Analysis of genetic and viral determinants of HBsAg levels in patients with chronic HBV infection

Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene can influence the course of treated and untreated HBV infection. However, the correlation between different IL28B-SNPs and HBVDNA and quantitative HBsAg (qHBsAg) in chronic HBV infection remains to be fully elucidated. Patients with chronic HBV infection were analysed for qHBsAg, HBVDNA, HBV genotype and six IL28B-SNPs (rs12980275, rs8105790, rs8099917, rs7248668, rs12979860, rs10853728). Seventy patients were recruited: 80% Caucasian, 56% genotype D, 44% treated with nucleos(t)ide analogues, 11% cirrhotic, 37% inactive carriers (IC). Median (IQR) qHBsAg and HBVDNA were 3.2 log10 IU/ml (2.2-3.9) and 2.2 log10 IU/ml (0.3-3.3), respectively. Lower levels of qHBsAg were associated in the whole study population with rs12979860 CC vs. CT (p=0.05), rs12980275 AA vs. AG (p=0.04), rs8105790 TT vs. CT (p=0.05) and genotype D vs. A+E (p=0.01). rs8105790 TT was present in 81% of IC vs. 46% non-IC (p=0.005). These data were also confirmed in the untreated patients' subgroup. In multivariate analysis, IL28B-SNP haplogroups were associated with lower qHBsAg: CC/AA at rs12979860/rs12980275 (-0.70 log IU/mL, 95% CI -1.26;-0.14; p=0.01), CC/TT at rs12979860/rs8105790 (-0.78 log IU/mL, 95% CI -1.33;-0.23; p=0.006) and AA/TT at rs12980275/rs8105790 (-0.71 log IU/mL, 95% CI -1.27;-0.17; p=0.01) both in the whole population and in the untreated subgroup. Specific IL28-SNP haplogroups might be associated with lower qHBsAg.