URSODEOXYCHOLIC ACID OR CLOFIBRATE IN THE TREATMENT OF NON-ALCOHOL-INDUCED STEATOHEPATITIS - A PILOT-STUDY

Non-alcohol-induced steatohepatitis (NASH) is characterized by elevate d serum aminotransferase activities with hepatic steatosis, inflammati on, and occasionally fibrosis that may progress to cirrhosis. No estab lished treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatmen t of NASH. Forty patients were diagnosed with NASH based on a compatib le Liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty -four patients received 13 to 15 mg/kg/d of UDCA for 12 months, Sixtee n patients with hypertriglyceridemia were placed on clofibrate, 2 g/da y for 12 months, Twenty-five women and 15 men entered the study. Six o f 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later re quired liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate , no change from baseline was found in mean ALT, aspartate transaminas e (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histolo gical. grade of steatosis, inflammation, or fibrosis after 12 months o f treatment as compared with entry, Alkaline phosphatase activities de creased significantly from baseline. Despite the known lipid-lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1-year pilot study. However, treatment o f NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible be nefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.