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HCV ADVOCATE WEEKLY NEWS REVIEW:
A Review of HCV, HBV and HIV/HCV Coinfection Related News and Highlights

Week Ending: May 26^th , 2007

Alan Franciscus
Editor-in-Chief

To download pdf version click here

This Issue:

• Number 10 hiding blood scandal facts
• Could Statins Be A New Option For Hepatitis C Patients?
• The hepatitis C link: Diagnose, treat, transplant
• WHO experts in Viet Nam to assist in LG vaccine probe
• Inovio Biomedical Partner Tripep Provides Update on its Hepatitis C DNA Vaccine Program
• Hepatitis C and its long-term effects are a growing problem
• HIV/hepatitis C coinfected may have less risk of lipodystrophy and diabetes
• Hepatitis C On The Rise In Washington
• Genmab's HuMax-HepC Prevents Hepatitis C Virus Infection in Animal Model
• Cure For Hepatitis C Announced By Researcher
• Surviving Hepatitis C – Do You Harbor this Silent Killer?
• InterMune Presents Research on ITMN-191 in Hepatitis C at Digestive Disease Week Meeting
• 20 Questions: Christopher Kennedy Lawford
• Thousands of Ontarians Don't Know They Have Hepatitis C
• Researchers urge some to be tested for hepatitis C
• Drugs found effective against hepatitis C
• Baraclude (Entecavir) Treatment Demonstrated Greater Viral Load Reduction Compared to Adefovir at 48 Weeks in Study of Antiviral-Naive Chronic Hepatitis B E-Antigen Positive Patients
• The Optimal Liver for Transplant in Hepatitis-C Patients? Presented at DDW
• Reversibility of Hepatic Fibrosis and Cirrhosis--Is it all Hype?
• New HCV Protease Inhibitor Effective Against Hepatitis C
• Many Hemophilia Patients With Chronic Hepatitis C Develop End-Stage Liver Disease
• Nurses say many may have hepatitis C and not know it
• Government refusing to release thousands of blood scandal document – Willott
• Hepatitis C victims dying while compensation stalled
• Biolex Therapeutics Raises $30 Million to Advance Its Hepatitis C Drug Candidate and Other Pipeline Programs
• Hepatitis B patients' understanding of infection and treatment deficient
• Scientists Model Hepatitis C Virus
• Further evidence that HIV/hepatitis C coinfected patients have poorer immunological response to HIV therapy
• Investigative Eltombopag Shows Promise for Thrombocytopenia in Hepatitis C Patients: Presented at DDW

May 20th , 2007


Number 10 hiding blood scandal facts
http://observer.guardian.co.uk
Jo Revill, Whitehall editor
The Observer

Inquiry finds the truth on shredding was withheld after infected transfusions killed 1,700 patients

An independent public inquiry into how thousands of haemophiliacs contracted HIV or hepatitis C from contaminated blood discovered last night that Downing Street is withholding crucial information about how hundreds of relevant documents were shredded.

More than 1,700 patients died and many more are now terminally ill as a result of one of the biggest medical disasters of recent times, when haemophiliacs were given infected blood clotting products during the late Seventies and early Eighties. The products came from American prisoners who were allowed to sell their blood even though there were fears about the risks of contamination.

But it has since emerged that many of the files detailing the scandal were shredded by civil servants in the Nineties. This week, the second hearing of the contaminated blood inquiry, chaired by the former Solicitor-General, Lord Archer of Sandwell, will ask why the results of an internal inquiry into the destruction of crucial files are being withheld.

Jenny Willott, Liberal Democrat MP for Cardiff Central, has discovered that Downing Street is holding back the report, carried out by the Department of Health in 2000, when Alan Milburn was Health Secretary. Some of the destroyed documents detailed meetings between the blood transfusion service, health boards, government officials and consultants during the Seventies and Eighties. The records also contained information on when precisely the government became aware of the risks from imported blood and what measures were taken to warn patients.

The Haemophilia Society said last night that Downing Street's decision was 'incomprehensible, given the public interest'. In 1989, the society brought legal action on behalf of thousands of patients who had become infected with HIV after being given the clotting product Factor 8. Haemophilia is a rare hereditary condition in which the blood does not clot properly. British doctors used the American products despite some senior scientists knowing that there was a risk. Compensation was then agreed with the Tory government in 1990 and thousands of patients received one-off payments of between £21,000 and £80,000.

However, it then transpired that hundreds of documents relating to the case were shredded, allegedly by accident, by junior civil servants. It is now known that there were two separate instances of documents being destroyed, or mislaid, at some point between 1990 and 1998. Some copies of documents had been made by a solicitor's firm, and these were returned to the government, but others are thought to have been lost forever. The total number of destroyed documents is not known. In 2000, the Department of Health held the audit but it was never published.

An email from the Department of Health passed to The Observer revealed that an official has confirmed that the audit has been withheld at the request of no 10. Yesterday, it remained unclear why Downing Street had blocked moves to put it into the public domain. The Observer was still awaiting a reply last night from No 10 officials about the reasons for the lack of disclosure.

Willott said: 'We discovered that this internal audit had happened through the Freedom of Information Act, and asked to see a copy of it. We now find that No 10 have withheld it. That raises the very big question about whether there is incriminating evidence in there.

'We were always told that the documents were shredded by mistake by a junior civil servant. It is very important that we know because it's hard to hold an inquiry when you are not getting the full picture. There are thousands of people living with the results of this terrible disaster who deserve to know the truth.'

One of them is Gareth Lewis, chairman of the campaign group Tainted Blood, and a trustee of the society, who became infected with HIV and Hepatitis C in 1984.

'I'm 48 years old, and I've lived with this nightmare for more than two decades,' he said. 'I find it very hard to understand why a government minister would not want to know the whole truth about this, and not want us to know. I have been to 98 funerals of haemophiliacs who have died as a result of receiving contaminated blood. We really owe it to them to be open and honest about what went wrong.'

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Could Statins Be A New Option For Hepatitis C Patients?
http://www.medicalnewstoday.com

Research presented today at Digestive Disease Week 2007 (DDW) demonstrates the potential of statins, important cholesterol management therapies, for improving the management of hepatitis C - a disease that affects nearly four million Americans. Although there have been no new treatments for hepatitis C since the introduction of pegylated interferon in 2001, the opportunity to develop a new generation of therapies that offer better outcomes may be imminent. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"Studies such as these are designed to improve the effectiveness of antivirals - the standard of care therapy for hepatitis C," said John Vierling, M.D., Baylor College of Medicine. "The findings from these studies support the rationale and need for larger, controlled trials that may provide additional and more advantageous hepatitis C treatment options."

Statins Improve ALT Values in Chronic Hepatitis C Patients with Abnormal Values (Abstract #M1783)
Researchers have yet to report on the concept that hepatitis C virus (HCV) patients who take statins may experience improvements in alanine transaminase (ALT, liver enzymes) levels. Use of statins for hepatitis C has not occurred in the past as the FDA-approved package insert for every statin lists "active liver disease" as a contraindication for use and hepatitis C would certainly qualify as an active liver disease. In such a setting, a researcher must request a special license form from the FDA called an investigational new drug (IND) license. As part of an IRB and FDA-approved 14-day study looking at the antiviral effect of fluvastatin (FLV) in vivo, researchers reported the total bilirubin (TB, yellow breakdown product) and ALT results and compared the findings to an existing hepatitis C registry data.

Initial results showed that three patients with abnormal ALTs at baseline experienced significant improvement and nine patients who started with normal ALTs stayed normal. In addition, there were no significant changes in TB levels. No liver problems were noted despite FLV doses that were up to four times the highest FDA-approved dose.

