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.

Liver enzyme normalization predicts success of Hepatitis C oral direct-acting antiviral treatment

“…Other factors that affect liver enzyme levels including concurrent medications and alcohol consumption were not fully explored [14]. Furthermore, our analysis does not take into account genetic polymorphisms that have been shown to affect liver enzyme levels and treatment successes in HCV patients: for example, in HLA-C C2-positive individuals, ALT activity decreases more after treatment than in HLA-C C2-negative individuals [20]. Due to the high success rates of oral DAA HCV treatments, the proportion of our study cohort failing to achieve SVR was small, which limited the statistical power to identify factors predictive of treatment failure.…”

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

“…In China, approximately 40 million individuals are infected with hepatitis C virus (HCV), and it is estimated that 50%–to 85% have developed CHC, while 20%–30% of these patients will progress to liver cirrhosis that may lead to hepatocellular carcinoma (J. Li & Zhuang, ). Up to now, the mechanism of CHC and its haematological progress is not clear; however, the host immune system genes, such as human leucocyte antigen (HLA) genes, and their killer‐cell immunoglobulin‐like receptors (KIR) genes could play a role in HCV clearance and the development of CHC (Marangon et al, ; Mozer‐Lisewska et al, ; Ruiz‐Extremera et al, ; Sung et al, ).…”

“…human leucocyte antigen (HLA) genes, and their killer-cell immunoglobulin-like receptors (KIR) genes could play a role in HCV clearance and the development of CHC (Marangon et al, 2011;Mozer-Lisewska et al, 2016;Ruiz-Extremera et al, 2017;Sung et al, 2011).…”

Gender as a factor affecting the NK cell activity in patients successfully treated for chronic hepatitis C with DAA

“…As a result, in HCV-associated cirrhosis male patients with hepatocellular carcinoma (HCC) have a worse outcome than women 26 . Short HCV infections treated with interferon-based therapies had higher chances of success in female 27 . Among HCV-infected patients treated with direct-acting antivirals, HCC recurrence and occurrence rate is higher among men 28 .…”