Key results
Our study included 33 HCC complicating HCV-related cirrhosis patients (HCC group), 37 cirrhotic patients without HCC (cirrhosis group), and 20 healthy individuals who were included as a control (control group). The HCC patients were 26 (78.8%) males and 7 (21.2%) females, and the cirrhotic patients were 14 males (37.8%) and 23 females (62.2%) while the control group included 15 (75%) males and 5 (25%) females.
The current study is conducted aiming to analyze IL-18 single nucleotide gene polymorphism and its value in predicting HCC among HCV-related cirrhotic patients by studying 33 HCC patients with HCV-related cirrhosis, 37 cirrhotic patients without HCC, and 20 healthy individuals properly selected as a control.
Of interest, the presence of GG genotype is more in healthy control than in HCC patients (P = 0.04) (Table 5). A finding that could consider the presence of genotype GG of IL-18 as a good predictive marker against HCC development evidenced by lack of difference between the other genotypes (AA, AC, CC, and GC) in the studied groups and each other or the control.
Of interest, Estfanous et al. [12] reported that IL-18 polymorphism GG genotype and G allele were significantly associated with a lower risk of chronic HCV infection.
Furthermore, we find that G allele can be a protective factor against cirrhosis HCC development. This is not matching with Bouzgarrou et al. [13] who reported that IL-18 polymorphism C allele was associated with a higher risk of cirrhosis and HCC.
There were scanty studies of IL-18 single nucleotide gene polymorphism in HCV patients with or without cirrhosis. Previous studies of HCC in HBV patients confirmed abstinence of significant association of different genotypes of IL-18 in the studied patients.
Dai et al. [14] reported that GG genotype carriers may increase the risk of HCC in healthy populations and the risk of LC in chronic hepatitis B carriers while Zhang and colleagues [15] reported that the AA genotype and A allele frequencies of IL-18 SNP were positively correlated with HBV-related HCC.
A previous study conducted by Bao and colleagues [16] proved that GC genotype and C allele significantly associated with decreased HCC risk.
In contrast to our results, Bakr et al. [17] proved that IL-18 polymorphism AA and GG genotypes were significantly related to a higher risk of developing HCC, and GC genotype and C allele were significantly associated with a lower risk of developing HCV-related cirrhotic patient.
Lau and colleagues [11] reported that the IL-18 polymorphism with GC+CC genotypes and G allele could be factors that increase the risk of HCC compared with those carrying the wild-type GG.
The explanation for the disparity of results between us and other studies may be attributed to the variation in genetic background between different ethnicities, different environmental factors, exposure to different carcinogens in different populations, and to a somewhat smaller sample size of our study population.
Finally, analysis of IL-18 single nucleotide gene polymorphism could be a valuable marker for 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 in our studied patients.
Limitations
Elastography was not done as it is very expensive for our patients. Also, the relatively small number of patients was due to the difficulty in acceptance by patients to be included in a research study in addition to the high expense of the kits.
Interpretation
Our results should be interpreted with caution because of several limitations. Firstly, though we recruited 90 samples in this study, the sample size of each group was relatively small which may restrict its detailed subgroup analysis by the clinical index. Secondly, considering we just controlled four factors (D.M., gender, smoking, and obesity), other factors including environmental background, treatment protocols, and living habits may cause some bias. Thirdly, all participants were all from Mansoura Specialized Medical Hospital outpatient clinics, Egypt, which may not stand for all the Egyptian population.
Generalizability
The fundamental experiments should be further conducted to validate our results and explore the possible mechanism.