Experts also examined the existing HCV registry and noted both the number of patients who improved their abnormal ALT levels after statin therapy and the number of patients who maintained their normal ALT levels after initiation of statin therapy. Of the abnormal ALT group (13 of 60 pts), 12 had improved ALT and one stayed unchanged. Of the 47 beginning in the normal range, 45 maintained their ALTs. The remaining two who developed a mildly abnormal ALT after beginning a statin were noted as suffering from heavy alcohol abuse, suggesting an unrelated cause for the change.

"This is the first report of prospectively using fluvastatin in HCV patients," says Ted Bader, M.D., of University of Oklahoma in Oklahoma City, Okla., and lead author of this study. "Two remarkable observations were made and data not only supports the lack of harm in this situation, but also seems to suggest a possible salutary effect that needs further study."

Dr. Bader will present this study on Monday, May 21, at 8:30 a.m. in Hall E.

Retrospective Analysis of the Effect of Taking a Statin Along with Peginterferon and Ribavirin (PI+R) on SVR (Abstract #M1845)
Researchers retrospectively analyzed the effect of taking peginterferon and ribavirin (PI+R, hepatitis C treatment options) and PI+R plus a statin to measure the sustained viral response (SVR, negative virus in blood six months after the end of treatment) rate in hepatitis C patients. A modified intent to treat approach was taken to compare the therapy alone to the therapy with addition of a statin.

In this study, 104 patients taking PI+R were compared to 30 patients who took PI+R plus a statin. Almost all patients (25 of the 30) taking a statin were on simvastatin, two were on lovastatin, two were on atorvastatin and one on fluvastatin. According to study results, the patients on standard treatment achieved a 37 percent SVR rate - the highest SVR reported to date in the medical literature for a VA-based population. Having a high SVR rate means a cure is 95 percent of the time based upon long-term follow up that is greater than six months after treatment. The SVR rate for patients taking triple therapy, PI+R plus a statin, was 63 percent.

Statins appear to be associated with a higher SVR rate when added to standard PI+R therapy. Retrospective data are subject to many problems and inaccuracies and should be only used to plan prospective trials.

"It is important for statins to be studied prospectively for their effect on hepatitis C," says Ted Bader, M.D., of University of Oklahoma in Oklahoma City, Okla., and lead author of this study. "Further study may contribute to developing a more effective outcome of treatment."

Dr. Bader will present this study on Monday, May 21, at 8:30 a.m. in Hall E.

###

Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 19-24, 2007 in Washington, D.C. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

Contact: Aimee Frank
American Gastroenterological Association

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The hepatitis C link: Diagnose, treat, transplant
http://www.eurekalert.org/

Examining gene expression, drug compounds and liver transplantation

WASHINGTON, D.C. (May 20, 2007) -- Hepatitis C not only affects more than 3.9 million Americans, but continues to impact and influence the occurrence of related inflammatory conditions. Research presented today at Digestive Disease Week® 2007 (DDW®) analyzes advancements in the diagnosis of hepatitis C and therapies available to patients who suffer from the disease. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"Almost four million Americans have chronic hepatitis C infections and are at risk for of cirrhosis, liver failure, liver cancer and transplantation," said John Vierling, M.D., Baylor College of Medicine. "These studies advance our understanding for the potential for developing markers to detect liver cancer, to increase our capacity to treat hepatitis C and provide evidence that livers from persons with hepatitis C can be successfully used for transplantation."

Is Autotaxin (ENPP2) the Link Between Hepatitis C and Hepatocellular Cancer" (Abstract #676)
Chronic active hepatitis C (HCV) remains the strongest connection to the development of hepatocellular carcinoma (HCC, liver cancer). Unfortunately, the mechanism behind hepatitis-associated cancer remains puzzling. Such effects as oxidative stress and DNA damage are known to occur in hepatitis, through which the role of the liver in nucleic acid metabolism may be impacted. This study evaluated the key elements in nucleic acid metabolism that might account for the biologic behavior of hepatitis-associated cancer.

Autotaxin (ENPP2) is a tumor cell motility-stimulating factor and has been linked to tumor invasion and cancer growth in several human cancers, such as breast cancer and non-small-cell lung cancer. ENPP2 has also been linked to adenosine triphosphate (ATP) and purinergenic pathways, chemical reactions occurring within a cell to maintain homeostasis. To assess the key elements in nucleic acid metabolism, researchers looked at liver tissue collected prospectively from three patient subtypes: 1) patients undergoing liver resection for non-hepatitis related diseases; 2) HCV cancer-free transplant patients; and 3) HCV patients with biopsy-confirmed HCC.

Using microarray analysis, the group sought to profile patients with respect to cancer risk. The goal of the study was to determine whether one could identify patients at high risk for the development of cancer. Differences between groups were tested by ANOVA, a statistical test that determines the significance of any given observation.

Within purine metabolism, several genes were expressed between normal liver and both HCV groups. Of these, autotaxin was significantly elevated in patients with cancer compared to HCV patients without cancer or normal liver. In addition, genes associated with autotaxin, such as the lypophosphatidic acid receptor (LPA), a potent signaling molecule, were also over-expressed in HCV patients.

"Early detection of liver cancer is crucial. For patients eligible for liver transplant, early detection is associated with excellent long term cancer survival," said Mary Maluccio, M.D., of Indiana University in Indianapolis, Ind., and senior author of the study. "Autotaxin is one of the few genes within the purine metabolic pathway that is up-regulated in the liver of cancer patients versus their non-tumor bearing counterparts, and therefore may be a novel and important marker for early stage HCC in the hepatitis C-infected liver."

Dr. Maluccio will present this study on Tuesday, May 22, at 3:00 p.m. in Hall E.

Phase II Study of Celgosivir in Combination with Peginterferon Alfa-2b and Ribavirin in Chronic Hepatitis C Genotype-1 Non-Responder Patients (Abstract #442)
Celgosivir is a new class of antiviral medicine in clinical development for the treatment of chronic hepatitis C virus (HCV) infection. Researchers tested this new antiviral medicine and measured its potential to offer improved treatment outcomes when combined with other anti-HCV drugs.

The current study evaluated 57 chronic HCV genotype-1 patients, separated by prior treatment status into non-responders or partial responders and randomized to three treatment groups: 1) celgosivir 400 mg once daily in combination with peginterferon alfa-2b and ribavirin (PRC); 2) celgosivir 400 mg once daily in combination with peginterferon alfa-2b (PC); or 3) placebo with peginterferon alfa-2b and ribavirin (PR, active control). All patients were treated for 12 weeks. The non-responders cohort enrolled 36 patients (PRC: 15; PC: 11; PR: 10) and the partial responder cohort had 21 patients (PRC: 3; PC: 9; PR: 9).

For prior non-responder patients, an Early Viral Response (EVR) was achieved in 42 percent (5/12) of those in which celgosivir was added to the standard peginterferon alfa-2b and ribavirin therapy compared with only 10 percent (1/10) of patients receiving just peginterferon alfa-2b and ribavirin. Non-responder patient study results also demonstrate an improved mean decrease in HCV viral loads when celgosivir is added to peginterferon alfa-2b and ribavirin of 1.63 log10 IU/mL versus 0.92 log10 IU/mL in patients treated with peginterferon alfa-2b and ribavirin alone. Eleven of the 36 non-responder patients were classified as a very difficult-to-treat patient subgroup (null responders) as they were shown to have a prior HCV treatment response of ≤0.4log10 to optimized therapy. In the present study, the mean decrease in HCV viral loads in these null responder patients was 1.86 log10 IU/mL with celgosivir plus peginterferon alfa-2b and ribavirin while the two null responder patients treated with peginterferon alfa-2b and ribavirin was 0.32 log10 IU/mL. The observed difference in mean viral load between the PRC and PR treatment groups provides evidence that the combined effect of celgosivir with peginterferon alfa-2b and ribavirin provides a clinically significant treatment benefit for difficult-to-treat chronic HCV infected patients.

