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Alcoholic Hepatitis

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28901. Effect of alcohol use and highly active antiretroviral therapy on plasma levels of hepatitis C virus (HCV) in patients coinfected with HIV and HCV. Full Text available with Trip Pro

Effect of alcohol use and highly active antiretroviral therapy on plasma levels of hepatitis C virus (HCV) in patients coinfected with HIV and HCV. The interactions between human immunodeficiency virus (HIV), hepatitis C virus (HCV), alcohol, and antiretroviral therapy are complex.We retrospectively assessed persons coinfected with HIV and HCV who achieved HIV suppression to < 500 copies/mL and continued to take antiretrovirals for > or = 6 months. Frozen plasma specimens were retrieved (...) for quantitation of HCV RNA levels at baseline and 3, 6, and 12 months after beginning antiretroviral treatment.Median HCV RNA levels increased (0.35 log10 IU/mL) at month 3 (n = 44). HCV RNA levels decreased to below baseline by 12 months in patients consuming < 50 g of alcohol/day, whereas patients consuming > or = 50 g/day had a sustained increase (> 0.6 log10 IU/mL) from baseline (P = .04).Because low levels of HCV RNA are predictive of a virological response to therapy for HCV infection, it may

2005 Clinical Infectious Diseases

28902. Effect of exposure to injection drugs or alcohol on antigen-specific immune responses in HIV and hepatitis C virus coinfection. Full Text available with Trip Pro

Effect of exposure to injection drugs or alcohol on antigen-specific immune responses in HIV and hepatitis C virus coinfection. Ongoing substance use is a potential confounder for immunological studies on hepatitis C virus (HCV), but there is little in the literature regarding the effects of injection drug use (IDU) or alcohol on HCV-specific immune responses. We wanted to determine whether IDU or alcohol affected immune responses in HCV-infected and human immunodeficiency virus (HIV)/HCV (...) subjects with HCV. However, HIV/HCV injection drug users had HCV-specific IFN- gamma and IL-10 responses that were similar to those of HCV injection drug users and were significantly higher than in nonusers with HIV/HCV. Conversely, subjects who drank alcohol had similar immune responses to those who were abstinent, among both subjects with HIV/HCV and subjects with HCV.Studies that examine IFN- gamma or IL-10 immune responses in HIV/HCV-coinfected or HCV-infected persons need to consider current IDU

2007 Journal of Infectious Diseases

28903. Alcohol and hepatitis C. (Abstract)

Alcohol and hepatitis C. Alcohol abuse and hepatitis C virus (HCV) infection coexist with chronic liver disease in many patients. The mechanism of injury in these patients is probably multifactorial and involves, but is not limited to, a combination of diminished immune clearance of HCV, oxidative stress, emergence of HCV quasi-species, hepatic steatosis, increased iron stores, and increased rate of hepatocyte apoptosis. In patients with HCV infection, alcohol consumption is known to cause (...) accelerated progression of liver fibrosis, higher frequency of cirrhosis, and increased incidence of hepatocellular carcinoma (HCC). These patients also have decreased survival as compared with patients with either alcohol abuse or HCV liver injury alone. Alcohol abuse causes decreased response to interferon treatment in HCV patients. It is therefore necessary for patients with HCV infection to abstain from alcohol consumption.

2004 Seminars in Liver Disease

28904. Is alcoholic hepatitis an indication for transplantation? Current management and outcomes. (Abstract)

Is alcoholic hepatitis an indication for transplantation? Current management and outcomes. 1. In the absence of treatment, 50% of patients with severe alcoholic hepatitis (AH) [Maddrey function (DF) >or= 32] die 2 months later. Among patients with severe AH treated by corticosteroids, 80% had 2-month survival. Pentoxifylline is considered by some investigators to be an alternative option to corticosteroids. 2. Non-responders to corticosteroids (NRCs) have poor survival and require new (...) on transplantation and organ donation, and may cause reluctance on the part of clinicians to modify guidelines for alcoholic patients. 5. Therefore, a reasonable approach would be to carry out only pilot studies on only a small cohort of patients to determine whether transplantation improves survival in patients with severe AH.

2005 Liver Transplantation

28905. Acute esophageal necrosis associated with alcoholic hepatitis: is it black or is it white? (Abstract)

Acute esophageal necrosis associated with alcoholic hepatitis: is it black or is it white? Acute esophageal necrosis is an uncommon condition diagnosed during endoscopy from the black appearance of the esophagus. We report three cases of acute esophageal necrosis, associated with severe alcoholic hepatitis. The pathogenesis was multifactorial in our patients, with gastroesophageal reflux combined with hypoperfusion probably being the key factor for the esophageal lesions. The patients presented (...) "; and the diagnosis should subsequently be confirmed by mucosal biopsies. Our report showed that ethanol-induced acute esophageal necrosis can appear in patients with a high alcohol intake, especially in immunosupressed patients with alcoholic hepatitis.

