superimposed ice on the glacier Kongsvegen, Svalbard

DEFF Research Database (Denmark)

Brandt, Ola; Kohler, Jack; Lüthje, Mikael

2008-01-01

by GPR. Using the SI spatial depth distribution, we estimate the mean annual accumulation of superimposed ice to be 0.16 +/- 0.06 mw.e.a(-1) (locally up to 0.43 ma(-1) w.e.). This corresponds to similar to 15-33% of the local winter balance and similar to 5-10% of the total winter balance measured since...

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

Science.gov (United States)

Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Spontaneous evolution in bilirubin levels predicts liver-related mortality in patients with alcoholic hepatitis.

Directory of Open Access Journals (Sweden)

Minjong Lee

Full Text Available The accurate prognostic stratification of alcoholic hepatitis (AH is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort and 106 patients with AH between 2005 and 2012 (a validation cohort. The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC. For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001. In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.

Hepatitis E-induced severe myositis.

Science.gov (United States)

Mengel, Annerose M; Stenzel, Werner; Meisel, Andreas; Büning, Carsten

2016-02-01

Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV is rarely recognized by neurologists. This is a case report of myositis induced by HEV. We report the life-threatening case of a 57-year-old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months. This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery. © 2015 Wiley Periodicals, Inc.

CLINICAL PROFILE OF PATIENTS WITH ALCOHOLIC LIVER DISEASE IN UPPER ASSAM OF NORTH EAST INDIA

Directory of Open Access Journals (Sweden)

Ardhendu Kumar Sen

2017-05-01

Full Text Available BACKGROUND Alcohol is the most commonly abused drug worldwide causing liver injury with respect to dose, duration, type of alcohol consumption and drinking patterns and gender with diverse ethnicity and social customs. There is high prevalence of alcohol use in the society without much social taboo in the North Eastern States of India and also there is a high prevalence of different ethnic tribes with the custom of taking country made alcohol casually as a part of their tradition. The aim of this study is to study the clinical profile of patients with alcoholic liver disease in upper Assam of north east India. MATERIALS AND METHODS The study was a hospital-based observational study in which patients of 18 years and older and diagnosed to have alcoholic liver disease were included. Cases excluded were patients of NASH, viral hepatitis, drug-induced hepatitis, haemochromatosis, alcoholic liver disease with diabetes and kidney disease. Informed written consent was taken from the patients or their attendants. Ethical clearance was taken from the Institutional Ethical Committee. A total of 138 cases were selected for the study. A detailed evaluation of clinical history, examination and investigations and the results were recorded in a predesigned proforma. RESULTS Out of 138 patients, 113 were males and 25 were females with male:female ratio of 4.5:1. Majority of cases (34.78% were in the age group of (41-50 years. It was observed that 98 patients (71.01% belonged to the lower socioeconomic status group. The average duration of alcohol intake was 18.39 ± 6.24 years for males and 16.76 ± 6.59 years for females. The overall average duration of alcohol intake was 18.09 ± 6.29 years. The majority of the patients (104 cases, 75.36% took both foreign and country-made liquors. The most common clinical presentation was abdominal distension and swelling of feet (71 cases, 51.45% followed by jaundice (68 cases, 49.28% and anorexia (56 cases, 40.58%. The

Frequency and severity of steatosis in patients with chronic hepatitis-c

International Nuclear Information System (INIS)

Khan, A.N.; Said, K.; Gul, R.

2015-01-01

Hepatitis-C viral infection is a global health problem. It has been estimated that approximately 170 million individuals are infected with hepatitis-C virus. Hepatic steatosis is a frequent histological feature in patients with chronic hepatitis-C infection. Histological examinations show that up to 50% of these patients have variable degrees of hepatic steatosis, even in the absence of other possible steatogenic factors like alcohol, drugs or metabolic syndromes. The objective of this study was to determine the frequency and severity of steatosis in patients with Chronic Hepatitis-C. Methods: This cross sectional study was carried out from 1st January 2010 to 1st July 2010 at the department of Gastroenterology PIMS, Islamabad. A total of 127 patients of chronic hepatitis-C were enrolled in the study after taking informed written consent. Frequency and severity (mild, moderate and severe) of steatosis was assessed on the basis of liver biopsy. Results: A total of 127 patients were included in the study. Mean age of the patients was 36.24 years. Out of 127 patients, 48(38%) were male and 79(62%) were female. Steatosis was present in 50(39%) patients with chronic hepatitis-C infection. whereas steatosis was absent in 77(61%) patients. Conclusion: The presence of steatosis on liver biopsy in patients with chronic hepatitis-C is common (39% patients) and female patients had slightly more severe degree of steatosis as compared to male patients. (author)

Significant influence of the primary liver disease on the outcomes of hepatic retransplantation.

LENUS (Irish Health Repository)

Qasim, A

2012-02-01

BACKGROUND: There are many indications for hepatic retransplantation. AIM: To identify factors influencing retransplantation needs and outcomes. PATIENTS AND METHODS: Retransplantation records from January 1993 to March 2005 were analysed. Patient and disease characteristics and survival outcomes for retransplantation were compared between various groups. RESULTS: Totally, 286 primary and 42 hepatic retransplantations were performed. Retransplantation indications included primary sclerosing cholangitis (PSC), primary biliary cirrhosis, chronic hepatitis C (HCV), chronic active hepatitis (CAH), and alcohol-related disease. Mean follow-up post-retransplantation was 31 +\\/- 9 months. Actuarial patient survival at 3 months, 1 year, 3 years, 5 years, and at the end of study was 71.4, 69, 59.5, 54.7, and 50%, respectively. Early and late retransplantation had 1-year survival of 73 and 68.5%, respectively. Retransplantation need was significantly higher for PSC, HCV, and CAH. CONCLUSIONS: Hepatic retransplantation remains a successful salvage option for transplant complications; however, its need is significantly influenced by the primary liver disease.

An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

Science.gov (United States)

Hsu, Ching-Sheng; Kao, Jia-Horng

2017-08-01

Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

Ethyl alcohol: high risk toxin for human healt socially accepted

Directory of Open Access Journals (Sweden)

Jairo Téllez Mosquera

2006-01-01

Full Text Available Alcohol is the most widely used drugs in World wide so it is in Colombia too. The United Nations Organization (UN report on substance abuse 2004, esteem that 2.6000 millions of persons used alcohol occasional, habitual, abuse or addictive way. In Colombia, RUMBOS, the presidential office for drugs addictions esteem that 89.7 % of the students in universities were habitual consumer of alcohol. Alcohol is the first psicoactivas substances use for people than after use illegal substances. When ethyl alcohol is used in permanent and frequent way produced acute and chronic adverses effect on the health. The long run alcohol abusers has adverse effect in the nutricions, neurological, hepatic and teratogenic. The neurological, gastrointestinal, endocrine and acid-base equilibrium area affected in acute ways principally. The social aspects in quite important too alcohol has been related to interfamiliar violence, traffic accidents and violence in general. The high incidence in use and consumption, its toxic effect over human health, its negative social effect and the fact that it´s a legal and social accept substance made alcohol and real public health problem. Its necessary to say "be careful with alcohol in general"

Diagnostic significance of hepatic venography and retrograde portography in portal hypertension

Energy Technology Data Exchange (ETDEWEB)

Fukunaga, Masaki

1987-07-01

In this series, we studied about diagnostic significance of hepatic venography and retrograde portography in portal hypertension by using stepwise discriminant analysis. The accuracy rate of the discrimination was 95 % in liver cirrhosis (LC), 86 % in B' type LC, 83 % in primary biliary cirrhosis (PBC) and 57 % in idiopathic portal hypertension (IPH). The difficulty in differential diagnosis of IPH from PBC was due to similarity of hepatic vascular changes in both diseases. Next we studied about the relationship between venographic findings and the causes of LC. The size of regenerated nodule in alcoholic LC was significantly smaller than the others, so venographic findings were different from others. It was concluded that hepatic venography was useful examination for differential diagnosis in portal hypertension, and was effective for considering about the causes of LC.

Diagnostic significance of hepatic venography and retrograde portography in portal hypertension

International Nuclear Information System (INIS)

Fukunaga, Masaki

1987-01-01

In this series, we studied about diagnostic significance of hepatic venography and retrograde portography in portal hypertension by using stepwise discriminant analysis. The accuracy rate of the discrimination was 95 % in liver cirrhosis (LC), 86 % in B' type LC, 83 % in primary biliary cirrhosis (PBC) and 57 % in idiopathic portal hypertension (IPH). The difficulty in differential diagnosis of IPH from PBC was due to similarity of hepatic vascular changes in both diseases. Next we studied about the relationship between venographic findings and the causes of LC. The size of regenerated nodule in alcoholic LC was significantly smaller than the others, so venographic findings were different from others. It was concluded that hepatic venography was useful examination for differential diagnosis in portal hypertension, and was effective for considering about the causes of LC. (author)

Validation of Lifetime Prediction of IGBT Modules Based on Linear Damage Accumulation by Means of Superimposed Power Cycling Tests

DEFF Research Database (Denmark)

Choi, Ui-Min; Ma, Ke; Blaabjerg, Frede

2018-01-01

In this paper, the lifetime prediction of power device modules based on the linear damage accumulation is studied in conjunction with simple mission profiles of converters. Superimposed power cycling conditions, which are called simple mission profiles in this paper, are made based on a lifetime ...... prediction of IGBT modules under power converter applications.......In this paper, the lifetime prediction of power device modules based on the linear damage accumulation is studied in conjunction with simple mission profiles of converters. Superimposed power cycling conditions, which are called simple mission profiles in this paper, are made based on a lifetime...... model in respect to junction temperature swing duration. This model has been built based on 39 power cycling test results of 600-V 30-A three-phase-molded IGBT modules. Six tests are performed under three superimposed power cycling conditions using an advanced power cycling test setup. The experimental...

PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

Science.gov (United States)

Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

2014-01-01

Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

Augmented environments for the targeting of hepatic lesions during image-guided robotic liver surgery.

Science.gov (United States)

Buchs, Nicolas C; Volonte, Francesco; Pugin, François; Toso, Christian; Fusaglia, Matteo; Gavaghan, Kate; Majno, Pietro E; Peterhans, Matthias; Weber, Stefan; Morel, Philippe

2013-10-01

Stereotactic navigation technology can enhance guidance during surgery and enable the precise reproduction of planned surgical strategies. Currently, specific systems (such as the CAS-One system) are available for instrument guidance in open liver surgery. This study aims to evaluate the implementation of such a system for the targeting of hepatic tumors during robotic liver surgery. Optical tracking references were attached to one of the robotic instruments and to the robotic endoscopic camera. After instrument and video calibration and patient-to-image registration, a virtual model of the tracked instrument and the available three-dimensional images of the liver were displayed directly within the robotic console, superimposed onto the endoscopic video image. An additional superimposed targeting viewer allowed for the visualization of the target tumor, relative to the tip of the instrument, for an assessment of the distance between the tumor and the tool for the realization of safe resection margins. Two cirrhotic patients underwent robotic navigated atypical hepatic resections for hepatocellular carcinoma. The augmented endoscopic view allowed for the definition of an accurate resection margin around the tumor. The overlay of reconstructed three-dimensional models was also used during parenchymal transection for the identification of vascular and biliary structures. Operative times were 240 min in the first case and 300 min in the second. There were no intraoperative complications. The da Vinci Surgical System provided an excellent platform for image-guided liver surgery with a stable optic and instrumentation. Robotic image guidance might improve the surgeon's orientation during the operation and increase accuracy in tumor resection. Further developments of this technological combination are needed to deal with organ deformation during surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessment of Hepatic Mitochondrial Oxidation and Pyruvate Cycling in NAFLD by (13)C Magnetic Resonance Spectroscopy

DEFF Research Database (Denmark)

Petersen, Kitt Mia Falck; Befroy, Douglas E; Dufour, Sylvie

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and there is great interest in understanding the potential role of alterations in mitochondrial metabolism in its pathogenesis. To address this question, we assessed rates of hepatic mitochondrial oxidation...... in subjects with and without NAFLD by monitoring the rate of (13)C labeling in hepatic [5-(13)C]glutamate and [1-(13)C]glutamate by (13)C MRS during an infusion of [1-(13)C]acetate. We found that rates of hepatic mitochondrial oxidation were similar between NAFLD and control subjects. We also assessed rates...

Three-dimensional mapping of local cerebral perfusion in alcoholic encephalopathy with and without Wernicke-Korsakoff syndrome

International Nuclear Information System (INIS)

Hata, T.; Meyer, J.S.; Tanahashi, N.

1987-01-01

Seventeen severe chronic alcoholic patients with and without Wernicke-Korsakoff syndrome (WKS) were examined prospectively after being treated by withdrawal from alcohol. The WKS patients also received thiamine supplements. Three-dimensional measurements of local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were made utilizing xenon contrast computed tomography (Xe CT-CBF). Results were displayed as color-coded brain maps before and after treatment and these were correlated with neurological and cognitive examinations. Before treatment chronic alcoholics without WKS (n = 10) showed diffuse reductions of LCBF values throughout all gray matter including hypothalamus, vicinity of nucleus basalis of Meynert, thalamus, and basal ganglia. Similar, but more severe, reductions were seen in patients with WKS (n = 7), however, white matter perfusion was also reduced. In WKS, most prominent reductions of LCBF were also seen in hypothalamus and basal forebrain nuclei but thalamus, basal ganglia, and limbic systems were severely reduced. After treatment, both groups with alcoholic encephalopathy showed marked clinical improvement and cerebral perfusion was restored toward normal. Chronic alcohol abuse, in the absence of thiamine deficiency, reduces CBF by direct neurotoxic effects. If thiamine deficiency is also present, more severe and localized hemodynamic reductions are superimposed

Liver cirrhosis as a result of chronic hepatitis C

Directory of Open Access Journals (Sweden)

A. A. Sukhoruk

2014-01-01

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

A System on a Programmable Chip Architecture for Data-Dependent Superimposed Training Channel Estimation

Directory of Open Access Journals (Sweden)

Fernando Martín del Campo

2009-01-01

with the information, a series of known symbols, whose analysis is used to define the parameters of the filters that remove the distortion of the data. Nevertheless, a part of the available bandwidth has to be destined to these symbols. Until now, no alternative solution has demonstrated to be fully satisfying for commercial use, but one technique that looks promising is superimposed training (ST. This work describes a hybrid software-hardware FPGA implementation of a recent algorithm that belongs to the ST family, known as Data-dependent Superimposed Training (DDST, which does not need extra bandwidth for its training sequences (TS as it adds them arithmetically to the data. DDST also adds a third sequence known as data-dependent sequence, that destroys the interference caused by the data over the TS. As DDST's computational burden is too high for the commercial processors used in mobile systems, a System on a Programmable Chip (SOPC approach is used in order to solve the problem.

Experimental Verification and Capacity Prediction of FE-OCDMA Using Superimposed FBG

Science.gov (United States)

Ayotte, Simon; Rochette, Martin; Magné, Julien; Rusch, Leslie A.; Larochelle, Sophie

2005-02-01

This paper presents the experimental demonstration and simulation results of a frequency-encoded optical code-division multiple-access (FE-OCDMA) system using broad-band incoherent source, superimposed fiber Bragg gratings for encoding/decoding of unipolar m -sequence codes, and balanced detection. The bit-error rate is measured for up to four simultaneous users at 155 and 622 Mb/s. Exploiting the excellent match between simulation and experiment, the paper concludes with a prediction of the potential capacity of an optimized FE-CDMA system.

Orlistat-induced fulminant hepatic failure.

Science.gov (United States)

Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

2014-12-01

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

Amelioration of High Cholesterol Diet Caused Lipids Accumulation in Hepatic Cells by Rutin and Ascorbic Acid

OpenAIRE

Abdulaziz M. Aleisa

2013-01-01

Non Alcoholic Fatty Liver Disease (NAFLD) has become a very common metabolic disorder. It refers to a group of conditions where excess fats are deposited in hepatic cells. Several approaches have been considered for the management of NAFLD including dietary changes, which were reported to suppress hepatic lipids accumulation in previous studies. The present study was designed to investigate the possible synergistic effects of Rutin (RT) and Ascorbic Acid (AA) against lipids accumulation in he...

Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

Directory of Open Access Journals (Sweden)

Zhenting Zhou

2017-01-01

Full Text Available Alcoholic liver disease (ALD is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP zebrafish larvae (4 dpf. The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1. In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.

New insights in the pathogenesis of non-alcoholic fatty liver disease

NARCIS (Netherlands)

Gaemers, Ingrid C.; Groen, Albert K.

2006-01-01

PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent

Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

Energy Technology Data Exchange (ETDEWEB)

Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

1985-07-01

The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

Alcoholic Liver Disease and Malnutrition

Science.gov (United States)

McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

2013-01-01

Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy. PMID:21284673

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat

DEFF Research Database (Denmark)

Tygstrup, N; Jensen, S A; Krog, B

1997-01-01

BACKGROUND/AIMS: To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS: Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tu...

Aetiology and pathogenesis of alcoholic liver disease.

Science.gov (United States)

Lieber, C S

1993-09-01

Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical

Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Deng, Jie; Fishbein, Mark H; Rigsby, Cynthia K; Zhang, Gang; Schoeneman, Samantha E; Donaldson, James S

2014-11-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*W) and fat (T2*F) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P fat fraction, T2*W (27.9 ± 3.5 ms) decreased, whereas T2*F (20.3 ± 5.5 ms) increased; and T2*W and T2*F became increasingly more similar when fat fraction was higher than 15-20%. Histological fat

Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease

Energy Technology Data Exchange (ETDEWEB)

Deng, Jie; Rigsby, Cynthia K.; Donaldson, James S. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Fishbein, Mark H. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Gastroenterology, Hepatology, and Nutrition, Chicago, IL (United States); Zhang, Gang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Biostatistics Research Core, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

2014-11-15

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*{sub W}) and fat (T2*{sub F}) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*{sub W} (27.9 ± 3.5 ms) decreased, whereas T2*{sub F} (20.3 ± 5.5 ms) increased; and T2*{sub W} and T2*{sub F} became increasingly more similar when fat

Structural differences between alcoholic and diabetic parotid sialosis.

