الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus infection, one of the major causes of liver disease worldwide, is highly prevalent in Egypt with a predominance of HCV genotype 4. The standard of care for chronic HCV infection consists of pegylated interferon-α plus ribavirin (PEG-IFN/RBV) which is prolonged and costly, and is associated with dose-limiting side-effects, increasing the need for accurate prediction of treatment failure.
The treatment of HCV is affected by many Host/Virus factors that must be precisely evaluated and optimized before treatment initiation. Furthermore, it has recently been reported that a single nucleotide polymorphism (SNP) of the host gene IL28B is significantly associated with the response to PEG-IFN/RBV therapy.
Interleukin-28B (IL-28B) gene encodes Interferon lambda 3 (IFNλ3), which induces antiviral activity by itself and through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) complex, which induces IFN-stimulated genes (ISGs) that also have antiviral activity against HCV.
The aim of this study was to evaluate the interferon / ribavirin therapy in Egyptian HCV patients and predictors of response, and assess the predictive value of IL-28B rs12979860 polymorphism in response to PEG-IFN/RBV therapy in Egyptian HCV patients and the frequencies of alleles of this gene in HCV patients as compared with healthy controls. This study included 130 chronic HCV Egyptian patients who were recruited from interferon clinic of National Liver Institute, Menoufiya University during the period from July 2011 to July 2013. They were 92 (70.8%) males and 38 (29.2%) females and their ages ranged from 18 to
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57 years (mean 39.60± 9.28). The study also included 40 healthy voluntaries as a control.
All patients received weekly injection of peg-IFN-α plus daily oral ribavirin treatment for 48 week, and according to the response to therapy, they were be classified into three groups: First group included 70 patients with SVR; in these patients HCV RNA was negative at the end of PEG-IFN/RBV therapy (48 weeks) and HCV RNA remain negative during the follow-up of 6 months. Second group included 49 patients who failed to response and had persistent detectable HCV RNA after 12 weeks duration of treatment (Non- responder group) and third group included 11 patients with relapse; in these patients HCV RNA was negative at the end of therapy (48 weeks) and recurrence of HCV RNA occurs during the follow-up of 6 months (relapse group). The fourth group included 40 healthy volunteers as a control group.
All patients and controls were subjected to the following laboratory investigations: Liver function tests, Complete blood count, Prothrombin time and concentration, Hepatitis B surface antigen (HBsAg), Hepatitis B core antibodies (HBcAb) by ELISA, HCV antibodies by ELISA technique and detection of schistosomal antibody by schistosoma IgG-ELISA.
HCV-RNA was performed for patients by Real time-PCR before treatment and at 12, 24 and 48 weeks of treatment and six months after stoppage of treatment and liver biopsy was performed before treatment to assess fibrosis stage. Genotyping for the IL-28B rs12979860 polymorphism was performed for patients by polymerase chain reaction based restriction fragment length polymorphism assay.
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The current study showed that:
The frequency of IL-28B genotypes CC, CT and TT in the studied 130 chronic HCV patients were 34.6%, 42.3% and 23.1% respectively with CT genotype the commonest in the studied patients.
The frequency of IL-28B genotypes CC, CT and TT in health controls were 52.5%, 32.5% and 15% respectively. The frequency of IL-28B CC genotype was lower in HCV patients than in controls (34.6% versus 52.5%) and this difference is of no significant importance.
A significant difference was detected between the HCV patients and controls as regard the IL-28B alleles, as the frequency of C allele was lower in HCV patients than healthy controls (55.8% versus 68.8%) and T allele was higher in HCV patients than controls (44.2% versus 31.2%).
After therapy, 70 patients (53.8%) among overall 130 HCV patients were achieved SVR (responders), and the remaining 60 (46.2%) of patients failed to respond which includes 49 (37.7%) primary non-responders and 11 (8.5%) relapsers.
A significant relation was detected between young age and response to treatment in the univariate logistic regression analysis. Patients achieved SVR were younger than non-responsder or relapse patients.
A significant relation was detected between low body BMI and response to treatment in the univariate logistic regression analysis.
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The HCV patients with CC genotype of IL-28B rs12979860 achieved high SVR (84.4%), which is significantly higher compared to CT (45.5%) and TT (23.3%) genotypes.
A significant difference was detected between SVR group and Non-SVR as regard age, BMI, fibrosis degree and IL 28B genotypes on univariate analysis. However in multivariable regression analysis, the current study showed that only the fibrosis stage and IL-28B genotypes were independent predictors of SVR, while age and BMI were not significant.
Conclusion:
IL-28B polymorphism is an independent predictor of SVR to PEG-IFN / RBV in Egyptian HCV patients. Besides increasing the chances to achieve SVR, determining IL-28B SNPs prior to initiating treatment will be cost-effective and reduces adverse effects. This is essential in low-income, developing countries with a high prevalence of HCV infection like Egypt where treatment cost is a major concern.
Our data shed the light on the pattern of IL-28B SNP in chronic HCV patients and its association with the different variables that can alter the physician’s decision prior to therapy. Lastly, we describe an effective, simple and low-cost approach of IL-28B SNP genotyping using PCR-RFLP procedure. characterization of IL-28B rs12979860, in correlation with variables like liver fibrosis stage, would maximize the cost–benefit of therapy in Egypt and prevent advanced liver disease, including hepatocellular carcinoma.