CHANGES IN SERUM HEPATITIS-C VIRUS-RNA TITER AND RESPONSE TO INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS-C

Response to interferon (IFN) therapy for chronic hepatitis C has been determined by the alteration of serum alanine aminotransferase (ALT) v alues. However, eradication of hepatitis C virus (HCV) could be anothe r aim of the therapy. Thus, we serially measured serum HCV RNA levels during therapy and for at least 12 months after cessation of therapy i n 65 patients with chronic hepatitis C who received IFN-alpha (49 case s) or -beta (16 cases). The presence of HCV and its amount were measur ed by the combination of nested and competitive PCR. Twenty-seven pati ents, who were categorized as complete responders, showed sustained no rmalization of ALT values for more than six months posttreatment. The viral RNA titers at pretreatment were significantly lower in complete responders (logarithmic copy numbers/ml: 5.4 +/- 1.3, P < 0.001) than in partial and nonresponders. Complete response rate was significantly higher in patients with HCV genotype III (68.4%, P < 0.01) than those with type II (23.6%). Among 27 complete responders, HCV RNA became un detectable in only 13 patients six months after completion of therapy, and 11 still had low levels of viremia; however, none experienced rel apse of the disease during follow-up of 12-24 months. Three complete r esponders showed lasting high-titered viremia, and their ALT values ro se again during follow-up. Our data suggest that IFN treatment of chro nic hepatitis C is often ineffective in eradicating HCV infection even in responders, and long-term follow-up study is necessary to determin e the sustained beneficial effect of IFN.