Science.gov (United States)

Carda, Carmen; Carranza, Miriam; Arriaga, Adriana; Díaz, Anselmo; Peydró, Amando; Gomez de Ferraris, Maria Elsa

2005-01-01

Between the sialosis' etiologic agents, we can find the chronic alcoholism and diabetes. Both nosologic entities are described using a similar histopathologic pattern. The purpose of this work has been analyzing and comparing the histopathological differences between the diabetic and alcoholic sialosis. We studied 7 parotid glands samples of diabetic patients and 4 samples of normal glands obtained from surgical material were used as a control. For the comparative study, we used 12 parotid glands from chronic alcoholic patients with clinical diagnosis of cirrhosis and 6 autopsies on individuals who had died from alcoholic hepatic cirrhosis. This material was fixed in formaline, processed for embedding in paraffin, standard coloration techniques and immunotechnique for cytokeratin EA/1 y EA/3. In the cases of diabetics, the parotid gland was characterised by the presence of small acini, a bigger number of lipid intracytoplasmic droplets in the acinar and ductal cells, as well as an abundant adipose infiltration in the stroma when compared to the alcoholics. We observed that the cytokeratins' expression was heterogeneous at the acinar level, and very positive in the hyperplasic ducts, compared to the alcoholic and control groups. These qualitative valorations indicate the differences between the histopathologic pattern of sialosis with different origins.

Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

DEFF Research Database (Denmark)

Johansen, J S; Møller, S; Price, P A

1997-01-01

YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2...... with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P ... with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis....

Identifying changes in the synaptic proteome of cirrhotic alcoholic superior frontal gyrus.

Science.gov (United States)

Etheridge, N; Mayfield, R D; Harris, R A; Dodd, P R

2011-03-01

Hepatic complications are a common side-effect of alcoholism. Without the detoxification capabilities of the liver, alcohol misuse induces changes in gene and protein expression throughout the body. A global proteomics approach was used to identify these protein changes in the brain. We utilised human autopsy tissue from the superior frontal gyrus (SFG) of six cirrhotic alcoholics, six alcoholics without comorbid disease, and six non-alcoholic non-cirrhotic controls. Synaptic proteins were isolated and used in two-dimensional differential in-gel electrophoresis coupled with mass spectrometry. Many expression differences were confined to one or other alcoholic sub-group. Cirrhotic alcoholics showed 99 differences in protein expression levels from controls, of which half also differed from non-comorbid alcoholics. This may reflect differences in disease severity between the sub-groups of alcoholics, or differences in patterns of harmful drinking. Alternatively, the protein profiles may result from differences between cirrhotic and non-comorbid alcoholics in subjects' responses to alcohol misuse. Ten proteins were identified in at least two spots on the 2D gel; they were involved in basal energy metabolism, synaptic vesicle recycling, and chaperoning. These post-translationally modified isoforms were differentially regulated in cirrhotic alcoholics, indicating a level of epigenetic control not previously observed in this disorder.

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor?

Science.gov (United States)

Hinds, Terry D; Adeosun, Samuel O; Alamodi, Abdulhadi A; Stec, David E

2016-10-01

Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels. We have recently described a novel function of bilirubin as a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), which we show specifically binds to the nuclear receptor. Bilirubin may function as a selective PPAR modulator (SPPARM) to control lipid accumulation and blood glucose. However, it is not known to what degree bilirubin activation of PPARα is responsible for the protection afforded to reduce hepatic steatosis. We hypothesize that bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism through a PPARα-dependent mechanism which reduces hepatic lipid accumulation and protects against hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Copyright © 2016 Elsevier Ltd. All rights reserved.

Feature Hepatitis: Hepatitis Can Strike Anyone

Science.gov (United States)

... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

Resemblance of the properties of superimposed volume holograms to the properties of human memory

Science.gov (United States)

Orlov, V. V.

2006-09-01

According to current concepts in psychology, a collection of patterns stored in human memory has the property of integrity and contains new information not contained in the individual patterns. It is shown that superimposed volume holograms possess similar properties if the information in them is written by a method that excludes the appearance of crosstalk of the holograms.

Hepatic diseases related to triglyceride metabolism.

Science.gov (United States)

Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

2013-10-01

Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

Inaccessibility of alcohol-induced cirrhosis of the liver to radiopharmaceutical methods of investigation. Fehlende Leberdarstellung im Szintigramm bei alkoholischer Leberzirrhose

Energy Technology Data Exchange (ETDEWEB)

Roh, T G

1983-12-08

Three cases of chronic alcohol abuse are described where the scintigrams recorded completely failed to visualise the hepatic structures. The female patients included in the study abused alcohol over a period of several years and the quantities consumed were far above the dose generally believed to cause cirrhosis in women. All of them displayed signs of advanced cirrhosis of the liver like portal hypertension, icterus, coagulation disorders, hepatic encephalopathy, etc. and the disease eventually led to the death of the patients. Hepatic scintiscanning was performed using Au198, Hg197, Tc99m sulfur colloid, Tc99m antimonial colloid as well as rose bengal iodine 131 tagged isotope; one patient was additionally subjected to radionuclide examination of the abdominal cavity. The causes of the described phenomenon still remain obscure. Damage to the reticuloendothelial system appears to be one of the predominant factors in the etiology of the disease. (TRV).

Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat.

Directory of Open Access Journals (Sweden)

Briana Spolding

Full Text Available BACKGROUND AND AIMS: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat. METHODS: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat or a standard rodent diet supplemented with 2% cholesterol (w/w for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. RESULTS: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. CONCLUSIONS: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

Science.gov (United States)

Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

2017-08-01

Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients.

Science.gov (United States)

Kim, Hee Yeon; Kim, Chang Wook; Choi, Jong Young; Lee, Chang Don; Lee, Sae Hwan; Kim, Moon Young; Jang, Byoung Kuk; Wo, Hyun Young

2016-01-01

Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Metformin and metabolic diseases: a focus on hepatic aspects

Science.gov (United States)

Woo, Shih-Lung; Hu, Xiang; Botchlett, Rachel; Chen, Lulu; Huo, Yuqing

2015-01-01

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases. PMID:25676019

Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

Science.gov (United States)

Sharma, Bhawana; Dabur, Rajesh

2016-01-01

Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Effects of sh-reagents on rat hepatic aldehyde dehydrogenase activity

Energy Technology Data Exchange (ETDEWEB)

Konoplitskaya, K.L.; Kuz' mina, G.I.; Grigor' yeva, M.V.; Poznyakova, T.N.

The liver serves as the primary organ for the oxidation of ingested ethanol via a pathway involving alcohol- and aldehyde dehydrogenase. In view of the problem of alcoholism, three enzymes are of particular interest in understanding the biochemical mechanism that may be involved in alcohol addiction and in the formulation of therapeutic approaches. While alcohol dehydrogenase has been studied in considerable detail, current attention is centered on aldehyde dehydrogenase. A comparative analysis of the effects of a series of SH-active reagents - tetraethylthiuram disulfide (TETD), 5,5-dithiobisnitrobenzoic acid (DTNB), p-chloromercurybenzoate (PCMB), and N-ethylmaleimide (NEM) - were tested for their effects on the activity of aldehyde dehydrogenase of the hepatic mitochondrial (isozymes I and II) and microsomal (isozyme II) fractions of outbred albino rats. DTNB was found to be inhibited by 100 and 50% mitochondrial isozymes I and II, respectively, and by 20%, the microsomal enzyme under the conditions employed. DTNB and NEM inhibited by 30 and 50% isozymes I and II of the mitochondria, but had no effect on the microsomal isozyme. 24 references, 3 figures.

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

Directory of Open Access Journals (Sweden)

Teruaki Toyota

2012-01-01

Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

Alcoholic liver injury: defenestration in noncirrhotic livers--a scanning electron microscopic study

DEFF Research Database (Denmark)

Horn, T; Christoffersen, P; Henriksen, Jens Henrik Sahl

1987-01-01

The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall...... (fractional area of fenestrae) was observed in acinar Zone 3, both in biopsies with and without Zone 3 fibrosis as judged by light microscopy. A significant reduction of porosity as shown in this study may influence the blood hepatocytic exchange and contribute to the alcohol-induced liver injury....

Comparison of risk factors among blood donors, volunteers and replacement individuals, infected or not by hepatitis C virus

Directory of Open Access Journals (Sweden)

MJDB Felippe

2009-01-01

Full Text Available Hepatitis C is transmitted primarily parenterally by contaminated blood and is often associated with: intravenous drug abuse, invasive procedures, blood transfusions, acupuncture, tattooing, and alcohol and tobacco use. This study aimed to quantify and evaluate the risk factors among blood donors, volunteer blood donors and replacement individuals, infected or not by the C virus. The main transmission routes of C virus were identified in 55 men and 25 women (GI monitored by the Ambulatory Unit of the Department of Tropical Diseases, Botucatu Medical School, and in 24 men and 26 women (GII, all active blood donors at the Bauru State Hospital Transfusional Agency. Both groups were similar in: tobacco and alcohol consumption, sexual behavior, tattooing and illicit drug use. The duration of alcohol and tobacco consumption and blood transfusions in GI were longer, whereas the option for steady partners, condom use, disposable materials and piercings were predominant in GII. In conclusion, the risk factors for hepatitis C demonstrate the necessity of health policies that act on the primary and secondary prevention levels (respectively, reduction of infection incidence and hepatopathy risk.

