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

Background: 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. Aim: To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk. Patients and Methods: 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-a genotyping. Results: 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. Conclusion: Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.

Automated summary

This study investigated the contribution of LTA gene polymorphism in different stages of chronic hepatitis C and hepatocellular carcinoma (HCC) risk. It was found that the G/G genotype was more common in HCC patients and was associated with Child classes. Patients with A/G genotype had higher MELD scores in HCC. Detection of LTA G/G genotype in chronic HCV patients could help identify high-risk patients for disease progression and HCC development.