The relationship between hepatitis B virus S gene mutations and hepatitis B virus-related acute on chronic liver failure

Objective To investigate and analyze the relationship between hepatitis B virus (HBV) S gene mutations and the occurrence of HBV-related acute on chronic liver failure (HBV-ACLF). Methods A total of 377 patients were enrolled in this study, including 51 inactive hepatitis B surface antigen (HBsAg) carriers, 78 chronic hepatitis B (CHB) patients, 101 HBV-ACLF patients, 69 HBV-related liver cirrhosis (LC) patients and 78 HBV-related hepatocellular carcinoma (HCC) patients. Serum samples were collected from July 2012 to September 2017 in Guangzhou Eighth People′s Hospital. Nested polyoneras chain reaction (PCR) was performed for all the samples, the HBV whole genome and HBV S gene were amplified. PCR products were sequenced by Sanger sequencing method. HBV genotypes were determined by the phylogenetic tree based on HBV S gene constructed by Mega 7.0 software with the neighbor-joining method. Geneious R10.0.5 software was used to analyze the mutations of the HBV genome. The data in different groups were compared by χ2 test or Fisher′s exact test. The correlation analysis was done by logistic regression. Results Among the 377 patients enrolled in this study, the HBV-ACLF, CHB, inactive HBsAg carriers, and HCC patients infected with HBV genotype B were 83, 51, 34, 31, and 35 cases respectively, and the patients infected with HBV genotype C were 18, 27, 17, 38, and 43 cases respectively. The results of this study showed that 11 mutations were significantly higher in HBV-ACLF patients than CHB patients who were infected with HBV genotype B, including T216C, G285A and A529G in HBV S gene, A1317G in HBV enchanter I, A1762T/G1764A in basal core promoter (BCP) gene, A1846T, C1913A, G1896A, T2045A, C2078G, C2304A in HBV preC/C gene. However, no significant difference mutations were found in HBV-ACLF patients and CHB patients who were infected with HBV genotype C. In the patients infected with HBV genotype B, the prevalence of T216C (sL21S) mutation in HBV-ACLF was significantly higher than those in inactive HBsAg carriers, CHB and HCC patients (χ2=14.474, 10.982, and 5.440, respectively, all P 0.05). Logistic regression analysis showed that male (OR=6.90, 95% CI: 1.52-24.39, P=0.010), hepatitis B e antigen negative (OR=4.73, 95% CI: 1.60-13.94, P=0.005), HBV genotype B (OR=4.80, 95% CI: 1.82-12.16, P=0.006) and G285A mutation (OR=7.72, 95% CI: 5.64-16.37, P=0.006) were the independent risk factors associated with HBV-ACLF. Conclusions The HBV S gene mutation may be associated with HBV-ACLF. Key words: Hepatitis B virus; Mutation; Acute on chronic liver failure