Efficacy of ursodeoxycholic acid in association with α-interferon for chronic hepatitis C in α-interferon non-responder patients

Background. The aim of the present study was to evaluate the effect of combined treatment with α-interferon (α-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to α-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 α-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same α-IFN dose, or to continue α-IFN alone (IFN-controls, 50 patients). After stopping α-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal γGT, genotype distribution and liver histology, while mean age was lower in controls (53 ± 1.8 vs 46 ± 1.8 years; P < 0.01), Results. Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of αIFN, 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 of them. Portal and periportal inflammation showed a statistically significant improvement (Fisher's exact test P < 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. Conclusions. These data demonstrate that UDCA improves the response rate to α-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance. (C) 2000 Lippincott Williams and Wilkins.