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.
Highlights
Hepatitis C virus (HCV) has a single-stranded RNA genome and belongs to Flaviviridae family
We searched for links between selected clinical data and the presence of genes encoding these receptors and their ligands in hepatitis C virus-infected individuals subjected to pegylated interferon-a and ribavirin therapy
Our results suggest an importance of clinical parameters and the contribution of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes to the course of hepatitis C virus infection and the response to therapy
Summary
Hepatitis C virus (HCV) has a single-stranded RNA genome and belongs to Flaviviridae family. The outcome of chronic infection depends on HCV genotype, viral kinetics, immune response in patient, antiviral treatment, as well as other factors A favorable outcome in HCV infection is considered to be a sustained virologic response (SVR), manifested as a lack of detectable HCV RNA in the patient serum directly after completion of the antiviral therapy and 24 weeks later, verified by the qualitative test. This result is achieved, in about 50 % of patients only (Asselah et al 2010; Ghany et al 2009). Statistics and their confidence intervals were estimated with bootstrap approach if necessary
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