Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

Xu, Zhihui; Ren, Xiaoqiang; Liu, Yan; Li, Xiaodong; Bai, Siyu; Zhong, Yanwei; Wang, Lin; Mao, Panyong; Wang, Huifen; Xin, Shaojie; Wong, Vincent Wai-Sun; Chan, Henry Lik-Yuen; Zoulim, Fabien; Xu, Dongping

OBJECTIVE: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. PATIENTS AND METHODS: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. CONCLUSIONS: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.