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Part 2 Afternoon Session June 10 (No surprises today)
Reported by Jules Levin
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Miriam Alter, PhD, of the CDC, is presenting about prevention and spread of
HCV. In October '98 the most recent recommendations were issued. The most
efficient transmission was by percutaneous exposure, IVDU. Mucosal exposures
and sex with multiple partners can transmit but at a much lower rate. Dental
care procedures can present a risk. Tattooing was very rarely reported. One
of the problems with studies is that they have trouble in identifying modes
for risk of exposure that can occur at very low rates of risk. Health care
workers can transmit to patients, such as through surgery, although it
appears to occur at a low rate of risk. Health care related transmission
appears relatively rare and so it's difficult to find these risks through
studies. These transmissions can be due to health care worker substance
abuse. IVDU and transfusion is however consistently found to be associated
with isk. In contrast, in only 1 of 6 studies was risk found in intranasal
cocaine use. In 3 studies but not in other studies tattooing was found to be
a risk. Body piercing also appears in to be found inconsistently to be a
risk. Only one study found acupuncture associated with risk. Study
methodology leads to difficulties in interpreting these studies and clearly
identifying risk. Most new infections (68%) are due to IVDU. I think she said
13% due to multiple sex partners. And only in 9% are risk factors
unidentifiable. Individuals with biochemical evidence of liver disease should
be tested for HCV. IVDUs should be tested. Alter said current routine testing
recommendations should remain the same. Sex is not a risk in monogomous
relationships and does not require testing. HCV is not spread by kissing or
intimate behaviors like that. Risk reduction counseling is recommended for
people using IVDs.
Norah Terrault, MD, from the Division of GI at UCSF, is discussing sexual
transmission. This is a common and controversial question. 18% of patients
presenting with acute HCV say their only risk factor is sex and 2/3 of their
partners have HCV. On average the rate varies from 4-6% for sexual risk among
at-risk groups. Although up to 26% has been reported. When you also look at
IVDU in these studies, HIV+, number of partners (recent & lifetime), and high
risk sexual trauma are associated with sex risk when eliminating IVDU. Among
monogomous couples the risk appears to be 3-5% in studies. She emphasized how
difficult it is to study sex risk because of the presence of other potential
risk factors such as potential modes of household exposures (toothbrushes,
etc). Typically in these studies they do not consider these potential modes
of transmission.
Terrault said HIV coinfection appears to be associated with a greater
likelihood of a partner getting HCV. But she did not feel that there is
evidence showing sex is the source of the transmission. A study suggests
women may be at greater risk for sexual transmission. Terrault said that in
sexually active individuals the risk is greater but still very low. Sexual
transmission occurs but risk is low. HIV may increase risk. She recommends no
requirement for barrier methods. But in HIV she recommends barrier methods be
used. In individuals with STDs or engage in behaviors of sexual trauma should
use barrier methods or abstain from sex. Viral tier should be better evalua
ted as a risk for transmission. Terrault tells patients that there is a
small risk of sexual transmission & should discuss risk with partners. If
they are uncomfortable with small risk they should consider barriers. Sex
partners should be tested. She tells patients that among monogomous
relationships the recommendation is it is not neccesary to use barriers.
Although data doesn't support this, plausability supports that sexual
behavior that traumatizes mucosa and the presence of STDs may increase risk.
Alan Clear and Alan Trachtenberg raised concerns about IVDUs and HCV, needle
exchange, access to treatment. Clear raised the point that IVDUs using needle
exchange may experience reduced risk for transmitting HCV. Clear also
suggests that IVDUs should not necessarily be excluded from access to
treatment, but it should be based on the individual situation.
An audience participant in the audience said that higher viral load may
promote sexual transmission and maternal-fetal transmission. Terrault said we
don't understand what factors increase the risk for sexual transmission.
Terrault & Alter said increased sex risk is increased with multiple sex
partners.
