Bezafibrate Treatment of Primary Biliary Cirrhosis Following Incomplete Response to Ursodeoxycholic Acid

Abstract

Ursodeoxycholic acid (UDCA) is the only current pharmacologic treatment for primary biliary cirrhosis (PBC). However, some patients show persistent liver biochemical abnormalities even after 6 to 12 months treatment. Bezafibrate retard is a commonly used medication for hyperlipidemia. In Japanese studies, it was found to lower liver enzyme levels, apparently through its action on multiple drug resistance gene 3, a transport element of the ATP-dependent bile secretion system, and on peroxisome proliferator-activated receptor-alpha. The aim of this study was to evaluate the effect of adding bezafibrate to the treatment regimen in patients with PBC and a partial response to UDCA. The study group included 8 White patients, 7 women and 1 man, aged 52 to 76 years with PBC who had been treated at our Liver Institute with UDCA (900 mg/d to 1500 mg/d) for 2 to 11 years (mean, 5.7 y) with only a partial response (19% to 56% reduction in alkaline phosphatase level). Bezafibrate (400 mg/d) was added to UDCA and the patients were followed for 4 to 12 months. Alkaline phosphatase levels (normal range, 35 to 104 U/L) decreased in all patients, from 140 to 360 U/L (mean, 201.2) to 68 to 158 U/L (mean, 98.4), and normalized in 6 patients. In addition, levels of gamma-glutamyl transferase (normal range, 6 to 42 U/L) decreased from 70 to 192 U/L (mean, 130) to 41 to 122 U/L (mean, 71.8). These findings were maintained throughout follow-up. Combination therapy with bezafibrate and UDCA improves the biochemical profile of patients with PBC who respond only partially to UDCA. A larger controlled study is needed to evaluate the clinical implications of these findings.