Brief Article
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World J Gastroenterol. Apr 28, 2014; 20(16): 4681-4691
Published online Apr 28, 2014. doi: 10.3748/wjg.v20.i16.4681
Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children
Suzan El Naghi, Tawhida Y Abdel-Ghaffar, Hanaa El-Karaksy, Elham F Abdel-Aty, Mona S El-Raziky, Aleef A Allam, Heba Helmy, Hanaa A El-Araby, Behairy E Behairy, Mohamed A El-Guindi, Hatem El-Sebaie, Aisha Y Abdel-Ghaffar, Nermin A Ehsan, Ahmed M El-Hennawy, Mostafa M Sira
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt
Suzan El Naghi, Tawhida Y Abdel-Ghaffar, Yassin Abdel Ghaffar Charity Center for Liver Disease and Research, 2851 Cairo, Egypt
Tawhida Y Abdel-Ghaffar, Pediatric Department, Ain Shams University, 11566 Cairo, Egypt
Hanaa El-Karaksy, Mona S El-Raziky, Heba Helmy, Department of Pediatrics, Cairo University Pediatric Hospital, 11562 Cairo, Egypt
Elham F Abdel-Aty, Aleef A Allam, Hanaa A El-Araby, Behairy E Behairy, Mohamed A El-Guindi, Mostafa M Sira, Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
Hatem El-Sebaie, Biochemistry Department, National Liver Institute, 32511 Menofiya, Egypt
Aisha Y Abdel-Ghaffar, Clinical Pathology Department, Ain Shams University, 11566 Cairo, Egypt
Nermin A Ehsan, Pathology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
Ahmed M El-Hennawy, Pathology Department, Cairo University, Faculty of Medicine, Kasr El-Aini, 11562 Cairo, Egypt
Author contributions: El Naghi S, Abdel-Ghaffar TY, El-Karaksy H, El-Raziky MS, El-Araby HA, Behairy BE, El-Guindi MA and Sira MM were involved in the study concept and design; El Naghi S, Abdel-Ghaffar TY, El-Karaksy H, Abdel-Aty EF, El-Raziky MS, Allam AA, Helmy H, El-Araby HA, Behairy BE, El-Guindi MA and Sira MM were involved in recruitment of patients, clinical management, follow up and contributed to data acquisition; Sira MM performed the statistical analysis and designed the figures; El Naghi S, Abdel-Ghaffar TY, El-Karaksy H and Sira MM performed the data interpretation; El Naghi S, Abdel-Ghaffar TY, El-Raziky MS and Sira MM wrote the manuscript; Abdel-Ghaffar AY and El-Sebaie H performed laboratory tests and genotyping; Ehsan NA and El-Hennawy AM performed histopathological examinations; all the authors reviewed the manuscript.
Supported by Yassin Abdel-Ghaffar Charity Center for Liver Disease and Research, Cairo, Egypt, in collaboration with the National Liver Institute, Menofiya University, Egypt and Cairo University Pediatric Hospital, Cairo, Egypt; Antiviral medications (PEG-IFN-alpha-2a and ribavirin) and HCV genotyping were offered as donation from Yassin Abdel-Ghaffar Charity Center for Liver Disease and Research, Cairo, Egypt
Correspondence to: Mostafa M Sira, MD, Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Gamal Abd El-Nasir, Shebin El-koom, 32511 Menofiya, Egypt. msira@liver-eg.org
Telephone: +20-48-2222740 Fax: +20-48-2234586
Received: October 20, 2013
Revised: January 7, 2014
Accepted: March 4, 2014
Published online: April 28, 2014
Abstract

AIM: To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection.

METHODS: Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493).

RESULTS: Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well.

CONCLUSION: Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Keywords: Children, Chronic hepatitis C, Hansenula polymorpha, PEGylated interferon, Response rate, Ribavirin, Treatment

Core tip: Egypt has the highest prevalence of hepatitis C virus (HCV) infection in the world (15%-25%) and the main (90%) genotype is type 4. Prevalence in Egyptian children was found to be 3% in upper Egypt and 9% in lower Egypt. PEG-IFN-alpha-2a or -2b and ribavirin have been used in small numbers of HCV-infected children, whose SVRs are higher in genotypes 2/3 than in genotypes 1/4. A novel 20-kDa PEG-IFN-alpha-2a (Reiferon Retard) derived from the Hansenula polymorpha expression system has been used in adults with chronic HCV, achieving an SVR ranging from 56% to 60.7%, while no studies have been reported in children before.