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


CONCLUSIONS
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.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. charlton.michael@mayo.edu
Michael R
MR
Charlton
Alexander
A
Thompson
Bart J
BJ
Veldt
Kym
K
Watt
Hans
H
Tillmann
John J
JJ
Poterucha
Julie K
JK
Heimbach
David
D
Goldstein
John
J
McHutchison
D000328:Adult; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Nature. 2009 Sep 17;461(7262):399-401
19684573
J Hepatol. 2007 Jun;46(6):1009-17
17328985
J Invest Dermatol. 2009 Jul;129(7):1628-42
19262602
J Immunol. 2005 Feb 15;174(4):1932-7
15699120
Nature. 2009 Oct 8;461(7265):798-801
19759533
Gastroenterology. 2010 Jul;139(1):120-9.e18
20399780
Nat Immunol. 2003 Jan;4(1):63-8
12469119
Science. 2001 Jan 26;291(5504):664-7
11158680
Virol J. 2005 Sep 07;2:80
16146571
Nat Genet. 2009 Oct;41(10):1100-4
19749758
J Virol. 2005 Mar;79(6):3851-4
15731279
J Hepatol. 1994 Oct;21(4):536-42
7814799
Gastroenterology. 2010 Apr;138(4):1338-45, 1345.e1-7
20060832
Am J Transplant. 2008 Nov;8(11):2426-33
18727694
Gastroenterology. 2010 Jun;138(7):2307-14
20176026
Nat Immunol. 2003 Jan;4(1):69-77
12483210
Nat Genet. 2009 Oct;41(10):1105-9
19749757