Pegylated interferon-alpha 2b–ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis M. Derbala, 1 A. Amer, 2 A. Bener, 3 A. C. Lopez, 4 M. Omar, 5 and M. El Ghannam 5 1 Departments of Gastroenterology and 2 Hematology, 3 Medical Statistics and Epidemiology, 4 Histopathology, Hamad Medical Corporation, Doha, Qatar and 5 Theodore Bilharz Research Institute, Giza, Egypt Received June 2003; accepted for publication October 2004 SUMMARY. Egypt has a high prevalence rate of hepatitis C (HCV) infection and as much as 90% is genotype 4. Response to interferon (IFN) varies with viral genotype and degree of fibrosis. Genotype 4 is poorly sensitive to standard IFN and IFN–ribavirin combination. We evaluated pegylated interferon (PEG-IFN)-a2b in our patients. Sixty-one patients with compensated chronic HCV genotype 4 were enrolled in two groups: group A (31 patients) received IFN-a2b 3 MU three times per week and group B (30 patients) received 1.5 lg/kg PEG-IFN-a2b once weekly. Ribavirin was added to each regimen in a dose of 800–1200 mg based on body weight. Patients were followed up for 24 weeks to assess the sustained response (SR). End-of-treatment response (ETR) was achieved in 11 of 31 patients (35.48%) in group A, and 13 of 30 patients (43.33%) in group B (P < 0.05). Only eight patients in group A and 10 in group (B) achieved a sustained virological response (25.8 and 33.3%, respec- tively) (P < 0.05). By computing ETR, SR or relapse and pretreatment baseline data (pretreatment, viral load, alanine transaminases, necroinflammatory and hepatic fibrosis), both inter- and intragroup, no significant correlations could be detected. In terms of safety and tolerability, PEG-IFN-a2b and IFN-a2b were comparable. In spite of mild insignificant increase in ETR and SR with the pegylated form, the poor response of genotype 4 in Egypt (genotype 4a) to different forms of IFNs may be related to an intrinsic resistance to the direct antiviral effect of IFN. Keywords: Chronic HCV, genotype 4, pegylated interferon. INTRODUCTION Hepatitis B and C are, and will remain for some time, major health problems in Egypt and the entire continent of Africa. Both infections can lead to an acute or silent course of liver disease, progressing from liver impairment to cirrhosis and decompensated liver failure or hepatocellular carcinoma (HCC) in a 20–30-year period [1]. Genotype 4 hepatitis C virus (HCV) is the most prevalent type in Egyptian chronic active hepatitis (CAH) patients [2]. Interferon-alpha (IFN-a) is a clinically effective therapy used in a wide range of viral infections and cell proliferative disorders. However, standard IFN-a has the drawbacks of a short serum half-life and rapid clearance [3] and even when combined with ribavirin, more than 50% of the patients do not eliminate the virus [4]. Options to enhance response rates include modification of the IFN dosing schedule with daily dose, and introduction of new generations such as consensus interferon. The short half-life of IFN, resulting in wide fluctuations in antiviral activity, led to the development of longer-lasting PEG-IFN through the attachment of a large polyethylene glycol molecule. Two pegylated forms, peginterferon a-2b (PEG- IFN-2b; Peginteron, Schering-Plough, Kenilworth, NJ, USA) and peginterferon a-2a (PEG-IFN-2a; Pegasys, Hoffman La Roche, Basel, Switzerland) have been developed and tested clinically. Pegylated interferons with or without ribavirin were shown in several studies to improve sustained virolo- gical response compared with standard IFNa-2b therapy [5]. The efficacy of PEG-IFNa-2a alone or in combination with ribavirin in inducing high rates of sustained virologic re- sponse may be due to the higher efficacy of PEG-IFN in induction and maintenance of significant multi-specific HCV- specific CD4+ T-helper 1 responses [5]. HCV genotype 1 and 4, high pretreatment viral load and cirrhosis were all considered as predictors of poor response to antiviral therapy [6]. We evaluated the efficacy of ribavirin and PEG-INF-a2b compared with IFN-a2b and ribavirin in treatment naı ¨ve Abbreviations: CAH, chronic active hepatitis; ETR, end-of-treatment; PEG-IFN, pegylated-interferon; SR, sustained response. Correspondence: Dr M.F. Derbala, Gastroenterology Department, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar. E-mail: moutazderbala@hotmail.com Journal of Viral Hepatitis, 2005, 12, 380–385 doi:10.1111/j.1365-2893.2005.00604.x Ó 2005 Blackwell Publishing Ltd