title: 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.
abstract: 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.
authors.affiliation: Allogen Laboratories, Cleveland Clinic, Cleveland, OH, USA. AskarM@ccf.org
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.forename: Robin
authors.initials: R
authors.lastname: Avery
authors.forename: Rebecca
authors.initials: R
authors.lastname: Corey
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Dawn
authors.initials: D
authors.lastname: Thomas
authors.forename: Diane
authors.initials: D
authors.lastname: Pidwell
authors.forename: Bijan
authors.initials: B
authors.lastname: Eghtesad
authors.forename: Charles
authors.initials: C
authors.lastname: Miller
authors.forename: John
authors.initials: J
authors.lastname: Fung
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Zein
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology; D024882:Drug Resistance, Viral / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a