Toll样受体2多态性与乙肝相关疾病进展及肝细胞癌发生之间的相关性研究:一项针对埃及患者的病例对照研究
Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients.
作者信息
Elabd Naglaa S, Helal Marwa L, Elkhayat Mohsen, Abd-ElKhalek Heba Kamal, Ahmed Doaa M, El-Shemy Asmaa M, Elsaadawy Yara S, Abdelmoneum Rasha A, AboShabaan Hind S, Seddik Randa M
机构信息
Department of Tropical Medicine Faculty of Medicine Menoufia University, Shebin El-Kom, Menoufia, Egypt.
Department of Clinical Biochemistry and Molecular Diagnostics National Liver Institute Menoufia University, Shebin El-Kom, Menoufia, Egypt.
出版信息
Can J Infect Dis Med Microbiol. 2024 Jul 19;2024:5797895. doi: 10.1155/2024/5797895. eCollection 2024.
METHODS
In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR.
RESULTS
IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups ( < 0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (=0.03, OR = 2.45, and 95% CI: 1.69-3.65), IL-6 levels (=0.04, OR = 3.45, and 95% CI: 2.01-6.9), and TRL2 variants (=0.01, OR = 4.25, and 95% CI: 2.14-13.5) are independent risk factors associated with disease progression from cirrhosis to HCC.
CONCLUSION
In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.
方法
本病例对照研究共纳入170例慢性乙型肝炎患者和50例年龄及性别匹配的健康对照者。进行了临床、实验室和影像学评估。采用酶联免疫吸附测定法(ELISA)测定血清白细胞介素-6(IL-6)水平,并使用实时聚合酶链反应(PCR)进行Toll样受体2(TLR2,rs3804099)基因分型等位基因鉴别分析。
结果
肝癌组的IL-6值显著高于肝硬化组,其次是慢性肝炎组和对照组(<0.001),与疾病活动度和进展参数显著相关。对照组中TLR2纯合子TT最为常见,但CC基因型在肝癌组中的流行率显著高于其他组。此外,CC基因变异与所有乙肝患者较高的IL-6水平和病毒载量相关,而TT基因型与更大的肿瘤大小相关。多因素回归分析表明,在慢性乙肝患者中,病毒载量和TLR2多态性是与慢性肝炎进展为肝硬化及肝癌相关的独立危险因素。同样,乙肝病毒载量(=0.03,OR = 2.45,95%可信区间:1.69 - 3.65)、IL-6水平(=0.04,OR = 3.45,95%可信区间:2.01 - 6.9)和TLR2变异(=0.01,OR = 4.25,95%可信区间:2.14 - 13.5)是与疾病从肝硬化进展为肝癌相关的独立危险因素。
结论
在慢性乙肝患者中,TLR2多态性和较高的IL-6水平与肝癌发生的较高可能性以及慢性乙型肝炎疾病活动度和进展呈正相关。
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本文引用的文献
CA Cancer J Clin. 2021-1
Hepatology. 2021-1