The Frontline Beacon
Volume 2 December 2000 Issue Beth Leffler, Editor

Message from the President Welcome to the second edition of the Beacon. The President gets to do the important things like beg for you to subscribe to this or for others who may not have email. Send a message with the name and address of the recipient along with $10 for a year subscription to: Frontline Hepatitis Awareness 2712-1/2 13th Ave S Seattle, WA 09144 OR: ane@frontline-hepatitis-awareness.com This is how we will be able to continue to make information available to those without use of the computer and thus pay for postage and handling costs. Thank You! Frontline Hepatitis Awareness 2712-1/2 13th Ave. South Seattle, WA 98144	ASK JAMIE COLUMN Jaime Hart-Osborne Subject: Need Posting of Factors that may indicate progression of HepC A while back there was a posting of biochemistry lab results that may be more precise indictor of Hep C progression/regression than AST or SGOT. One of them I believe was Bilirubin. Thanks for your help! Dear Patient in Georgia: ALT and AST don't tell you much of anything about progression. The only thing is with cirrhosis, the AST is generally higher than the ALT. Without cirrhosis, the ALT is higher. Tests of function that are indicators of progression are the bilirubin, prothrombin time and albumin. These are true liver 'function' tests; whereas the ALT and AST only tell you that liver cells are dying and releasing their enzymes, ALT and AST. The bilirubin tells you how well the cells are excreting bilirubin (the product of red cell metabolism) into the bile. The protime is a measure of the time it takes for a prothrombin clot to form. As the liver is the only organ that makes clotting factors, this is a measure of how well the liver is doing on making them. The longer the time, the less clotting factor there is. The same is for albumin. Albumin is the principal blood protein you own and the liver is the only place that makes it. Not enough functioning cells, the lower the albumin is. Hope this helps. Small Wings a flappin' GA
Articles in the Frontline Beacon are not to be used in place of a doctor's advice. Please seek expert medical advice in either the natural or allopathic setting for medical questions, thanks!	Send in Questions for "Ask Jaime Column" and Articles for this newsletter! We are also accepting personal stories that Relate to HCV and related issues.
AASLD- American Association for the Study of Liver Diseases October 27-31 2000 Dallas Reported by Jules Levin Progress in Developing New HCV Drugs Today's opening sessions had a good deal of promising information. Several new drugs in development for HCV were discussed. And new data on a couple of these drugs will be presented at this meeting over the course of the next few days. In addition there was a talk today on vaccine development. The speaker presented encouraging information on the possibility for development of a preventative and a therapeutic vaccine for HCV. But he cautioned that he didn't expect a drug until 2006. He suggested that a successful vaccine would have to stimulate both a CD4 response specific for HCV and a CD8 CTL response. In animals, that type of response was promising against HCV. The same type of response appears important to responding to HIV and a vaccine has yet to be developed. They discussed a naked DNA vaccine and felt that it wouldn't elicit a potent enough response to be effective against HCV. New information from studies will be reported here in Dallas on Pegylated Interferon. On Monday Schering Plough will report new data on Peg Intron in combination with ribivarin. Roche will be presenting new data on Pegaysis. New data on responses from African Americans and Hispanics will be reported here. Acutely infected humans who clear HCV characteristically produce a vigorous, polyclonal, and multispecific CTL (cytotoxic lymphocyte) response. In contrast, those that progress to chronic infection fail to display HCV specific CTL or develop a narrowly focused T cell response. Obviously, most people are unable to mount an effective response upon infection because 80-85% develop chronic infection. HCV Protease Although the structure of the HCV protease has been characterized, this structure seems to be difficult