title: Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.
abstract: Natural killer cells play an important role as effectors of innate immunity and regulators of adaptive immunity. They are important elements of the innate response to viral infections, which they detect using human leukocyte antigen (HLA) class I-binding receptors. Most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which exist as two basic isotypes, activating or inhibitory receptors and are encoded by genes distributed differently in unrelated individuals. We searched for links between selected clinical data (including HCV viremia, liver enzymes level and liver histology parameters) and the presence of genes encoding these receptors and their ligands in hepatitis C virus-infected individuals subjected to pegylated interferon-α and ribavirin therapy. Genomic DNA samples from two hundred and ninety-two chronically infected patients were typed by polymerase chain reaction for the presence or absence of genes for KIRs and their ligands, class I HLA molecules, and clinical data of the patients were collected. Our results suggest an importance of clinical parameters and the contribution of KIR and HLA genes to the course of hepatitis C virus infection and the response to therapy. The study revealed that levels of liver enzymes before therapy were about 30% higher in patients who possessed a variant KIR2DS4 gene with 22-base pair deletion. Decrease of ALT activity after treatment was higher in HLA-C C2-positive than negative individuals. Beside it, patients demonstrated early virologic response to the therapy if the time lag before treatment was short, particularly in women.
authors.affiliation: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Mozer-Lisewska
authors.affiliation: Laboratory of Virology, Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114, Wrocław, Poland. kjzwolinska@iitd.pan.wroc.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zwolińska
authors.affiliation: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Arleta Elżbieta
authors.initials: AE
authors.lastname: Kowala-Piaskowska
authors.affiliation: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Bura
authors.affiliation: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Błażej
authors.initials: B
authors.lastname: Rozpłochowski
authors.affiliation: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pauli
authors.affiliation: Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Żeromski
authors.affiliation: Laboratory of Virology, Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Egbert
authors.initials: E
authors.lastname: Piasecki
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114, Wrocław, Poland. pkusnier@iitd.pan.wroc.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
mesh_terms: D000328:Adult; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D008099:Liver / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage
chemical_list: D054316:Biomarkers, Pharmacological; D015236:HLA-C Antigens; C048767:HLA-C*02 antigen; D016898:Interferon-alpha; C473953:KIR2DS4 protein, human; D054340:Receptors, KIR; D012254:Ribavirin
keywords: ALT; AST; Early virologic response; HCV chronic infection; HLA-C C2; KIR2DS4