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Ultrarapid Hepatitis C Virus Clearance By Daily High-Dose Interferon in Non-Responders to Standard Therapy

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  • claudine intexas
    Ultrarapid hepatitis C virus clearance by daily high-dose interferon in non-responders to standard therapy. J Hepatol 1998 Jun;28(6):960-4 (ISSN: 0168-8278)
    Message 1 of 1 , Jul 31, 2000
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      Ultrarapid hepatitis C virus clearance by daily
      high-dose interferon in non-responders to standard
      therapy.

      J Hepatol 1998 Jun;28(6):960-4 (ISSN: 0168-8278)

      Bekkering FC; Brouwer JT; Leroux-Roels G; Van
      Vlierberghe H; Elewaut A; Schalm SW [Find other
      articles with these Authors]
      Department of Hepatogastroenterology and Internal
      Medicine, University Hospital Rotterdam--Dijkzigt, The
      Netherlands.

      BACKGROUND/AIMS: To analyze the kinetics of the
      hepatitis C virus and the patterns of resistance to
      interferon alpha, we assessed HCV RNA levels early
      during retreatment with high-dose interferon in
      patients who did not respond to standard treatment.
      METHODS: Eleven non-responders to previous therapy
      with 3-6 MU interferon three times a week were
      retreated with daily 10 MU. Plasma was sampled at days
      0, 1, 2, 3, 14 and 28; all samples were prepared
      within 2 h and stored at -70 degrees C without thawing
      until analysis. The quantitative HCV RNA level was
      assessed by the Superquant assay (NGI, USA). The
      Eurohep reference panel, tested blindly, confirmed the
      linearity of the assay with a detection limit for
      genotypes 1 and 3 between 10(2) and 10(3) copies/ml.
      RESULTS: All patients showed a fall in viral load
      between week 0 and week 2 (2.6 log, i.e. 99.7%, range
      1.3-4.7 log), whereas no fall was detected after week
      2. Closer examination in nine patients revealed that
      all had a dramatic fall in the first 2 days (first day
      1.8 log, 0.8-3.5; second day 0.8 log, -0.2-1.3),
      without any significant fall thereafter. The
      calculated half-life of viral decay in plasma was 5
      (2-8.9) h, corresponding to a clearance of 2.4
      (0.2-13.7) x 10(11) virions per day. Sustained
      responders showed a significantly greater fall in
      viral load in the first day (3.2 log, 2.8-3.5) than
      those who did not respond (1.4 log, 0.8-2.1, p=0.001).
      All three sustained responders had undetectable plasma
      HCV RNA at day 14. CONCLUSION: In patients without a
      response to standard interferon, the hepatitis C virus
      has a high daily turnover rate similar to that
      reported in naive patients. Our findings suggest that
      an early clearance of HCV RNA from the circulation is
      the key to a sustained response, which might be
      induced in about 25% of these patients by treatment
      with high (10 MU) daily doses of interferon. These
      findings have important implications for the concept
      of treatment of hepatitis C, which should shift its
      focus from long-term mild treatment towards aggressive
      therapy aiming at a fast viral disappearance within
      the first few days.



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      Claudine
      claudinecrews@...

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