Source 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy. pietro.lampertico@unimi.it.

BACKGROUND.: Interleukin(IL)28B polymorphisms have been associated to interferon(IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult to cure HBeAg-negative chronic hepatitis B, is unknown.

METHODS.: 101 HBeAg-negative patients (92% genotype D) with compensated chronic hepatitis B (84% males, 46 years, HBV DNA 6.0 log cp/ml, ALT 136 IU/L, 42% with cirrhosis) were followed for a median of 11 (1-17) years after median 23 (10-48) months of either standard or pegylated (Peg)IFN alfa therapy. A post-treatment response was defined as HBsAg clearance with or without anti HBs seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays.

RESULTS.: During a median of 11 years of post-treatment follow-up, 21 (21%) patients cleared serum HBsAg, including 15 who developed >10 IU/ml anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) CT and 11 (11%) TT, the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC genotype carriers (p=0.039). Baseline HBV DNA levels <6 log cp/ml (OR 11.9, CI 2.8-50.6, p=0.001), ALT levels >136 IU/ml (OR 6.5, CI 1.8-22.5, p=0.003), duration of IFN (OR 1.16, CI 1.02-1.31, p=0.021) and genotype CC (OR 3.9, CI 1.1-13.2, p=0.025) independently predicted HBsAg clearance.

CONCLUSIONS.: IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of hepatitis B virus.