Interleukin-18 polymorphism as a diagnostic tumor marker for hepatocellular carcinoma in patients with hepatitis C-related cirrhosis

Abstract

Background Egypt has the highest hepatitis C virus prevalence worldwide where about 24% of the people are estimated to carry HCV and more than 50% of blood donors have anti-HCV in some towns. The burden of hepatocellular carcinoma has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. Thus, the aim of the present study was to analyze the interleukin-18 single nucleotide polymorphisms (SNPs) as a diagnostic tumor marker for hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Results This study included 33 hepatocellular carcinoma (HCC) complicating HCV-related cirrhosis patients, 37 cirrhotic patients without HCC (cirrhosis group), and 20 healthy individuals who were included as a control for 9 months of follow-up. SNPs of the IL-18 gene were genotyped by polymerase chain reaction. There was a statistically significant difference in the GG genotype in the HCC group in comparison with the control group (P = 0.04). There was a statistically significant difference in the G allele in the cirrhosis and HCC groups in comparison with the control group (p1 < 0.001 and p2 = 0.03, respectively). Patients with GC genotype have a risk for developing HCC by 6.33-folds more than those with GG genotype while patients with GC genotype have a risk for developing cirrhosis by 5.43-folds more than those with GG genotype, and cirrhotic patients with CC and GC genotype had a risk for developing HCC by 1.17-folds more than those with GG genotype. Conclusion Our findings revealed that the analysis of IL-18 single nucleotide gene polymorphism could be a valuable marker for the prediction of progress towards cirrhosis in chronic HCV patients and also to subsequent development of HCC in HCV cirrhotic patients proved by the results of both GG genotype and its G allele; also, cirrhotic patients with CC and GC genotype have a risk for developing HCC by 1.17-folds more than those with GG genotype.

Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression

“…Therefore, the expression of rhIL-18 and an antiapoptotic mechanism involving NF-κB activation in HCC cells may be related to poor prognosis in HCC patients [ 53 ]. Corroborating with these findings, a 2020 study indicated that IL-18 single nucleotide gene polymorphism could be a marker for HCC in patients with HCV-related cirrhosis [ 54 ], and IL-18 gene polymorphisms could be used as a potential non-invasive diagnostic tool for HCC patients at early stages [ 55 ], which is supported by recent findings that IL-18 high levels are found in HCC patients with poor prognosis [ 56 ].…”

Clinical Significance of Interleukin 18 in Chronic Liver Disease: Review Article

“…Hepatic encephalopathy, a result of liver cirrhosis, was also positively correlated with IL-18 (21) . Studying IL-18 single nucleotide gene polymorphism may be a significant diagnostic for predicting cirrhosis progression in CHC patients, as the probability of developing HCC is 1.17-fold greater in those with the GC or CC genotypes compared to those with the GG genotype (22) . Vascular endothelial growth factor, which is involved in sinusoidal remodeling and the formation of portal-systemic collaterals in PH, is activated by IL-18, which plays a crucial role in the development of PH and esophageal varieces.…”