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Efficacy and Safety of a Novel Pegylated Interferon Alpha-2A in Egyptian Patients with Genotype 4 Chronic Hepatitis C

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Efficacy and Safety of a Novel Pegylated Interferon Alpha-2A in Egyptian Patients with Genotype 4 Chronic Hepatitis C ORIGINAL ARTICLE Efficacy and safety of a novel pegylated interferon alpha-2a in Egyptian patients with genotype 4 chronic hepatitis C Alaa Awad Taha MD1, Ahmad El-Ray MD1, Maged El-Ghannam MD1, Bahaa Mounir MD2 AA Taha, A El-Ray, M El-Ghannam, B Mounir. Efficacy and L’efficacité et l’innocuité d’un nouvel safety of a novel pegylated interferon alpha-2a in Egyptian patients with genotype 4 chronic hepatitis C. Can J Gastroenterol interféron alpha-2a pégylé chez des patients 2010;24(10):597-602. égyptiens atteints d’une hépatite C chronique de génotype 4 BACKGROUND: Hepatitis C virus (HCV) genotype 4 is a common infection in Egypt and is the leading cause of liver disease. HISTORIQUE : Le virus de l’hépatite C (VHC) de génotype 4 est une OBJECTIVE: To study the efficacy and safety of a novel 20 kD pegy- infection courante en Égypte et constitue la principale cause de mala- lated interferon alpha-2a derived from Hansenula polymorpha in com- die hépatique. bination with ribavirin for the treatment of Egyptian patients with OBJECTIF : Étudier l’efficacité et l’innocuité d’un nouvel interféron genotype 4 chronic hepatitis C (CHC). alpha-2a pégylé 20 kD dérivé de l’Hansenula polymorpha associé à de la METHODS: One hundred seven patients with genotype 4 CHC were ribavirine pour traiter des patients égyptiens atteints d’hépatite C involved in the present study. Liver biopsy was performed in all chronique (HCC) de génotype 4. patients. All patients received a fixed weekly dose of 160 µg of a novel MÉTHODOLOGIE : Cent sept patients atteints d’HCC de génotype 4 pegylated interferon in combination with ribavirin in standard and ont participé à la présente étude. Ils ont tous subi une biopsie hépa- adjusted doses. Serum HCV RNA levels were assessed by a real-time tique et reçu une dose hebdomadaire fixe de 160 µg d’un nouvel inter- sensitive polymerase chain reaction assay at four, 12, 48 and 72 weeks féron pégylé en association avec de la ribavirine en doses standards et after the start of therapy. Patients demonstrating an early virological rajustées. Les taux d’ARN du VHC sérique ont été évalués au moyen response (EVR) completed a 48-week course of treatment. du titrage d’une réaction en chaîne de la polymérase sensible en temps RESULTS: The overall sustained virological response (SVR) was réel quatre, 12, 48 et 72 semaines après le début du traitement. Les 60.7%. The SVR in patients with a rapid virological response was sig- patients démontrant une réponse virologique précoce (RVP) ont reçu nificantly higher (91.7%) than in patients with complete EVR un traitement de 48 semaines. (67.74%) (P=0.033) and partial EVR (56.14%) (P=0.003). SVR was RÉSULTATS : La réponse virologique soutenue (RVS) globale était also significantly higher in patients with a low degree of liver fibrosis de 60,7 %. La RVS chez les patients ayant une réponse virologique according to Metavir score (F1 and F2) (67.57%) compared with those rapide était considérablement plus importante (91,7 %) que chez les with a high degree of liver fibrosis (F3 and F4) (45.45%) (P=0.017). patients ayant une RVP complète (67,74 %) (P=0,033) et partielle The baseline viral load had no impact on SVR in the present series nor (56,14 %) (P=0,003). La RVS était également considérablement plus were any serious adverse events reported. importante chez des patients ayant une fibrose hépatique légère selon CONCLUSION: The novel pegylated interferon alpha-2a assessed l’indice de Metavir (F1 et F2) (67,57 %) que chez ceux ayant une in the present study was effective for the treatment of patients with fibrose hépatique marquée (F3 et F4) (45,45 %) (P=0,017). La charge genotype 4 CHC, and was safe and well tolerated. virale de départ n’avait pas de répercussions sur la RVS dans la présente série, et aucun événement indésirable grave n’a été déclaré. Key Words: Chronic hepatitis C; Genotype 4; Hansenula polymorpha; CONCLUSION : Le nouvel interféron alpha-2 pégylé évalué dans la Pegylated interferon présente étude était efficace, sécuritaire et bien toléré pour le traite- ment des patients atteints d’HCC de génotype 4. he prevalence of chronic hepatitis C (CHC) in Egypt is combination of conventional interferon and ribavirin (3-6). Textremely high, affecting 15% to 20% of the population. However, after the introduction of pegylated interferon, subse- Hepatitis C virus (HCV) is the leading cause of liver disease quent studies reported favourable response to treatment with in Egypt and is one of the country’s major health problems. pegylated interferon alpha (a)-2a and a-2b in combination with Genotype 4 is the predominant genotype of HCV in Egyptian ribavirin (7-11), with the exception of a single report (12). patients (up to 91%) (1). Genotype is one of the most import- In the past decade, only two pegylated interferon products ant pretreatment