Epidemiology of precore mutants of hepatitis B in the United Kingdom

A point mutation assay was used to study the codon 28 and codon 1 precore m utant status of 310 chronic hepatitis B carriers (82 HBeAg positive and 228 HBeAg negative). Fourteen of 228 (6%) of HBeAg negative carriers had high levels of serum HBV DNA. Nine of these were explained by precore variants, three by core promoter variants, and two were not explained by recognised p recore changes. Nested PCR detected serum HBV DNA in 36% (82/228) of HBeAg negative carriers and 63% (52/82) of these had precore variants. Four of 82 (4%) of the HBeAg positive carriers had precore variants, all as mixed mut ant/wild type populations and evidence indicated that these carriers were s eroconverting. Overall 23% (52/228) of HBeAg negative carriers had both ser um HBV DNA and codon 1 or 28 precore mutations. A sexual transmission event from an HBeAg negative carrier with a relatively low serum HBV DNA level ( 10(4)-10(6) genome copies/ml) and only core promoter mutations was observed . Despite high rates of variant carriage in the antenatal sub-group perinat al transmission was not observed. The results of direct sequencing on 45 ca rriers validated the,point mutation assay and also showed that codon 28 mut ations were only seen in carriers with the genotype CCT at codon 15. For th e Caucasian population a higher prevalence of codon 28 mutations (13/25 or 52%) than expected was seen. Liver biopsy data indicated that there was no link between the presence or absence of precore mutants and the severity of liver disease. J. Med. Virol. 62:463-470, 2000. (C) 2000 Wiley-Liss, Inc.