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.

IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B / P. Lampertico, M. Viganò, C. Cheroni, F. Facchetti, F. Invernizzi, V. Valveri, R.M. Soffredini, S. Abrignani, R. De Francesco, M.G. Colombo. - In: HEPATOLOGY. - ISSN 0270-9139. - 57:3(2013 Mar), pp. 890-896.

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

P. Lampertico;C. Cheroni;F. Facchetti;F. Invernizzi;R.M. Soffredini;S. Abrignani;R. De Francesco;M.G. Colombo
2013

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.
adult ; antiviral agents ; drug resistance, viral ; female ; follow-Up studies ; genetic testing ; genotype ; hepacivirus ; hepatitis B surface antigens ; hepatitis B e antigens ; hepatitis C, chronic ; humans ; interferon-alpha ; interleukins ; male ; middle aged ; polyethylene glycols ; polymorphism, single nucleotide ; predictive value of tests ; recombinant proteins ; retrospective studies
Settore MED/12 - Gastroenterologia
mar-2013
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/235179
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