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Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

ABSTRACT: UNLABELLED:Polymorphism in the interleukin-28B (IL28B) gene region, encoding interferon (IFN)-?3, is strongly predictive of response to antiviral treatment in the nontransplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. The cohort study included 189 consecutive patients infected with hepatitis C virus (HCV) who underwent liver transplantation between January 1, 1995, and January 1, 2005, at the Mayo Clinic, Rochester, MN. Genotyping of the polymorphism rs12979860 was performed on DNA collected from all donors and recipients in the cohort. Sixty-five patients received IFN-based antiviral therapy. The CC IL28B variant was less common in the chronic HCV-infected recipients than in non-HCV donor livers (33% versus 47%, P = 0.03). IL28B recipient genotype was significantly predictive of fibrosis stage, with TT genotype being associated with more rapid fibrosis (Pearson chi-square P = 0.024 for the comparison G versus A). Donor and recipient IL28B genotype were independently associated with sustained virologic response (P < 0.005). The presence of IL28B CC variant in either the recipient (R) or donor (D) liver was associated with increased rate of sustained virologic response (D-non-CC/R-non-CC = 3/19 [16%] versus D-CC/R-non-CC = 11/22 [50%] versus D-non-CC/R-CC = 5/12 [42%] versus R-CC/D-CC = 6/7 [86%], P = 0.0095). IL28B genotype was not significantly associated with survival (overall/liver-related). CONCLUSION:Recipient IL28B TT genotype is associated with more severe histological recurrence of HCV. Recipient and donor liver IL28B genotype are strongly and independently associated with IFN-based treatment response in patients after orthotopic liver transplantation. The data suggest that CC donor livers might be preferentially allocated to patients with HCV infection.

SUBMITTER: Charlton MR

PROVIDER: S-EPMC3835596 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

Charlton Michael R MR Thompson Alexander A Veldt Bart J BJ Watt Kym K Tillmann Hans H Poterucha John J JJ Heimbach Julie K JK Goldstein David D McHutchison John J

Hepatology (Baltimore, Md.) 20110101 1

<h4>Unlabelled</h4>Polymorphism in the interleukin-28B (IL28B) gene region, encoding interferon (IFN)-λ3, is strongly predictive of response to antiviral treatment in the nontransplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. The cohort study included 189 consecutive patients infected with hepatitis C virus (HCV) who underwent liver transplantation between January 1, 1995, and January ...[more]

PMID: 21254179

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Project description:AimTo analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.MethodsA total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.ResultsSNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).ConclusionThe higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

Dataset Information

Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

Publications

Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

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