Hepatitis C virus-related liver damage is related to cold activation of complement.

A high positivity of cold activation of complement has been reported in Japanese patients having hepatitis B virus-negative chronic hepatitis. Although the cause of cold activation of complement is unknown, the involvement of hepatitis C virus (HCV) has been suspected. We studied the positivity of cold activation of complement in 253 patients, including 93 patients with chronic hepatitis C infection who received 6MU natural interferon-alpha per day for 24 continuous weeks. Cold activation was positive in 38% of patients with chronic hepatitis C and in 46% of patients with liver cirrhosis C. We did not detect cold activation in asymptomatic HCV carriers; patients with chronic hepatitis B, liver cirrhosis B, or alcohol-related liver damage; or in the controls. Cold activation was also negative in HCV-RNA-negative patients who responded completely to interferon-alpha, and in HCV-RNA-positive patients who responded partially whose serum alanine transaminase levels were normalized after interferon treatment. In the patients who had a relapse of hepatitis C after interferon treatment, positivity of cold activation increased sharply. We conclude that HCV-associated liver damage is related to the development of cold activation of complement. Cold activation is useful for monitoring the response to interferon in patients with chronic hepatitis C infection.

Usefulness of HCV-RNA assays in efficacy evaluation of interferon treatment for chronic hepatitis C: Amplicor HCV assay and branched DNA probe assay.

We investigated the usefulness of Amplicor HCV assay and branched DNA probe assay in efficacy evaluation of interferon therapies for chronic hepatitis C. Subjects were 164 HCV-RNA positive chronic hepatitis C patients who received interferon-alpha (IFN-alpha, HLBI) 3-6 MU per day for 14-24 weeks. Their HCV-RNA levels were examined five times by using reverse transcription-polymerase chain reaction (RT-PCR) assay, Amplicor HCV assay, and branched DNA probe assay. Complete response rate in the low virus level patients was significantly higher than in the high virus level patients (P < 0.001). In complete responders, the rate of HCV-RNA disappearance 2 weeks after the initiation of IFN therapy was higher than in non-responders (P < 0.001). The HCV-RNA positive rates in RT-PCR assay and Amplicor HCV assay agreed by 98% or more. The HCV-RNA negative patients 6 months later were still negative 12 months later by Amplicor HCV assay. Before starting interferon therapy for chronic hepatitis C, it is advisable to make a prediction of treatment efficacy by using branched DNA probe assay. In addition, disappearance of HCV-RNA after 2 weeks of treatment could be a useful predictor of the therapeutic efficacy of IFN. Amplicor HCV assay is useful in detecting HCV-RNA and for efficacy evaluation during and after a given interferon therapy.