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. J. Med. Virol. 82:1843–1849, 2010. © 2010 Wiley‐Liss, Inc.