Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.

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.

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia.

BACKGROUND: Natural killer (NK) cells are an important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection. NK cells express a large panel of inhibitory and activating receptors. The most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which are encoded by multiple genes that may be present or absent in given individuals depending on their genotype. This variability results in differential susceptibility to viral infections and diseases, including HCV infection and its consequences. AIMS AND METHODS: The aim of this study was to test whether chronical infection with HCV and the viremia levels are associated with any KIR gene in the Polish population. We typed 301 chronically HCV-infected patients and 425 non-infected healthy individuals for the presence or absence of KIR genes and their ligands, HLA-C C1 and C2 groups as well as HLA-B and HLA-A Bw4-positive alleles. RESULTS: We found that males, but not females, possessing KIR2DS2 and KIR2DL2 genes had a 1.7 higher probability to become chronically HCV-infected than males negative for these genes (p=0.0213). In accord with this, centromeric B region, containing KIR2DS2 and KIR2DL2 genes, was also associated with chronic HCV infection in males. In addition, patients of both genders possessing KIR2DS3 but not KIR2DS5 gene exhibited, on average, 2.6 lower level of viremia than HCV-infected individuals with other genotypes (p=0.00282). This was evident in those infected at a young age. KIR2DS3-positive patients also had lower mean levels of bilirubin than KIR2DS3-negative ones (p=0.02862). CONCLUSION: Our results suggest a contribution of the KIR2DS2 and KIR2DL2 genes (cenB haplotype) to the susceptibility to chronic HCV infection, and an association of the KIR2DS3 gene in the absence of KIR2DS5 with low viremia levels.