IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy

Background Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. Results Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. Conclusion Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Doubtful Role of IL28B Polymorphism in Occult Hepatitis B Infection

Aims: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. Patients and Methods: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. Results: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. Conclusions: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection.