الفهرس 
Hepatitis COnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) infection is the major cause of chronic liver disease and hepatocellular carcinoma worldwide. The combination of pegylated interferon (IFN)-α and ribavirin is the approved and well accepted standard-of-care (SoC) for chronic hepatitis C. The primary goal of HCV therapy is to cure the infection, which results in eliminating detectable circulating HCV after cessation of treatment. The relatively high cost of treatment with PEG-IFN/RBV regimens, the frequent side effects during and after therapy and the psychological impact on non-responders make it essential to optimize results by optimizing patient selection. So Before initiating treatment, it is useful for patients and physicians to determine the likelihood of achieving a SVR, so that they can decide whether treatment benefits outweigh its costs and risks. In the peg-IFN/RBV dual therapy era, predictors of response helped the patient and the physician to decide whether or not to start treatment. We aimed to evaluate the pretreatment IP-10 levels as well as the IL-28B rs12979860 C/T polymorphisms as a predictive biomarkers for response to viral hepatitis C therapy in Egypt. Our study was carried on 82 Egyptian patients with chronic active hepatitis C. These patients were prepared for receiving a course of treatment with: interferon (Peg-IFN) and ribavirin for 48 weeks.
• All included patients had an established diagnosis of CHC with detectable anti-hepatitis C antibodies and detectable serum HCV RNA with RT-PCR (Taqman technology in ABI 7900,Germany).
• Patients were selected according to the inclusion and exclusion criteria of national committee for control of viral hepatitis in Egypt (Egyptian national control strategy for viral hepatitis, 2008-2012).
• All patients received the same complete treatment of Peg-INFα-2a at a dose of 180μg/week subcutaneously and ribavirin (dose adjusted to body weight: total daily dose of 1000 mg for patients < 75kg and 1200 mg daily for those at least 75kg.
• Therapy was administered for a total of 48 weeks and patients were followed up for another 24 weeks after the completion of treatment.
IP-10 concentrations in the sera were measured using a double –antibody sandwich enzyme –linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (Human (IP10) ELISA Kit; SunRed, Shanghai) on baseline serum samples collected prior to initiation of treatment.
Genotyping for the IL-28B rs12979860 C/T polymorphism was performed by a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay. The amplification of the target genomic region that contains the SNP rs12979860 was done using direct amplification kit ( KAPA Blood PCR kits; KAPA BIOSYSYTEM®, U.S.A) then the PCR reaction mixture was digested with the Bsh12361( BstU-I) restriction endonuclease (Thermo scientific, EU).
Our results showed that patients with SVR had a significantly lower IP10 level as compared to NRs .
ROC curve analysis showed that the pretreatment IP-10 level with the best sensitivity- specificity for identifying SVR was 499.02 pg/ml.
There was a statistically significant association between IL28B genotype and treatment response as the carriage of a C allele at the IL-28B gene polymorphism (rs12979860) is favorably associated with treatment response.
There was also a statistically significant lower baseline plasma IP-10 levels in homozygous carriers of the favourable CC at rs12979860 and the risk allele, T is found to be statistically associated with elevation of baseline plasma IP-10 level.
We assessed whether other baseline parameters, in addition to IL28B genotype and serum IP-10, could significantly improve the prediction of SVR and we found that patients with SVR were younger, had lower BMI and lower baseline ALT and AST levels.
There was no significant difference in baseline HCV RNA levels between SVR and NRs.
There was also a statistically significant impact of necroinflammatory activity grade (A) and fibrosis stage (F) on treatment response as we found that patients with moderate fibrosis and mild activity (METAVIR score; A1F2) had a higher SVR rates
We did not find any statistically significant difference in response to treatment between patients co-infected with schistosomiasis and patients who are negative for Anti$ Abs.