Efficacy of ursodeoxycholic acid in association with alpha-interferon for chronic hepatitis C in alpha-interferon nonresponder patients

Background The aim of the present study was to evaluate the effect of combi ned treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (U DCA) on liver function tests and serum HCV-RNA in patients with chronic hep atitis C who had not responded to alpha-IFN alone. Methods One hundred and three patients (60 men, 43 women, mean age 49 +/- 1 .3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patient s, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha -IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month p eriod. The two groups were comparable for sex, basal ALT, basal gamma GT, g enotype distribution and liver histology, while mean age was lower in contr ols (53 +/- 1.8 vs 46 +/- 1.8 years; P < 0.01). Results Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared w ith only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA becam e undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P < 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P = NS) and HCV-RNA was still undetectable in four o f them, Portal and periportal inflammation showed a statistically significa nt improvement (Fisher's exact test P < 0.01) in IFN-UDCA patients as compa red with IFN-controls, while no effect was observed on portal fibrosis. Conclusions These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was su stained and associated with HCV-RNA clearance. (C) 2000 Lippincott Williams & Wilkins.