Bezafibrate treatment of primary biliary cirrhosis following incomplete response to ursodeoxycholic acid.

BACKGROUND AND GOALS: 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.

STUDY: 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.

RESULTS: 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.

CONCLUSIONS: 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.