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

Abstract

The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying 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 showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml⁻¹, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl ≥ 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg⁻ patients with HBV DNA > 10⁷, > 2 × 10⁵ and < 10⁴ copies ml⁻¹, respectively. In severe HBeAg⁻ hepatitis, patients with precore wild‐type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg‐positive (HBeAg⁺) patients, no correlation between HBV DNA level and liver damage was seen. Ninety‐six per cent of HBeAg⁻ patients with ALTi < 0.5 had HAIinfl ≤ 3. In HBeAg⁻ carriers with ALTi 0.5–1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 10⁵ copies ml⁻¹vs < 2 × 10⁵ copies ml⁻¹, was 14.7. In conclusion, in HBeAg⁻ carriers, HBV DNA < 10⁴ copies ml⁻¹ or ALTi < 0.5 indicates mild inflammation, while > 2 × 10⁵ copies ml⁻¹ of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia.