Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon

Background: Ursodeoxycholic acid (UDCA) could potentiate the effect of inte rferon (IFN) in patients with chronic hepatitis C resistant to IFN. We comp ared the efficacy of IFN with that of a combination of IFN and UDCA. Method s: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or p lacebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. Results: At entry 30% of pat ients had cirrhosis, and 70% had HCV genotype i. Five and four patients wit hdrew from the combination and the monotherapy groups, respectively. At 6 m onths alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group th an in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of t hem (5 in each group) HCV RNA levels became undetectable. At 1 year four ve rsus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic prog ression. In this setting, in contrast to chronic cholestasis, UDCA administ ration induced an increase in total serum bile acids and did not change pri mary bile acids. Conclusions: An IFN plus UDCA combination is more effectiv e than IFN alone in terms of ALAT but not in terms of the virologic respons e. These results favor the hypothesis that UDCA has an effect on the bioche mical indices of cellular injury independent of a change in primary bile ac ids.