HEPATITIS C VIRUS AS A CO-FACTOR IN AZATHIOPRINE-INDUCED CHOLESTASIS

Abstract

Background: Pre-existing liver disease is not believed to potentiate the risk of most idiosyncratic drug-induced hepatotoxicities. Fibrosing cholestatic hepatitis (FCH) related to the hepatitis C virus (HCV) has been reported in the transplant literature in immunocompromised patients on azathioprine (AZA), suggesting a synergistic toxicity of HCV and AZA. We report a case of prolonged AZA-induced intrahepatic cholestasis in a non-transplanted patient with HCV and non-alcoholic steatohepatitis. This case and a review of the medical literature suggest that patients with HCV may be at greater risk for AZA toxicity. Case Report: A 53 year-old African American man with chronic HCV and steroid-dependent polymyositis presented with a two-week history of jaundice and intense pruritus. Twelve weeks before presentation he was started on AZA 100 mg bid and four weeks before presentation his dose of prednisone was increased to 40 mg/d for control of worsening muscle weakness. Before the start of AZA, his baseline AST (U/L)/ALT (U/L)/Total bilirubin (mg/dl) was 147/172/0.8 and at the time of presentation, these values were 227/225/19.3. A liver biopsy showed intense intrahepatic cholestasis, feathery degeneration, moderately active steatohepatitis, and portal-portal bridging fibrosis. Ductopenia was not observed. Two months after discontinuation of AZA, his pruritus resolved and his bilirubin decreased to 11.5 mg/dL. Discussion: In the absence of other causes, the temporal relationship of AZA to the onset of jaundice implicates this drug as the cause of prolonged jaundice. The world medical literature documents only a few bona fide cases of AZA-induced cholestasis in patients without prior organ transplantation. One such case, reported before 1989, likely involved a patient with HCV. The present case bears clinical resemblance to FCH in patients with chronic HCV post-liver and kidney transplantation. In those cases, AZA was suspected to be a contributing factor in the development of cholestasis, but other immunosuppressive agents, as cofactors, could not be excluded. This case corroborates recent reports suggesting that HCV patients, independent of steroid immunosuppression, may be more susceptible to the hepatotoxic effects of AZA and that AZA may be responsible for FCH in the HCV post-transplant setting.