title: KIR3DL1-HLA-Bw4 combination and IL28B polymorphism predict response to Peg-IFN and ribavirin with and without telaprevir in chronic hepatitis C.
abstract: Natural killer cells play a key role in the immune control of viral infections. Killer immunoglobulin-like receptors (KIRs) regulate natural killer cell activation and inhibition through the recognition of their cognate HLA class I ligands. We assessed the predictive factors of a sustained virological response (SVR) in 200 Japanese patients with chronic genotype 1b hepatitis C who were treated with telaprevir (TVR), pegylated-interferon-α2b (PEG-IFN), and ribavirin (RBV) triple therapy (92 patients) or PEG-IFN/RBV therapy alone (108 patients). Sixteen KIR genotypes, HLA-A, -B and -C ligands, and an interleukin (IL) 28B polymorphism (rs8099917) were analyzed. We observed that triple therapy, white blood cell count, hemoglobin value, hepatitis C viral load, a rapid virological response (RVR), IL28B TT genotype, and KIR3DL1-HLA-Bw4 genotype were associated with an SVR. In multivariate regression analysis, we identified an RVR (P < 0.000001; odds ratio [OR] = 20.95), the IL28B TT genotype (P = 0.00014; OR = 5.53), and KIR3DL1-HLA-Bw4 (P = 0.004, OR = 3.42) as significant independent predictive factors of an SVR. In conclusion, IL28B and KIR3DL1/HLA-Bw4 are independent predictors of an SVR in Japanese patients infected with genotype 1b HCV receiving TVR/PEG-IFN/RBV or PEG-IFN/RBV therapy.
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: tumemura@shinshu-u.ac.jp.
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Wada
authors.affiliation: Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology, Ina Chuo Hospital, Ina, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozawa
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Gastroenterology, Suwa Red Cross Hospital, Suwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamijo
authors.affiliation: Department of Gastroenterology, NHO Matsumoto Medical Center, Matsumoto, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology, Saku General Hospital, Saku, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takamatsu
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan; Department of Gastroenterology, NHO Ueda Medical Center, Ueda, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011379:Prognosis; D054341:Receptors, KIR3DL1 / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015235:HLA-B Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D054341:Receptors, KIR3DL1; D011994:Recombinant Proteins; D012254:Ribavirin; C042388:HLA-Bw4 antigen; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C515083:KIR3DL1 protein, human; C486464:telaprevir; C417083:peginterferon alfa-2b
keywords: HCV; HLA; KIR; PEG-IFN; Telaprevir