Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Int J Immunogenet. 2021 Feb;48(1):16-24. doi: 10.1111/iji.12515. Epub 2020 Sep 22.
Hepatitis C virus (HCV)-infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin-like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV-infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), direct bilirubin (DB), alpha-fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well-established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence-specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA-C*12:02 and HLA-A3 and HLA-A11 were positively associated with the F3-F4 fibrosis group (p = .026; OR = 8.717, CI = 1.040-73.077; respectively, p = .047; OR = 2.187; 95% CI = 1.066-4.486). KIR2DL2-positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2-negative patients (p = .013, respectively, p = .028). KIR2DL2/KIR2DL2-C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2-C1-positive patients when compared to KIR2DS2-C1-negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV-infected patients. These connections should be taken into account when considering disease development and treatment.
丙型肝炎病毒（HCV）感染者在受到宿主、病毒和环境因素影响时，其肝纤维化、肝硬化和肝细胞癌（HCC）发展的速度可能更快。HCV 疾病的进展也与特定杀伤细胞免疫球蛋白样受体（KIR）的基因变异和主要组织相容性复合体（MHC）的基因有关。本研究旨在分析临床、病毒学和生化参数，并评估 KIR 基因及其 HLA Ⅰ类配体在丙型肝炎病毒感染患者中的可能影响。本研究共分析了 127 例慢性 HCV 感染患者的各种生化和遗传因素，这些因素可能影响疾病的进展和预后。使用成熟的生化方法分析丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、γ-谷氨酰转移酶（GGT）、直接胆红素（DB）、甲胎蛋白（AFP）、HCV RNA 水平和纤维化指数等肝功能参数。同时，采用聚合酶链反应序列特异性引物技术进行 KIR 和 HLA 基因分型。HLA Ⅰ类和 HLA 配体分析表明，HLA-C*12:02、HLA-A3 和 HLA-A11 与 F3-F4 纤维化组呈正相关（p=0.026；OR=8.717，CI=1.040-73.077；分别，p=0.047；OR=2.187；95%CI=1.066-4.486）。与 KIR2DL2 阴性患者相比，KIR2DL2 阳性患者治疗后 AST 和直接胆红素中位水平较高（p=0.013，p=0.028）。KIR2DL2/KIR2DL2-C1C1 基因型与 AST、ALT 和 GGT 水平升高有关。与 KIR2DS2-C1 阴性患者相比，KIR2DS2-C1 阳性患者的 GGT 水平也较高。本研究在 HCV 感染患者中证实了特定的临床、病毒学和生化参数与 KIR 基因及其 HLA 配体的表达之间的几种联系。在考虑疾病的发展和治疗时，应该考虑到这些联系。
