IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B

Authors

  • Pietro Lampertico,

    Corresponding author
    1. 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
    • M.D., Ph.D., First Division of Gastroenterology Fondazione Instituto Di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy
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    • fax: +39-0250320700

  • Mauro Viganò,

    1. 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
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  • Cristina Cheroni,

    1. Istituto Nazionale Genetica Molecolare, Milano, Italy
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  • Floriana Facchetti,

    1. 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
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  • Federica Invernizzi,

    1. 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
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  • Vincenza Valveri,

    1. Istituto Nazionale Genetica Molecolare, Milano, Italy
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  • Roberta Soffredini,

    1. 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
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  • Sergio Abrignani,

    1. Istituto Nazionale Genetica Molecolare, Milano, Italy
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  • Raffaele De Francesco,

    1. Istituto Nazionale Genetica Molecolare, Milano, Italy
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  • Massimo Colombo

    1. 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
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  • Potential conflict of interest: Dr. Lampertico advises and is on the speakers' bureau of Bristol-Myers Squibb, Roche, Gilead, and GlaxoSmithKline. Dr. Colombo advises, is on the speakers' bureau of, and received grants from Merck, Roche, Bristol-Myers Squibb, Gilead, Novartis, and Vertex. Dr. Vigano is on the speakers' bureau of Roche and Bristol-Myers Squibb. He is also in the speakers' bureau of and recieved grants from Gilead.

  • See Editorial on Page 870

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. (HEPATOLOGY 2013)

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