Suppression of Natural Killer Cell Activity by Regulatory NKT10 Cells Aggravates Alcoholic Hepatosteatosis

Directory of Open Access Journals (Sweden)

Kele Cui

2017-10-01

Full Text Available We and others have found that the functions of hepatic natural killer (NK cells are inhibited but invariant NKT (iNKT cells become activated after alcohol drinking, leaving a possibility that there exists interplay between NK cells and iNKT cells during alcoholic liver disease. Here, in a chronic plus single-binge ethanol consumption mouse model, we observed that NK cells and interferon-γ (IFN-γ protected against ethanol-induced liver steatosis, as both wild-type (WT mice treated with anti-asialo GM1 antibody and IFN-γ-deficient GKO mice developed more severe alcoholic fatty livers. As expected, IFN-γ could directly downregulate lipogenesis in primary hepatocytes in vitro. On the contrary, iNKT cell-deficient Jα18−/− or interleukin-10 (IL-10−/− mice showed fewer alcoholic steatosis, along with the recovered number and IFN-γ release of hepatic NK cells, and exogenous IL-10 injection was sufficient to compensate for iNKT cell deficiency. Furthermore, NK cell depletion in Jα18−/− or IL-10−/− mice caused more severe hepatosteatosis, implying NK cells are the direct effector cells to inhibit liver steatosis. Importantly, adoptive transfer of iNKT cells purified from normal but not IL-10−/− mice resulted in suppression of the number and functions of NK cells and aggravated alcoholic liver injury in Jα18−/− mice, indicating that IL-10-producing iNKT (NKT10 cells are the regulators on NK cells. Conclusion: Ethanol exposure-triggered NKT10 cells antagonize the protective roles of NK cells in alcoholic hepatosteatosis.

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

Science.gov (United States)

Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

Endovascular Treatment of Pseudoaneurysm of the Common Hepatic Artery with Intra-aneurysmal Glue (N-Butyl 2-Cyanoacrylate) Embolization

International Nuclear Information System (INIS)

Garg, Ashwin; Banait, Swati; Babhad, Sudeep; Kanchankar, Niraj; Nimade, Pradeep; Panchal, Chintan

2007-01-01

A 40-year-old man, a chronic alcoholic, presented with acute epigastric pain. Selective celiac arteriography showed a pseudoaneurysm arising from the common hepatic artery. We hereby describe a technical innovation where complete pseudoaneurysm exclusion was seen after intra-aneurysmal N-butyl 2-cyanoacrylate (glue) injection with preservation of antegrade hepatic arterial flow and conclude that intra-aneurysmal liquid injection may have potential as a therapeutic option to reconstruct a defective vessel wall and thereby maintain the antegrade flow

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

Science.gov (United States)

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

The clinical usefulness of portal venous flow ratio by hepatic angiography with 99mTc-Sn colloid in chronic liver diseases

International Nuclear Information System (INIS)

Takegoshi, Kunio; Tohyama, Tatsuhiko; Okuda, Kohji; Seto, Hikaru; Nakanuma, Yasuni.

1989-01-01

The ratio of portal venous to hepatic blood flow was measured in chronic liver diseases by radionuclide angiography with 99m Tc-Sn colloid and its clinical value was discussed. The ratio was proportionally decreased to the progression of the diseases (normal 74.5±7.3%, chronic hepatitis 58.8±9.2%, compensated liver cirrhosis 49.0±10.4%, and decokmpensated liver cirrhosis 29.3±19.3%). In alcoholic liver diseases, the standard deviation of the ratio was large as 52.7±23.7%, and the low ratio in the early period of the disease increased within one or two months as the disease recovered. In comparison with the histological findings of the liver, the ratio in the alcoholic liver diseases was well correlated with the severity of liver fibrosis and liver cell swelling. In conclusion, this noninvasive and simple method is valuable in diagnosing the chronic liver disease, especially alcoholic liver diseases, and also in estimating its clinical course. (author)

Controlling total spot power from holographic laser by superimposing a binary phase grating.

Science.gov (United States)

Liu, Xiang; Zhang, Jian; Gan, Yu; Wu, Liying

2011-04-25

By superimposing a tunable binary phase grating with a conventional computer-generated hologram, the total power of multiple holographic 3D spots can be easily controlled by changing the phase depth of grating with high accuracy to a random power value for real-time optical manipulation without extra power loss. Simulation and experiment results indicate that a resolution of 0.002 can be achieved at a lower time cost for normalized total spot power.

Hepatitis C

Science.gov (United States)

... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006-2008.

Science.gov (United States)

Linkins, Robert W; Chonwattana, Wannee; Holtz, Timothy H; Wasinrapee, Punneeporn; Chaikummao, Supaporn; Varangrat, Anchalee; Tongtoyai, Jaray; Mock, Philip A; Curlin, Marcel E; Sirivongrangson, Pachara; van Griensven, Frits; McNicholl, Janet M

2013-09-01

Despite the availability of safe and effective vaccines, little is known about prevalence and risk factors for hepatitis A (HAV) and hepatitis B virus (HBV) infection among Thai men who have sex with men. The prevalence of HAV and HBV infection among men who have sex with men cohort in Bangkok was assessed. Baseline blood specimens were drawn and demographic and behavioral data were collected. Bivariate and multivariate logistic regression analysis was used to analyze risk factors for prevalent HAV and HBV infection. One thousand two hundred ninety-nine Thai men who have sex with men 18 years and older were enrolled. Among those with results, 349/1,291 (27.0%) had evidence of past or current hepatitis A infection. Of the 1,117 (86.5%) men with unambiguous HBV test results, 442 (39.6%) had serologic evidence of past/current infection, 103 (9.2%) were immune due to hepatitis B vaccination, 572 (51.2%) had no evidence of immunological exposure to HBV or vaccine. Of those with past/current HBV infection, 130 (29.4%) were HIV positive. Age >35 years was independently associated with both HAV and HBV infection. University education was protective against both HAV and HBV infection. Increased alcohol consumption, number of lifetime male sexual partners ≥10, and prevalent HIV infection were also independently associated with HBV infection. The prevalence of past/current HAV and HBV infection was high in Bangkok men who have sex with men. Age-cohorts with a higher prevalence of hepatitis B vaccine induced immunity may be expected in the future. Hepatitis A and B vaccination is recommended. © 2013 WILEY PERIODICALS, INC. This is a US Government work, and, as such, is in the public domain in The United States.

Acute Hepatic Failure in a Dog after Xylitol Ingestion.

Science.gov (United States)

Schmid, Renee D; Hovda, Lynn R

2016-06-01

Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

Hepatitis A through E (Viral Hepatitis)

Science.gov (United States)

... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

Does limited virucidal activity of biocides include duck hepatitis B virucidal action?

Directory of Open Access Journals (Sweden)

Sauerbrei Andreas

2012-10-01

Full Text Available Abstract Background There is agreement that the infectivity assay with the duck hepatitis B virus (DHBV is a suitable surrogate test to validate disinfectants for hepatitis B virucidal activity. However, since this test is not widely used, information is necessary whether disinfectants with limited virucidal activity also inactivate DHBV. In general, disinfectants with limited virucidal activity are used for skin and sensitive surfaces while agents with full activity are more aggressive. The present study compares the activity of five different biocides against DHBV and the classical test virus for limited virucidal activity, the vaccinia virus strain Lister Elstree (VACV or the modified vaccinia Ankara strain (MVA. Methods Virucidal assay was performed as suspension test according to the German DVV/RKI guideline. Duck hepatitis B virus obtained from congenitally infected Peking ducks was propagated in primary duck embryonic hepatocytes and was detected by indirect immunofluorescent antigen staining. Results The DHBV was inactivated by the use of 40% ethanol within 1-min and 30% isopropanol within 2-min exposure. In comparison, 40% ethanol within 2-min and 40% isopropanol within 1-min exposure were effective against VACV/MVA. These alcohols only have limited virucidal activity, while the following agents have full activity. 0.01% peracetic acid inactivated DHBV within 2 min and a concentration of 0.005% had virucidal efficacy against VACV/MVA within 1 min. After 2-min exposure, 0.05% glutardialdehyde showed a comparable activity against DHBV and VACV/MVA. This is also the case for 0.7% formaldehyde after a contact time of 30 min. Conclusions Duck hepatitis B virus is at least as sensitive to limited virucidal activity as VACV/MVA. Peracetic acid is less effective against DHBV, while the alcohols are less effective against VACV/MVA. It can be expected that in absence of more direct tests the results may be extrapolated to HBV.

Female alcoholics: electrocardiographic changes and associated metabolic and electrolytic disorders

Directory of Open Access Journals (Sweden)

Borini Paulo

2003-01-01

Full Text Available OBJECTIVE: To identify the electrocardiographic changes and their associations with metabolic and electrolytic changes in female alcoholics. METHODS: The study comprised 44 female alcoholics with no apparent physical disorder. They underwent the following examinations: conventional electrocardiography; serologic tests for syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen, fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic change was identified in 33 (75% patients. In 17 (38.6% patients, more than one of the following changes were present: prolonged QTc interval in 24 (54.5%, change in ventricular repolarization in 11(25%, left ventricular hypertrophy in 6 (13.6%, sinus bradycardia in 4 (9.1%, sinus tachycardia in 3 (6.8%, and conduction disorder in 3 (6.8%. The patients had elevated mean serum levels of creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl transferase, as well as hypocalcemia and low levels of total cholesterol and LDL-cholesterol. The patients with altered electrocardiograms had a more elevated age, a lower alcohol consumption, hypopotassemia, and significantly elevated levels of triglycerides, postprandial glucose, sodium and gamma glutamyl transferase than those with normal electrocardiograms. The opposite occurred with fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The electrocardiographic changes found were prolonged QTc interval, change in ventricular repolarization, and left ventricular hypertrophy. Patients with normal and abnormal electrocardiograms had different metabolic and electrolytic changes.

Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

Science.gov (United States)

Jiao, Yang; Lu, Yan; Li, Xiao-ying

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia. PMID:25500875

NO removal characteristics of a corona radical shower system under DC and AC/DC superimposed operations

NARCIS (Netherlands)

Yan, K.; Yamamoto, T.; Kanazawa, S.; Ohkubo, T.; Nomoto, Y.; Chang, Jen-Shih

2001-01-01

In this paper, the effects of the applied voltage modes on the positive corona discharge morphology and NO removal characteristics from air streams are experimentally investigated. By using a DC superimposed high frequency AC power supply (10-60 kHz), a uniform streamer corona can be generated,

Protective effect of polysaccharide from maca (Lepidium meyenii) on Hep-G2 cells and alcoholic liver oxidative injury in mice.

Science.gov (United States)

Zhang, Lijun; Zhao, Qingsheng; Wang, Liwei; Zhao, Mingxia; Zhao, Bing

2017-06-01

To study the characterization and hepatoprotective activity of polysaccharide from maca (Lepidium meyenii), the main polysaccharide from maca (MP-1) was obtained by DEAE-52 cellulose column. The average molecular weight of MP-1 was 1067.3kDa and the polysaccharide purity was 91.63%. In order to assess the antioxidant activities of MP-1, four kinds of methods were used, including scavenging hydroxyl radical, DPPH, superoxide anion radical, and FRAP, and the results indicated high antioxidant activities. Furthermore, hepatoprotective activity of MP-1 was studied both in vitro and vivo. In vitro, the alcohol induced Hep-G2 cells model was established to evaluate the protective effect of MP-1, which demonstrated MP-1 can alleviate alcohol damage in Hep-G2 cells. In vivo, the Institute　of　Cancer　Researcch (ICR) mice were used to evaluate hepatoprotecive effects of MP-1 on alcoholic liver disease (ALD). Supplement with MP-1 supressed the triglyceride level both in serum and in hepatic tissue. In addition, MP-1 ameliorated serous transaminases increase induced by alcohol, including aspartate transaminase, alanine aminotransferase, and γ-glutamyl transpeptidase. Moreover, MP-1 also dramatically increased the superoxide dismutase, glutathione peroxidase, and glutathione s-transferase levels in alcoholic mice. Meantime, histopathologic results MP-1 lighten inflammation induced by alcohol. These results indicate that MP-1 possesses hepatoprotective activity against hepatic injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential metabonomic profiles of primary hepatocellular carcinoma tumors from alcoholic liver disease, HBV-infected, and HCV-infected cirrhotic patients

OpenAIRE

Cao, Ding; Cai, Can; Ye, Mingxin; Gong, Junhua; Wang, Menghao; Li, Jinzheng; Gong, Jianping

2017-01-01

Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC ...

Hepatic Elimination of Drugs in Gestational Diabetes.

Science.gov (United States)

Gonzalez, Claudio Daniel; Alvarinas, Jorge; Bolanos, Ricardo; Di Girolamo, Guillermo

2018-03-25

The liver is the major metabolic clearance organ for chemical agents from the human body. Pregnancy is associated with several physiological changes that may affect one or more of these factors, and also induces changes in the hepatic clearance of certain drugs.The aim of this paper was to review some of the currently available information in the field to provide some insights about the relevance of these changes on the clearance of some drugs. A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1970 first semester. Gestational Diabetes Mellitus (GDM) is a frequent disease commonly associated with other entities as obesity, hypertension, dyslipidemia, non-alcoholic fatty liver disease, pro-thrombotic conditions, changes in intestinal microbioma. These entities, together with the glycemic fluctuations associated with GDM might affect the determinants for the hepatic clearance (hepatic blood flow, the unbound fraction of drugs, and the hepatic intrinsic clearance). GDM is frequently associated with multi-drug treatments. While many of these drugs are cleared by the liver, little is known about the clinical relevance of these GDM associated pharmacokinetic changes. Considering the frequency of the disease and the effects that these pharmacokinetic changes might have on the mother and child, the need for further research seems advisable. In the meantime, cautious clinical judgment in the management of drug administration in women affected by this disease is recommended. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hepatitis isquémica Ischemic hepatitis

Directory of Open Access Journals (Sweden)

Marcos Amuchástegui (h

2006-10-01

Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

Molecular pathways in non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Berlanga A

2014-07-01

Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.......The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

Science.gov (United States)

Harrison-Findik, Duygu Dee; Lu, Sizhao

2015-05-06

This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Hepatitis C in prisoners and non-prisoners in Colatina, Espírito Santo, Brazil

Directory of Open Access Journals (Sweden)

Tânia Cristina Falquetto

2013-12-01

Full Text Available The aim of the present work was to compare hepatitis C prevalence, genotypes, and risk factors between prisoners and non-prisoners in the city of Colatina, Espírito Santo, Brazil. This cross-sectional study involved approximately 1,600 residents and 730 prisoners, all of whom were living in Colatina. The percentage of individuals who tested positive for anti-HCV was 0.1% (2/1,600 in the non-prisoner group and 1.0% (7/730 in the prisoner group, confirming a higher risk of hepatitis C in the latter group. The percentage of subjects who progressed to HCV-RNA negative was 11.1% (1/9, confirming the high probability of evolution to chronicity. Genotype 1 was the most predominant genotype found. Factors associated with increased risk of hepatitis C were being male, being institutionalized, having an income of less than three minimum wages, having low educational attainment, and using injected drugs. Alcohol use, pain in the liver, migraine, and reported history of hepatitis were markedly associated with hepatitis C. The prison population tested positive for anti-HCV at a higher rate than the non-prison population.

Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy

DEFF Research Database (Denmark)

Rudkjær Mikkelsen, Maria; Hendriksen, Carsten; Schiødt, Frank Vinholt

2015-01-01

PRACTICE: It can be assumed that professionals should support alcoholic liver disease patients' appraisal of, and coping with, physical and psychosocial problems based on acknowledgment, understanding and a sympathetic attitude. Professionals should proactively approach patients when they withdraw. It may...

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

Science.gov (United States)

Dupont, B; Dao, T; Joubert, C; Dupont-Lucas, C; Gloro, R; Nguyen-Khac, E; Beaujard, E; Mathurin, P; Vastel, E; Musikas, M; Ollivier, I; Piquet, M-A

2012-05-01

Malnutrition and jaundice are independent prognostic factors in cirrhosis. To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice. © 2012 Blackwell Publishing Ltd.

Observation and modeling of snow melt and superimposed ice formation on sea ice

OpenAIRE

Nicolaus, Marcel; Haas, Christian

2004-01-01

Sea ice plays a key role within the global climate system. It covers some 7% of earths surface and processes a strong seasonal cycle. Snow on sea ice even amplifies the importance of sea ice in the coupled atmosphere-ice-ocean system, because it dominates surface properties and energy balance (incl. albedo).Several quantitative observations of summer sea ice and its snow cover show the formation of superimposed ice and a gap layer underneath, which was found to be associated to high standing ...

Chronic alcohol exposure disturbs lipid homeostasis at the adipose tissue-liver axis in mice: analysis of triacylglycerols using high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling.

Directory of Open Access Journals (Sweden)

Xiaoli Wei

Full Text Available A method of employing high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling was developed in this study to investigate the effects of alcohol exposure on lipid homeostasis at the white adipose tissue (WAT-liver axis in a mouse model of alcoholic fatty liver. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage mouse feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver, epididymal white adipose tissue (eWAT and subcutaneous white adipose tissue (sWAT were analyzed. It was found that 13 and 10 triacylglycerols (TGs incorporated with a certain number of deuterium were significantly increased in alcohol induced fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of deuterium incorporated TGs in alcohol-induced fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in alcoholic fatty liver.

Temporal Trends of Non-alcoholic Fatty Liver Disease-related Hepatocellular Carcinoma in the Veteran Affairs Population

Science.gov (United States)

Mittal, Sahil; Sada, Yvonne H.; El-Serag, Hashem B.; Kanwal, Fasiha; Duan, Zhigang; Temple, Sarah; May, Sarah B.; Kramer, Jennifer R.; Richardson, Peter A.; Davila, Jessica A.

2014-01-01

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. Methods We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients’ full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, HCV), as well HCC surveillance and outcomes, among HCC patients. Results NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%–12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%–68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%–80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%–3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared to patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P<.05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared to patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than of patients with HCV-related HCC (77.5%; P<.01). However, 1-year survival did not differ among patients with HCC related to different risk factors

L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

Directory of Open Access Journals (Sweden)

Hisashi Ishikawa

Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC. Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid, an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1 high-fat diet (HFD (control group; 2 HFD mixed with 0.28% L-carnitine (L-carnitine group; and 3 HFD mixed with 0.01% α-tocopherol (α-tocopherol group. After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by

A window of opportunity: declining rates of hepatitis B virus infection among injection drug users in Rio de Janeiro, and prospects for targeted hepatitis B vaccination Ventana de oportunidad: reducción de las tasas de infección por el virus de la hepatitis B entre usuarios de drogas inyectadas en Río de Janeiro, Brasil, y planes futuros en torno a la vacunación contra la hepatitis B

Directory of Open Access Journals (Sweden)

