Galal Ghada, Tammam Hammam, Abdel Aal Amal, Fahmy Nahed, Sheneef Abeer, Ahmed Nagwa, Zaghloul Amr
Department of Tropical Medicine and Gastroenterology, Sohag University, Sohag, Egypt.
Department of Clinical Pathology, Assiut University, Assiut, Egypt.
Infect Drug Resist. 2021 May 25;14:1921-1930. doi: 10.2147/IDR.S306879. eCollection 2021.
Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course.
To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk.
Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCR-restriction fragment length polymorphism technique for lymphotoxin-α genotyping.
The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC.
Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.
肿瘤坏死因子（TNF）家族包括淋巴毒素-α（LTA），它是一种促炎细胞因子，在肝纤维化形成中起作用。LTA基因多态性在不同的炎症和免疫调节疾病中发挥作用。这种多态性也被认为会影响慢性丙型肝炎（CHC）的感染进程。
研究LTA基因多态性在不同慢性丙型肝炎阶段及肝细胞癌风险中的作用。
我们的研究纳入了108例慢性丙型肝炎患者，根据疾病阶段进行分组。A组：慢性丙型肝炎；B组：肝硬化（LC）；C组：肝硬化合并肝细胞癌（HCC）；D组：健康对照。进行了常规实验室检查、用于定量丙型肝炎病毒的聚合酶链反应（PCR）、腹部超声检查以及肝脏硬度测量（LSM）。计算了Child-Turcotte-Pugh评分、终末期肝病模型（MELD）评分以及基于4项指标的纤维化指数（FIB-4）评分。我们采用PCR-限制性片段长度多态性技术对淋巴毒素-α进行基因分型。
A/G基因型在所有组中均占主导。在肝细胞癌患者中，G/G基因型比肝硬化组（19.4%）、慢性丙型肝炎组（17.8%）和对照组（4.17%）更为常见（31.8%）。在肝细胞癌中发现LTA基因型与Child分级之间存在显著关联（P<0.01），但在肝硬化患者中未发现（P>0.05）。携带A/G基因型的肝细胞癌患者的MELD评分高于其他基因型。多因素二元逻辑回归分析证实，LTA G/G基因型和低血小板计数是丙型肝炎病毒相关肝硬化患者发生肝细胞癌的独立预测因素。
检测慢性丙型肝炎患者的LTA G/G基因型有助于识别疾病进展和肝细胞癌发生的高危患者。
