Disulfiram-Induced Acute Liver Injury

Abstract

Disulfiram is a drug used to treat alcohol dependence since many years. It interferes with the metabolism of alcohol, may be associated with neurological and dermatological symptoms, and can be hepatotoxic. Due to the frequent coexistent liver test alterations due to alcohol, the true incidence of disulfiram-associated liver injury is unclear and severity of injury may vary from mildly elevated liver enzymes to fulminant hepatitis leading to death. There are several reported cases of disulfiram hepatitis in the literature. Liver histology, when available, demonstrates some degree of portal inflammation with eosinophils and hepatocyte necrosis. We present here a well-documented case of acute hepatitis due to disulfiram with typical histological lesions, favorable outcome following drug withdrawal, and a brief steroid course. The risk of hepatotoxicity should be kept in mind when prescribing disulfiram.

Alcohol-Associated Liver Disease: Evolving Concepts and Treatments

“…Risk of overdose Tolerance with chronic use. Life-threatening withdrawal syndrome on cessation or reduction Disulfiram [ 85 , 92 , 119 , 121 , 124 ] For goal of abstinence only Hepatic metabolism Avoid if moderate–severe hepatic impairment Monitor LFTs every 2 weeks for first 3 months, especially if abnormal at baseline No 200–400 mg once daily Aldehyde dehydrogenase inhibitor. Results in unpleasant effects with alcohol consumption due to elevated blood acetaldehyde concentrations Meta-analysis of 22 RCTs showed no efficacy of disulfiram over placebo in blinded studies, suggesting that psychological fear of a reaction may be a mechanism of action (Skinner), as open-label RCTs showed a medium effect size (g = 0.70) in achieving each trial’s primary endpoint.…”

“…Naltrexone is well tolerated in compensated cirrhosis, but dose-dependent hepatotoxicity has been demonstrated in obesity trials and monitoring of liver function tests is recommended [ 84 ]. Disulfiram can also lead to hepatotoxicity and is not recommended in advanced liver disease [ 85 ]. Acamprosate, disulfiram and naltrexone (oral tablet and extended-release intramuscular injection) are approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for use in AUD [ 13 ].…”

Current Therapeutic Options and Potential of Mesenchymal Stem Cell Therapy for Alcoholic Liver Disease

“…Disulfiram, another drug to manage ALD, causes aversion to alcohol by inhibiting the major alcohol metabolizing enzyme, ADH, and producing more acetaldehyde, resulting in severe hangovers and unpleasant feelings after consuming alcohol [78,79]. However, for ALD patients with advanced liver disease, pharmacological treatments are limited because impaired liver function affects drug metabolism and can increase the risk of drug-related hepatotoxicity [80,81]. Furthermore, despite abstinence, some cases of ALD can progress to cirrhosis [82,83].…”