EFFICACY OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C ： A COOPERATIVE STUDY IN ELEVEN HOSPITALS

Abstract

We investigated the influences of liver histology，serum levels of hepatitis C virus (HCV) and HCV genotypes on responsiveness to interferon (IFN) therapy in 342 patients with chronic hepatitis C. Either 9 million units (MU) of lymphoblastoid alpha IFN or 3 MU of recombinant IFN-alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three groups on the basis of the results of polymerase chain reaction (PCR) assay detecting HCV-RNA in serum. Complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment，partial response (PR) as HCV elimination for a limited period，non-response (NR) as continuously positive for HCV-RNA in serum. Quantitation of pre-treament HCV-RNA amount in serum was determined by competitive PCR assay in 47 patients. HCV genotyping was performed in 114 patients by PCR with genotype-specific primers. CR was obtained in 97 patients (28.4%)，PR in 104 (30.4%) and NR in 141 (41.2%). IFN responses，represented by CR/PR/NR，were 15/18/11 in 44 patients with chronic persistent hepatitis (CPH)，72/65/73 in 210 patients with chronic aggressive hepatitis (CAH) 2a，and 10/21/57 in 88 patients with CAH2b. CR rate was lower in patients with CAH2b (11.4%) compared to those with CPH (34.1%) or CAH2a (34.3%). Averages of pre-treatment serum HCV-RNA amount (copies/50μl) were 10³·⁵⁵ in 13 CRs，10⁴·⁵⁶ in 17 PRs，and 10⁵·⁹⁵ in 17 NRs. There was a positive correlation between pre-treatment HCV-RNA levels and IFN unresponsiveness. HCV genotyping in 114 patients revealed that HCV type Ⅰ infection was observed in one，type Ⅱ in 94，type Ⅲ in 11，type Ⅳ in 6 and mixed (types Ⅱ and Ⅳ) in 2 patients，and their IFN responses (CR/PR/NR) were 0/0/1，28/26/40，3/5/3，1/3/2 and 0/1/1，respectively.