"This study is the first demonstration that celgosivir in combination with peginterferon alfa-2b and ribavirin results in a clinically significant decrease in HCV viral loads in patients highly resistant to current standard treatment," said Kelly D. Kaita, M.D., of the University of Manitoba in Canada, and lead author of this study. "Further clinical research on the best dosing regimen and combinations is warranted to optimize the potential of this innovative combination for chronic HCV patients."

Dr. Kaita will present this study on Monday, May 21, at 2:45 p.m. in Room 206.

Use of Hepatitis C-Infected Donors in Liver Transplantation: A Case-Control Study (Abstract #2)
To meet the increasing demand for donor livers, researchers are searching for opportunities to utilize non-optimal livers to offer some improvement to severely ill patients. Some centers are now transplanting livers from hepatitis C (HCV)-infected donors into recipients with HCV-related cirrhosis. This study compared transplant outcomes for liver recipients from HCV-infected donors to those for standard, non-extended criteria (ECD) donors to determine the possible benefits or consequences of this practice.

Researchers examined 37 recipients of livers and 76 ECD donors. Thirty percent of all donors met non-ECD criteria (standard donors) and were included as potential matches for the case-control study. Each HCV-positive liver donor recipient was matched to two standard donor recipients as matched standard donor controls (MSDC). MSDC were classified by recipient age, primary diagnosis, cancer stage for those with HCC, recipient MELD (Model for End-Stage Liver Disease system used to prioritize waitlist patients) and donor age. Patients were monitored for graft and patient survival at three months, one year and two years; perioperative death; and HCV recurrence by four-month and one-year fibrosis (F0-F4).

In this study, researchers note that when hepatitis C positive donors were used, no difference in survival was observed. However, the rate of fibrosis appeared to be slower in those receiving HCV-infected livers. These preliminary results suggest that HCV-infected liver transplant recipients receiving livers from HCV-infected donors may have a slower rate of fibrosis progression at one year.

"This is a trend we're seeing in survival advantage for those receiving HCV-donor grafts compared to standard donor controls," says Paul Kwo, M.D., of Indiana University in Indianapolis, Ind., and lead author of this study. "The use of HCV positive donors may be considered as a first line therapy to increase the available donor pool of organs in those undergoing OLT for HCV-related cirrhosis, which is the most common cause of cirrhosis leading to orthotopic liver transplantation. We hope to further extend this research to understand how we can maximize the use of extended criteria donor organs. This includes hepatitis C positive graft that may benefit HCV-infected individuals who require orthotopic liver transplantation, as well as gain insight as to why these organs may have a slower rate of fibrosis than non-HCV infected donor organs."

Dr. Kwo will present this study on Sunday, May 20, at 8:45 a.m. in Room 207.

###
Digestive Disease Week® (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 19-24, 2007 in Washington, D.C. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

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WHO experts in Viet Nam to assist in LG vaccine probe
http://vietnamnews.vnagency.com.vn/

HA NOI – An international team of World Health Organisation (WHO) experts arrived in Viet Nam yesterday to assist the country with investigations into the recent deaths of new-born babies allegedly caused by LG-made hepatitis-B vaccine.

WHO’s Communications Officer in Viet Nam, Dida Connor, said yesterday that the team was sent to Viet Nam following a request from the Ministry of Health. "WHO is working closely with the National Institute of Hygiene and Epidemiology to carry out full epidemiological and clinical investigations," she added.

Four local infants went into shock after being given Euvax B (hepatitis B) vaccine manufactured by the Republic of Korea’s LG Life Sciences between April 23 and May 7. Three of those infants died, prompting WHO and the health ministry to order temporary suspension of the use of that lot of vaccine.

HCM City’s Health Department said earlier this week that one of the local children died, not from the vaccine inoculation, but of a sudden heart attack.

The Health ministry, however, hasn’t come to any conclusions. "It’s too early at this stage to provide any conclusive assessment (into the case)," said Connor.

She also said that WHO would further advise on the probe’s outcomes and the quality and safety of Euvax B vaccine as well. WHO and UNICEF are also working with the Vietnamese Government to help overcome the current shortfall of hepatitis B vaccines.

In response to the reluctance among parents to immunise their children, WHO recommends that countries at risk should continue to provide hepatitis B vaccination, including the birth dose where applicable. Infants should receive the vaccine, with the first dose provided at birth, particularly in those areas where mother-to-child virus transmission is significant. — VNS

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May 21st, 2007


Inovio Biomedical Partner Tripep Provides Update on its Hepatitis C DNA Vaccine Program
http://www.pharmalive.com

SAN DIEGO--(BUSINESS WIRE)--May 21, 2007 - Inovio Biomedical Corp. (AMEX:INO), focused on the development of DNA-based vaccines for cancers and infectious diseases and a novel alternative to surgery to treat localized cancers, announced today that its partner, Tripep AB of Sweden, has provided an update regarding its application to the Swedish Medical Products Agency (MPA) to initiate a Phase I clinical trial for its proprietary DNA vaccine, ChronVac-C(R), administered using Inovio's MedPulser(R) DNA Delivery System. Tripep announced it intends to file with the MPA a modified application designed to permit clinical testing of ChronVac-C(R) in subjects already infected with hepatitis C virus instead of healthy volunteers, as per the original application. Tripep intends to initiate the phase I/II clinical study at the Center for Gastroenterology at Karolinska University Hospital in Sweden beginning in late 2007.

About Inovio's Immunotherapy Products
DNA-based immunotherapy products have the potential to by-pass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical data has indicated the potential ability of Inovio's technologies to safely and effectively deliver and significantly enhance the potency of such immunotherapies.

Inovio's DNA-based immunotherapy products consist of DNA plasmids and the Elgen and MedPulser DNA delivery systems. DNA plasmids are designed to express antigens that can induce an immune response specific to a cancer or infectious disease-causing organism. These plasmids are created synthetically and readily manufactured using well-established bacterial fermentation and purification technology. After a plasmid is delivered into muscle or tumor cells, production of the desired antigens may then induce a preventive or therapeutic immune response against the targeted disease. Inovio's advanced electroporation devices facilitate delivery and expression of such immunotherapies and have been shown in primate studies to boost the immune response by orders of magnitude over DNA plasmid alone. Breast cancer, prostate cancer, melanoma, HIV and hepatitis C virus are among the current targets of therapies employing Inovio technology.

Inovio is poised to deliver advanced DNA-based immunotherapies, devices and know-how in this rapidly advancing field. The company is actively licensing its technology to pharmaceutical and biotechnology companies and supporting early stage clinical studies arising from its own research efforts or through academic collaborations.

