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Pharmacological Therapy

Although ALD remains a major cause of morbidity and mortality in the United States, there is no FDA-approved therapy for either alcoholic cirrhosis or alcoholic hepatitis. However, several drugs have been used "off label."

Propylthiouracil (PTU). Orrego and colleagues examined long-term PTU therapy in more than 300 patients with various types of liver disease, including ALD. In this study, mortality was reduced by nearly 50 percent in patients receiving PTU. A recent review evaluated PTU therapy for ALD, including alcoholic fatty liver, alcoholic fibrosis, alcoholic hepatitis, and cirrhosis. Combining the results of six randomized clinical trials, these researchers did not find any significant effects of PTU versus placebo on mortality from all causes or liver-related mortality, complications of liver disease, or liver histology. The negative result of this review limits enthusiasm for PTU as a treatment for ALD.

Colchicine. Because of its antifibrotic effects, colchicine has been suggested as a treatment for ALD. Initial positive studies by Kershenobich and colleagues led to a large VA Cooperative Study evaluating colchicine therapy in patients with alcoholic cirrhosis. Results showed no beneficial effect on either overall mortality or liver-related mortality. A recent smaller study from Europe also showed no beneficial effects of colchicine. Thus, despite initial enthusiasm and biochemical rationale for use of this drug, it does not appear to be effective in ALD treatment.

Pentoxifylline (PTX). Akriviadis and colleagues evaluated PTX in a prospective, randomized, double-blind clinical trial in patients with severe alcoholic hepatitis. Forty-nine patients received PTX and 52 received placebo for 4 weeks. PTX treatment improved survival: 12 PTX patients died, compared with 24 placebo patients. PTX also decreased the percentage of deaths caused by hepatorenal syndrome. Renal failure was the cause of death of 6 of the 12 PTX-treated patients who died, compared with 22 of the 24 control patients who died. Multivariate analysis revealed that age, kidney test results for the waste product creatinine at randomization, and treatment with PTX were independent factors associated with survival.

Corticosteroids. Although corticosteroids are the most extensively studied form of therapy for alcoholic hepatitis, their role remains limited. The rationale for steroid use is to decrease the immune response and the proinflammatory cytokine response. Most randomized studies have supported the use of corticosteroids in moderate to severe alcoholic hepatitis, but a large multicenter VA study yielded negative results. Steroids have been found to be effective against severe acute alcoholic hepatitis by most meta-analyses, including the most recent study by Mathurin and colleagues. These investigators reported significantly improved survival at 28 days in severely ill alcoholic hepatitis patients having a DF greater than 32. This survival advantage may extend to 1 year but not 2. Independent prognostic factors associated with survival at 28 days in this meta-analysis were steroid treatment, age, and serum creatinine levels. Patients with infections, gastrointestinal bleeding, and many other common complications were excluded from these studies.

Most investigators agree that if corticosteroids are to be used, they should be reserved for patients with severe liver disease, and possibly those with hepatic encephalopathy. Steroids have well-documented side effects, including enhancing risk of infection, which already is substantial in patients with alcoholic hepatitis. Thus, a major disadvantage to corticosteroids is that they cannot be used by many patients with alcoholic hepatitis.

Complementary and Alternative Medicine (CAM) Agents. CAM agents have had some success in patients with liver disease and are widely used. Research demonstrates a strong rationale for using many of these CAM agents, such as S-adenosylmethionine, but shows that others may have no efficacy or may even cause harm, including liver injury.

Diagnosis and Treatment of the Complications of ALD

Proper diagnosis and management of the complications of ALD are vital to decreasing the deterioration of illness, improving quality of life, and possibly decreasing mortality. The complications of ALD reviewed here are: ascites (accumulations of fluid in the abdominal cavity), infections in this fluid that develop without any apparent cause, hepatorenal syndrome, and esophageal varices.

Ascites

Ascites is one of the most common complications of advanced liver disease and generally indicates a poor prognosis and a high likelihood of death. Approximately 8 of every 10 patients who have ascites in the United States have it as a consequence of cirrhosis of the liver. It is estimated that 3 of every 10 patients who have cirrhosis without complications will develop ascites within the next 5 years. In patients with ascites, the likelihood of death in the following year is approximately 50 percent, compared with 10 percent for cirrhosis patients without complications. Ascites cases can be classified as easily treatable or refractory and difficult to control. Patients with the latter type are likely to develop hepatorenal syndrome.

Treating ascites does not seem to prolong life in cirrhotic patients but improves the quality of life and protects patients from spontaneous infections of the fluid, which are associated with high death rates.

Patients who develop ascites for the first time, those with ascites who are admitted to the hospital because of illness, those who have difficult-to-control ascites, and those who develop symptoms because of tense ascites (the abdomen is tight with ascites) - all should have the fluid removed for diagnostic evaluation and to lessen discomfort in the abdomen. Because these patients are at high risk of infection in the fluid and because the fluid accumulation may be a consequence not only of liver disease but also of other associated disorders, this fluid should be thoroughly evaluated. Evaluation should include a cell count as well as determinations of total protein and albumin. At around the same time, a blood sample should be checked to measure the amount of albumin in order to facilitate interpretation of the findings on the ascitic fluid. For patients who have ascites because of portal vein hypertension, determining serum albumin concentration-ascitic albumin concentration is recommended. SAAG is calculated by subtracting the albumin concentration of the ascitic fluid from the albumin concentration of a serum specimen obtained on the same day. Patients with SAAGs of 1.1 grams per deciliter or higher may have cirrhosis or alcoholic hepatitis, among other conditions.

Tags: Alcoholism

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