to create a drug for. Johnson Lau, formerly with Schering Plough and now with ICN, is developing a new ribivarin type drug. In fact, at least 2 new and more effective ribivarin type drugs are in development. But Lau described why it is difficult to develop a protease inhibitor for HCV. There are multiple cavities into which a protease inhibitor would go, therefore Lau says a large molecule would be necessary to accomplish this. However, you need a small molecule for oral absorption. It may be possible to develop a drug administered by subcutaneous injection but obviously oral administration is preferred. In addition, if you put HCV into a cell culture with a drug to see if that drug inhibits replication, HCV disappears. This is unlike HIV where you can put HIV & a drug into a cell culture and see if replication is inhibited. This makes it difficult to develop drugs for HCV and to understand a potential protease inhibitor's resistance profile. But in today's lecture series it was said that several cell culture systems are being developed and researchers seemed encouraged about this prospect.. Ribozyme LY466700 is a ribozyme currently in human studies.	A ribozyme attaches itself to the virus to prevent replication. Larry Blatt from Ribozyme Pharmacueticals discussed ongoing research in humans. He said the drug showed to be potent anti-HCV in cell culture and was synergistic with interferon. The drug will be administered by once daily subcutaneous injections. Results from a single-dose dose- escalation and safety study will be presented in a poster in the next few days. Blatt gave a preliminary report today. It's a 28-day study using low doses. Three patients showed transient viral load reductions of about 1 log. Higher doses will be studied in combination with interferon and later with IFN+ribivarin. Since the study being presented in Dallas was not designed to chartacterize antiviral efficacy Blatt said he can't be sure whether the viral load reduction is due to the drug or not. He said it was well tolerated. HCV Polymerase Polymerase is part of HCV and is involved in the viral reproduction process. Blatt described today that a few companies have polymerase inhibitors in development. One of these products is in phase 1 studies in the UK. A few nucleoside analogues are being considered for development to inhibit polymerase. Antisense Antisense can inhibit viral replication. Gary Davis described today that major potential obstacles with antisense technologies have included delivery to the cell target. But an antisense product is in phase 1/2 studies including in HCV infected. VX-497 This is a ribivarin type drug being developed by Vertex Pharma and its in phase 1/2 studies. Vertex has said it should be more tolerable, safer and more potent than ribivarin. Maximine This is an immune based therapy for which 24 week data has been previously reported. It was studied at various doses in combination with interferon. Its administered by subcutaneous injection. The 24-week data is available on the NATAP web site but 48 week data will be presented in Dallas. Still, the study was not well designed enough to get a firm grip of the benefit Maximine gives. Although they previously reported 69% viral response, about 50% of the patients were genotype 2/3 and it was hard to tell how much of the benefit was from interferon or Maximine. Nonetheless, Roche has rights to study Maximine in combination with Pegasys. Il-10 This is an inhibitory cytokine that has anti-inflammatory, antifibrotic, and immune suppressor effects. Gary Davis said today that an effect might be anticipated because patients with severe chronic HCV have lower IL-10 production while those with milder disease have higher levels of Il-10. A pilot study of daily recombinant Il-10 normalized ALT and reduced hetic inflammation on liver biopsy in 19 of 22 chronic HCV patients. This was previously reported And fibrosis decreased dramatically in 14/22. But no change in HCV viral load was seen. A large trial is underway. Alfa Thymosin This immune modulator has been around a while and I thought it was written off. Davis said study results have been inconsistent but felt the drug may have promise. He said a large study is planned. The drug is approved in I think Japan.