About Inovio Biomedical Corporation
Inovio Biomedical (AMEX:INO) is focused on developing multiple DNA-based immunotherapies and commercializing its Selective Electrochemical Tumor Ablation (SECTA) therapy. Inovio is a leader in developing human applications of electroporation, which uses brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical and, in the case of DNA-based treatments, levels of gene expression. Inovio's DNA delivery partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, and the U.S. Army, with four DNA-based immunotherapies in Phase I clinical studies. The SECTA therapy for locally treating solid tumors is designed to selectively kill cancerous cells and minimize cosmetic or functional detriments often caused by surgical removal of the predominantly healthy tissue typically treated around a tumor. The SECTA therapy is advancing through pre-marketing studies for head & neck and skin cancers in Europe, where it has CE Mark accreditation, a U.S. Phase III pivotal study for head and neck cancer, and a Phase I/II trial for breast cancer. Inovio's technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that pre-clinical results referenced in this release may not be indicative of results achievable from testing in humans), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio's technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2006, our Form 10-Q for the three months ending March 31, 2007, and other regulatory filings. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, or that final results of clinical studies will be supportive of regulatory approvals required to market licensed products.

Contact
Inovio Biomedical Corp.
Bernie Hertel, 858-410-3101 (Investor Relations)
Jeff Richardson, 805-491-8313 (Media Relations)

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Hepatitis C and its long-term effects are a growing problem
http://www.gloucestertimes.com
By Health Beat , Elizabeth Eddy
Gloucester Daily Times

In the next decade, several million baby boomers will face the serious, long-term effects of the liver disease hepatitis C.

Three to four million people in the United States and an estimated 100,000 in Massachusetts have chronic hepatitis C, compared to 1 million who have HIV.

"(It's) a huge, huge problem worldwide," says Dr. Lucas Wolf, an infectious disease specialist who practices in Gloucester. "It's quickly becoming an extremely important disease in the U.S."

Wolf added that many baby boomers will be diagnosed with cirrhosis (fibrosis or scarring of the liver that prevents it from functioning properly) in the next 10 years, making hepatitis C a public-health threat.

Hepatitis C differs from the other types of hepatitis because nine out of 10 people who get it go on to suffer chronic infection. But unlike hepatitis A and B, there is no preventive vaccine for hepatitis C.

Hepatitis C also differs from the other types because there is virtually no acute phase. Often, it's only detected through routine liver function tests.

"It establishes itself with minimal or no symptoms other than some fatigue and abdominal pain," Wolf said. "People find out through an unexpected route as opposed to being symptomatic. Most of the 4 million infected don't know they have it."

The primary cause of hepatitis C is the sharing of infected needles, Wolf said. Blood-to-blood contact is required, he said, adding that the sharing of needles from heroin use is the most common route of transmission.

But while 80 percent of cases are due to intravenous drug use, there is a smattering of other transmission routes, including infection from nasally inhaled cocaine, tattoos made with dirty needles and blood transfusions before 1992.

Wolf encourages anyone who has ever shared a needle or who was a regular cocaine user to be tested.

"I generally see patients that are boomers and experimented with heroin once or twice in the late 1970s or 1980s," he said.

The North Shore Health Project in Gloucester focuses on hepatitis C and HIV services and offers testing, counseling and holistic health treatments such as acupuncture, massage, Reiki, energy healing, chiropractic care and yoga.

The group also provides case management and advocacy, assists clients with choosing medical care and offers congregate meals, educational programs and a drop-in center to support those facing hepatitis C. All services are free.

"We try to focus holistically on those undergoing interferon (immune stimulant) treatment because it is difficult," said executive director Susan Oleksiw. "We work with the whole person and advocate for stable housing and stable life situations, because dealing with hep C is a major life issue. When it hits you, it hits you hard."

Wolf added, "Hep C is extremely variable from person to person and hard to predict. You can live 20 to 30 years without symptoms, but in general, people are going to get to the point of cirrhosis in 30 to 40 years. The virus gets into the blood and sets up shop in the liver, and though it stays under the radar in the immune system, the liver becomes chronically inflamed and scarring accumulates over the fullness of time."

Treatment is determined after a liver biopsy, a minor procedure performed under anesthesia. Most patients are treated with a combination of interferon and the medication Ribavirin, which weakens the virus. Patients are advised to be vaccinated against hepatitis A and B, two other viruses that attack the liver.

"There is more treatment in the works," Wolf said, adding he is hopeful better treatments will be available in the future.

The current treatment regime is successful in about 60 percent of cases, but it is long and intensive, requiring a full year. And because the drug therapy is toxic to the body, there are significant side effects, including depression.

The North Shore Health Project helps newly diagnosed persons chart a course of action to ensure the best medical treatment and social support. Its office at 67 Middle St. is open Monday through Friday from 9 a.m. to 5 p.m. For more, call the project at 978-283-0101 or Sunny Robinson, Gloucester public health nurse, at 281-9971. Vaccinations against hepatitis A and B for people with hepatitis C are available for free through the Health Department.

This article, part of a regular health education series provided by the Gloucester Health Department and Addison Gilbert Hospital, is offered in recognition of May as Hepatitis Awareness Month.

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HIV/hepatitis C coinfected may have less risk of lipodystrophy and diabetes
www.aidsmap.com
Kelly Morris

Coinfection of HIV and hepatitis C virus (HCV) has been associated with metabolic changes, in particular lipodystrophy and diabetes, which are also linked with antiretroviral therapy. Now, two studies have failed to find a significant link between HIV/HCV coinfection and diabetes or lipodystrophy.

One-third of HIV-positive Americans are thought to be coinfected with HCV: coinfection has been linked previously with fat distribution changes, particularly lipoatrophy, and with diabetes. However, both these metabolic changes are also linked with HIV therapy. Moreover, previous studies have had various limitations. The May 1st edition of the Journal of the Acquired Immune Deficiency Syndromes reports two new US studies that help to clarify previous findings.

Phyllis Tien (University of California, San Francisco) and colleagues measured body composition using magnetic resonance imaging in 1,183 HIV-positive people, from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Multivariate modelling was used to detect associations between various factors, including HIV/HCV coinfection and antiretroviral therapy with body fat at various sites, particularly in the leg.

Investigators from Detroit studied the prevalence of diabetes and associated factors in an antiretroviral - naïve population of 2,565 adults from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Diabetes was diagnosed by self-report, while a subset of participants had fasting blood glucose measurements: findings did not substantially differ when diabetes was confirmed. These findings were compared with those from 6,585 participants in the National Health and Nutrition Examination Survey.

One-fifth of the men and around a quarter of the women in the lipodystrophy study had HIV/HCV coinfection, while 17% of CPCRA participants in the diabetes study also had HCV. CPCRA participants had a significantly lower rate of diabetes than the general population (3.3% versus 4.8%), but the known risk factors of black race, older age, and higher body-mass index were independently associated with diabetes in both cohorts. In univariate analyses, HIV/HCV coinfection was associated with diabetes but multivariate analyses failed to demonstrate an independent association, except possibly among black people. These findings suggest that the linkage between HIV/HCV coinfection and diabetes, in the absence of antiretroviral therapy, “is at best a weak one,” note Brar and colleagues.

In the lipodystrophy study, overall coinfection was not linked with body composition changes when compared with men and women infected with HIV alone. Coinfected men had more leg fat and coinfected women had more visceral fat than people solely infected with HIV, in a multivariate analysis. Stavudine (d4T) in particular (p < 0.001), and also ddI (p = 0.022) and, surprisingly, abacavir (p = 0.012) use were linked with less leg fat in HIV-monoinfected men than in HIV/HCV-coinfected men, while indinavir (p = 0.002) was linked with less leg fat in both groups, and nevirapine was linked with more leg fat in coinfected men (p = 0.016).

