T1762/A1764 variants of the basal core promoter of hepatitis B virus;: serological and clinical correlations in Chinese patients

Background: A double variant in the basal core promoter, converting nucleotide 1762 from A to T (T-1762) and nucleotide 1764 from G to A (A(1764)), has been described in patients with chronic hepatitis B infection. Its prevalence and significance in Chinese chronic HBV carriers are unknown. Methods: We studied 177 Chinese patients with chronic HBV infection (chronic hepatitis/asymptomatic: 89/88; hepatitis B e antigen positive/negative: 84/93). The double variant was detected by mismatched polymerase chain reaction and restriction fragment length polymorphism analysis. The reliability of this method was verified by sequencing in 41 serum samples with 100% matching. Results: The double variant T-1762/A(1764) was found in 52 of 89 patients with chronic hepatitis, but in only 6 of 59 asymptomatic carriers (p<0.001). The prevalence was significantly lower in hepatitis B e antigen positive patients (23/84) than in hepatitis B e antigen negative patients (35/64) (p<0.005). Precore variant, A(1896) was detected in 40 individuals; 31 of them suffered from chronic hepatitis and 9 were asymptomatic (p<0.001). A combination of both variants T-1762/A(1764) and A(1896) was seen in 3 of 59 asymptomatic and 22 of 89 patients with chronic hepatitis (p<0.005). Conclusions: Mismatched polymerase chain reaction with restriction fragment length polymorphism provides a reliable, easy and fast method for detection of the presence of the T-1762/A(1764) variant. In Chinese chronic hepatitis B carriers, T-1762/A(1764) variant was associated with both active liver disease and hepatitis B e antigen negativity.