Perspectives in clinical gastroenterology and hepatology
Alcoholic Hepatitis: Current Challenges and Future Directions

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Alcoholic hepatitis is a distinct clinical syndrome among people with chronic and active alcohol abuse, with a potential for 30%–40% mortality at 1 month among those with severe disease. Corticosteroids or pentoxifylline are the current pharmacologic treatment options, but they provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) ≥32 or Model for End-Stage Liver Disease score ≥18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months of abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis nonresponsive to steroids (Lille score ≥0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacologic treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies.

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Diagnosis of Alcoholic Hepatitis

In the absence of confirmatory tests, eliciting an accurate history of alcohol use is one of the major challenges in diagnosing AH. In an obese patient who drinks excessively, when it is unclear whether the etiology is alcoholic steatohepatitis or nonalcoholic steatohepatitis, the alcohol–non-alcohol index (ANI) may be used to determine the etiology. The ANI uses body mass index, mean corpuscular volume, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and gender to

Abstinence From Alcohol

The major focus of attention is prevention of alcohol use. Abstinence is the most important factor in predicting long-term outcome of patients surviving the acute AH episode.39, 40 Evaluation by a team experienced in the treatment of alcoholism is recommended during the hospitalization for AH and is helpful in increasing abstinence rates after hospital discharge.41 Tools used to maintain abstinence from alcohol include motivational interviewing and cognitive behavioral therapy. Motivational

Corticosteroids

Corticosteroids are the most widely used agents for the treatment of severe AH. However, the 13 RCTs evaluating corticosteroids for treating AH reported during the past 40 years have shown mixed results.48 Meta-analysis of individual patient data from 5 RCTs that used corticosteroids for severe AH showed an approximately 50% relative survival benefit at 1 month (65% vs 85% survival among untreated vs treated), with the number needed to treat being 5 patients to reduce 1 death.49 Despite this

Liver Transplantation for Alcoholic Hepatitis

Controversy exists on use of LT for AH that relates to both medical and ethical issues.70 On the basis of a rationale that AH may improve with medical management and that duration of abstinence can predict abstinence after transplant, many transplant centers require a period of 6-month abstinence before considering transplant in patients with AH.71 However, data on 6-month pre-transplant abstinence and risk of relapse after LT are conflicting. In a pooled analysis of 32 studies, 6-month

Suggested Approach for Management of Alcoholic Hepatitis

A high index of suspicion is needed for diagnosis of AH among patients with chronic and active alcohol abuse and recent onset of jaundice (Figure 1). Diagnosis is often made clinically, and liver biopsy is recommended when clinical diagnosis is uncertain. Patients with mild disease are treated with nutritional supplementation, management of alcohol withdrawal, counseling for abstinence, and supportive care for liver disease complications. Patients with severe disease (mDF >32 or MELD ≥20)

Future Directions

Because of the current limitations and therapeutic options for patients with AH, there remains a critical need for newer, more effective agents for treating this condition. Until recently, there were scarce clinical resources from government or industry aimed at identifying new therapies for AH. However, more recently, a major initiative from the National Institute on Alcohol Abuse and Alcoholism has spearheaded large multi-institutional consortia with the task of identifying new therapeutic

Acknowledgments

Dr Singal's current affiliation is the Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, Alabama.

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      Treatment regimens usually recommended by guidelines, prednisolone or prednisone 40 mg/d, is given orally for 28 days. Methylprednisolone is used in a dose of 32 mg given intravenously daily for patients unable to take medications orally.131,151,152,129 Additionally, the response to corticosteroid treatment can be predicted using the Lille model, where a value ≥ 0.45 predicts failure to corticosteroid treatment.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by National Institutes of Health grants AA021788 and AA021171.

    This article has an accompanying continuing medical education activity on page e32. Learning Objectives—At the end of this activity, the successful learner will be able to identify pathogenic steps and associated treatment recommendations in patients with alcoholic hepatitis.

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