Coinfected men had about a 2% loss of leg fat per year of stavudine use compared with 7% in monoinfected men, and there was no significant association between the use of any individual antiretroviral drugs and fat loss. Coinfected women also had slightly smaller decreases in leg fat with increasing duration of stavudine use. “These data suggest that the presence of HCV infection may, in fact, mitigate the leg fat loss that occurs as a result of HIV infection and stavudine use”, the authors note.

The changes in body composition found in the lipodystrophy study are unlikely to have clinical implications, since they would not have been visibly noticeable. However, the findings suggest that “the mechanisms by which HIV, antiretroviral drugs, and HCV may affect fat changes may be more complex than previously hypothesized and warrant further investigation in men and women”. In the diabetes study, “the relatively low prevalence [of diabetes] in the CPCRA cohort contrasts sharply with reports of other investigators”, Brar and colleagues write. Previous studies have found diabetes prevalence varied from 2.8% to 12% of HIV-positive participants, but none of these studies evaluated antiretroviral-naïve patients. The current findings do not preclude the need to screen co-infected patients for diabetes when protease inhibitor therapy is being contemplated. But “the results of the present study emphasize the need to screen patients with classic risk factors . . . Further studies are needed to elucidate the interaction between antiretroviral therapy, especially protease inhibitor therapy, and these other factors”, the authors conclude.

Reference

1. Brar I et al. A comparison of factors associated with prevalent diabetes mellitus among HIV-infected antiretroviral-naïve individuals versus individuals in the National Health and Nutritional Examination Survey Cohort. J Acquir Immune Defic Syndr 45: 66–71, 2007.
2. Tien PC et al. Association between hepatitis C virus coinfection and regional adipose tissue volume in HIV-infected men and women. J Acquir Immune Defic Syndr 45: 60–65, 2007.

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Hepatitis C On The Rise In Washington
http://www.emaxhealth.com

Hepatitis C has become one of the Washington state's top health concerns with an estimated 110,000 people infected statewide.

"Hepatitis C is significantly under-reported because two out of three people don't even know they're infected," said Washington State Health Officer Dr. Maxine Hayes. "The virus often presents no symptoms, and can remain undetected for more than 20 years in some cases."

While 40,000 cases have been reported to public health, the infection rate could actually be almost three times higher.

"Hepatitis C is the most common blood-borne infection in the United States and is the leading cause of liver transplants," said Wendy Dillon, hepatitis C coordinator for the Washington State Department of Health. "There are eight times as many hepatitis C cases as there are cases of HIV/AIDS infection in our state."

Recently, the agency launched a pilot public education campaign to increase awareness about the risks for hepatitis C. The campaign, which ran in the Tacoma-Pierce County area, featured billboards, transit ads and posters distributed throughout the community.

The campaign encouraged citizens to "Get on Board" and learn about the risks for becoming infected with hepatitis C and to get tested if they identify certain risks:

• Have EVER needle-injected drugs, steroids, silicone or hormones.
• Received a blood transfusion or organ transplants before 1992.
• Been on long-term kidney dialysis.
• Have had an occupational exposure to blood.s
• Had tattoos or body piercings with non-sterilized equipment.
• Shared straws for snorting drugs.
• Were born to a mother infected with hepatitis C

Based on the success of the Pierce County effort, the state health agency plans to target the Spokane area with a radio campaign next. Governor Chris Gregoire has also declared the month of May as Viral Hepatitis Awareness Month to raise the profile of the disease.

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Genmab's HuMax-HepC Prevents Hepatitis C Virus Infection in Animal Model
http://www.pr-inside.com/

COPENHAGEN, Denmark, May 21 /PRNewswire-FirstCall/ -- Genmab A/S announced today its fully human antibody HuMax-HepC(TM) prevented Hepatitis C virus (HCV) infection in a novel animal model. In the pre-clinical study, mice with a compromised immune system were transplanted with human liver cells (hepatocytes) and exposed to a mixture of patient-derived HCV of different genotypes.

Replication of HCV was not observed in 5 of 6 mice (83%) treated with HuMax-HepC, indicating that HuMax-HepC completely prevented HCV infection. The sixth mouse was infected with HCV, but the virus was subsequently cleared.

In comparison, 5 of 6 mice who received a control antibody developed and sustained a robust HCV infection.

"We are pleased to present this pre-clinical data which indicates that HuMax-HepC may provide effective protection against HCV infection of human hepatocytes in vivo," said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab.

This data will be presented today at the American Association for the Study of Liver Diseases' (AASLD) Digestive Disease Week(R) in Washington, DC, USA.

About HuMax-HepC HuMax-HepC was originally isolated from a patient who suffered from mild chronic hepatitis. HuMax-HepC binds to a conformational epitope of envelope protein 2 (E2), which is expressed on the surface of Hepatitis C virus and plays an important role in the entry of hepatitis C virus into target cells. In pre-clinical studies, HuMax-HepC was shown to be broadly cross-reactive with several HCV genotypes and potently neutralized binding of HCV-E2 to susceptible cells.

About Hepatitis C virus (HCV)
Worldwide more than 170 million people are chronically infected with HCV, including approximately 3.9 million in the United States and 8.9 million in Europe. Most infected people develop increasing liver fibrosis over time that can lead to cirrhosis, liver failure or liver cancer. From population-based studies it is estimated that in the United States 8,000-10,000 deaths occur each year due to HCV-related chronic liver disease. Moreover, Hepatitis C is the main cause of about half of the estimated 10,000 liver transplants in Europe and the United States each year. A major complication of liver transplantation in HCV-patients is re-infection of the graft by HCV. Studies conducted in several laboratories support the rationale for using antibodies to prevent liver infection or re-infection with HCV.

About Genmab A/S
Genmab A/S is a biotechnology company that creates and develops human antibodies for the treatment of life-threatening and debilitating diseases. Genmab has numerous products in development to treat cancer, infectious disease, rheumatoid arthritis and other inflammatory conditions, and intends to continue assembling a broad portfolio of new therapeutic products. In addition, Genmab has developed UniBody(TM), a new proprietary technology that creates a stable, smaller antibody format. Genmab has operations in Europe and the US. For more information about Genmab, visit http://www.genmab.com/.

This press release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with product discovery and development, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. Genmab is not under an obligation to up-date statements regarding the future following the publication of this release; nor to confirm such statements in relation to actual results, unless this is required by law.

Genmab(R); the Y-shaped Genmab logo(R); HuMax(R); HuMax-CD4(R); HuMax-EGFr(TM); HuMax-Inflam(TM); HuMax-CD20(TM); HuMax-TAC(TM); HuMax-HepC(TM), HuMax-CD38(TM); HuMax-ZP3(TM); and UniBody(TM) are all trademarks of Genmab A/S.

Contact: Helle Husted, Sr. Director, Investor Relations, T: +45-33-44-77-30, M: +45-25-27-47-13, E: hth@genmab.com

Source: Genmab A/S

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Cure For Hepatitis C Announced By Researcher
http://www.sciencedaily.com

Science Daily — The use of peginterferon alone, or in combination with ribavirin, points to a cure for hepatitis C, the leading cause of cirrhosis, liver cancer and the need for liver transplant, a Virginia Commonwealth University researcher recently said.

Mitchell Shiffman, M.D., professor in the VCU School of Medicine, and chief of hepatology and medical director of the Liver Transplant Program at the Virginia Commonwealth University Medical Center, is one of the lead investigators in the study, which was presented at the 38th annual Digestive Disease Week conference in Washington, D.C. VCU was among about 40 sites worldwide studying pegylated interferon alfa-2a, manufactured by Roche Inc.

