A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha-2a or peginterferon alfa-2b) is most effective. We performed a systematic review of head-tohead randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects metaanalysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04-1.19; P ‫؍‬ 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two peginterferons. Conclusion: Current evidence suggests that peginterferon alpha-2a is associated with higher SVR than peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010;51:1176-1184 G lobally, an estimated 170 million people are chronically infected with hepatitis C virus, and 3 to 4 million persons are infected each year. 1 Analysts estimate the United States prescription market for hepatitis C to be approximately $3 billion annually. A combination of weekly subcutaneous injections of longacting pegylated interferon (peginterferon) and oral ribavirin represents the current standard of care according to the American Association for the Study of Liver Diseases practice guideline. 2 Currently, there are two licensed products: peginterferon alpha-2a (Pegasys, Hoffmann-La Roche) and peginterferon alfa-2b (PegIntron, ScheringPlough Corporation). Lately, there has been considerable controversy over which treatment options are the most Abbreviations: CI, confidence interval; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; OIS, optimum information size; peginterferon, pegylated interferon; RCT, randomized clinical trial; RR, risk ratio; SVR, sustained virological response. From the

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BackgroundEgypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results.ObjectivesAssessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients.Patients and MethodsThis retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects.ResultsThe ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a.ConclusionsPeginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients.

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Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.

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