Relationship between HBcAg in serum and liver and HBV replication in patients with HBsAg‐positive chronic liver disease

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Abstract
The expression of hepatitis B core antigen (HBcAg) in serum and in hepatocytes was evaluated in relation to HBV replication. Fifty chronic HBsAg carriers with histological evidence of liver disease were studied, including 24 HBeAg‐positive patients, 2 HBeAg/anti‐HBe‐negative patients, and 24 anti‐HBe‐positive cases, two of them with evidence of delta agent infection. Serum HBV‐DNA was evaluated in all patients and related to HBcAg examined at the same time in frozen liver biopsies by immunofluorescence and to HBcAg detected in the corresponding serum by a recently developed radioimmunoassay.HBV‐DNA was present in serum in 20 (83%) HBeAg‐positive patients, all positive for serum HBcAg, whereas liver core antigen was detected in 14 (73%) of 19 cases. Among HBeAg‐negative patients, 50% showed the presence of circulating DNA viral sequences, and HBcAg was identified in five of 26 (19%) cases in serum and in six of 24 (25%) in the liver respectively. In 15 patients, liver fragments permitted examination in parallel by immunofluorescence for HBcAg and molecular hybridization for viral DNA in liver cells. A DNA pattern characteristic of viral replication was found in cases with evidence of active virion production, independently from HBeAg and anti‐HBe, and in these patients HBcAg was present both in serum and in hepatocytes. In two cases with free HBV‐DNA, without evidence of replicative activity, core antigen was not detected in the liver, but in one patient HBcAg was found in the serum. A similar finding was also noted in another patient, in whom the hybridization pattern was consistent with integration of viral genome into high‐molecular‐weight cellular DNA. Whether serum HBcAg detected in these patients without HBV‐DNA in serum reflects the presence of defective viral particles or of core antigen released as a viral protein remains to be determined.