Host genetic factors in predicting response status in chronic hepatitis B patients discontinuing nucleos(t)ide analogs

Background/Aims: The optimal duration of nucleos(t) ide analogs (NAs) therapy in chronic hepatitis B (CHB) patients remains unsatisfactory. Previous studies have confirmed the important role of host genetic factors in determining the outcome of HBV infection. This study tries to determine the role of host genetic factors in predicting response status in CHB patients discontinuing NAs according to stringent cessation criteria. Patients and Methods: Participating patients came from a prospective NAs-discontinuation cohort since June 1999. Six single-nucleotide polymorphisms (SNPs) were selected according to previous report. SNaPshot assay was used for DNA SNPs analyses. Results: Seventy-six CHB patients were enrolled in our study, of which 61 patients were HBeAg-positive and 15 patients were HBeAg-negative. rs1883832 in the Kozak sequence of CD40 displayed an AUROC of 0.778 in predicting response status in CHB patients with HBeAg seroconversion and a genotype of CT was associated with sustained response in this subpopulation. The diagnostic performance of combinative index (rs1883832, age, and HBsAg at discontinuation) seemed to be better than that of rs1883832, but no statistical difference was observed. rs1883832 was also evaluated as an independent factor for response status by multivariate logistic regression. For HBeAg-negative CHB patients, rs9277535 at HLA-DP presents a Spearman correlation coefficient of 0.582 (P = 0.023) with virological relapse after discontinuation of NAs. Conclusions: rs1883832 serves as a valuable predictive factor for CHB patients with HBeAg seroconversion. rs9277535 at HLA-DP might also be a valuable predictive factor for CHB patients with HBeAg-negative, however, further verifications are recommended due to study limitations.