Association of hepatitis B virus basal core promoter T1762/A1764 and precore A1896 mutations with serum hepatitis B virus DNA load, hepatitis B e antigen status, serum α-fetoprotein and hepatitis B virus-related liver disease progression

The frequency of the basal core promoter (BCP) T1762/A1764 and precore (PC) A1896 mutations of Hepatitis B virus (HBV) and their association with clinical parameters in patients with chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma (HCC) were assessed. Serum samples from 237 hepatitis B surface antigen-positive patients were collected. BCP T1762/A1764 and PC A1896 mutation were assessed by sequencing the precore region and the mismatch amplification mutation assay (MAMA-PCR). Serum HBV DNA was quantified by qPCR and hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), alpha -fetoprotein (AFP) and clinical data were obtained from the hospital database. The BCP T1762/A1764 mutation was associated with HBV-related liver disease progression, reduced HBV replication, increased HBeAg seroconversion and seroclearance, and correlated positively with higher serum AFP (correlation coefficient 0.136, P<0.01) and HCC development (correlation coefficient 0.346, P<0.001). The PC A1896 mutation was not associated with HCC development (correlation coefficient 0.068, P>0.05), but was associated with HBeAg seroconversion (correlation coefficient 0.212, P<0.01) and higher serum AFP (correlation coefficient 0.109, P<0.05). This study suggested that the BCP T1762/A1764 mutant of HBV is closely associated with the development HBV-related cirrhosis and HCC, as it may prevent HBV replication, abolish HBeAg secretion and increase serum AFP. The PC A1896 mutation of HBV may play an important role in HBeAg seroconversion and was associated with higher serum AFP, but was not related to the development of HCC.