Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children.
OBJECTIVE
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.


CONCLUSIONS
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.
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Suzan
S
El Naghi
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Tawhida Y
TY
Abdel-Ghaffar
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Hanaa
H
El-Karaksy
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Elham F
EF
Abdel-Aty
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Mona S
MS
El-Raziky
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Aleef A
AA
Allam
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Heba
H
Helmy
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Hanaa A
HA
El-Araby
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Behairy E
BE
Behairy
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Mohamed A
MA
El-Guindi
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Hatem
H
El-Sebaie
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Aisha Y
AY
Abdel-Ghaffar
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Nermin A
NA
Ehsan
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Ahmed M
AM
El-Hennawy
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt.
Mostafa M
MM
Sira
D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
Children; Chronic hepatitis C; Hansenula polymorpha; PEGylated interferon; Response rate; Ribavirin; Treatment