Associations between hepatitis B virus basal core promoter/pre-core region mutations and the risk of acute-on-chronic liver failure: a meta-analysis

Background: Several studies have suggested a relationship between hepatitis B virus (HBV) basal core promoter/pre-core mutations and HBV-induced acute-on-chronic liver failure (ACLF). Therefore, we evaluated this potential relationship using a meta-analysis. Methods: Chinese or English studies from 1966 to January 31, 2014 were included in the analysis. A random or fixed-effects model was used to merge the odds ratios (ORs). Results: We identified 31 case-control studies containing a total population of 1995 ACLF and 3822 chronic hepatitis B (CHB) patients. Several mutations were significantly correlated with ACLF: T1753V (1.889, 95 % confidence interval (CI) [1.357-2.631]), A1762T (2.696 [2.265-3.207]), G1764A (3.005 [2.077-4.347]), A1762T/G1764A (2.379 [1.519-3.727]), C1766T (1.849 [1.403-2.437]), T1768A (2.440 [1.405-3.494]), A1846T (3.163 [2.157-4.639]), G1896A (2.181 [1.800-2.642]), G1899A (3.569 [2.906-4.385]) and G1896A/A1762T/G1764A (1.575 [1.172-2.116]). Additionally, HBeAg-negative status was also statistically significant for the progression to ACLF (OR = 2.813, 95 % CI = 2.240-3.533, p < 0.001). However, there was no association between ACLF development and HBV genotype. Conclusions: The HBV basal core promoter/pre-core mutations T1753V, A1762T, G1764A, C1766T, T1768A, A1846T, G1896A and G1899A, and an HBeAg-negative status correlate with an increased risk of HBV-ACLF.