Role of Lymphotoxin-α Gene Polymorphism in Hepatitis C Virus-Related Chronic Liver Disorders

• Published in: Infection and drug resistance 2021-01, Vol.14, p.1921-1930
• Main Authors: Galal, Ghada, Tammam, Hammam, Abdel Aal, Amal, Fahmy, Nahed, Sheneef, Abeer, Ahmed, Nagwa, Zaghloul, Amr
• Format: Article
• Language: English
• Subjects: Abdomen; Chronic infection; Cirrhosis; Creatinine; Cytokines; Disease; Fibrosis; Gene polymorphism; Genes; Genotyping; Hepatitis C; hepatitis c virus; Hepatocellular carcinoma; Immunomodulation; Infections; Laboratories; Liver cancer; Liver cirrhosis; Liver diseases; Lymphotoxin; lymphotoxin alpha; Original Research; Pathogenesis; Polymerase chain reaction; Polymorphism; Restriction fragment length polymorphism; Risk groups; Thermal cycling; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-β; Tumors
• ISSN: 1178-6973; 1178-6973
• DOI: 10.2147/IDR.S306879

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 (P0.05). 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.