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  NIH HCV Consensus Development Conference
June 10-12, 2002
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Part 2 Afternoon Session June 10 (No surprises today)
Reported by Jules Levin
  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.
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.