2009 Southern Regional Meeting Abstracts

Purpose of Study: Fenofibrate is a synthetic phenoxy-isobutyric acid derivative first synthesized in 1975 and belongs to clofibrate and gemfibrozil family It is currently used to treat all classes of hyperlipidemia and is highly effective in reducing serum triglycerides, total cholesterol and LDL-C and in raising HDL-C level. Hepatic injury is extremely rare and to our knowledge, only 11 cases were described in the French, Italian or Spanish literature and one case was reported from Taiwan. Here, we report the first case of fenofibrate induced acute cholestatic hepatitis in the United States.
A 56-year old female was referred with a one month history of gradually worsening jaundice, pruritis and tea-colored urine associated with anorexia and 13 pound weight loss. She had a history of type 2 diabetes mellitus and systemic hypertension for 15 years and hyperlipidemia for 5 years and was maintained on metformin and amlodipine. Fenofibrate at a dose of 145 mg daily was prescribed 4 weeks prior to the onset of her current symptoms. The patient denies any history of blood transfusion, illicit drug or alcohol use. Physical examination showed normal vital signs, deeply icteric sclera and skin with itching marks all over but no stigmata of chronic liver disease. The rest of her examination was unremarkable
Laboratory data showed normal hepatic profile from a laboratory data obtained 3 months ago. Current laboratory data showed a total bilirubin (TB) of 9.9 mg/dl (normal range0-1 mg/dl) with a mainly elevated direct proportion (DB) of 7.3 mg/dl (0-0.2 mg/dl), alanine aminotransferase (ALT) of 81 IU/L(0-41 IU/L), aspartate aminotransferase (AST) of 43 IU/L (0-32 IU/L), alkaline phosphatase of 183 IU/L (35-129 IU/L), gamma-glutamyl transferase (γGT) of 871 IU/L (4-50 IU/L). Prothrombin time was 11 seconds (control 12 seconds), albumin 3.4 g/l (3.5-5.3 g/l), hepatitis profile was negative, serum ceruloplasmin was 40 mg/dl (18-53 mg/dl), alpha-1 antitrypsin 155 mg/dl (90-200 mg/dl), antinuclear, antiactin and antimitichondrial antibodies were negative. Iron studies were normal. CA 19-9 15.2 U/ml(0.6-35 U/ml)Abdominal ultrasonography showed a normal liver architechture and normal biliary tree.A magnetic resonance cholangiopancreatography showed a slightly thickened gallbladder wall but was otherwise unremarkable.
A percutaneous liver biopsy showed bile stasis in pericentral and periportal areas, hyperplasia of Kupffer cells, minimal steatosis, mild mononuclear inflammatory cell infiltrate, occasional apoptotic bodies. The trichome stain showed showed increased collagen deposition in the spaces of Disse. The reticulin stain showed focal and minimal thickening of the liver plates (see figure1)
Based on a high index of suspicion, fenofibrate was held, even before liver biopsy was performed. The patient was given an antipruritic agent, cyproheptadine and sent home. On follow up 6 weeks later, her symptoms had completely resolved. Laboratory data at that time showed a slightly raised total bilirubin (1.5 mg/dl), alanine aminotransferase was elevated at 89 IU/L. At 12 weeks follow up, she was still asymptomatic and her ALT, AST, Alkaline phosphatase and total bilirubin were all completely in the normal range
Methods Used: NA
Summary of Results: NA
Conclusions: NA