title: IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B.
abstract: Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN-alpha therapy. A post-treatment response was defined as hepatitis B surface antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow-up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and 11 (11%) had TT, with 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 (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16; 95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% 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 the pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of HBV.
authors.affiliation: Migliavacca Center for the Study of Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy. pietro.lampertico@unimi.it
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.forename: Mauro
authors.initials: M
authors.lastname: Viganò
authors.forename: Cristina
authors.initials: C
authors.lastname: Cheroni
authors.forename: Floriana
authors.initials: F
authors.lastname: Facchetti
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.forename: Vincenza
authors.initials: V
authors.lastname: Valveri
authors.forename: Roberta
authors.initials: R
authors.lastname: Soffredini
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a