Evidence for hepatitis B and other virus infection in HBsAg-negative chronic active hepatitis.

Antibody to the hepatitis B core antigen (anti-HBc) was detected in sera from 6 (19%) of 32 patients with HBsAg-negative chronic active hepatitis. In three cases with the highest anti-HBc titers, core antigen was detected in liver cell nuclei and in one case HBsAg was also present in hepatocytes, suggesting continuing hepatitis B virus infection. During follow-up, anti-HBc titers fell slowly in those with no viral antigens in liver tissue, and in two cases with virus in the liver at presentation, viral antigens were no longer demonstrable four and eight years later. In one case, clearance of virus was preceded by the appearance of HBsAg in liver and serum, suggesting reactivation of viral replication. In three of the anti-HBc-negative cases a nuclear antigen unrelated to the hepatitis B virus was detected by immunofluorescence, and it is possible that liver disease in these patients may be related to persistent non-A, non-B virus infection.