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

Abstract

Background Polymorphism in the IL28B gene region, encoding interferon-lambda(λ)-3, is strongly predictive of response to antiviral treatment in the non-transplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. Methods Cohort study including 189 consecutive hepatitis C virus (HCV) patients who underwent liver transplantation between 1-1-1995 and 1-1-2005 in the Mayo Clinic, Rochester. Genotyping of the polymorphism rs12979860 was performed on DNA collected from all donors and recipients in the cohort. 65 patients received IFN-based antiviral therapy. Results The CC IL28B variant was less common in the CHC recipients than in non-HCV donor livers (33% vs 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 vs A). Donor and recipient IL28B genotype were independently associated with SVR (P<0.005). The presence of IL28B CC variant in either the recipient (R) or donor (D) liver was associated with increased rate of SVR (D-non-CC / R-non-CC = 3/19 (16%) vs D-CC / R-non-CC=11/22 (50%) vs D-non-CC / R-CC=5/12 (42 %) vs R-CC / D-CC=6/7 (86%), P=0.0095). IL28B genotype was not significantly associated with survival (overall / liver related). Conclusion Recipient IL28B 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 post-OLT. The data suggest that CC donor livers might be preferentially allocated to patients with HCV infection.

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

“…Genetic variants of IL28B explain differences in IFN efficacy between races due to different distributions of individual gene alleles [7][8][9][10][11]. Studies on HCV provided an inspiration for investigations of the influence of IL28B polymorphisms on infections with the other hepatotropic viruses, since IFN λ shows broad and non-specific antiviral activity [18].…”

“…Homozygous genotypes classified as CC at locus rs12979860 were associated with more than twice as high SVR rate in comparison with TT alleles, whereas CT heterozygotes exerted an intermediate treatment response [7][8][9][10]. A favorable CC constellation was also shown to increase spontaneous HCV clearance and predicts better outcomes of HCV reinfection after liver transplantation [11].…”

HCV-Recurrence After Liver Transplantation

“…Furthermore, the impact of genetic differences in donor and recipient may vary according to the duration of post-transplant follow-up [57]. Results of intensive investigations demonstrated that donor polymorphisms of IL-28B-gene may partially predict the outcome of antiviral treatment [60].…”

Impact ofIL-28Bpolymorphism on outcome in patients with hepatitis C after liver transplantation

“…A SNP in this locus (rs12979860) has been shown to be associated with the development of at least F2 fibrosis in the graft 1 year after transplantation in 154 HCV-infected recipients [12]. Again, as for the TLR4 SNP, only the recipient genotype but not the donor genotype, was predictive of fibrosis progression.…”

“…Three recent studies have analyzed a higher number of HCVinfected patients and have provided follow-up data for at least 5 years [11][12][13]. The first of these studies assessed the importance of a nonsynonymous TLR4 SNP (D299G) on graft survival following LT.…”