Relationship between TNF-<alpha> Gene Promoter Polymorphisms and Outcomes of Hepatitis B Virus Infections: A Meta-Analysis

BACKGROUND The clearance of hepatitis B virus (HBV) is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis factor (TNF-) gene promoter. However, previous reports regarding the relationship between polymorphisms in the TNF- promoter and HBV clearance have been inconsistent. Therefore, we performed a meta-analysis on a large population to address this inconsistency. METHODS A meta-analysis was performed to examine the association between TNF- promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A and-238G/A) and chronic hepatitis B infection. Odds ratio (OR) and its 95 % confidence interval (CI) were used. RESULTS Twelve studies were chosen in our meta-analysis, involving 2,754 chronic HBV infection cases and 1,630 HBV clearance cases. The data showed that TNF--863 CC genotype was significantly associated with HBV clearance (-863 CC vs. AA: OR, 0.64; 95% CI, [0.42, 0.97]; p = 0.04) while patients carrying -308 GG genotype had a significantly increased risk of HBV persistence compared with those with GA or AA genotype (GG vs. GA+AA: OR, 1.35; 95% CI, [1.08, 1.70]; p = 0.01). For the other polymorphisms, no association with HBV infection outcome was found. CONCLUSIONS The data showed that polymorphisms -863 A and -308 G in the TNF- gene promoter region might be risk factors for HBV persistence. Furthermore, ethnicity might play an important role in HBV infection outcome, leading to conflicting results. More studies on individuals from various ethnic groups will be necessary to determine the role of TNF- promoter polymorphisms in the outcome of HBV infection.