2005 Endoscopy

28906. Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C. (Abstract)

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C. Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC.A consecutive series of 349 patients were evaluated for steatosis. At liver biopsy, patients were tested (...) for virological, and laboratory analysis and questioned for alcohol consumption.Logistic regression analysis demonstrated that steatosis was independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P

2004 Journal of Hepatology

28907. Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis. (Abstract)

Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis. In alcoholic hepatitis (AH), soluble TNF alpha receptor-1 (sTNF-R1) is increased. Elevated TNF alpha predicts mortality, but infection influences TNF alpha values. In patients with AH, we determined the prognostic value of TNF alpha, sTNF-R1, and lipopolysaccharide binding protein (LBP) and CD14, both involved in endotoxemia-associated inflammation.One hundred and eight

2004 Journal of Hepatology

28908. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. (Abstract)

Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. To compare carotid intima-media thickness (IMT) - an index of early atherosclerosis - among patients with non-alcoholic steatohepatitis (NASH), patients with chronic hepatitis B (HBV) or C (HCV) and control subjects.We studied 60 consecutive patients with biopsy-proven NASH, 60 patients with HCV, 35 patients with HBV, and 60 healthy controls who were (...) affected by adjustment for age, sex, body mass index, smoking, LDL cholesterol, insulin resistance (by homeostasis model assessment) and components of the Adult Treatment Panel III-defined metabolic syndrome. Concordantly, in logistic regression analysis, NASH, HBV and HCV predicted carotid IMT independent of potential confounders.These data suggest that NASH, HCV and HBV are strongly associated with early atherosclerosis independent of classical risk factors, insulin resistance and metabolic syndrome

2007 Journal of Hepatology

28909. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. (Abstract)

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. Mortality in patients with alcoholic hepatitis (AH) remains high, and although corticosteroids are widely used for treatment, the results vary considerably. In AH, neutrophils are primed and infiltrate the liver to produce injury, but paradoxically, the main cause of death in such patients is infection. Our prospective study addressed this paradox of primed neutrophils on the one hand (...) and increased risk of infection on the other. We hypothesized that the full activation of neutrophils by a humoral factor such as endotoxin renders them unable to respond to further bacterial challenge. We analyzed neutrophil oxidative burst and phagocytosis in whole blood by fluorescence-activated cell sorting analysis in 63 alcoholic patients with cirrhosis and patients with cirrhosis with superimposed AH (cirrhosis+AH). In 16 patients, ex vivo studies determined whether the removal of endotoxin restored

2007 Hepatology

28910. Hepatitis C and hospital outcomes in patients admitted with alcohol-related problems. (Abstract)

Hepatitis C and hospital outcomes in patients admitted with alcohol-related problems. Alcohol is known to act synergistically with chronic hepatitis C virus (HCV) infection to cause liver disease; however, their combined effect on outcomes in acutely hospitalized patients is less clear. We examined the impact of HCV infection on hospital mortality and length of stay among hospitalized patients with alcohol abuse problems.We retrospectively identified 6354 admissions to an urban, public hospital (...) between July 1996 and January 2002 with discharge diagnoses related to alcohol dependence or abuse. Hepatitis C diagnosis and other information were extracted from a clinical database and tested for associations with death and length of hospital stay using multivariable regression techniques.The prevalence of diagnosed HCV infection in this sample of patients with alcohol abuse was 15%. Patients with HCV were about twice as likely to die during hospital admission (4.4 vs. 2.4%; P-value < 0.01

2006 Journal of Hepatology

28911. Hepatic gene expression profile associated with non-alcoholic steatohepatitis protection by S-nitroso-N-acetylcysteine in ob/ob mice. (Abstract)

Hepatic gene expression profile associated with non-alcoholic steatohepatitis protection by S-nitroso-N-acetylcysteine in ob/ob mice. To understand the molecular mechanisms underlying non-alcoholic steatohepatitis (NASH) prevention by S-nitroso-N-acetylcysteine (SNAC), an NO donor that inhibits lipid peroxidation, we examined hepatic differentially expressed genes between ob/ob mice receiving or not SNAC treatment concomitantly with a methionine-choline deficient (MCD) diet.Ob/ob mice were

2006 Journal of Hepatology

28912. Intrahepatic gene expression in human alcoholic hepatitis. (Abstract)

Intrahepatic gene expression in human alcoholic hepatitis. Alcoholic hepatitis remains an important cause of morbidity and mortality. Treatment remains unsatisfactory, in part, due to limited understanding of the pathogenesis. The aim of this study is to define the global intrahepatic expression profile of human alcoholic hepatitis.Gene expression was analysed by DNA microarray on RNA isolated from liver of patients with alcoholic hepatitis (AH, n = 8), alcoholic steatosis (AS, n = 9 (...) ) and explants from non-diseased donor liver controls (ND, n = 7). Differential expression of selected genes was confirmed by real-time RT-PCR and immunohistochemistry.Cluster analysis allowed differentiation of alcoholic hepatitis from alcoholic steatosis. The gene expression profile of AH revealed 586 genes differentially expressed from AS and 211 genes differentially expressed from that of ND liver. In comparison, only 98 genes were differentially expressed in AS from ND. Novel differentially expressed