Sabrina A. N. Oliveira

2005-11-01

Full Text Available OBJECTIVES: To measure hepatitis B virus (HBV infection rates among injection drug users in Rio de Janeiro, Brazil, and to report their knowledge of and attitudes toward hepatitis and HBV vaccination. METHODS: 609 injection drug users recruited in Rio de Janeiro between 1999 and 2001 answered a questionnaire and were tested for hepatitis B and other blood-borne infections. Questions covered sociodemographic information, alcohol and illicit drug consumption, drug injection and sexual practices, medical history, and knowledge about HIV, AIDS and viral hepatitis. RESULTS: The prevalence of HBV infection was 27.1% , with 3.4% of the sample positive for HbsAg (active infection and 0.8% positive for anti-HBs (indicating previous HBV vaccination. Most interviewees (81.3% were aware of at least one form of viral hepatitis and received information from many different sources. In agreement with laboratory findings, 96.7% of the interviewees stated they had never been vaccinated against hepatitis B, but almost all unvaccinated interviewees (97.8% said they would volunteer to be vaccinated if HBV vaccination were available. CONCLUSIONS: Few of the injection drug users surveyed had ever been vaccinated against HBV. Although most were aware of the risks posed by viral hepatitis, this awareness seldom translated into consistent behavioral change. The participants' willingness to be vaccinated against HBV suggests that the implementation of vaccination for this population may help decrease rates of hepatitis B infection.OBJETIVOS: Calcular las tasas de infección por el virus de la hepatitis B (VHB en usuarios de drogas inyectadas en Río de Janeiro, Brasil, y dar a conocer sus conocimientos y actitudes en torno a la hepatitis y a la vacunación contra el VHB. MÉTODOS: Seiscientos nueve usuarios de drogas que se reclutaron en Río de Janeiro entre 1999 y 2001 respondieron a un cuestionario y fueron sometidos a pruebas para detectar la presencia de hepatitis B

Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

Directory of Open Access Journals (Sweden)

Fei Kong

2014-01-01

Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

Alcohol Consumption and Chronic Liver Disease Mortality in New Mexico and the United States, 1999-2013.

Science.gov (United States)

Tomedi, Laura E; Roeber, Jim; Landen, Michael

Current chronic liver disease (CLD) mortality surveillance methods may not adequately capture data on all causes of CLD mortality. The objective of this study was to calculate and compare CLD death rates in New Mexico and the United States by using both an expanded definition of CLD and estimates of the fractional impact of alcohol on CLD deaths. We defined CLD mortality as deaths due to alcoholic liver disease, cirrhosis, viral hepatitis, and other liver conditions. We estimated alcohol-attributable CLD deaths by using national and state alcohol-attributable fractions from the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact application. We classified causes of CLD death as being alcohol-attributable, non-alcohol-attributable, or hepatitis C. We calculated average annual age-adjusted CLD death rates during five 3-year periods from 1999 through 2013, and we stratified those rates by sex, age, and race/ethnicity. By cause of death, CLD death rates were highest for alcohol-attributable CLD. By sex and race/ethnicity, CLD death rates per 100 000 population increased from 1999-2001 to 2011-2013 among American Indian men in New Mexico (67.4-90.6) and the United States (38.9-49.4), American Indian women in New Mexico (48.4-63.0) and the United States (27.5-39.5), Hispanic men in New Mexico (48.6-52.0), Hispanic women in New Mexico (16.9-24.0) and the United States (12.8-13.1), non-Hispanic white men in New Mexico (17.4-21.3) and the United States (15.9-18.4), and non-Hispanic white women in New Mexico (9.7-11.6) and the United States (7.6-9.7). CLD death rates decreased among Hispanic men in the United States (30.5-27.4). An expanded CLD definition and alcohol-attributable fractions can be used to create comprehensive data on CLD mortality. When stratified by CLD cause and demographic characteristics, these data may help states and jurisdictions improve CLD prevention programs.

Imaging of non alcoholic fatty liver disease: A road less travelled

Directory of Open Access Journals (Sweden)

Divya Singh

2013-01-01

Full Text Available Non alcoholic fatty liver disease (NAFLD is a spectrum that includes simple steatosis, nonalcoholic steatohepatitis and cirrhosis. It is increasingly emerging as a cause of elevated liver enzymes, cryptogenic cirrhosis and hepatocellular carcinoma. The morbidity and mortality related to NAFLD is expected to rise with the upsurge of obesity and type 2 diabetes mellitus. The need of the hour is to devise techniques to estimate and then accurately follow-up hepatic fat content in patients with NAFLD. There are lots of imaging modalities in the radiological armamentarium, namely, ultrasonography with the extra edge of elastography, computed tomography, and magnetic resonance imaging with chemical shift imaging and spectroscopy to provide an estimation of hepatic fat content.

Increased serum cortisol binding in chronic active hepatitis

International Nuclear Information System (INIS)

Orbach, O.; Schussler, G.C.

1989-01-01

A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

The role of heme oxygenase-1 in drug metabolizing dysfunction in the alcoholic fatty liver exposed to ischemic injury

Energy Technology Data Exchange (ETDEWEB)

Park, Sang Won [Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 52727 (Korea, Republic of); Kang, Jung-Woo [School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419 (Korea, Republic of); Lee, Sun-Mee, E-mail: sunmee@skku.edu [School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419 (Korea, Republic of)

2016-02-01

This study was designed to investigate the role of heme oxygenase-1 (HO-1) in hepatic drug metabolizing dysfunction after ischemia/reperfusion (IR) in alcoholic fatty liver (AFL). Rats were fed a Lieber–DeCarli diet for five weeks to allow for development of AFL and were then subjected to 90 min of hepatic ischemia and 5 h of reperfusion. Rats were pretreated with hemin (HO-1 inducer) or ZnPP (HO-1 inhibitor) for 16 h and 3 h before hepatic ischemia. After hepatic IR, ethanol diet (ED)-fed rats had higher serum aminotransferase activities and more severe hepatic necrosis compared to the control diet (CD)-fed rats. These changes were attenuated by hemin and exacerbated by ZnPP. The activity and gene expression of HO-1 and its transcription factor (Nrf2) level increased significantly after 5 h of reperfusion in CD-fed rats but not in ED-fed rats. After reperfusion, cytochrome P450 (CYP) 1A1, 1A2, and 2B1 activities were reduced to levels lower than those observed in sham group, whereas CYP2E1 activity increased. The decrease in CYP2B1 activity and the increase in CYP2E1 activity were augmented after hepatic IR in ED-fed animals. These changes were significantly attenuated by hemin but aggravated by ZnPP. Finally, CHOP expression and PERK phosphorylation, microsomal lipid peroxidation, and levels of proinflammatory mediators increased in ED-fed rats compared to CD-fed rats after reperfusion. These increases were attenuated by hemin. Our results suggest that AFL exacerbates hepatic drug metabolizing dysfunction during hepatic IR via endoplasmic reticulum stress and lipid peroxidation and this is associated with impaired HO-1 induction. - Highlights: • Endogenous HO-1 is generated in insufficient quantities in steatotic ischemic injury. • Impaired HO-1 induction leads to excessive ER stress response and lipid peroxidation. • Alcoholic steatosis exacerbates IR-induced hepatic drug-metabolizing dysfunction. • HO-1 induction is required for appropriate medication

Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Sonja M. Kessler

2014-04-01

Full Text Available Non-alcoholic steatohepatitis (NASH represents a risk factor for the development of hepatocellular carcinoma (HCC and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice. Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.

COMPARATIVE STUDY OF DECOMPENSATION PATTERN IN ALCOHOLIC AND VIRAL LIVER DISEASE AND ANALYSIS OF DECOMPENSATION OF MORTALITY

Directory of Open Access Journals (Sweden)

Susrutha C. Suresh

2017-11-01

Full Text Available BACKGROUND Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. The aim of the study is to compare various decompensation patterns in alcohol-related and hepatitis B and hepatitis C virus-related chronic liver disease and to analyse the mortality after decompensation. MATERIALS AND METHODS The study was conducted in a tertiary referral hospital between June 2014 - April 2016. It is a prospective observational study of the 385 patients who were diagnosed as suffering from chronic liver disease and managed for various decompensations both on an outpatient and as well on an inpatient basis. RESULTS During the study period, a total of 385 patients were diagnosed with chronic liver disease. Among the patients with the diagnosis of CLD, 152 (77.2% were diagnosed of alcoholic aetiology and 45 (22.8% of viral aetiology liver disease. The most common forms of decompensation in alcoholic chronic liver disease were found to be ascites (71.7%, jaundice (56.6% and oesophageal varices (32.2%. The most common forms of decompensations in viral-related chronic liver disease were jaundice (42.2%, ascites (35.6% and oesophageal varices (28.9%. Patients with viral-related CLD were diagnosed with higher incidence of hepatocellular carcinoma of (24.4% compared to only 5.3% of patients of alcoholic liver disease. Ascites was found to be the most common form of decompensation associated with mortality (76%. Jaundice (56%, hepatorenal syndrome (44% and hepatic encephalopathy (24% were the other common decompensations associated with mortality. CONCLUSION In this study, ascites was found to be most common form of decompensation patterns in alcoholic liver disease and jaundice in viral-related CLD. The incidence of hepatocellular carcinoma was found to be higher in viral aetiology CLD. Ascites was found to be the most

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

Science.gov (United States)

Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Tiroiditis autoinmune inducida por interferón en pacientes con infección por virus de la hepatitis C. Interferon-induced autoimmune thyroiditis in a patient with hepatitis C virus infection

Directory of Open Access Journals (Sweden)

José L. Pinto

2011-06-01

Full Text Available Se reporta el caso de un varón de 43 años de edad, sin antecedentes patológicos de importancia, que acudió por elevación asintomática de la alanino aminotransferasa (ALT. El paciente negó ser bebedor crónico de alcohol. Se hizo el diagnóstico serológico de infección activa por hepatitis C y la biopsia de hígado reveló inflamación crónica activa. Con estos resultados, se inició tratamiento con interferón-alfa y ribavirina. Durante el tratamiento de 48 semanas, el paciente presentó anticuerpos antitiroideos positivos con variaciones en sus niveles de tirotropina (TSH y hormonas tiroideas. En el seguimiento postratamiento, el paciente continuó con hipertiroidismo por enfermedad de Graves. La tiroiditis autoinmune es una complicación frecuente del uso de interferón en pacientes con hepatitis C. En algunos casos se presenta como hipertiroidismo por enfermedad de Graves. Se debe evaluar la función tiroidea y los anticuerpos antitiroideos antes y durante el tratamiento con interferón.A 43 year old man presented with asymptomatic elevation of alanine aminotransferase (ALT and no relevant past history. The patient denied being a chronic alcohol drinker. Work-up revealed an active hepatitis C, and liver biopsy showed active inflammation. Treatment was started with interferon-alfa and ribavirin. During the 48 weeks of treatment, the patient developed positive thyroid antibodies with varying level of thyrotropin (TSH and thyroid hormones. At follow-up after treatment, the patient continued with hyperthyroidism due to Graves’ disease. Autoimmune thyroiditis is a common complication of using interferon in patients with hepatitis C. In some cases, it is presented as hyperthyroidism because of Graves’ disease. Thyroid function and thyroid antibodies should be evaluated before and during treatment with interferon.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.