THERAPY FOR HCV
Karen Lindsay, MD, from USC, gave an introduction to HCV therapy. SVR is a
surrogate but clearly associated with clinical outcome. Among patients
achieving SVR significant improvement in quality of life has been shown in
study. Less than 1% relapsed in 2 studies using either PegIntron and Pegasys
two years after achieving SVR. She discussed several studies in patients with
SVR which showed histology improves, but we are not yet sure how much this
improves longevity. It's expected longevity should increase, but we need
studies to examine this. She referred to preliminary study data showing
adherence improves response to treatment. She mentioned we need to better
understand the mechanisms by which interferon works and the efficacy of
maintenance therapy. She also said patients take complementary therapy but we
understand them very little so we ought to study them. Interferon therapy is
contraindicated in pregnancy. Patients with >80% adherence appear to achieve
better responses, based on preliminary studies. Using antidepressants or
growth factors (EPO) addressing reduced hemoblobin and neutropenia can
improve side effects and adherence.
Adrian Di Bisceglie, MD, from St Louis University School of Medicine
discussed optimal therapy in HCV. He reviewed the 3 major pegylated
interferon studies in treatment naive partients: the Manns study of
PegIntron/RBV and the two Pegasys/RBV studies presented at DDW 2001 and EASL
2002. The data from these studies are available in detail on the NATAP
website. In the Manns study 44% with more advanced liver disease responded
compared to 57% with less advanced HCV. Patients with non-1 genotype 80% SVR
is reported from studies. Response rates depend on genotype and viral load.
The EASL Pegasys study was the only of the 3 studies that compared 24 weeks
to 48 weeks therapy. They found that patients receiving Pegasys/RBV with
genotype 1 required 48 weeks therapy to optimize results. And patients
receiving Pegasys/RBV with genotype non-1 in this study achieved the same
results with 24 weeks therapy compared to patients receiving 48 weeks therapy. Again see the NATAP website for more
details from the studies. There is a difference between the results reported from these studies for the
responses to therapy by patients with high viral load & genotype 1. Most
patients in the US have high viral load & genotype 1. Its estimated that 80%
of HCV/HIV coinfected patients have genotype 1 and over 90% of African
Americans have genotype 1. He reported that in the Manns study 29% receiving
interferon or PegIntron plus 800 mg RBV achieved SVR. In the DDW study
reported by Fried in 2001 patients receiving standard interferon+1000/1200 mg
RBV with genotype 1 & high viral load had an SVR of 33% vs 41% for patients
receiving Pegasys/RBV 1000/1200 mg. In the EASL Pegasys/RBV study patients
receiving pegasys+800 mg RBV achieved a 35% SVR. He reported that 46% of
patients receiving 1000/1200 mg RBV with Pegasys in the EASL study achieved
an SVR.
Mitchell Shiffman, MD, from Virginia Commonwealth University, discussed
retreatment of HCV. He reviewed preliminary data on nonresponders to previous
therapy with interferon+RBV combination therapy. Ira Jacobson reported this
study at DDW a few weeks ago. The data is available on the NATAP website.
Patients previously treated with interferon, with partial response, relapsers
are most likely to achieve the best responses from retreatment. He went onto
discuss the use of maintenance therapy or interferon to slow or stop HCV
progression. In his study patients who were able to achieve viral load
reduction, this was associated with improved fibrosis and these patients were
able to maintain that with continued interferon maintenance therapy, while
patients who stopped therapy were not able to maintain improvement. The
long-term clinical benefit is the subject of the HALT-C study. He advocated
maintenance therapy for patients with reduced viral load and improved liver
disease. For patients with advanced liver disease he suggested maintenance
therapy be considered as well.
In the final talk of the HCV Therapy section, Mark Sulkowski, MD, from Johns
Hopkins, concluded that the data suggests that amantadine is not a useful
therapy. He reviewed studies showing IFN slows disease. He reported that the
studies that have been done examining the potential benefit of interferon in
slowing disease have shown a slowing of disease. He mentioned the many
limitations of these studies including that they did not study a variety of
different types of patients, the studies were retrospective, and other study
limitations. He also said we need studies to examine the long-term clinical
outcome for patients with SVR.
The last section today is on the Role of Biopsy and I will not report on this
here. In sum, today's discussions and presentations did not present much in
the way of new data or new analysis of data. Again, the detailed results from
the 3 large pegylated interferon+RBV studies are available on the NATAP
website.
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