2006 Journal of Hepatology

28913. A pilot study of the safety and tolerability of etanercept in patients with alcoholic hepatitis. (Abstract)

A pilot study of the safety and tolerability of etanercept in patients with alcoholic hepatitis. Alcoholic hepatitis is a cause of major morbidity and mortality, and effective therapeutic regimens to treat this condition are lacking. Both experimental and clinical evidence indicates that tumor necrosis factor alpha (TNF), and the downstream cytokine interleukin-6 (IL-6), correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis, thereby (...) implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis.The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor:FC fusion protein (etanercept), an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial.Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value

2004 American Journal of Gastroenterology

28914. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Full Text available with Trip Pro

Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Alcoholic liver disease is associated with abnormal hepatic methionine metabolism, including increased levels of homocysteine and S-adenosylhomocysteine (SAH) and reduced levels of S-adenosylmethionine (SAM) and glutathione (GSH). The concept that abnormal methionine metabolism is involved in the pathogenesis of alcoholic liver disease was strengthened by our previous findings in a micropig model where combining (...) of accelerated alcoholic liver injury can be ascribed to specific effects of ethanol with or without folate deficiency on the expressions and activities of hepatic enzymes that regulate transmethylation reactions. These novel effects on transmethylation reactions may be implicated in the pathogenesis of alcoholic liver disease.

2004 Hepatology

28915. Low-grade steatosis and major changes in portal flow as new prognostic factors in steroid-treated alcoholic hepatitis. (Abstract)

Low-grade steatosis and major changes in portal flow as new prognostic factors in steroid-treated alcoholic hepatitis. The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid-treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound findings were collected at inclusion and at month 2. Patients were (...) higher than 45%, and hepatofugal splenic blood flow were associated with a lower 1-year survival. Cox regression analysis showed that steatosis < 20% (relative hazard [RH] = 9.3, P = .0009) and major changes in portal flow (RH = 3.1, P = .04), were independently associated with poor survival. In conclusion, major changes in portal flow are frequent in patients with severe alcoholic hepatitis. Altered portal flow and steatosis < 20% are new prognostic factors in steroid-treated alcoholic hepatitis

2004 Hepatology

28916. MELD accurately predicts mortality in patients with alcoholic hepatitis. (Abstract)

MELD accurately predicts mortality in patients with alcoholic hepatitis. Assessing severity of disease in patients with alcoholic hepatitis (AH) is useful for predicting mortality, guiding treatment decisions, and stratifying patients for therapeutic trials. The traditional disease-specific prognostic model used for this purpose is the Maddrey discriminant function (DF). The model for end-stage liver disease (MELD) is a more recently developed scoring system that has been validated

2005 Hepatology

28917. Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis. (Abstract)

Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis. Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases. Our study assessed whether (...) ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in alcoholic hepatitis patients, and determined any relationship with severity of portal hypertension (hepatic venous pressure gradient measurement) and outcome. Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher (P = 0.001) than cirrhosis alone, and correlated with ADMA measurement. Plasma ADMA

2007 Hepatology

28918. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Full Text available with Trip Pro

The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Early identification of patients with severe (discriminant function > or = 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development

2007 Hepatology

28919. MELD score is a better prognostic model than Child-Turcotte-Pugh score or Discriminant Function score in patients with alcoholic hepatitis. (Abstract)

MELD score is a better prognostic model than Child-Turcotte-Pugh score or Discriminant Function score in patients with alcoholic hepatitis. The aim of the present study was to compare MELD score, Child-Turcotte-Pugh (CTP) score, modified Maddrey's Discriminant Function (DF) score, and the related variables in predicting in-hospital mortality of patients with alcoholic hepatitis.A retrospective chart review and statistical analyses were done on 202 patients consecutively admitted for alcoholic (...) , the first week MELD score >/=20 had the best sensitivity (91%) and specificity (85%) compared with admission or first week change MELD score.The present study indicates that in patients with alcoholic hepatitis, admission, first week, and first week change in MELD score are significantly independent predictors for in-hospital mortality. MELD score is a more valuable model than CTP or DF score in patients admitted with alcoholic hepatitis.

2005 Journal of Hepatology

28920. Deficient Stat3 DNA-binding is associated with high Pias3 expression and a positive anti-apoptotic balance in human end-stage alcoholic and hepatitis C cirrhosis. (Abstract)

Deficient Stat3 DNA-binding is associated with high Pias3 expression and a positive anti-apoptotic balance in human end-stage alcoholic and hepatitis C cirrhosis. In vitro and animal data suggest that alcohol and hepatitis C virus (HCV) proteins might interfere with Stat3 signaling, a potential regulator of liver cell apoptosis and proliferation.We assessed Stat3 expression, activity and the apoptotic-proliferation balance in end-stage HCV and alcoholic liver disease (ALD) in man. Explanted

2005 Journal of Hepatology

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