Disulfiram-induced Fulminant Hepatic Failure

Abstract

Introduction: Disulfiram has been used as an adjunct therapy in treatment of chronic alcoholism. Disulfiram-induced liver injury can range from asymptomatic elevations in serum aminotransferases to symptomatic liver injury with jaundice, and, rarely, to fulminant hepatic failure and death. We present a rare case of disulfiram-induced fulminant hepatitis. Case Presentation: A 66-year-old male with history of hypertension, diabetes mellitus, and atrial fibrillation on Coumadin was admitted with acute liver failure. He had a history of heavy alcohol use, and decided to quit alcohol three weeks prior to admission. He was started on disulfiram, but did not tolerate the medication, and stopped it 10 days prior to current admission. He presented with hypoglycemia, and was found to have elevation of liver enzymes with total bilirubin of 13, AST of 2749, ALT of 3423, and alkaline phosphatase of 293. INR was greater than 10. Work-up was negative for acute viral hepatitis, Tylenol, and salicylate toxicity. Coagulopathy initially reversed with vitamin K, and was felt to be due to Coumadin toxicity. There was no evidence of encephalopathy on admission. However, INR continued to remain elevated even after discontinuing Coumadin. CT did not show cirrhosis, but showed evidence of portal hypertension. He was started on N-Acetylcysteine protocol for acute liver failure. Liver function tests (LFTs) continued to increase, with bilirubin peaking at 36 mg/dL. Liver biopsy was planned, but deferred, as the patient developed fulminant hepatitis. He was not a liver transplant candidate due to recent alcohol use. Encephalopathy and coagulopathy continued to worsen, and the family opted for hospice. Discussion: Disufiram has been used in treatment of chronic alcoholism since 1948. It inhibits acetaldehyde dehydrogenase enzyme leading to accumulation of acetaldehyde. This leads to flushing, tachycardia, nausea, vomiting, and confusion. Chronic therapy with disulfiram is associated with mild aminotransferase elevations, but elevations above three times the upper limit of normal (ULN) occur in up to 4% of patients. Liver injury usually occurs within 2-12 weeks of starting disulfiram, but latency period tends to be shorter in cases of re-exposure. The clinical presentation of disulfiram-induced hepatotoxicity resembles acute viral hepatitis. In severe injury, the fatality rate is at least 10%. Histologically, findings include focal hepatocellular necrosis, lobular disarray, and chronic inflammatory cell infiltrates with eosinophils. Conclusion: Disulfiram-induced hepatotoxicity is associated with high mortality, and should lead to immediate discontinuation of the drug. If stopped early, complete recovery is expected within 4-6 weeks.