Profile of pre-S deletions in the natural history of chronic hepatitis B infection.

It have been suggested that hepatitis B virus (HBV) pre-S deletions may play a role in hepatocarcinogenesis. The aim of the study was to determine the prevalence of pre-S deletions in chronic hepatitis B patients in Hong Kong, the factors associated with the deletions and its relationship with hepatitis B e antigen (HBeAg) seroconversion. HBV pre-S deletions were determined by nucleotide sequence analysis in 178 patients with chronic HBV (cross-sectional study). Eighty-four patients had paired samples before and after HBeAg seroconversion (longitudinal study). The prevalence of pre-S deletions was 12.9% (23/178). A majority of the pre-S deletions (73.9%) occurred in the 5' terminus of pre-S2 region whereas deletions in the pre-S1 region appeared less frequently (47.8%). There was no relationship between age and pre-S deletions. Male gender [odds ratio (OR) =10.88; 95% confidence interval (CI) =1.37-86.52; P=0.024] and HBV genotype C (OR=13.85; 95% CI=3.05-62.92; P=0.001) were independent factors associated with pre-S deletions. Only 17 out of the 84 patients with paired samples before and after HBeAg seroconversion had pre-S deletions. The patterns of pre-S deletions before and after HBeAg seroconversion were variable. Compared with genotype B, HBV genotype C was associated with earlier emergence of pre-S deletions. In conclusion, 12.9% of chronic HBV carriers had pre-S deletions (predominantly pre-S2 deletions) in a geographical area highly endemic for chronic hepatitis B. Male gender and HBV genotype C were associated independently with the development of pre-S deletion mutations. There was no clear relationship between HBeAg seroconversion and pre-S deletions.