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Abstract Summary Chronic HCV is the main cause of liver cirrhosis and liver cancer in Egypt and, indeed, one of the top five leading causes of death (Mohamed MK 2004). The current standard of care for treating previously untreated patients with chronic hepatitis C virus infection is combination pegylated interferon alfa by subcutaneous injection once weekly and oral ribavirin daily (Patel K et al. 2006). The results of clinical trials support a recommendation that patients with genotype 1 require 48 weeks of pegylated interferon therapy with daily ribavirin (1000-1200 mg dosed according to weight). Patients with the more treatment favorable genotypes 2 and 3 need to be treated for only 24 weeks with 800 mg of ribavirin daily (Manns MP et al. 2001, FriedMW et al., 2002 and Hadziyannis SJ et al. 2004). Given that many of the large clinical trials have been based in Europe or North America, data on treatment efficacy for genotypes 4-6 are limited. As a result, these patients are treated as for genotype 1 infection (Patel K et al. 2006). Retrospective analysis of three randomized trials demonstrated a rapid virologic response (RVR) to be superior to HCV genotype at predicting sustained virologic response. By varying the treatment duration based on an individual’s early response, unnecessary side effects and costs of interferon and ribavirin can be spared. As factors other than genotype emerge as predictive of future treatment success, clinicians gain more insight into guiding their patients toward a customized, best possible outcome (Fried MW et al. 2008). 111 Summary The aim of current study was to determine if a shorter course of Peginterferon and ribavirin therapy will be sufficient in carefully selected patients with chronic hepatitis C virus genotype 4 infections, as compared to the standard 48 weeks duration. This prospective study was planned and supervised by National Liver Institute (NLI) Menoufiya University and was conducted at Kafr El-Sheikh Liver Research Center. During study period extended from September 2008 to June 2011. Carefully selected 150 patients (109 adult men and 41 non pregnant women, mean age 38.6±9.4 (21-58), with documented chronic hepatitis C infection were enrolled in the study. The 150 selected patients were randomized given Pegylatedinterferon alfa-2a at a fixed dose of 180 μg/week subcutaneously together with ribavirin 1,000 to 1,200 mg daily (1,000 mg for those who weight 75 kg and 1,200 mg for those who weight >75 kg) , or Pegylated-interferon alfa-2b ;1.5 μg/kg/week given subcutaneously dosed according to body weight, together with weight-based oral ribavirin (800 mg for patients 65 kg; 1,000 mg for patients weighing 65 to 85 kg; 1,200 mg for patients weighing 85 to 105 kg) for either fixed duration of 48 weeks (control group) or a variable duration of 28, 36 weeks. All of 150 selected patients enrolled in the study should have undetectable HCV RNA at the end of week 4 and week 12 of treatment and categorized as super-responders, having attained RVR (Rapid Virologic Response) Patients had been classified according to the course of treatment into three groups; the first group with course of treatment for 28 weeks; the second group with course of treatment for 36 weeks and 112 Summary the third group with standard course of treatment for 48 weeks. Each group had been followed for 24 weeks after completion of treatment. Histopathological evaluation of pre-treatment liver biopsies was performed. Serial quantitative HCV RNA will be done at week 0, 4, 12, 24 and at the end of assigned course of treatment and at 24 weeks after completion of treatment for all groups. A total of 133 patients (40 in group I, 43 in group II, and 50 in group III) completed the proposed therapy protocol. Results: - End of treatment Response (ETR) In the variable-duration treatment group, viral clearance at the end of treatment (ETR) was achieved in 39/40 (97.5 %) of patients treated for 28 weeks in group I, versus 41/43 (95.3 %) of patients treated for 36 weeks in group II, while in standard treatment group for 48 weeks; viral clearance at the end of treatment (ETR) was achieved in 49/50 (98 %) of patients treated for 48 weeks in group III. So No significant difference at end of treatment response (ETR) between variable-duration treatment groups and standard treatment group had been noted (p=0.738). - Sustained Virologic Response (SVR) In the variable-duration treatment group sustained virologic response (SVR) was achieved in 34/40 (85%) patients treated for 28 weeks in group I , versus 38/43(88.4%) patients treated for 36 weeks in group II, while in standard treatment group; 46/50 (92%) patients treated for 48 weeks in group III. So No significant difference of sustained virologic response (SVR) between variable-duration 113 Summary treatment groups and standard treatment group had been noted (p= 0.578). |