Nearly all -- 99 percent -- of patients with hepatitis C who were treated successfully with peginterferon alone, or in combination with ribavirin, had no detectable virus up to seven years later. Researchers say this data validates the use of the word "cure" when describing hepatitis C treatment as successful treatment is defined as having undetectable hepatitis C virus in the blood six months following treatment.

"We at VCU are encouraged by this data because it is rare in the treatment of life-threatening viral diseases that we can tell patients they may be cured," Shiffman said. "In hepatitis C today, we are able to help some patients achieve an outcome that effectively enables them to put their disease behind them."

The results are based on a long-term follow-up study designed to determine if the virus re-emerges in patients who have achieved treatment success. The study reviewed 997 patients, either mono-infected with chronic HCV or co-infected HCV and HIV, who achieved a sustained viral response (SVR) following treatment with either Pegasys (peginterferon alfa-2a) monotherapy or combination therapy with Pegasys and ribavirin.

After successful treatment, researchers monitored serum levels of HCV once a year for an average of 4.1 years (range 0.4 to 7 years). Of the 997 patients, 989 maintained undetectable levels of HCV. The remaining eight patients tested positive for HCV at an average of two years following treatment completion. The study found that these eight patients exhibited no consistency in age, gender or HCV genotype, and it has not yet been determined if these patients experienced a relapse or if they were re-infected with HCV.

Hepatitis C is a blood-borne infectious disease of the liver and a leading cause of cirrhosis, liver cancer and the need for liver transplants. According to the Centers for Disease Control and Prevention, an estimated 4.1 million Americans have been infected with hepatitis C, and 3.2 million are chronically infected. The number of new infections per year declined from an average of 240,000 in the 1980s to about 26,000 in 2004, the latest year for which statistics are available. The CDC estimates the number of hepatitis C-related deaths could increase to 38,000 annually by the year 2010, surpassing annual HIV/AIDS deaths.

Note: This story has been adapted from a news release issued by VirginiaCommonwealthUniversity.

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Surviving Hepatitis C – Do You Harbor this Silent Killer?
http://www.bloggernews.net/
By Carol Bogart
 
Five years ago, a woman named Sally in Seattle called me in Ohio to talk about her Hepatitis C. She was, as I recall, nearing 70 and a retired teacher. Her niece, an adult lawyer, had taken me to lunch to talk to me about her. She said Sally was the dearest sweetest woman; one whose husband was gone, had not had children, and was now alone.

I was a columnist for the local newspaper and had been writing about my own Hepatitis C. For a year, I endured a clinical trial that was very much like chemotherapy. The niece told me Sally was afraid to have a liver biopsy, and wondered if I’d mind if her aunt called me.

As a result of my weekly column, many people you would never suspect to have this “dirty” disease often linked with injecting illegal drugs had come forward to either get tested and start treatment, or to simply thank me for giving voice to a condition about which so many are ashamed.

Like me, Sally had no idea how she’d gotten Hepatitis C. A diabetic, she wondered whether she’d been infected during a blood draw to check her sugar. I wondered whether it was a single acupuncture session for my herniated disk. I don’t remember, either, how Sally found out she had it. That I did was a lucky twist of fate.

I was symptom-free in 1995 (the liver is an “uncomplaining” organ) and covering a terrible story for a Cleveland television station. It was about a paramedic who, coming home from work, had flipped the light switch, not knowing that in the basement, the leaking furnace had filled the house with gas. A small spark from the switch triggered an explosion that blew him out the door into his backyard, burned over 75 percent of his body.

As the videographer and I swung into the parking lot at Metro Health Center, paramedics, firefighters and cops filled the waiting room and halls. Throughout the night, it was touch and go as their friend and co-worker needed so many transfusions that the hospital was starting to run out of platelets.

Two days later, the firefighters staged an emergency blood drive. I urged the TV station’s assignment editor to let me cover what was to me a poignant human interest story: the coming together as one of those whose occupations so often put them in harm’s way.

The first person I interviewed was the paramedic’s dad, a retired firefighter and, usually, self-contained stoic man. Now, with his son hovering at death’s door, he could barely hold back his tears. I talked, too, to the paramedic’s partner on the ambulance, a man so broken up he could barely speak.

When I learned that the paramedic’s blood type was O-negative, the same as mine, I set my reporter’s notebook aside - signing up on the spot to donate blood, despite my lifelong fear of needles.

God moves in mysterious ways.

Two weeks later, a letter from the Red Cross arrived. It said in bold capital letters across the top: “THIS IS NOT A LETTER ABOUT AIDS BUT … .” I was informed that my blood had tested positive for Hepatitis C and had been discarded. I was never again to give blood, the letter said, nor was I to be an organ donor. I thought about the organ donor sticker that had been on my driver’s license for many years.

A visit to my internist confirmed the diagnosis.

The paramedic made a slow recovery. I might have died but for that decision to give blood. That’s not to say I instantly started treatment. I didn’t. In 1995, despite country singer Naomi Judd’s success with Interferon for her Hepatitis C, for many, it meant terrible side effects, but no eradication of the virus. I had a young boy at home. I decided to wait until medicine could offer something better.

By 2001, though, I was feeling very fatigued. Regular monitoring of my liver enzymes – a barometer of how much damage the Hep C is doing in your liver – found that they were getting worse. My son was now 16. It was time.

Like Sally, the idea of a liver biopsy terrified me. It was, however, required of those who wanted to take part in a clinical trial being offered by the Cleveland Clinic. For the first time, those with Hepatitis C had a shot at a new “combination” therapy – a three-drug treatment it was hoped might up their odds of surviving what some call a silent epidemic.

The day of my biopsy, I was grateful to my doctor, head of the clinic’s gastroenterology department, for coming in early to hold my hand as the “routine” procedure was performed. I would later assure Sally it really wasn’t all that bad. When asked afterward if I needed pain relief, I truthfully answered, “No.”

The result, though, was pretty scary. Stage 3 liver fibrosis (scarring): bridging and portal. One stage away from full blown cirrhosis. I’d be starting the trial just in time.

For a year, I injected Pegylated Interferon into fatty tissue in my tummy once a week and took Ribavarin and Amantadine capsules every day. I lost 60 pounds and handfuls of hair and, by the 10th month, once failed to recognize a friend I saw at Kroger’s. At the same time the drugs were attacking the virus, healthy stuff was dying, too.

At night, I ached so much I couldn’t sleep. In the last month, the side effects were so bad that, with the approval of my research nurse, I started cutting back the dose of both the Interferon and the pills. It was either that, or just stop taking everything altogether.

I’d been getting the meds and supplies for free thanks to the clinical trial – a good thing because, otherwise, I couldn’t have afforded to get treated. Pegylated Interferon alone costs a fortune.

Once a month I’d drive the two hours to Cleveland to have eight vials of blood drawn to monitor my liver enzymes. I wasn’t allowed to take Advil during those 12 months (an anti-inflammatory, it could have skewed the results) – but that meant no relief for my osteoarthritis.

As I was going through my clinical trial, two very close friends were enduring what would prove to be their final unsuccessful round of chemotherapy – one for breast cancer, one for leukemia. We told each other that which we didn’t tell those we loved: We were in so much misery, we really didn’t care if we died, but we worried what would happen to those we left behind; in my case, my 16 year old son. My friends, farm wives, had both been married for more than 40 years.

Dolores and Shirley finally decided: No more chemo. One after the other, they passed away. At the end of my treatment, my blood work came back “clean.” No trace at all of the Hepatitis C. My enzymes were back to normal.

