Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

Introduction Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients. .

Pegylated α interferon 2B plus ribavirin in the treatment of HCV genotype 4 infection.

Objective. To evaluate safety and efficacy of Peg-INF combined with ribavirin for genotype 4 infected children. Methods. Seven children were included, five were infected parentrally, One vertically and one had both exposures. Clinical and laboratory evaluation were undertaken as well as quantitative PCR for HCV RNA before therapy at, 12, 24 and 52 weeks during treatment and one year after therapy. Liver biopsy was performed before and at the end of therapy. Four children had low and three had moderate viremia. Results. At twelve weeks, two children (28.6%) lost viremia. Another child lost viremia at 52 weeks. ETR was 42.9%. During follow up one relapsed, thus SVR was 28.6%. Children with SVR were the youngest, their mean duration of infection was 4.5 vs 12.7 years in the others. Side effects of both INF & ribavirin was mild, required no reduction in doses. Conclusion. Combination therapy of peg interferon-alpha with ribavirin is well tolerated in children and adolescents studied.

Improvement of steatosis after interferon therapy in HCV genotype 4 is related to weight loss.

Introduction Hepatic steatosis is common in patients with chronic hepatitis C virus (HCV) infection, and its occurrence may be related to both host and viral factors. Relationship between improvement in steatosis and response to anti-viral treatment remains unclear. This study assessed the factors associated with steatosis in patients infected with genotype 4 HCV, and to correlate degree of changes in steatosis with host factors and response to treatment. Methods Records of 175 patients with chronic genotype 4 HCV infection, who had received interferon and ribavirin combination therapy, were reviewed retrospectively to extract data on body mass index (BMI), presence of diabetes mellitus, and liver histology findings. Paired BMI data and liver biopsies (pre- and 24-weeks post-treatment) were available in 86 patients. Baseline steatosis and its changes (before and after treatment) were the dependent variables in a univariate and multivariate analyses. Results Steatosis was found in 88/175 (50.3%) of baseline biopsies. Its presence was related to baseline BMI (r=0.33, P<0.01), but not with viral load, or grade of liver inflammation or fibrosis. On follow up, improvement in steatosis was significantly associated with degree of weight loss but not with response to anti-viral treatment. Conclusion Steatosis is common in genotype 4 HCV infection, and its presence appears to be related to high BMI, but not to viral load or degree of liver injury.