Current management of alcoholic liver disease.

Alcoholic liver disease accounts for significant economic burden with second most common cause for liver transplantation in the US. Although alcohol abstinence is most crucial, morbidity and mortality occur amongst those with continuing alcohol intake and with established end stage liver disease due to lack of specific treatment modalities to manage this disease. Patients with severe acute alcoholic hepatitis, a distinct subset of alcoholic liver disease have a potential for mortality in about 25% within about 1 month despite treatment with available specific agents such as corticosteroids and/or pentoxifylline. Hence, there is clear need for newer and better treatment options to manage these patients. In this article, potential emerging newer targets to manage this disease are discussed including intestinal decontamination, caspase inhibitors, antioxidants, and interlukins. In the background of encouraging emerging data (retrospective data from the UNOS database and data from a case matched prospective French study) on the beneficial effects of liver transplantation amongst patients with alcoholic hepatitis who are non-responders to current medical treatments, this article would also deal controversies surrounding the role and use of liver transplantation in patients with alcoholic hepatitis. Issues such as rule of 6 months of abstinence, ethical issues, and shortage of donor organs will be debated.

Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians.

AIM: To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients. METHODS: A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis. RESULTS: Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH. CONCLUSION: Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.

Hepatocellular carcinoma predicts in-hospital mortality from acute variceal hemorrhage among patients with cirrhosis.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common complication among patients with cirrhosis. Data are limited on the impact of HCC on in-hospital mortality from acute variceal hemorrhage (AVH) in patients with cirrhosis. METHODS: National in-hospital sample (1998 to 2007) was used to analyze admissions with AVH in cirrhotics to study impact of concomitant HCC on the in-hospital mortality. RESULTS: Of 27,442 admissions with cirrhosis and AVH, 540 had HCC. Admissions with HCC differed from those without HCC for age, sex, race, hospital characteristics, and complications of cirrhosis. A total of 2633 (9.6%) patients died during average hospital stay of 6 days with higher in-hospital mortality among admissions with HCC compared with without HCC (19% vs. 9%; P<0.0001). On logistic regression analysis, in-hospital mortality decreased by about 9%/y during 1998 to 2007 [odds ratio, 0.91 (95% confidence interval, 0.89-0.92)]. Receipt of endoscopic treatment was associated with reduced in-hospital mortality. After adjusting for all variables including calendar year and endoscopic treatment, HCC independently predicted in-hospital mortality from AVH: odds ratio, 2.15 (95% confidence interval, 1.67-2.77). Logistic regression model using clinically important variables predicted in-hospital mortality with area under the receiver operating characteristics of 0.80 with strong predictors being presence of HCC, hepatorenal syndrome, hypovolemic shock, sepsis, portosystemic encephalopathy, and use of Sengstaken Blakemore tube. CONCLUSIONS: HCC predicts in-hospital mortality from AVH in patients with cirrhosis. Studies are needed to examine and understand mechanisms of these findings to further develop better modalities of management of AVH in patients with cirrhosis and HCC.

Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: exploratory analysis from the UNOS database.

UNLABELLED: Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004-2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow-up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five-year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five-year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol-related in any patient. CONCLUSION: Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long-term outcome after liver transplantation in patients with alcoholic hepatitis.

Antioxidants as therapeutic agents for liver disease.

Oxidative stress is commonly associated with a number of liver diseases and is thought to play a role in the pathogenesis of chronic hepatitis C, alcoholic liver disease, non-alcoholic steatohepatitis (NASH), haemochromatosis and Wilson's disease. Antioxidant therapy has thus been considered to have the possibility of beneficial effects in the management of these liver diseases. Despite this promise, antioxidants have produced mixed results in a number of clinical trials of efficacy. This review summarizes the results of clinical trials of antioxidants as sole or adjuvant therapy of chronic hepatitis C, alcoholic liver disease and non-alcoholic steatohepatitis (NASH). Overall, the most promising results to date are for vitamin E therapy of NASH but some encouraging results have been obtained with antioxidant therapy of acute alcoholic hepatitis as well. Despite evidence for small reductions of serum alanine aminotransferase, there is as yet no convincing evidence that antioxidant therapy itself is beneficial to patients with chronic hepatitis C. Problems such as small sample size, short follow up duration, inadequate endpoints, failure to demonstrate tissue delivery and antioxidant efficacy, and heterogeneous nature of the 'antioxidant' compounds used have complicated interpretation of results of the clinical studies. These limitations and their implications for future trial design are discussed.

Pathogenesis of alcoholic hepatitis: Role of inflammatory signaling and oxidative stress.

Inflammatory signaling and oxidative stress are two major components in the pathogenesis of alcoholic hepatitis. Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in the production of inflammatory and immunogenic mediators such as tumor necrosis factor-alpha (TNF-α) and interferons. Chronic consumption of alcohol causes priming of this process in which there is enhanced production of cytokines, interferon, interleukins, and TNF-α. Oxidative stress, genetic predisposition, and the unfolded protein response are other contributory mechanisms. Novel therapies aimed at these pathways may prevent, decrease, or delay the complications of alcoholic hepatitis.

Peginterferon alfa-2a is superior to peginterferon alfa-2b in the treatment of naïve patients with hepatitis C virus infection: meta-analysis of randomized controlled trials.

BACKGROUND: Pegylated interferon (PEGIFN) and ribavirin combination is the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naïve HCV-infected patients have shown conflicting results. AIM: We performed a systematic review and meta-analysis of studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in HCV-infected patients naïve to treatment. METHODS: Nine studies (five abstracts) with 3,546 patients (1,771 treated with PEGIFN alfa-2a) comparing PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naïve HCV patients were analyzed. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects (SAE). RESULTS: Pooled data on outcomes (reported as odds ratios [ORs] with 95% confidence intervals [CIs]: [OR (95% CI)]) showed higher SVR in patients treated with PEGIFN alfa-2a as compared to treatment with PEGIFN alfa-2b [1.36 (1.07-1.73); P=0.01]. Subgroup analysis of good quality studies on SVR in genotypes 2 and 3 also favored PEGIFN alfa-2a over PEGIFN alfa-2b (1.91 [1.09-3.37]; P=0.02). SVR results obtained with the two types of IFN showed no impact of viral load and the presence or absence of cirrhosis. Treatment discontinuation rates due to SAE, reported in six studies (two abstracts) on 3,211 patients (1,604 treated with PEGIFN alfa-2a), were similar in the two types of PEGIFN [0.66 (0.37-1.16); P=0.15]. CONCLUSIONS: PEGIFN alfa-2a has superior efficacy with higher SVR as compared to PEGIFN alfa-2b in treatment-naïve HCV-infected patients. The safety profile of the two types of PEGIFN was similar.