Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: A multicenter randomized controlled trial



The aim of this study was to determine whether 12 months course of interferon alfa (IFN-α) therapy could improve the beneficial effect of IFN in chronic hepatitis C. Eighty-eight patients were treated with natural IFN-α for either 28 weeks (45 cases) or 52 weeks (43 cases). Sustained response was achieved in 15 (33.3%) of 45 cases treated for 28 weeks and in 23 (53.5%) of 43 cases treated for 52 weeks. Transient response with relapse of alanine transaminase (ALT) after completion of therapy was observed in 13 cases (28.9%) treated for 28 weeks and in 4 cases (9.3%) treated for 52 weeks. Thus, ALT relapse was suppressed by prolonged IFN treatment. No response was found in 17 cases (37.8%) treated for 28 weeks and in 16 cases (37.2%) treated for 52 weeks, indicating that approximately 38% of the patients with chronic hepatitis C were resistant to IFN therapy even with prolonged treatment. The rate of sustained response was significantly higher in patients with type 2a or 2b than in those with type 1b. Even in type 1b cases, it was higher in the 52-week treatment group than in the 28-week treatment group, and the rate of transient response was lower in the 52-week treatment group, indicating that relapse in type 1b cases was suppressed by prolonged IFN therapy. IFN therapy was not effective for patients with advanced liver fibrosis. In multivariate regression analysis viral genotype and pretreatment level of serum hepatitis C virus (HCV) RNA were correlated independently with sustained response. Periportal necrosis, intralobular inflammation, and hepatic fibrosis scores were significantly improved in the sustained response group by IFN therapy. In the transient response group, a significant decrease in scores for intralobular inflammation and portal inflammation was observed, whereas all four histological scores were not improved in the no response group. In conclusion, prolonged IFN therapy can suppress relapse of chronic hepatitis C, even in type 1b patients. However, approximately 38% of the patients are resistant to prolonged IFN therapy, suggesting the need to develop a new therapy. (HEPATOLOGY 1995;21:291–297.)