M. J. F. Fowler

Detection of serum HBV-DNA by molecular hybridisation: Correlation with HBeAg/Anti-HBe status, racial origin, liver histology and hepatocellular carcinoma

The relationship of the presence of hepatitis B virus (HBV) DNA in serum, a measure of HBV-replication, to HBeAg/anti-HBe status has been examined. In Northern Europe, there is a strong positive correlation between the presence of HBV-DNA and HBe antigenaemia and a negative correlation with the presence of anti-HBe. These associations are less marked in patients from Southern Europe, Africa, the Middle and Far East. When HBV-DNA is present in the serum of anti-HBe carriers, it is usually associated with the presence of severe liver disease or carcinoma. Forty percent of patients with hepatocellular carcinoma had evidence of continuing HBV replication.

Studies of HBV replication during acute hepatitis followed by recovery (and acute hepatitis progressing to chronic disease

The serologic and viral profiles of 24 patients who presented with acute hepatitis B virus (HBV) infection were studied. Although in rare cases, HBV-DNA was detectable before hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), in the majority the viral proteins appeared first. In acute hepatitis followed by recovery, as IgM anti-HBc (hepatitis B core antigen) titres rose, the level of HBV replication fell and serum transaminases became elevated. In patients progressing to chronic HBV infection, IgM anti-HBc titres rose early, viral replication was initially low but continued to rise as the serum transaminase levels became elevated. 7S IgM anti-HBc, although present in the phase of established chronic HBV infection, was not found in the early phase of the chronic infection. Thus this antibody appears to be a consequence of, rather than a causative factor in, chronic HBV infection.

Cloning and analysis of integrated hepatitis B virus DNA of the adr subtype derived from a human primary liver cell carcinoma

A 10 kb genomic DNA fragment derived from a human primary liver cell carcinoma (PLC) and containing integrated hepatitis B virus (HBV) DNA was cloned and analysed. Physical mapping showed the viral DNA to comprise a linear sequence of at least 2.8 kb (87%) of the HBV genome and to be of the adr subtype. Integration appeared to have occurred in the region of the viral genome spanning the cohesive ends. The cellular flanking DNA sequences to one side of the integrated viral DNA contained repeats of the Alu family. The finding of no apparent rearrangements of the integrated HBV DNA sequences in this clone is in contrast to the situation in the huSP and PLC/PRF/5 PLC cell lines in which the integrated viral DNA sequences are greatly rearranged and suggests that such rearrangements may be atypical of solid PLCs.

Defective Hepatitis B Virus DNA Molecules Detected in a Stable Integration Pattern in a Hepatoma Cell Line, and in Induced Tumours and Derived Cell Lines

Hepatitis B virus (HBV) DNA was found to be integrated into seven sites in the DNA of the PLC/PRF/5 hepatoma cell line as determined by digestion with the restriction endonuclease HindIII which does not cut through the viral genome. The integration pattern was stable in the cell line, in tumours induced in athymic mice by this line and in cell lines derived from such tumours. Syntheses of hepatitis B surface antigen and alphafoetoprotein were maintained in the induced tumours and derived cell lines. A defective HBV DNA molecule (approx. 2.8 kilobase pairs) appears to be integrated in a head-to-tail tandem arrangement and it is proposed that such defective molecules may be involved in the process of neoplastic transformation by HBV.