Frontline is compiling a list of Support groups across the US to be on the web page: Send any current support info to: Bruce@frontline-hepatitis-awareness.com




UPCOMING EVENTS 'Dancing With the Dragon' A Benefit for HCV in Seattle January 27, 2001 8-Midnight 'The Duffy Bishop Band" 'Jr. Cadillac' Dave Conant & the D-Rangers Frontline Hepatitis Awareness is proud to announce the first of a series of R&R and Blues Concerts to Benefit HCV/HIV Coinfection. HCV Testing (free for high risk Join us for a night of Dancing, persons) Silent Auctions and Food & Refreshments Contact Info and Pricing: In WA State: 206-328-5381 & 206-732-0311 Eastern WA 509-545-6338 In OR State: Signs Today 4811SE Jennings Milwauki, OR 503-353-8808 Advance $25 (before 11/30) At the Door $30	Liver Urgency Scale to Advance to UNOS Board for Consideration RICHMOND, Va., Oct. 23 /PRNewswire/ A proposed improved, objective scale to classify medical urgency of patients needing liver transplants will be considered for adoption by the UNOS Board of Directors at its meeting Nov. 16 and 17 in Washington, D.C. The UNOS Liver and Intestinal Organ Transplantation Committee, meeting October 12 in Chicago, recommended approval of the proposed policy after consideration of written public comments and feedback offered at a public forum held Sept. 28 in Irving, Texas. The proposed policy refinement would create a continuous scale to rank liver patients based on medical test results that are significantly associated with short-term death without a liver transplant. The scale would be more refined than the current medical urgency codes used in liver allocation, and the application of a continuous scale would de-emphasize the need to apply a patient's waiting time to determine priority for liver offers. The proposed scale would not affect the current UNOS Status 1 designation, which addresses the needs of extremely urgent patients with acute liver failure. After the UNOS Board of Directors considers the proposal, it will submit its recommendations to the U.S. Department of Health and Human Services for consideration under federal regulation for the U.S. organ transplant system. For more than 15 years, UNOS, a nonprofit charitable organization, has effectively maintained the nation's organ transplant waiting list and brought together medical professionals, transplant recipients and donor families to develop organ allocation policy under contract with the Health Resources and Services Administration of the U.S. Department of Health and Human Services. SOURCE: United Network for Organ Sharing CO: United Network for Organ Sharing; U.S. Department of Health and Human Services
High Hepatitis C Virus Levels: Patients Clear Virus More Slowly, More Likely to Relapse PHILADELPHIA, July 22 /PRNewswire----Sustained responders to anti-HCV treatment clear virus more slowly if they start out with higher virus levels. Researchers reported at the Digestive Disease Week conference that the pre-treatment viral concentration closely correlates with the rate that sustained responders clear the virus from their bodies. And a higher starting viral load increases the likelihood of a relapse after treatment. Researchers categorized 232 previously untreated patients according to their "baseline" viral concentrations into four groups. All patients received 9 micrograms of consensus interferon (Infergen) three times a week for 24 weeks, and then were observed for another 24 weeks after treatment. The percent of patients who responded (undetectable serum HCV RNA values) by week 12 was 71%, 53%, 34%, and 34%, from the lowest to the highest viral concentrations, respectively. More patients with lower baseline concentrations responded early compared to patients with the highest starting concentrations. These findings may help predict early in treatment who will benefit from therapy, says lead researcher F. Blaine Hollinger, M.D., professor of medicine, virology, and epidemiology at Baylor College of Medicine, Houston, Texas. "Patients want to know what their probability of success is, and we've looked at a lot of factors: the concentration of virus in the blood stream, whether or not they have cirrhosis, what their [viral] genotype is," Dr. Hollinger says. "Those that have a very low concentration of virus will lose their virus much more quickly and are more likely to have a sustained response than those who have a higher baseline concentration." Dr. Hollinger says that patients with the highest concentrations of virus do respond to treatment, but not as rapidly or as completely as patients with a low baseline level. For many of these patients, their viral level declines during therapy, but then increases after treatment stops. "This suggests that what we really need to do is treat them at higher concentrations," he says, "in this case 15 micrograms of the consensus interferon or 5 million units of Intron or Roferon, that perhaps you will pull some of the non responders into the sustained responder [group]." SOURCE Patients Newswire CO: Patients Newswire; Baylor College of Medicine ST: Pennsylvania, Texas
Note from the Editor: In the last couple months we are pleased with the support that all of you have given us. Without you, there would be no Frontline. We are here for you and others who suffer with HCV. When I was diagnosed I promised that no one would ever be alone with this silent epidemic. All of the Officer's and State Representatives feel the same way. That is why we are Frontline. To help all of you to live and deal with Hepatitis C. We have dedicated ourselves to the promotion of education, testing and awareness. We will find a cure. That is our hope and that is our promise. You can e-mail any of the Officers or State Representatives at www.frontline-hepatitis-awareness.com under "Who We Are". Beth Leffler, Editor and Pennsylvania State Representative Beth@Frontline-Hepatitis-Awareness.com