Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis B

The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studyin g whether 'healthy carriers' can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen-negative (HBeAg -) patients, the majority with mild liver disease, log HBV DNA levels showe d a Gaussian distribution around a geometric mean of 33 000 genome copies m l(-1), and increasing HBV DNA level was associated with significantly highe r inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT / the upper reference value). Severe inflammation (HAIinfl greater than or equal to 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one o f 37) of HBeAg- patients with HBV DNA > 10(7), > 2 x 10(5) and < 10(4) copi es ml(-1), respectively. In severe HBeAg- hepatitis, patients with precore wild-type infection had lower HBV DNA levels than those with precore mutant s. In 36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA l evel and liver damage was seen. Ninety-six per cent of HBeAg- patients with ALTi < 0.5 had HAIinfl less than or equal to 3. In HBeAg- carriers with AL Ti 0.5-1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 x 10(5) copies ml(-1) vs < 2 x 10(5) copies ml(-1), was 14.7. In conclusi on, in HBeAg- carriers, HBV DNA < 10(4) copies ml(-1) or ALTi < 0.5 indicat es mild inflammation, while > 2 x 10(5) copies ml(-1) of HBV DNA may justif y further investigations. Precore status may be relevant for the interpreta tion of viraemia.