Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection.

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Histological inflammatory activity was strongly related to liver HBcAg expression regardless of HDV superinfection, as confirmed by multivariate analysis. Our results confirm previous studies about the concordance between intrahepatic HBV-DNA replicative pattern and liver HBcAg expression and about inhibition by HDV of high-level HBV replication. However, they suggest that low-level HBV replication may have an important role in causing liver damage also among HDV-infected patients, in a population where the spreading of HBV and HDV is a naturally occurring event.