Impact of IFNL-3 (IL-28B) polymorphism on the kinetics of HBV DNA and qHBsAg and HBsAg clearance during therapy with peginterferon α-2a in patients with HBeAg-negative chronic hepatitis B, genotype D

Abstract

Abstract.In recent years baseline predictors of Peg-INF response have been identified, one of the host factors may be include: genetic polymorphism IFNL-3 (IL-28B). The aim of the study. In recent years baseline predictors of Peg-INF response have been identi We investigated the effect of IFNL-3 polymorphism (SNP 12979860, SNP rs8099917) fied, one of the host on HBV DNA kinetics, qHBsAg, SVR rate and HBsAg clearance. as one of the positive prognostic factors of SBB induction. Methods. We investigated the effect of IFNL-3 polymorphism (SNP 12979860, SNP rs8099917) on the kinetics of HBV DNA, qHBsAg, the rate of SVR and HBsAg clearance. 108 patients with HBeAg-negative hepatitis B, genotype D were enrolled into the study. Results. Of 46 patients with CC SNP 12979860, a decline in the concentration of HBsAg>0.5 log10 at 12 weeks of treatment, was noticed in 23 (50.0%) persons in the group of 61 patients, and in 14 (23.0%) with CT alleles (OR=3.36, 95% CI 1.35–8.4, P<0.005). SVR was achieved in 19 (41, 3%) and 12 (19.7%), respectively (OR=3.35, 95% CI 1.12–7.5, P<0.005). Decline in HBV DNA >2 log10 at week 12 was observed in 42 (91.3%), and in 61 patients with CT — in 54 (88.5%) (OR=1.36,CI 0.32–6.75, P=0,0639). At 24 weeks of therapy, the decline in HBV DNA by 2 log10 in the group of patients with CC was detected in 46 (100%) and in those with CT in 61 patients (100%). SVR was achieved in 20 persons (43.5%) and in 11 (18%), respectively (OR=3.5, 95% CI 1.34–9.31, P<0.005). In 1 patient with TT alleles, a 2 log10 decrease in HBV DNA was recorded at 12 and 24 weeks of therapy. In the group of TT SNP rs8099917 alleles carriers (n=63), a decline in HBsAg concentration >0.5 log10 at week 12 was achieved in 27 (42.8%), in the TG group (n=45) — only in 5 (11.1%) (OR=6.0, 95% CI 1.96–21.74, P<0.001). SVR was documented in 24 (38.1%) and 7 (15.6%), respectively (OR=3.34, 95% CI 1.20–10.19, P<0.01). At 12 weeks of therapy in the group with TT alleles, a 2 log10 decline in HBV DNA was observed in 58 individuals (92.0%), in the group with TG — in 40 (88.8%) (OR=1.45, 95% CI 0.31–6.73 P=0.575). At week 24: in TT — 63 patients (100.0%) and in TG — 45 patients (100.0%). SVR was achieved in 23 (36.5%) and 8 (17.7%), respectively (OR=2.66, 95% CI 0.99–7.7, P<0.05). Conclusion. The presented study demonstrates that favorable genetic polymorphism IFNL-3 (SNP 12979860 and SNP rs8099917) is one of the most significant baseline positive predictive factors on SVR induction. Keywords HBeAg-negative chronic hepatitis B, peginterferon, IFNL-3 (IL-28B) polymorphism, sustained virological response, HBsAg.