Acute Cholestatic Hepatitis Induced by Gemfibrozil - A Case Report: ACG/AstraZeneca Clinical Vignette Award

Abstract

Purpose: Gemfibrozil is a fibric acid derivative and an activator of peroxisome proliferator-activated receptor-alpha (PPARα), a nuclear receptor involved in the metabolism of carbohydrates and fats.We report a rare case of cholestatic hepatitis due to gemfibrozil. A 55-year-old African-American man presented with abdominal pain, fatigue, pruritis and jaundice over the preceding month. He had a past medical history including HTN, DM type 2 and hypertriglyceridemia. He also reports a history of chronic hepatitis C previously treated with interferon but discontinued due to intolerance. Three months prior to presentation he was prescribed gemfibrozil 600 mg twice daily for hypertriglyceridemia. Upon presentation, his physical examination was unremarkable. Laboratory data over several months revealed peak values of ALT 241 IU/L, ALKP 359 IU/L, and TB 11.5 mg/dL. His coagulation profile, acute hepatitis serology, and amylase/lipase were normal. Work-up for other etiologies were negative including autoimmune, toxic and genetic causes. Malignancy was also excluded. Liver ultrasound showed normal blood flow but mild, diffuse increased echogenicity consistent with fatty infiltration. CT abdomen revealed cholelithiasis without cholecystitis and no ascites. Liver biopsy was performed revealing chronic portal inflammation with interface hepatitis and bridging fibrosis (METVIR grade 2-3, stage II). Few eosinophils and rare neutrophils were seen among the lymphocytes. Prominent hepatocellular and canalicular bilirubinostasis with the formation of “cholestatic” rosettes, neocholangiolar proliferation, and focal duct injury were seen. Early collagen deposits in areas of collapse with pericellular and perisinusoidal fibrosis were noted indicating a possible drug injury on top of a pre-existing chronic liver disease. Upon discontinuation of gemfibrozil, liver enzymes trended down with normalization over 8 weeks with the exception of alkaline phosphatase which remained elevated at 305 IU/L. Further review of this patient's record revealed two prior incidents of gemfibrozil initiation resulting in liver injury attributed to chronic hepatitis C. The product information for gemfibrozil indicates elevations in liver function tests have been observed previously for which periodic monitoring is recommended. This case represents the first report of gemfibrozil-induced cholestasis in a patient with chronic hepatitis C. By presenting this case, we hope to characterize the pattern of liver damage and to increase the awareness of hepatotoxicity associated with gemfibrozil. Early recognition, withdrawing the use of gemfibrozil, and supportive treatment play an important role in preventing further liver injury.