factors that affect response to therapy (2). have been available: pegylated interferon a-2a (Pegasys, Genotype 4 is the least studied HCV genotype, and is prevalent Hoffmann-LaRoche, Switzerland) and pegylated interferon in developing countries in Africa and the Middle East. This a-2b (PegIntron, Schering-Plough, USA). Interferon therapy particular genotype was considered difficult to treat with the will likely remain the backbone of treatment for CHC despite 1Department of Hepatogastroenterology, Theodor Bilharz Research Institute; 2Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Correspondence: Dr Alaa Awad Taha, Theodor Bilharz Research Institute, Department of Hepatogastroenterology, Cornich El-Nile, Imbaba, Cairo, Al Qahirah, Egypt. Telephone 2-010-100-2964, fax 2-023-540-8125, e-mail [email protected] Received for publication April 3, 2010. Accepted May 26, 2010 Can J Gastroenterol Vol 24 No 10 October 2010 ©2010 Pulsus Group Inc. All rights reserved 597 Taha et al the large number of oral anti-HCV agents under development. antihepatitis B core antigen antibodies, major depressive ill- Attempts to introduce novel interferons with the aim of ness, solid organ transplant, schistosomiasis or concomitant increasing therapeutic efficacy, reducing adverse events and/or clinically significant disease (uncontrolled diabetes mellitus, reducing the cost of therapy are important. Many novel inter- significant ischemic heart disease, severe hypertension, auto- ferons, such as consensus interferon and albinterferon, were immune disorders and thyroid disease). developed and studied for their efficacy in the treatment of CHC in the past few years. Albinterferon a-2b was reported to Patient evaluation and liver histology be effective for the treatment of CHC genotypes 2 and 3 (13) and All patients were clinically assessed by full history and thor- genotype 1 (14), with the advantage of a better dosing schedule ough clinical examination. Laboratory tests included the fol- but at the expense of cost. In 2007, a novel interferon was intro- lowing: complete blood count, alanine aminotransferase duced in Egypt and was approved for the treatment of CHC. (ALT), aspartate aminotransferase, bilirubin, international Reiferon Retard (Rhein MinaPharm, Egypt) is a linear 20 kD normalized ratio, serum albumin, creatinine, fasting and post- pegylated interferon a-2a derived from Hansenula polymorpha. prandial blood glucose, circulating schistosomal antigen and The cost of this novel interferon is markedly less than that of the thyroid-stimulating hormone. Abdominal ultrasound examina- existing peginterferons. To date, only a single study (15) inves- tion was performed in all patients. Serum HCV RNA levels tigating the efficacy and safety profile of this novel pegylated were assessed using a real-time sensitive PCR assay (Cobas interferon for the treatment of Egyptian patients with geno- Amplicor HCV monitor, version 2.0, Roche Diagnostics; lower type 4 CHC is available. limit of quantitation = 50 IU/mL). HCV genotyping was per- The H polymorpha expression system has been known for its formed by restriction fragment length polymorphism analysis. superior characteristics for decades. Due to an increasing num- A baseline viral load of 600,000 IU/mL or greater was defined ber of products and protein candidates derived from this as high viral load (HVL), while a level ranging from the expression system, it has been gaining greater popularity in lower detection limit of the assay (50 IU/mL) to less than recent years. H polymorpha represents a stable, robust and safe 600,000 IU/mL was defined as low viral load (LVL). expression system (GRAS 1 organism), which boasts one of Liver biopsy was performed in all patients using a Menghini the highest productivities ever described for a recombinant needle (Hepafix 1.4, B Braun Melsungen AG, Germany). Biopsy protein (13.5 g/L of recombinant phytase). In addition, pro- specimens were assessed by an experienced pathologist who was duction processes based on H polymorpha technology are very blinded to the clinical and laboratory data. Metavir score was used cost effective. The cost effectiveness is strongly related to very for the assessment of necroinflammation grade (A0 to A3) and short fermentation times and to a significantly reduced number the degree of fibrosis (F0 to F4). Upper gastrointestinal endos- of downstream steps, resulting in a higher purity, with no forms copy was performed in patients with F3 and F4 fibrosis grade to of oxidized interferon being detected (16). The aim of the exclude the presence of esophageal or gastric varices. present study was to assess the efficacy and safety profile of this novel 20 kD pegylated interferon a-2a derived from H polymor- Study design and assessment of response pha (Reiferon Retard) in combination with ribavirin for the All patients received a fixed weekly dose of 160 µg of a novel treatment of Egyptian patients with genotype 4 CHC. 20 kD linear pegylated interferon a-2a (Reiferon Retard) derived from H polymorpha in combination with ribavirin in METHODS standard and adjusted doses.
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