role of interleukin-18 promoter polymorphisms [-607 C/A and 137 G/C ] in determining HCV clearance or persistence

Two interleukin [IL-18] Polymorphisms [- 607 C/A and -137 G/C] and their haplotypes are known to affect the IL-18 expression. A number of SNPs [single nucleotide polymorphisms] that influence IL- 18 production are found in the gene promoter region. The study will determine HCV clearance or persistence as a result of IL-18 promoter polymorphisms [-607 C/A and 137 G/C] in chronic hepatitis C virus infected patients during interferon and ribavirin treatment. Eighty patients with chronic hepatitis C virus infection, their age ranges between [23-57] years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay and specific sequence primer polymerase chain reaction [PCR] IL-18-137, 607 SNP. There was no significant difference in the frequencies of -137 allelic distribution in CHCV infection patients and healthy controls. The -607 AA allele was higher among controls than in patients with CHCV infection. The -607 CC allele was higher among the CHCV patients than in the healthy controls. 87.5% of the studied CHCV patients had response to IFN therapy, the majority of cases had A1F1 biopsy results. IL-18 promoter polymorphism at -607 position with AA allele is a potential protective marker, as it is higher among healthy controls than the CHCV patients. That IL-18 could be considered as a target for therapeutics

Tumour necrosis factor-alpha gene expression in chronic Hepatitis C virus infection

Objective: Tumour necrosis factor [TNF]-alpha, a prototype proinflammatory cytokine, has been implicated as an important pathogenic mediator in a variety of liver conditions. Some genetic polymorphisms in the human TNF-alpha promoter region, such as the G-A transitions -308 and - 238, have been shown to influence TNF-alpha expression in chronic hepatitis C virus infection

Aim of the work: The present study was to investigate the influence that the- 308and- 238 TNF- alpha promoter polymorphisms have on the response to interferon and ribavirin therapy in chronic hepatitis C virus infection

Patients and methods: One hundred forty patients with chronic hepatitis C virus infection, their age ranges between [20-56] years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and thirty five healthy individuals were included to serve as controls, the patients and controls were divided into two groups the first group forty patients and fifteen controls for the detection of TNF-alpha -308, -238 genotypes polymorphisms, the second group were one hundred patients and twenty healthy controls for the detection of serum levels of TNF-alpha. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay, genotyping of 308, 238 TNF-alpha promoter polymorphism and serum levels of TNF-alpha

Results: There was no statistically significant difference between chronic HCV patients and healthy controls as regarding TNF-alpha -238 different alleles. The frequencies of TNF-alpha gene polymorphism with A/G and G/G mutation at – 308 were significantly higher in chronic HCV patients than those in the controls. The serum level of TNF-alpha was markedly higher in the chronic HCV patients than in the healthy controls. There were significant association between TNF-alpha gene polymorphism in the- 308 A/G, G/G alleles and increased serum TNF- alpha in CHCV infection

Conclusion: The results indicate that the TNF-alpha gene polymorphism at position -308 is associated with susceptibility of chronic HCV infection

Recommendations: Our major concern was to improve the response to treatment in patients with chronic HCV infection, whether the disadvantage of having the TNF-alpha -308 allele became more apparent after interferon and ribavirin therapy is unclear and needs further study that detecting the polymorphism of the -308 TNF-alpha allele before administering interferon therapy may be valuable for predicting the treatment response, especially in difficult- to treat patients