Molecular analysis of the hepatitis B virus presurface and surface gene in patients from eastern China with occult hepatitis B

Abstract

This study was designed to detect and analyze mutations that occur within the presurface and surface (pre-S/S) gene of HBV in patients with occult hepatitis B, and determine their relationship to that disorder. Among 254 HBsAg negative samples of blood collected in eastern China, 183 were positive for anti-HBc alone, 61 were positive for anti-HBe alone, and 10 samples were positive for HBeAg. Within this group, 15 samples were found to be HBV DNA positive by real-time PCR and were designated Group I. A control group of 28 HBsAg positive samples were chosen at random from patients with chronic hepatitis B and designated Group II. The HBV pre-S/S gene was amplified by PCR and subjected to sequencing analysis. Occult hepatitis B was found in 1.6% of the patients with anti-HBc alone and in 3.3% of those with anti-HBe alone. Occult hepatitis B also was found in all HBsAg negative but HBeAg positive samples. Sequencing analysis showed a significant correlation between point mutations within the "a" determinant and occult hepatitis B (P < 0.0001), and a close relationship between pre-S deletion mutations and occult hepatitis B (P = 0.06). There were unique amino acid mutations at the G145 position other than G145R. The HBV DNA levels in patients with occult hepatitis B were significantly lower than those found in the control group. The "a" determinant mutations and pre-S deletions may play important roles in occult hepatitis B by affecting the expression, synthesis and secretion of the S protein and by impeding viral release and replication.

A description of the hepatitis B virus genomic background in a high-prevalence area in China

“…According to a similar study of HBV genetic diversity in American blood donors, the prevalence of the well-known neutralization escape mutation G145R in the HBV envelope protein was as high as 22% [15]. However, in contrast to those results, in our study, the G145R mutation was heavily underrepresented (2.07%), from which it can be inferred that the genotype B, C and D strains in Northwest China may have less likelihood of vaccine escape [20]. Furthermore, compared to the G145R mutation, several mutations within the major hydrophilic region were detected at high prevalence, such as M134Y and S143T/L.…”

Clinical implications of hepatitis B virus mutations: Recent advances

“…Since the reported mutations were completely different from those reported to be associated with OBI in genotypes B and C [52] , it was suggested by the authors that OBI associated mutations are unique for each HBV genotype. Indeed, several studies comprising genotypes B and C identified G145R/A to be among major mutations responsible for OBI [51][52][53] .…”

“…Many recent studies are addressing the possible association of BCP and Pre-C mutations with more severe outcome of liver disease, namely with appearance of ful-the S protein [53,55] .…”

Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review

“…Some OHB infections in patients with HCC are associated with HBV variants, including preS2‐defective and/or core promoter mutants or X‐mutated strains, which may have pro‐oncogenic activities . HBV preS/S mutations could be one of the reasons why HBsAg is unmeasurable in the HBV‐infected subjects . Chen et al .…”

“…Some OHB infections in patients with HCC are associated with HBV variants, including preS2-defective and/or core promoter mutants or X-mutated strains, which may have pro-oncogenic activities [39]. HBV preS/S mutations could be one of the reasons why HBsAg is unmeasurable in the HBV-infected subjects [79][80][81]. Chen et al [50] suggested that different virological features of HBV are found in HCC patients with OHB when compared with overt HBV in chronic hepatitis B patients with HCC.…”