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.

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