Acute Cholestatic Hepatitis Associated with Reinitiation of Statin Treatment

Abstract

We report a case of acute cholestatic hepatitis after reinitiation of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HMG-CoA RI). A 51 year old patient with a remote history of heavy alcohol abuse was admitted with jaundice, epigastric pain, and weakness. 2 years previously he received atorvastatin. Subsequently, he was found to have elevated aspartate and alanine aminotransferase and alkaline phosphatase with a normal bilirubin level. Liver biopsy at that time was consistent with chronic hepatitis and stage 3 fibrosis. The liver enzymes returned to normal after discontinuing atorvastatin. 6 weeks before his most recent admission, he was started on a medication containing simvastatin and ezetimibe. He developed worsening fatigue and jaundice, and presented to our institution. A hard, enlarged, minimally tender liver was noted. Serological tests of viral hepatitides, iron studies, auto-antibodies against the liver were either normal or negative. Contrast CT scan showed an enlarged liver with fatty change. Liver biopsy showed stage 4 fibrosis with focal cannalicular cholestasis. Over the next 4days of hospitalization off all medications, his symptoms resolved, and he was discharged. Patients taking HMG-CoA RI's rarely develop mild serum transaminase elevations, however, acute cholestatic hepatitis is seldom reported. The exact mechanism is unknown. Our patient developed an acute cholestatic hepatitis induced by an HMG-CoA RI's on two separate occasions, explained by the temporal relationship to the initiation of therapy, and development of liver injury, followed by improvement in symptoms and laboratory data after discontinuing the therapy. This case is compatible with the diagnosis of severe acute cholestatic hepatitis due to the reintroduction of an HMG-CoA RI, to which this chronic liver disease patient had been previously sensitized. HMG-CoA RI's occasionally cause acute cholestatic hepatitis. Further liver injury related to re-initiating HMG-CoA RI's has been reported previously. Our case highlights that a patient with underlying chronic liver disease, who develops mild liver toxicity when an HMG-CoA RI is initiated, may develop a more severe liver toxicity if this drug class is reinitiated even after a long time lag. This suggests a possible immuno-allergic mechanism of liver toxicity which may develop against the entire class of HMG-CoA RI's. Thus, it is important to avoid the reintroduction of HMG-CoA RI's in those who have underlying chronic liver disease.