Every six months, I get the liver panel done. To date – and it’s been four years – I remain Hepatitis free. I’m a Type 2. Ninety percent of the Type 2s in the clinical trial had the same result. For Type 1’s, who are more resistant to treatment, the success rate was 60 percent. In the ’90s, when I was first diagnosed, Interferon, the sole drug available at the time, cleared the virus in only 10-15 percent of those treated for Hep C. I felt like a living miracle.

Sally, after we talked at length several times, did have her biopsy and started treatment. She’d waited too long. She died.

Dr. William Carey, my gastroenterologist, warned me often that the longer I waited, the more opportunity the virus had to “replicate” and become stronger.

Hep C is a quiet killer. Health officials estimate 4.1 million Americans are infected. Many are unaware. If you think there’s any chance you might have it, get tested. It could save your life.

For information on testing for Hepatitis C, contact your state or local health department.

Carol Bogart blogs at http://carolbogart.blogspot.com
Contact her at 3bogart@sbcglobal.net.

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InterMune Presents Research on ITMN-191 in Hepatitis C at Digestive Disease Week Meeting
http://www.earthtimes.org
Press Release

WASHINGTON, May 21 /PRNewswire-FirstCall/ -- InterMune, Inc. today presented new preclinical data on the company's Hepatitis C virus (HCV) NS3/4A protease inhibitor, ITMN-191, during a scientific session of the Digestive Disease Week (DDW) meeting being held May 19-24 in Washington, D.C. The reported study (DDW abstract #M1816) examined ITMN-191 potency and binding kinetics in biochemical assays.

The new InterMune study represents an in-depth characterization of the mechanism of inhibition of the HCV NS3/4A serine protease by ITMN-191. Full characterization of the inhibition mechanism indicated that ITMN-191's true biochemical potency of 36 picomolar (pM) was approximately ten-fold better than previously inferred (~ 250 pM reported at DDW 2006). The presented data also suggest that ITMN-191 binds to the NS3/4A protease target in a two-step binding mechanism in which ITMN-191 initially associates with NS3/4A in a collision complex that isomerizes to a long-lived but non-covalent drug-target complex. The half life of the complex between ITMN-191 and NS3/4A was estimated to be five hours or more, and inhibition of protease activity of NS3/4A was stable over this same time period. Slow dissociation of ITMN-191 from the NS3/4A protease may have a relevant in vivo consequence, as a two-hour exposure of ITMN-191 to tissue culture cells that harbor an HCV replicon resulted in an antiviral effect equal to that delivered by continuous exposure of ITMN-191.

Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune, said, "This preclinical study of ITMN-191 provides a better understanding of its attractive potency and binding characteristics. While ITMN-191 is a non-covalent, reversible inhibitor of the protease, the onset of inhibition and slow dissociation compare favorably with those observed with covalent protease inhibitors currently in development. The immediate onset of inhibition and slow dissociation observed with ITMN-191 suggest that liver concentrations may underestimate its antiviral activity, since ITMN-191 will likely remain bound to the protease target after unbound drug is cleared from the liver."

About ITMN-191
Preclinical toxicology and pharmacokinetic studies in multiple species suggest that ITMN-191 has attractive characteristics, including significant liver exposure, slow dissociation from the NS3/4 protease, high in vitro potency and specificity, and an advantageous cross-resistance profile, including considerable effectiveness against variants of the NS3/4A protease that are resistant to other HCV protease inhibitors currently in development. The preclinical pharmacokinetic results support the exploration of twice-daily oral dosing. In early May 2007, InterMune reported that it had completed dosing in a Phase 1a single ascending-dose (SAD) trial of ITMN-191 in healthy subjects. No serious adverse events were reported in the SAD trial. Preliminary safety data from the SAD trial suggests that ITMN-191 was well tolerated and safe at the doses intended for the Phase 1b multiple-ascending dose (MAD) trial of ITMN-191. InterMune currently anticipates that the MAD trial will begin in the third quarter of 2007 and initial top-line viral kinetic data reported in the fourth quarter of 2007. InterMune and Roche have a collaboration agreement for the research, development and commercialization of ITMN-191 (referred to as R7227 within the Roche research and development programs) and second-generation HCV protease inhibitor compounds.

About HCV and HCV Protease Inhibitors
According to the Centers for Disease Control and Prevention (CDC), an estimated 3.9 million Americans (1.8%) have been infected with HCV, of whom 2.7 million are chronically infected. It is estimated that there are 170 million people worldwide afflicted with this disease. While currently available therapies can cure many patients, there is considerable need for the development of novel therapeutic approaches. The HCV NS3/4 protease is an attractive drug target because of its potential involvement in viral replication and suppressive effects on host response to viral infection. Inhibitors of the HCV protease, such as ITMN-191, represent a promising new class of drugs for HCV.

Forward-Looking Statements
Except for the historical information contained herein, this press release contains certain forward-looking statements that involve risks and uncertainties, including without limitation the statements related to the progress, future patient enrollment in and timing of our clinical trials and announcements of results thereof. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune's actual results could differ materially from those described in InterMune's forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in InterMune's annual report on Form 10-K filed with the SEC on March 30, 2007 (the "Form 10-K"), and other periodic reports filed with the SEC, including the following: (i) risks related to the development of our product and product candidates; (ii) risks related to timely patient enrollment and retention in clinical trials, including the use of third parties to conduct such clinical trials; (iii) risks related to achieving positive clinical trial results; (iv) risks related to our intellectual property rights; and (v) risks related to the uncertain, lengthy and expensive clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the Form 10-K and InterMune's other periodic reports filed with the SEC.

InterMune, Inc.

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20 Questions: Christopher Kennedy Lawford 
http://thehill.com/
By Betsy Rothstein

This week 20Questions chats with Christopher Kennedy Lawford, cousin to Rep. Patrick Kennedy (D-R.I.) and nephew to President John F. Kennedy and Sen. Edward Kennedy (D-Mass.). Lawford visits Capitol Hill today to discuss his experiences with hepatitis C and the importance of a public health response to the disease. Five years ago, Lawford was diagnosed with hepatitis C. He received treatment and is considered cured. He lives in Los Angeles.

You’ve been to Washington a lot lately, for addiction-related press conferences, the Capitol File after-party in conjunction with the White House Correspondents’ dinner, and now as spokesman for hepatitis C. Is Washington becoming home away from home for you?

Well, I love going to Washington. But I wouldn’t want to work there, it’s not a home away from home. It’s one of my homes away, unfortunately.

When were you first diagnosed?
In 2001, I was getting a physical. My doctor told me he was going to test me for HIV and hepatitis C. I told him not to bother. He did it anyway. He called me two weeks later and said, “I have good news and bad news.” He said, “You are not HIV-positive, but you have hepatitis C.”

How did you even know to be checked, since it’s a silent disease? You had no symptoms, right?
No, no symptoms. I was tired. It’s a pretty asymptomatic sickness. Fatigue is the major symptom. Most people in their 40s who are working [and have] children are tired. I had been exposed to one of the major risk exposures.

What were you exposed to?
I used drugs when I was younger, both IV and inhalant. But it was in my distant past — 20 years earlier. I had no idea that something I’d done 20 years earlier could come back to threaten my life.

What kind of drugs did you use?
I used pretty much all kinds. I started using drugs when I was 13 and stopped when I was 30 — IV drugs, inhalants, cocaine. All addicts are running away from something, they just use different-colored sneakers. And I pretty much used every colored sneaker in the closet.

Did the diagnosis frighten you?
I was shocked and pretty afraid. There’s a lot of misinformation out there.

