of patients with a high likelihood of response to IFN-b. In chronic hepatitis C virus (HCV) infection, geno-(HEPATOLOGY 1997;25:750-753.) types other than genotype 1b of HCV (HCV-1b) and low serum HCV-RNA levels are known to be associated with favorable outcome of interferon alfa (IFN-a) therapy. In The hepatitis C virus (HCV) is the major cause of chronic addition, we recently reported a close correlation benon-A, non-B hepatitis, a disease that seldom resolves spontween the number of mutations in amino acid sequences taneously and that can progress to cirrhosis and hepatocellu-2209 to 2248 of the nonstructual protein 5A gene lar carcinoma over several decades. 1 The development of ef-(NS5A2209-2248) of HCV-1b and the response to IFN-a. fective treatments to eradicate HCV infection is of great In the present study, we analyzed these viral factors in medical importance. relation to the efficacy to IFN-b, another type I IFN. The Interferon alfa (IFN-a) a type I IFN, has been used to treat pretreatment sera of 40 patients treated with IFN-b inchronic hepatitis C throughout the world since the first report travenously at 6 MU daily for 42 days were studied. HCV of its beneficial effects in 1986. 2 IFN-b is also a type I IFN genotypes, serum HCV-RNA levels, and the amino acid that is commonly used in the treatment of acute and chronic sequence of NS5A2209-2248 in HCV-1b were determined. hepatitis C in Japan. 3-5 It has been believed that type I IFNs A sustained complete response to IFN therapy occurred bind to the same receptor; however, recent evidence suggests in none of the ten patients with the wild-type HCV-1b the existence of a second receptor-associated protein that is who had an NS5A2209-2248 sequence identical to the involved specifically in the IFN-b signaling pathway. 6 Inprototype HCV-1b and in none of the six patients with deed, in vitro experiments have shown that different type I the intermediate-type HCV-1b that had 1 mutation. In IFNs induce different biological responses. 7,8 Thus, IFN-a contrast, complete responses occurred in the following: and IFN-b may exhibit different characteristics in the treat-4 of 6 patients with the mutant-type HCV-1b that had ment of chronic hepatitis C. five to ten mutations; 6 of 13 patients with genotype 2a
The majority of clinical trials in hepatitis C have employed of HCV (HCV-2a); and 2 of 5 patients with genotype 2b recombinant or natural IFN-a and have shown that HCV of HCV (HCV-2b). Among patients with the mutant-type genotypes and serum HCV-RNA levels correlate with long-HCV-1b or genotype 2 of HCV (HCV-2) the rate of comterm beneficial responses to IFN-a. Thus, genotype 1b of HCV plete response was significantly higher (12 of 24 vs. 0 of (HCV-1b) has been found to be more resistant to IFN-a than 16 patients, P õ .001) and HCV-RNA levels were signifiwas genotype 2 of HCV (HCV-2), and patients with high cantly lower (4.