Hansenula-Derived Pegylated-Interferon Alpha-2a in Egyptian Children With Chronic HCV
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional

Summary: 
      Egypt has the highest prevalence of hepatitis C virus infection in adults (up to 20%) and
      children (up to 5.5%). The major genotype (90%) is type 4. Pegylated interferon-alpha-2a or
      -2b and ribavirin have been used in small numbers of hepatitis C virus-infected children with
      sustained virological response being higher in genotypes 2 and 3 than in genotypes 1 and 4.
      Genotype 4 is has been described as difficult-to-treat genotype. Several attempts to modify
      treatment protocols have been tried in adults in an attempt to achieve higher rates of
      sustained virological response. Shortening injection interval and/or treatment duration
      prolongation have been tried with variable outcome reports.

      A novel Hansenula- derived pegylated interferon alpha 2a: 20 Kilo dalton (Reiferon Retard)
      has been used over the last 4 years in the Egyptian market.

      We aimed to investigate the safety and efficacy of Reiferon retard plus ribavirin customized
      regimen in hepatitis C virus-RNA seropositive Egyptian children. Forty six children with
      chronic hepatitis C virus aged 3-19 years were selected from 3 hepatic tertiary centers.

      Clinical and laboratory evaluation were undertaken. Quantitative polymerase chain reaction
      (PCR) for HCV-RNA was done before starting treatment, at 4, 12, 24, 48, 72 weeks during
      treatment and 6 months after stoppage of treatment. All patients were assigned to receive a
      weekly subcutaneous injection of pegylated interferon alpha 2-a ( Reiferon Retard) plus oral
      Ribavirin daily for 12 weeks ,then cases were divided according to PCR results into 2 groups.

      Group I: Patients who continued treatment on weekly basis: this group included patients who
      had negative PCR at week 12 as well those who had positive PCR without any change in viremia.
      Group II: Patients who continued treatment on a 5- days schedule: this group included
      patients who had any decrease in viremia at week 12.

      Patients who were PCR-negative at week 48 and had at least one PCR-positive test during
      therapy were assigned to have an extended treatment course of 6 months duration.

      The occurrence of adverse effects was assessed during treatment and follow up
    

Detailed description: 
      hepatitis C virus is a major health problem, not only in adults but also in the pediatric age
      group. In Egypt, the prevalent genotype is the difficult-to-treat genotype 4. Attempts are
      being made to improve the treatment outcomes. In the current study we aim to investigate the
      effect of customized pegylated interferon-alpha-2a plus ribavirin in children with chronic
      hepatitis C virus. For that, 46 children with chronic hepatitis C virus were recruited from
      three tertiary Pediatric Hepatology centers. All were assigned to receive weekly subcutaneous
      pegylated interferon-alpha-2a plus daily ribavirin for 12 weeks. At this point, the study
      population was divided into two arms. Arm 1 included those who became hepatitis C virus-RNA
      negative by polymerase chain reaction and those who showed no change of viremia or a decrease
      of less than 1 log. This group continued treatment on weekly bases for 48 weeks, even those
      who are hepatitis C virus-RNA positive. Arm 2; included patients who had a decrease in
      viremia more than one log of pre-treatment viremia level. For those patients, injection
      interval was shortened to every 5-day for a completion period of 48 weeks. Patients from
      either group who were polymerase chain reaction-negative at week 48, but had at least one
      polymerase chain reaction-positive test during therapy, were assigned to have an extended
      treatment course up to 72 weeks.

      So the first customization was,

        1. prolongation of treatment duration for up to 48 weeks regardless response type

        2. Shortening injection interval in some patients to every 5-day injection

        3. The third customization was the prolongation of treatment for extra 6 months, i.e. up tp
           72 weeks in some patients.

      The occurrence of adverse effects, virological and biochemical responses were assessed during
      treatment and follow up.
    

Intervention name(s): Reiferon R; Ribavirin
Intervention type(s): Drug; Drug
Intervention description(s): subcutaneous injection of 100 μg/m2; 15 mg/kg daily on two divided doses
Other intervention name(s): Hansenula-derived pegylated interferon alpha 2a; Reiferon Retard
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Children; Chronic hepatitis C; Hansenula polymorpha; Pegylated interferon; Response rate; Ribavirin; Treatment