Science.gov (United States)

Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N; Jones, Byron C; Lu, Lu; Wang, Xusheng

2018-01-01

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

Directory of Open Access Journals (Sweden)

Jie Luo

2018-04-01

Full Text Available Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1, down-regulation in NOE but rescue in RSE (pattern 2, up-regulation in both restraint stress followed by a saline injection (RSS and NOE, and further amplification in RSE (pattern 3, and up-regulation in RSS but reduction in both NOE and RSE (pattern 4. We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

Science.gov (United States)

Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

2017-03-01

Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease.

Science.gov (United States)

Ter Horst, Kasper W; Serlie, Mireille J

2017-09-06

Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.

Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates

NARCIS (Netherlands)

Shiri-Sverdlov, Ronit; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J.; Noel, Benoit; Buffat, Laurent; Staels, Bart; Maeda, Nobuyo; van Bilsen, Marc; Hofker, Marten H.

2006-01-01

The molecular mechanisms leading to Non-Alcoholic Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome proliferator activated receptor alpha, which regulates hepatic triglyceride metabolism. This study

The theoretical shear strength of fcc crystals under superimposed triaxial stress

Energy Technology Data Exchange (ETDEWEB)

Cerny, M., E-mail: cerny.m@fme.vutbr.cz [Institute of Engineering Physics, Faculty of Mechanical Engineering, Brno University of Technology, Technicka 2, CZ-616 69 Brno (Czech Republic); Pokluda, J. [Institute of Engineering Physics, Faculty of Mechanical Engineering, Brno University of Technology, Technicka 2, CZ-616 69 Brno (Czech Republic)

2010-05-15

The influence of a triaxial stress applied normally to shear planes and shear direction during affine shear deformation of face-centered cubic crystals on the theoretical shear strength is studied for the <112-bar >{l_brace}111{r_brace} shear system using first-principles methods. The applied relaxation procedure guarantees that the modeled system is subjected to a superposition of shear, normal and in-plane stresses with individually adjustable in-plane and normal stress values. The theoretical shear strengths of individual elements prove to be qualitatively different functions of the superimposed stresses. In the special case of hydrostatic loading, however, these functions are qualitatively uniform. This behavior is discussed in terms of the electronic structure.

Major drivers influencing adherence and quality of life during antiviral triple therapy in patients with chronic hepatitis C

Directory of Open Access Journals (Sweden)

Suceveanu Andra I.

2016-05-01

Full Text Available Background & Aims. Triple therapy with Peg-IFNs, Ribavirin and protease inhibitors raise the treatment success for hepatitis C up to 83%, but also bring together with the significantly higher rates of sustained virologic response (SVR more side effects, interfering with patient’s quality of life (QoL and work productivity. We aimed to analyze the factors influencing the adherence and the QoL during triple therapy using Peg-IFNs, Ribavirin and protease inhibitors in 50 patients diagnosed with chronic hepatitis C with first line therapy failure. Multivariate Cox proportional hazards regression was used to analyze determinants of retreatment initiation and treatment compliance, according to patient features. Results: We identified as major drivers of retreatment initiation the younger age, the female gender, the urban provenience, the high income, and the psychiatric and alcohol or drugs abuse history. The adherence and the QoL during retreatment therapy were similar, despite the regimen used, and obvious lower in patients with history of previous abandon, drugs and alcohol abuse or hematologic/ psychiatric decompensation. A lower capacity to work and a temporary withdrawal from job necessary to continue the therapy were seen similar in patients taking Boceprevir/Telaprevir. Abandon of therapy without a known reason was more frequent in males, with alcohol and drugs intake history, from rural region, with low income, and with psychiatric disturbances in personal history. Conclusion. Physicians should focus to develop medical strategies or drugs to increase the adherence and to provide a better QoL for patients with chronic hepatitis C making antiviral therapy.

Increased mortality among persons infected with hepatitis C virus

DEFF Research Database (Denmark)

Omland, Lars Haukali Hvass; Jepsen, Peter; Krarup, Henrik

2011-01-01

Background & Aims The long-term mortality of patients infected with hepatitis C virus (HCV) is not known; few studies have controlled for potential confounders, investigated how mortality changes with age at diagnosis and length of follow-up period, provided absolute risk estimates of death......, or analyzed specific causes of death. Methods Using a Danish population, we compared mortality of a cohort of 10,991 HCV-infected patients with that of an age- and sex-matched cohort. Using regression analysis, we adjusted for municipality of residence, history of psychiatric illness, comorbidities, alcohol...... and drug abuse, and income. We analyzed causes of death and effects of HCV with age and length of follow-up period. Results HCV-infected patients had lower income levels and more comorbidities, psychiatric illnesses, and substance and alcohol abuse than the comparison cohort. The 10-year survival rate...

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

Science.gov (United States)

Frantz, Eliete Dalla Corte; Medeiros, Renata Frauches; Giori, Isabele Gomes; Lima, Juliana Bittencourt Silveira; Bento-Bernardes, Thais; Gaique, Thaiane Gadioli; Fernandes-Santos, Caroline; Fernandes, Tiago; Oliveira, Edilamar Menezes; Vieira, Carla Paulo; Conte-Junior, Carlos Adam; Oliveira, Karen Jesus; Nobrega, Antonio Claudio Lucas

2017-09-01

What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l -1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day -1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and

Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.

Science.gov (United States)

Sutherland, Greg T; Sheedy, Donna; Sheahan, Pam J; Kaplan, Warren; Kril, Jillian J

2014-04-01

Alcohol abuse is the world's third leading cause of disease and disability, and one potential sequel of chronic abuse is alcohol-related brain damage (ARBD). This clinically manifests as cognitive dysfunction and pathologically as atrophy of white matter (WM) in particular. The mechanism linking chronic alcohol intoxication with ARBD remains largely unknown but it is also complicated by common comorbidities such as liver damage and nutritional deficiencies. Liver cirrhosis, in particular, often leads to hepatic encephalopathy (HE), a primary glial disease. In a novel transcriptomic study, we targeted the WM only of chronic alcoholics in an attempt to tease apart the pathogenesis of ARBD. Specifically, in alcoholics with and without HE, we explored both the prefrontal and primary motor cortices, 2 regions that experience differential levels of neuronal loss. Our results suggest that HE, along with 2 confounders, gray matter contamination, and low RNA quality are major drivers of gene expression in ARBD. All 3 exceeded the effects of alcohol itself. In particular, low-quality RNA samples were characterized by an up-regulation of translation machinery, while HE was associated with a down-regulation of mitochondrial energy metabolism pathways. The findings in HE alcoholics are consistent with the metabolic acidosis seen in this condition. In contrast non-HE alcoholics had widespread but only subtle changes in gene expression in their WM. Notwithstanding the latter result, this study demonstrates that significant confounders in transcriptomic studies of human postmortem brain tissue can be identified, quantified, and "removed" to reveal disease-specific signals. Copyright © 2014 by the Research Society on Alcoholism.

Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification

Science.gov (United States)

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) has been an emerging major health problem, and the most common cause of chronic liver disease in Western countries. Traditionally, liver biopsy has been gold standard method for quantification of hepatic steatosis. However, its invasive nature with potential complication as well as measurement variability are major problem. Thus, various imaging studies have been used for evaluation of hepatic steatosis. Ultrasonography provides fairly good accuracy to detect moderate-to-severe degree hepatic steatosis, but limited accuracy for mild steatosis. Operator-dependency and subjective/qualitative nature of examination are another major drawbacks of ultrasonography. Computed tomography can be considered as an unsuitable imaging modality for evaluation of NAFLD due to potential risk of radiation exposure and limited accuracy in detecting mild steatosis. Both magnetic resonance spectroscopy and magnetic resonance imaging using chemical shift technique provide highly accurate and reproducible diagnostic performance for evaluating NAFLD, and therefore, have been used in many clinical trials as a non-invasive reference of standard method. PMID:28994271

Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

Science.gov (United States)

BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

Failure to incriminate hepatitis B, hepatitis C, and hepatitis E viruses in the aetiology of fulminant non-A non-B hepatitis.

