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Lack of killer immunoglobulin‐like receptor 2DS2 (KIR2DS2) and KIR2DL2 is associated with poor responses to therapy of recurrent hepatitis C virus in liver transplant recipients
Author(s) -
Askar Medhat,
Avery Robin,
Corey Rebecca,
Lopez Rocio,
Thomas Dawn,
Pidwell Diane,
Eghtesad Bijan,
Miller Charles,
Fung John,
Zein Nizar N.
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21878
Subject(s) - ribavirin , medicine , hepatitis c virus , odds ratio , immunology , pegylated interferon , natural killer cell , sofosbuvir , liver transplantation , gastroenterology , virus , transplantation , biology , cytotoxic t cell , biochemistry , in vitro
Killer immunoglobulin‐like receptors (KIRs) expressed on natural killer and natural killer T cells are involved in activation of these cells and can influence antiviral immunity in the liver. This study investigated the association between KIR genetic diversity and sustained virologic response (SVR) to Peginterferon and Ribavirin (Peg/RBV) therapy in liver transplant (LT) recipients with hepatitis C virus (HCV) recurrence. We tested KIR genotypes in 44 HCV‐infected LT recipients treated with Peg/RBV for 48 weeks. Patients were categorized as having KIR genotypes A/A or B/x and analyzed for association with SVR. Fifteen of 44 (34%) patients had SVR. Only 2 of 18 (11%) who lacked KIR2DS2/KIR2DL2 achieved SVR compared to 13 of 26 (50%) who carried these two genes (odds ratio: 8.0, 95% confidence interval: 1.5‐42.0, P = 0.008). The association between lack of KIR2DS2/KIR2DL2 and SVR remained significant after exclusion of 10 patients with non‐genotype 1 HCV. No correlation was found with other activating or inhibitory KIR genes. Absence of KIR2DS2 and/or KIR2DL2 is associated with failure of Peg/RBV therapy in patients with recurrent HCV after LT. These findings support the role of natural killer and natural killer T cells in HCV clearance after LT and might be generalizable to treatment of HCV infection outside the setting of LT. Liver Transpl 15:1557–1563, 2009. © 2009 AASLD.