Metronidazole Induced Liver Injury: A Rare Immune Mediated Drug Reaction

Drug induced liver injury (DILI) can result either from dose-dependent direct hepatotoxicity or from an unpredictable dose-independent idiosyncratic reaction. Incidence of idiosyncratic DILI is estimated to be approximately 10–15 per 100,000 patient years. Here we report an extremely rare case of metronidazole induced delayed immune-allergic hepatocellular liver injury masquerading as autoimmune hepatitis. A previously healthy 54-year-old Caucasian male, who was treated with metronidazole for Clostridium difficile associated diarrhea, presented 3 months later with right upper quadrant abdominal pain. Laboratory tests revealed total bilirubin level of 12.7？mg/dL, direct bilirubin of 7.2？mg/dL, alanine aminotransferase (ALT) of 973？IU/L, aspartate transaminase (AST) of 867？IU/L, alkaline phosphatase (AP) of 96？IU/L, and an INR of 1.9, suggestive of hepatocellular pattern of injury. A detailed workup for hepatitis revealed no other etiology. A clinical diagnosis of metronidazole induced liver injury was made. With a persistent rise in his bilirubin and transaminase levels, the patient was started on oral prednisone. At the 2-week posthospitalization follow-up visit, the patient reported a significant improvement in his overall sense of being well and liver functions tests trended down substantially (total bilirubin 7.2？mg/dL, ALT 420？IU/L, AST 276？IU/L, AP 183？IU/L, and INR 1.5). 1. Introduction Reactive chemical metabolites formed during hepatic drug metabolism can incite hepatocellular damage from oxidative stress and mitochondrial dysfunction causing drug induced liver injury (DILI). DILI can result from either dose-dependent direct hepatotoxicity (e.g., acetaminophen toxicity) or from an unpredictable dose-independent idiosyncratic reaction. Genetic polymorphisms in the drug bioactivation and detoxification pathways along with host immunological factors are responsible for these rare and potentially fatal idiosyncratic DILI [1]. Of the several mechanisms proposed to elucidate the mechanism underlying immune-allergic idiosyncratic DILI, the “hapten hypothesis” is the most favored [2]. Drugs and/or their metabolites covalently bind to host proteins forming drug-protein adducts (i.e., haptens) that are processed by the antigen-presenting cells and trigger a T-cell mediated cytotoxicity or B-cell antibody response. Incidence of idiosyncratic DILI is estimated to be approximately 10–15 per 100,000 patient years [3]. About 1 in 7 cases of acute liver failure are related to an adverse drug reaction, making DILI the most common indication for liver