129 patients with chronic hepatitis C Early on-treatment response as a predictor of sustained virological response in genotype 4 HCV naive Egyptian patients treated with peginterferon plus ribavirin Haitham G. Zakaria1, Samira Saleh2, Manal El Hamamsy3, Mohamed S. El Din4, Hassan El Batae4, Ahmed El Maadawy5 1Pharmacology & Toxicology Department, October 6 University,2Pharmacology & Toxicology Department, Cairo University, 3Clinical Pharmacy Department, Ain Shams University, 4 Tropical Medicine and Infectious Disease Department, Tanta University,5Consultant in Kafr El Sheikh Liver and Cardiac Center Effect of body weight Introduction Fig. 4: Comparison between the numbers of naïve Egyptian patients (%) treated with combination of pegylated interferon and ribavirin with body weight ≤ 75 Kg and those with body weight >75 Kg who showed SVR, relapse or were non responders Introduction Study design Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) and is a major problem throughout the world. There are an estimated 300 million persons chronically infected with HCV globally. 129 patients with chronic hepatitis C Egypt reports the highest prevalence of HCV worldwide, ranging from 6% to more than 40% among regions and demographic groups. Predicting the impact of the epidemic has been difficult because of the long-latency period and low resource setting. The highest incidence rate was calculated among those over 35 years of age. These results support the claim of high HCV incidence in Egypt and suggest that HCV may lead to a substantial health and, consequently, economic burden over the next 10-20 years. Genotype 4 is found mainly in the Middle East and North Africa and its prevalence rates ranges from 3-5% in Saudi Arabia to 90% in Egypt. Treatment with PEG IFN α 2a + RBV Treatment with PEG IFN α 2b + RBV Each column represents the % of patients Fig. 5: Comparison between the numbers of Female and male naïve Egyptian patients (%) treated with combination of pegylated interferon and ribavirin that showed SVR, relapse or were non responders The combination therapy with pegylated interferon (PEG)-IFN and ribavirin (RBV) in genotype 4 patients showed response rates at an intermediate level compared to genotype 1 and genotypes 2 or 3, with sustained virological response (SVR; seronegative for HCV RNA at 24-week follow-up) rates between 65% and 72%. In a retrospective analysis of the predictive value of an rapid virological response (RVR; seronegative for hepatitis C virus [HCV] RNA at 4 weeks) in persons with HCV genotype 1 treated with peginterferon alfa-2a, those who achieved an RVR had an SVR rate of 91%, those who achieved a complete EVR had an SVR rate of 75%, and those who achieved an undetectable HCV RNA at week 24, had an SVR rate of 45%. RVR Positive Negative EVR Each column represents the % of patients Positive Negative Fig. 6: between the numbers of naïve Egyptian patients (%) treated with combination of pegylated interferon and ribavirin with baseline viral load ≤ 6 x 105 IU/ml and those with baseline viral load > 6 x 105 IU/ml, who showed SVR, relapse or were non respondersComparison STOP Non-responder PCR at week 48 Aim of Study Aim of Study Positive Negative The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, predictors of treatment success in routine clinical practice remain to be established. The aim of the current study was to estimate the importance of RVR and other host and viral factors in naïve Egyptian patients treated with 48 weeks of pegylated interferon and ribavirin. STOP Non-responder 24 weeks follow up Positive “Relapse” Negative “SVR” Each column represents the % of patients Material and Methods Results Fig. 7: Comparison between the different activity grades (by Metavir score system) in naïve Egyptian patients treated with combination of pegylated interferon and ribavirin that showed SVR, relapse or were non responders The studied subjects were classified into two groups according to HCV RNA by PCR at week 4:- Group 1 (gp І): Ninety five patients with negative PCR at week 4 (N=95). Group 2 (gp П): Twenty six patients with positive PCR at week 4 (N=26). Egyptian patients with chronic hepatitis C, aged 18 – 65 yr. Undergone a liver biopsy that was consistent with chronic Inclusion criteria: Seropositive for HCV antibodies, RNA. No pregnancy or lactation, and the use of a reliable method of contraception. hepatitis within 1 year before entry. Genotype 4 infection. Figures Fig. 1: Viral response during treatment and at week 24 after treatment termination in naïve Egyptian patients of group I and II Each column represents the % of patients Fig. 8: Comparison between the different Fibrosis stages (by Metavir score system) in naïve Egyptian patients treated with combination of pegylated interferon and ribavirin that showed SVR, relapse or were non responders Each column represents the % of patients **Significant compared to what at p< 0.01 Patient selection Each column represents the % of patients *Significant at P< 0.05 Fig. 2: Comparison between the numbers of naïve Egyptian patients (%) treated with combination of pegylated interferon and ribavirin with negative PCR at week 4 and those with negative PCR at week 12 who showed SVR, relapse or were non responders Overall, SVR was achieved by 85 patients (70.2%), while 26 patients relapsed (21.5%). RVR occurred in 95 patients where 77 of them achieved SVR (81%) and 14 of them relapsed (14.7%). Also patients with pretreatment low fibrosis stage achieved SVR by 75.4%, 70.8% and 25% and relapsed by 18.5%, 18.8% and 62.5% for F1, F2 and F3 (according to Metavir score) respectively. Human immunodeficiency virus infection, autoimmune hepatitis. Exclusion criteria: Presence of hepatitis B surface antigen. Decompensated cirrhosis, overt hepatic failure, psychiatric condition. Primary biliary cirrhosis, sclerosing cholangitis. Previous liver transplantation, or with evidence of hepatocellular carcinoma. Wilson disease, alpha1-antitrypsin deficiency. Abnormal thyroid function, clinically significant retinal abnormalities. Poorly uncontrolled diabetes, body mass index >35. Alcohol or I.V. drugs abusers were excluded from the study. Conclusion RVR is a strong predictor of SVR. However, it is independent of patients’ pretreatment status, including age, weight, gender and grade of hepatocytes inflammation. Low pretreatment fibrosis stage is a good predictor of SVR. Age, weight, gender, Pretreatment viral load and viral activity didn’t definitely differ in achieving SVR. Each column represents the % of patients Fig. 3: Comparison between the numbers of naïve Egyptian patients (%) treated with combination of pegylated interferon and ribavirin with age ≤ 45 years and those with age >45 years who showed SVR, relapse or were non responders Effect of age Each column represents the % of patients

Early on-treatment response as a predictor of sustained virological response in genotype 4 HCV naive Egyptian patients treated with peginterferon plus ribavirin Captions to be set in Times or Times New Roman or equivalent, italic, 18 to 24 points the length of the column in case a figure takes more than 2/3 of column width.