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Predictors of response to treatment of HCV-CH

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    Predictors of response to treatment of HCV-CH In clinical trials of Ch Hep C, sustained response to treatment is defined as absence of HCV RNA for more than 6
    Message 1 of 1 , Jan 10, 2000
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      Predictors of response to treatment of HCV-CH

      In clinical trials of Ch Hep C, sustained response to treatment is defined
      as absence of HCV RNA for more than 6 months following therapy.
      Responsiveness of the virus to therapy is dependent upon host and viral
      factors, including genotype, quantity of circulating HCV, presence of
      hepatic fibrosis or cirrhosis, viral titer, use of ethanol during therapy,
      patient's race, and
      perhaps the quantity of iron within liver cells. Those individuals with
      genotype 1 HCV will be the least responsive to therapy. Unfortunately, this
      is the most common form of HCV in the United States.
      Identification of those patients most likely to respond to therapy is an
      important consideration in the management of chronic HCV. Symptoms related
      to HCV infection are not predictive of disease activity. Histological liver
      disease may be present without physical signs. Virologic predictors of
      sustained response to therapy include HCV genotype, pretransplant viral
      load, early disappearance of HCV-RNA during treatment, and a negative
      HCV-RNA 6 months after treatment. Stopping interferon therapy based on serum
      ALT response misses about 33% of sustained responders at week 12 compared
      with 7% using HCV-RNA levels. The sensitivity/specificity of week 4 HCV-RNA
      is higher than that of ALT at weeks 4, 8, and 12. Response appears to be
      affected by genotype (lower rates for genotype 1), race, and previous
      nonresponse to interferon therapy. In addition, alcohol intake, presence of
      cirrhosis, and pretherapy viral load are important factors for predicting
      response, as well as estimating duration, dose, and pattern of
      administration for interferon.
      The titer of HCV can also be a factor in responsiveness. Data has shown that
      when viral titer in type 1 HCV is > 2 million copies/mL, only 3% of patients
      will have a sustained response after 48 weeks of therapy (compared with a
      19% sustained response for those with < 2 million copies/mL.For non-1
      genotypes, the response is 19% and 50%, respectively, based on viral titer.

      Viral load

      HCV viral load by RT-PCR measured in copies/ml with a bearing on follow up
      and treatment outcome is as follows:

      Negative <100 copies
      Low < 1 million copies
      High >2 million copies

      Interferons

      The three interferons that are approved for the treatment of HCV in
      include recombinant interferon alfa-2b (rIFN-alpha2b, INTRON�A,
      Schering-Plough Corporation, Kenilworth, NJ), interferon alfa-2a
      (Roferon-A�, Hoffmann-La Roche Laboratories, Basle, Switzerland) and
      interferon alfacon-1 (INFERGEN�, Amgen Inc., Thousand Oaks, Calif). A
      fourth interferon, interferon alpha-1n (Wellferon�, Glaxo Wellcome Inc.,
      Research Triangle Park, NC), is also approved to treat HCV infection in a
      number of countries. These four interferons appear to be clinically
      equivalent.

      Pegylated interferon alpha-2A (PEG) versus standard interferon alpha-2A
      (IFN) for the treatment of hepatitis C has been the subject of recent
      studies.
      The serum half-life of the pegylated interferon was greater than 90 hours
      as compared to a half life of 4 to 6 hours for IFN. The addition of PEG to
      the standard interferon decreases renal clearance of interferon and reduced
      the need for injection from 3 times/week to 1 time/week whch is its major
      advantage.

      Daily alpha interferon therapy is also emerging as a viable treatment
      option. In a study daily interferon therapy for 1 year was associated with
      normalization of serum ALT in 58% of patients and marked improvement in
      liver inflammatory activity. Furthermore, daily high-dose alpha interferon
      therapy (10 MIU) has been associated with high success rates in terms of
      biochemical and virologic responses .

      (With inputs from AASLD meet)


      Dr Sharat C Misra MD, DM
      Consultant Gastroenterologist & Hepatologist
      Each morning is the doorway to a new world,
      A beginning of infinite possibilities.

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