Therapy for alcoholic liver disease

Abstract

Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.

Keywords: Alcoholic cirrhosis; Alcoholic hepatitis; Alcoholic liver disease; Alcoholic steatosis; Alcoholism; Corticosteroids; Liver disease; Liver transplantation; Pentoxifylline.

Figure 1

Photomicrograph. A: Photomicrograph showing a Mallory body (arrowhead), with twisted rope-like appearance, and fat vacuoles (arrows) as seen in alcoholic steatohepatitis (image from http://en.wikipedia.org/wiki/Alcoholic_hepatitis, licensed under Creative Commons Attribution-Share Alike 3.0 Unported); B: Photomicrograph showing a regenerating nodule (arrowhead) and bridging fibrosis (arrow) as seen in alcoholic cirrhosis (image from http://en.wikipedia.org/wiki/Alcoholic_cirrhosis, licensed under Creative Commons Attribution-Share Alike 3.0 Unported).