The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Chronic Hepatitis C
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Observational

Summary: 
      The efficacy of combination antiviral therapy for chronic hepatitis C is influenced by many
      factors. Important patient-specific factors include, age, gender, race, body weight.
      Important virus-specific factors include HCV genotype and serum HCV RNA level. Finally,
      important treatment-related factors include the type of interferon, dose of ribavirin and the
      duration and adherence to treatment.

      Despite the importance of patient- and virus-specific factors, the most important indicator
      of treatment success is a rapid, profound and sustained decrease in serum HCV RNA levels
      after the start of treatment.

      The on-treatment virological response can thus be used to predict the probability that a
      given patient will achieve an SVR if they remain on therapy. It can also be used to
      individualize the duration of treatment.

      In this study, treatment for patients with chronic hepatitis C was individualized on the
      basis of clinical characteristics and the on-treatment virological response. The aim was to
      investigate the usefulness of undetectable HCV RNA levels at week 4 (RVR) and 12 in tailoring
      the duration of treatment and predicting SVR in Chinese patients with chronic hepatitis C.
    

Detailed description: 
      297 consecutive patients with chronic hepatitis C who were admitted to hospital or treated as
      outpatients at Beijing Ditan Hospital were eligible for the study. The diagnosis of chronic
      hepatitis C was based on the detection of anti-HCV antibodies (anti-HCV) by a third
      generation microparticle chemoluminescence assay and HCV RNA by a reverse transcription
      polymerase chain reaction (RT-PCR) assay. Patients were required to have evidence of HCV
      infection for at least 6 months.

      patients received peginterferon alfa-2a (40KD) (Pegasys®; Roche, Basel, Switzerland) 135 or
      180 µg by subcutaneous injection once weekly.

      Among treatment-naive patients, the duration of therapy was determined by HCV genotype and
      the on-treatment virological response at week 4, 12 or 24. Genotype 1 infected patients were
      assigned to complete a 48~72 weeks of treatment, and those who had not responded to a
      previous course of therapy were assigned to complete a total of 72 weeks of treatment.

      Dose adjustment: In the event that a patient did not achieve an RVR at week 4, and provided
      they were not experiencing adverse events, the daily dosage of ribavirin was increased by 200
      mg or 300 mg, and in the case of those who started treatment on the lower dosage of
      peginterferon alfa-2a (40KD) or conventional interferon alfa, the dosage of peginterferon
      alfa-2a (40KD) was increased from 135 µg/week to 180 µg/week. In the event of adverse events
      that could not be ameliorated with symptomatic treatment, the dose of peginterferon alfa-2a
      (40KD) was reduced from 180 µg/week to 135 µg/week and of ribavirin by 200 mg/day or 300
      mg/day.

      Quantitative HCV RNA testing was performed before starting treatment (week 0), at week 4, 12,
      and 24, and at the end of treatment, and 24 weeks after completion of treatment using a
      commercially available real-time fluorescence quantitative PCR kit. The primary efficacy
      end-point was achievement of SVR defined as undetectable HCV RNA at the end of a 24-week
      untreated follow-up period. The percentage of patients with undetectable HCV RNA (<500
      copies/mL) at week 4 (RVR), and 12 were secondary efficacy endpoints.
    

Intervention name(s): Pegylated interferon alfa-2a and ribavirin
Intervention type(s): Drug
Intervention description(s): all patients were given peginterferon alfa-2a (40KD) (Pegasys®; Roche, Basel, Switzerland) 135 or 180 µg by subcutaneous injection once weekly, and received twice daily oral ribavirin at a target total daily dose of 13 mg/kg/day. .
Other intervention name(s): Pegasys®; Roche, Basel, Switzerland
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Consecutive patients with chronic hepatitis C who were admitted to hospital or treated as
        outpatients at Beijing Ditan Hospital were eligible for the study.