Mansoura University Faculty of Medicine, Clinical Pathology.
Mansoura University Faculty of Medicine, Pharmacy.
Afr Health Sci. 2023 Mar;23(1):198-212. doi: 10.4314/ahs.v23i1.22.
During the first years of the use of direct acting Hepatitis C antiviral drugs (DAAS), several studies reported a possible correlation between this new era of treatment and an increased risk of Hepatocellular carcinoma (HCC). Its development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with them. For this reason, this study aimed to address the immunological effect of DAAS.
SUBJECT & METHODS: Prospective paired -sample design, carried out on 90 naïve chronically infected HCV patients before and after receiving a combination therapy of sofosbuvir; at a dose of 400 mg once daily and daclatasvir; at a dose of 60 mg once daily for 12 weeks and follow up for one year. immunological tests including: total T cell count, T helper cell count, T cytotoxic cell count and natural killer cell count in peripheral blood through (CD3, CD3/CD4, CD3/CD8 and CD56 respectively) by Fluorochrome monoclonal antibodies labelled with specific dyes through Multiparameter, FACSCanto ™ II flow cytometer (Becton Dickinson, USA).
Concerning the immunological changes, total T cells (CD3+), Natural killer cells showed non-significant decrease at end of therapy while significant decrease in T helper cells (CD3+CD4+) T cytotoxic cells (CD3+CD8+) compared to pre-treatment value. Long follow up revealed 26.6% developed focal HCC, in more addition, multivariate analysis show CD4/CD8 ratio could be predictor as well as sex for early development of HCC after combined DAAS therapy.
HCV treatment by DAAS produces significant decrease in T helper, T cytotoxic cells in CHC patients at the end of therapy. 26.6% developed focal HCC with independent CD4/CD8 predictor for burden malignancy. Further large extended population study is needed for clarify this concern.
在直接作用的丙型肝炎抗病毒药物(DAAS)使用的最初几年中,几项研究报告说,在这个新的治疗时代,与丙型肝炎病毒感染(HCV)感染后消除的免疫环境变化和不同的细胞行为可能存在相关性,这可能与这种新的治疗时代存在相关性。因此,本研究旨在探讨 DAAS 的免疫效应。
前瞻性配对样本设计,对 90 例初治慢性 HCV 感染患者进行研究,这些患者在接受索磷布韦(400mg,每日 1 次)联合达拉他韦(60mg,每日 1 次)治疗 12 周及随访 1 年后,分别在治疗前后采集外周血进行免疫检测,包括:总 T 细胞计数、辅助性 T 细胞计数、细胞毒性 T 细胞计数和自然杀伤细胞计数(分别通过 CD3、CD3/CD4、CD3/CD8 和 CD56 荧光标记的单克隆抗体),采用多参数流式细胞术(FACSCanto II 型,BD 公司,美国)。
在免疫变化方面,与治疗前相比,总 T 细胞(CD3+)、自然杀伤细胞(NK 细胞)在治疗结束时呈非显著性下降,而辅助性 T 细胞(CD3+CD4+)、细胞毒性 T 细胞(CD3+CD8+)显著下降。长期随访发现 26.6%的患者发生局灶性 HCC,此外,多变量分析显示,CD4/CD8 比值以及性别是 DAAS 联合治疗后 HCC 早期发生的预测因素。
DAAS 治疗丙型肝炎可导致 CHC 患者治疗结束时辅助性 T 细胞、细胞毒性 T 细胞显著减少。26.6%的患者发生局灶性 HCC,CD4/CD8 比值是独立的恶性肿瘤负担预测因素。需要进一步进行更大规模的扩展人群研究来阐明这一问题。