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AASLD - report day 2 / Pegylated Interferon Improves Liver Histology

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  • claudine intexas
    NATAP www.natap.org AASLD Summaries archived on NATAP web site ... AASLD - Association for the Study of Liver Diseases October 27-31 2000 Dallas Reported by
    Message 1 of 1 , Oct 29 6:46 PM
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      AASLD Summaries archived on NATAP web site

      AASLD - Association for the Study of Liver Diseases
      October 27-31 2000
      Reported by Jules Levin

      Pegylated Interferon Non-Responders Still Appear to
      Improve Histology (liver
      condition) 50% of the Time

      Its hot, muggy, and rainstorming in Dallas. In an oral
      presentation today,
      Robert Reindollar from the Carolinas Center for Liver
      Diseases (Charlotte,
      NC) reported on a comparison of PEGylated Interferon
      (40kDa: 40 kilodalton
      weight) (Pegasys) to Roferon (regular interferon).
      Data from multiple studies
      was assembled to examine the relationship between
      virologic and histologic
      responses following treatment with either Peg IFN a-2a
      or regular IFN a-2a in
      IFN-na�ve (patients never before treated with
      interferon) patients. Data
      from two large Pegasys clinical trials were gathered
      to examine baseline
      predictors of histologic improvement in patients
      without a virologic
      response. The two trials were multi-national pivotol
      studies including one
      study in people with chronic HCV and another in
      patients with compensated

      Only patients with paired liver biopsies were included
      in the study. That is,
      patients who had biopsies before and after treatment.
      The total number of
      patients were 599, and 430 had paired biopsies.
      Patients were randomized to
      receive either IFN a-2a 3 MIU three times weekly
      (n=202) or PEGasys IFN a-2a
      180 ug once weekly (n=228). They received 48 weeks of
      treatment and 24 weeks
      follow-up after treatment ended. A baseline liver
      biopsy within 12 months of
      starting this study, and a biopsy at the end of 24
      weeks of follow-up were

      DEFINITIONS OF RESPONSES for the purposes of this
      Histological response: improvement of at least 2
      points in total HAI score on
      biopsy 24-weeks post-treatment (week 72).

      Sustained virologic response: undetectable HCV-RNA
      (<100 copies/ml) at the
      end of follow-up (week 72).

      Partial virologic response: at least a 2-log decrease
      from baseline PCR value
      at any time during the study. This group also included
      individuals who had a
      complete virologic response but did not have a
      sustained virologic response.
      Presumably, patients who were undetectable at end of
      treatment but relapsed.

      Patients who were excluded because they did not have
      paired biopsies had an
      equal amount (41% vs 43%) of cirrhosis or bridging
      fibrosis as the group with
      paired biopsies. This was established to show that the
      study analysis did not
      leave out sicker patients. Reindollar also said this
      data shows the high
      number of patients in this analysis who are difficult
      to treat because they
      have advanced fibrosis.

      An equal amount of patients with cirrhosis or bridging
      fibrosis were in both
      treatment arms, IFN & PEG IFN (39% vs 43%,
      respectively; non-cirrhotics, 61%
      vs 57%).

      The demographics between the two treatment groups were
      also the same with
      regards to: sex, race, age (45 yrs), genotype,
      baseline HCV-RNA (7.4 million
      copies/ml), baseline HAI score, and baseline ALT (93
      vs 103).

      In non-cirrhotics: 35% (Pegasys) vs 15% (regular
      In cirrhotics or bridging fibrosis: 30% (Pegasys vs 8%
      (regular interferon)

      HISTOLOGIC RESPONSES (improved condition of the liver)
      57% (130/228) receivng Pegasys achieved a histologic
      41% (83/202) receiving regular interferon achieved a
      histologic response

      In those individuals who achieved a sustained
      virologic response, the percent
      achieving a histologic response was about the same
      regardless of which
      treatment a person received (79% [19/24] IFN, 83%
      [62/75] PEG IFN; p=0.76)..

      Partial Virologic Responders (decrease of 2-log in
      viral load)
      In this group, as well, the percent achieving a
      histologic response was the
      same regardless of which treatment group a person was
      in-- 43% (36/84, IFN),
      44% (47/108) PEG IFN; p=1.00.

      This is the interesting and perhaps most important
      data. The patients
      receiving PEG IFN-- 47% (21/45) had a histologic
      improvement. In the group
      receiving regular interferon, 30% (28/94) had a
      histologic improvement;

      This suggests that PEG IFN improves histology or the
      condition of the liver
      more than regular interferon for persons who do not
      achieve a good virologic
      response. It is uncertain if this improved histology
      will translate into a
      long-term real clinical benefit and studies are
      ongoing to examine this. But
      many doctors believe that this benefit is real and
      very important for
      individuals particularly with advanced fibrosis who
      are in danger of
      progressing to cirrhosis. For those individuals,
      maintenance therapy may be
      crucial in preventing progression of HCV. Although,
      this is not proven
      either, studies are ongoing to examine this. Again,
      doctors use maintenance
      therapy and believe that it may be helpful for
      individuals with advanced
      fibrosis who are at risk of progressing to cirrhosis.

      In summary Reindollar said:

      About 80% of patients who achieve a sustained
      virologic response have a
      histologic response. Perhaps, most importantly,
      patients without a virologic
      response (non-responders) more individuals receiving
      PEG IFN gain a
      histologic improvement than those receiving regular
      IFN (47% vs 30%).

      You may be asking why individuals receiving PEG IFN
      achieve a better
      histologic improvement than individuals receiving
      regular interferon. It may
      be because of the additional amount of interferon a
      person is exposed to with
      PEG IFN and the fact that interferon levels in the
      blood are constantly
      maintained at a high level. When taking regular
      interferon the blood levels
      go up and down every time you take a dose. It is
      thought that interferon has
      two effects--an antiviral effect and immune-modulatory
      effect. That is, it
      reduces viral load and improves the immune response to
      HCV. It is believed
      you can improve the immune response to HCV even if you
      don't improve the
      viral load. This has not been established but the
      ongoing studies are
      examining this. If it is true that an immune response
      improvement occurs and
      is beneficial, this can be crucial for individuals who
      cannot achieve a
      virologic response, particularly for those with
      advanced fibrosis who are in
      danger of progressing to cirrhosis.

      Analysis is still ongoing to discover the predictors
      of a histologic response
      and Reindollar said results should be available soon.

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