OpenAIRE

Mutimer, D; Shaw, J; Neuberger, J; Skidmore, S; Martin, B; Hubscher, S; McMaster, P; Elias, E

1995-01-01

Sporadic non-A, non-B hepatitis is the most common indication for liver transplantation in patients presenting with fulminant and subacute liver failure. This study used serological, histological, and molecular biological techniques to examine specimens from 23 consecutive patients transplanted for sporadic non-A, non-B hepatitis. No evidence was found of hepatitis C virus, hepatitis E virus, or 'cryptic' hepatitis B virus infection.

Superimposed Training-Based Channel Estimation for MIMO Relay Networks

Directory of Open Access Journals (Sweden)

Xiaoyan Xu

2012-01-01

Full Text Available We introduce the superimposed training strategy into the multiple-input multiple-output (MIMO amplify-and-forward (AF one-way relay network (OWRN to perform the individual channel estimation at the destination. Through the superposition of a group of additional training vectors at the relay subject to power allocation, the separated estimates of the source-relay and relay-destination channels can be obtained directly at the destination, and the accordance with the two-hop AF strategy can be guaranteed at the same time. The closed-form Bayesian Cramér-Rao lower bound (CRLB is derived for the estimation of two sets of flat-fading MIMO channel under random channel parameters and further exploited to design the optimal training vectors. A specific suboptimal channel estimation algorithm is applied in the MIMO AF OWRN using the optimal training sequences, and the normalized mean square error performance for the estimation is provided to verify the Bayesian CRLB results.

Hepatitis

Science.gov (United States)

... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

Simultaneous MR quantification of hepatic fat content, fatty acid composition, transverse relaxation time and magnetic susceptibility for the diagnosis of non-alcoholic steatohepatitis.

Science.gov (United States)

Leporq, B; Lambert, S A; Ronot, M; Vilgrain, V; Van Beers, B E

2017-10-01

Non-alcoholic steatohepatitis (NASH) is characterized at histology by steatosis, hepatocyte ballooning and inflammatory infiltrates, with or without fibrosis. Although diamagnetic material in fibrosis and inflammation can be detected with quantitative susceptibility imaging, fatty acid composition changes in NASH relative to simple steatosis have also been reported. Therefore, our aim was to develop a single magnetic resonance (MR) acquisition and post-processing scheme for the diagnosis of steatohepatitis by the simultaneous quantification of hepatic fat content, fatty acid composition, T 2 * transverse relaxation time and magnetic susceptibility in patients with non-alcoholic fatty liver disease. MR acquisition was performed at 3.0 T using a three-dimensional, multi-echo, spoiled gradient echo sequence. Phase images were unwrapped to compute the B 0 field inhomogeneity (ΔB 0 ) map. The ΔB 0 -demodulated real part images were used for fat-water separation, T 2 * and fatty acid composition quantification. The external and internal fields were separated with the projection onto dipole field method. Susceptibility maps were obtained after dipole inversion from the internal field map with single-orientation Bayesian regularization including spatial priors. Method validation was performed in 32 patients with biopsy-proven, non-alcoholic fatty liver disease from which 12 had simple steatosis and 20 NASH. Liver fat fraction and T 2 * did not change significantly between patients with simple steatosis and NASH. In contrast, the saturated fatty acid fraction increased in patients with NASH relative to patients with simple steatosis (48 ± 2% versus 44 ± 4%; p magnetic susceptibility decreased (-0.30 ± 0.27 ppm versus 0.10 ± 0.14 ppm; p magnetic susceptibility as NASH marker was 0.91 (95% CI: 0.79-1.0). Simultaneous MR quantification of fat content, fatty acid composition, T 2 * and magnetic susceptibility is feasible in the liver. Our preliminary results

Scoring system in cirrhotics due to viral hepatitis

International Nuclear Information System (INIS)

Abbasi, A.; Bhutto, A.R.; Butt, N.; Lal, K.; Munir, S.M.

2012-01-01

Objective: To determine the association of serum cholesterol levels with Child-Pugh class in patients with decompensated chronic liver disease due to viral hepatitis. Methodology: Consecutive patients attending outpatient department or admitted in medical unit III were eligible if they had a diagnosis of cirrhosis secondary to viral hepatitis. Patients were excluded if alcoholic, diabetic, hypertensive, or with non-alcoholic fatty liver disease, autoimmune, metabolic, cardiovascular, cerebrovascular or kidney diseases and recent use of lipid-regulating drugs. Serum lipid profile was determined after an overnight fast of 12 hours. On the basis of serum total cholesterol, patients were divided into four groups; Group I with serum total cholesterol = 100 mg/dl, Group II with level of 101-150 mg/dl, Group III with level of 151-200 mg/dl and Group IV with serum total cholesterol level of > 200 mg/dl. Hepatic dysfunction was categorized according to Child-Pugh scoring system. Chi-square and Spearman's correlation testing with p < 0.05 was accepted as significant. Results: One hundred and fourteen patients met the inclusion criteria with a mean age of 40.32 +- 13.59 years. Among these 32 were females (28.1%) while 82 were males (71.9%). According to Child-Pugh class; 34 patients (29.8%) presented with Child-Pugh class A, 34 (29.8%) in class B and 46 (40.4%) were in class C. Serum cholesterol (total) and triglycerides had significant association with Child-Pugh class (p = 0.0001 and p = 0.004 respectively) suggesting that as severity of liver dysfunction increases; serum cholesterol and triglycerides levels decrease. Results also revealed that males were significantly more hypocholesterolemic than females (p = 0.006). Conclusion: Hypocholesterolemia is a common finding in decompensated chronic liver disease and has got significant association with Child-Pugh class. It may increase the reliability of Child-Pugh classification in assessment of severity and prognosis in

Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

Science.gov (United States)

Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

2006-06-01

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Pathomorphological characteristics of 102 cases of Thorotrast-related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma

International Nuclear Information System (INIS)

Nakashima, T.; Kojiro, M.; Ito, Y.; Mori, T.; Kido, C.

1987-01-01

We described the pathomorphological characteristics of 102 autopsy cases of Thorotrast (Th) related hepatic malignancies, and compared these to the features of non-Th-related cases. Among the 102 Th-related hepatic malignancies, 44 (43.1%) were cholangiocarcinoma (CHC), 39 (38.3%) were angiosarcoma (AGS), 16 (15.7%) were hepatocellular carcinoma (HCC), and 3 (2.9%) were double cancer. Grossly, the majority (91.7%) of Th-related CHC was located in the middle-peripheral portion of the liver. Th-related AGS was classified into four types: diffuse micronodular, multinodular, massive and mixed multinodular, and massive. Histologically, in CHC and HCC cases, there were no significant differences between Th-related and non-Th-related cases. AGS was characterized by two cell types (spindle-shaped cells and polyhedral cells) and three growth patterns (sinusoidal, carvernous, and solid). In non-cancerous areas, foci of varying degrees of sinusoidal dilatation with hyperplastic changes of sinusoidal lining cells were observed in all AGS cases and in some of the cases of Th-related CHC and HCC cases. In Th-related CHC cases, papillary proliferation of the epithelium of relatively large bile ducts was seen in 11 (29.7%) of the 37 cases, and proliferation of small bile ducts and/or bile ductules was seen in 9 (24.3%) of the 37 cases. However, similar histologic changes were also observed in the non-Th- related CHC cases. In Th-related HCC cases, mixed macro- and micronodular cirrhosis was superimposed on varying degrees of hepatic fibrosis related to Th deposition in 4 cases. (21.1%). (author)

Hepatitis Vaccines

OpenAIRE

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

Modulation of gut microbiota contributes to curcumin-mediated attenuation of hepatic steatosis in rats.

Science.gov (United States)

Feng, Wenhuan; Wang, Hongdong; Zhang, Pengzi; Gao, Caixia; Tao, Junxian; Ge, Zhijuan; Zhu, Dalong; Bi, Yan

2017-07-01

Structural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated. Next generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding. We found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated 'functionally relevant phylotypes'. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin. These results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats. Compounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatitis Vaccines

Directory of Open Access Journals (Sweden)

Sina Ogholikhan

2016-03-01

Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

Hepatitis Vaccines

Science.gov (United States)

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

Primary hepatic artery embolization in pediatric blunt hepatic trauma.

Science.gov (United States)

Ong, Caroline C P; Toh, Luke; Lo, Richard H G; Yap, Te-Lu; Narasimhan, Kannan

2012-12-01

Non-operative management of isolated blunt hepatic trauma is recommended except when hemodynamic instability requires immediate laparotomy. Hepatic artery angioembolization is increasingly used for hepatic injuries with ongoing bleeding as demonstrated by contrast extravasation on the CT scan. It is used primarily or after laparotomy to control ongoing hemorrhage. Hepatic angioembolization as part of multimodality management of hepatic trauma is reported mainly in adults, with few pediatric case reports. We describe our institution experience with primary pediatric hepatic angioembolization and review the literature with regard to indications and complications. Two cases (3 and 8 years old), with high-grade blunt hepatic injuries with contrast extravasation on the CT scan were successfully managed by emergency primary hepatic angioembolization with minimal morbidity and avoided laparotomy. To date, the only reports of pediatric hepatic angioembolization for trauma are 5 cases for acute bleeding and 15 delayed cases for pseudoaneurysm. The role of hepatic angioembolization in the presence of an arterial blush on CT in adults is accepted, but contested in a pediatric series, despite higher transfusion rate and mortality rate. We propose that hepatic angioembolization should be considered adjunct treatment, in lieu of, or in addition to emergency laparotomy for hemostasis in pediatric blunt hepatic injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

Science.gov (United States)

... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

OpenAIRE

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-01

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic stea...