Discontinuation of nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) remains a global but controversial problem. Clinical outcomes of NA cessation depend on the interplay between viral factors and host immunity. Recent studies have shown that genetic polymorphisms might influence the immune response in chronic HBV infection. A total of 33 single-nucleotide polymorphisms (SNPs) from 16 genes (BCL6, CD40, CD40L, CTLA-4, CXCL13, CXCR5, ICOS, IL-21, HLA-C, NTCP, UBE2L3, STAT4, IFN-λ3, CYP27B1, INST10, and IPS1) were selected and analyzed in 106 CHB patients enrolled in an off-treatment cohort. Significantly unbalanced distributions between patients who experienced clinical relapse and those who did not were found regarding two SNPs, rs676925 in CXCR5 and rs733618 in CTLA-4. Furthermore, the genotype 'GC' of rs676925 were associated with decreased risk of clinical relapse, implicating that rs676925 may serve as a protective factor for HBV control and facilitate a virus-specific immune response. We also compared the expression of CXCR5 in lymphocytes and its ligand CXCL13 in plasma between different genotypes of rs676925. However, no significant differences were observed. In conclusion, this study suggested that the rs676925 'GC' genotype of the CXCR5 gene were associated with decreased risk of clinical relapse after discontinuation of long-term NA therapy in CHB patients.
Keywords: CXCR5; Chronic hepatitis B; Clinical relapse; Single-nucleotide polymorphism; Treatment cessation.
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