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Background: Single-nucleotide polymorphisms (SNP) of two-gene locus cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 and CD86 +1057 were previously reported to influence the outcome of liver transplantation (LT) with respect to allograft acceptance. SNP at CTLA-4 +49 was also suggested to be associated with the individual difference in the clearance of hepatitis B virus (HBV). However, their influence on the incidence of post-LT HBV reinfection was not clear. With the increasing knowledge of costimulatory mechanisms on LT and host immune response, we designed this study to investigate the relationship between different alleles as well as genotypes at these two locations and HBV reinfection after LT. Methods: Genomic DNA from 167 LT recipients with HBV-related diseases was genotyped for CTLA-4 +49 and CD86 +1057 genomic polymorphisms using a sequence-specific primer-polymerase chain reaction (PCR-SSP). HBV recurrence was diagnosed based on the serological and pathological finding of HBV DNA and HBsAg. Results: The present study indicated that the recipients with CTLA-4 +49 GG genotype had a reduced risk (6.67%) of HBV recurrence compared with non-CTLA-4 +49 GG-carrying individuals (20.7%) (relative risk 3.098) ( P=0.032). The allelic frequency of CTLA-4 +49 G was also significantly lower in patients with HBV recurrence, compared with that in patients without HBV recurrence ( P=0.013, odds ratio 2.176, 95% confidence interval 1.170–4.046). However, no significant association was found between CD86 +1057 and HBV recurrence. Conclusion: Our result on CTLA-4 +49 A/G polymorphism indicated that the CTLA-4 +49 GG genotype was related to a reduced risk in the incidence of HBV recurrence. [ABSTRACT FROM AUTHOR]