How are you related to the Kennedys?
My mom, Patricia, was a sister of John F. Kennedy, Robert and Ted Kennedy. She was the sixth child of Joseph and Rose, my grandparents.

How’s your acting career going?
It’s good. It’s hard to be an actor and a busy advocate at the same time. I did a movie last summer called “Slip Stream” that premiered at the Sundance Film Festival. It’s in theaters in September [and stars] Anthony Hopkins and Christian Slater. I wrote a book, Symptoms of Withdrawal, a couple of years ago. Right now I’m writing Moments of Clarity, about spiritual epiphanies that allow people to move from addiction to recovery. I’m interviewing 50 well-known people who have had that experience.

Will Patrick Kennedy be one of those 50 people?
He will be.

Do you play a role in your cousin Patrick’s recovery?
I love Patrick and I support him in his work on [mental health] parity legislation whenever I can. I prefer Patrick’s bill to the Senate bill because it doesn’t allow the insurance companies to reveal what the mental illness is. I am a friend to him and we walk this path together. I do cherish my relationship with him.

Do you ever worry about him?
No, he’s doing great. This is an illness that is contingent on spiritual recovery daily and working a program daily. I have been doing it for 21 years. He has been doing it for a year. I worry as much for him as I worry about all alcoholics and addicts who are struggling. 

What kind of advice to offer to people about hepatitis C?
The reason I’m coming to Washington is because I’m supporting my uncle Ted’s bill, the Hepatitis Control and Prevention Act. The biggest thing about it is if you have exposure to one of the major risk factors, there’s a risk you might have this illness, so you ought to get tested. This is the largest blood-borne illness in the country.

Once you have it, do you always have it or do you take medication and everything is OK?
You need to see a liver specialist about getting treated. There is good treatment out there. I did the treatment. I had genotype 2. Just next week we’re going to release a study that basically says if you’ve been virus-free for five years, we consider that a cure.

Have you been virus-free?
I have been virus free for five years, so I consider myself cured.

So good news, yes?
Very good news.

Do you still have to take medication?
No, not at all. You take it for six or 11 months and if it works for you, you’re done.

Is it hard to be a spokesman for this cause because it forces you to reveal your own experiences?
That’s the good part. Look, I have credibility with this thing because I had it. I can talk about my own experience. I can also talk about the legislation. It’s a blessing to have your own personal experience to come from.

Would you ever consider running for office yourself?
A lot of people ask me that now because I spend a lot of time on the road, giving speeches on a lot of different things. I have a strong ethic in my life of public service. I like trying to effect change. [But] the political process right now seems so difficult and not what I would want. There’s too much money in it and too much scrutiny. People are not allowed to be who they really are.

But all your shortcomings are already out there.
Absolutely. You still have to be careful what you say and how you say it. I’m not good at that. [Pauses.] Well, I am good at it. I think we need fewer focus groups and polls. We’re missing a real connection between the people and their leadership. If I ever did, I would let it all hang out.

So you’re not ruling it out.
Not ruling it out, no.

Are you supporting anyone in the presidential election?
Not yet. I am a third-party guy. I get mad when I see people hedging their true selves and true positions to get elected. I love [Rep.] Dennis Kucinich (D-Ohio), you know what I mean? I love Dennis, he’s great. He’s never in a million years going to get elected. I want to see the Democrats win, so I’ll support the nominee.

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May 22nd, 2007


Thousands of Ontarians Don't Know They Have Hepatitis C
http://www.newswire.ca
By John Plater, Chair of Ontario's Hepatitis C Task Force and President of Hemophilia Ontario.

TORONTO, May 22 /CNW/ - Approximately 3,400 people in Ontario are newly infected with hepatitis C every year.

One of the problems with hepatitis C is that you can have it, sometimes for many years, without knowing you have it.

Hepatitis C is a viral infection that is carried in the blood and can cause severe damage to the liver. It can lead to cirrhosis of the liver after 10-20 years and liver cancer after 20-40 years.

Often there are no symptoms, no signs of the disease until well after infection. In Ontario, it is estimated that up to 35,000 people have hepatitis C, or HCV, but don't know that they're infected.

Currently, sharing drug-using equipment is the most predominant risk factor for HCV however other risks include blood transfusions prior to 1992, inadequately sterilized equipment used in medical procedures or injections, sharing tattoo needles or ink, and sharing piercing equipment.

Now it's easier than ever to determine whether you may be at risk. The Ontario government has launched a web site, www.hepContario.ca, where you can log on and take a simple, self-assessment test that will allow you to evaluate your risk of having HCV.

The self-assessment tool and the results are completely private and anonymous. You'll be able to decide on your own based on the results whether you should speak to your health care provider about getting tested.

If you think you may be at risk of having acquired hepatitis C, it's time to get tested.

Early detection is very important in controlling the virus. If detected early, outcomes for treatment of hepatitis C are excellent. Early detection is also the best way to prevent the spread of HCV to others.

If you believe you may have been exposed to the hepatitis C virus, ask your health care provider to test you. For more information visit www.hepContario.ca  or talk to your health care provider.

For further information: Please contact the Ministry of Health media line, (416) 314-6197

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Researchers urge some to be tested for hepatitis C
http://www.adn.com
By JULIA O'MALLEY
Anchorage Daily News

BIRTH DATE KEY: If you were born in Anchorage before 1992 and were in the neonatal ICU, get checked out.

If you or your child were in an Anchorage neonatal intensive care unit before 1992, talk to a doctor about getting tested for hepatitis C, say researchers with the Alaska Native Tribal Health Consortium.

As many as 8 percent of babies who received transfusions before 1992 could have contracted the disease, experts say.

Before 1992, donated organs and blood couldn't be reliably tested for hepatitis C, a viral infection that can become chronic, leading to liver disease and in rare cases, death. About 3.9 million people nationwide have the disease.

Seven percent are believed to have gotten it from a tainted transfusion.

Babies in neonatal ICUs were particularly susceptible to infection because they were more likely to have more transfusions from more donors, said Henry Cagle, a researcher with the consortium's Liver Disease & Hepatitis Program.

Cagle and others recently published the results of a "lookback program" that began in 2001, where researchers tried to track down and notify people who may have received infected blood here as babies.

At the Alaska Native Medical Center and Providence Alaska Medical Center 1,786 babies had transfusions between 1975 and 1992. Researchers, using blood bank and hospital records, were able to contact 651 of those.

Only 215 reported getting tested for the disease. Seven of those tested positive. That's about 3 percent.

No one who tested positive knew previously they had the disease, Cagle said. People with hepatitis C can go for years without symptoms.

There are still 898 people who haven't been notified about their potential risk.

"It is possible that as few as 1 percent and as much as 8 percent were infected by transfusion," he said.

"A lot of parents didn't know their child was transfused. ... It's a high stress time," Cagle said. "They may not perceive or know their child may be at risk."

The Centers for Disease Control recommend that anyone who received a blood transfusion or donor organs before July 1992 be screened, Cagle said.

Researchers conducted a smaller lookback program for adult patients at the Alaska Native Medical Center. A similar proportion of patients turned out to be infected with the virus, Cagle said. There has not been a lookback program for patients in other Anchorage hospitals.

The hepatitis virus is transmitted through blood-to-blood contact. Currently, IV drug use is the most common way people become infected. Tattoos, body piercing and sex can also spread the disease.

Symptoms include jaundice, fatigue, dark urine, abdominal pain, loss of appetite and nausea, according to the CDCl. There is no vaccine for the C virus, Cagle said, but it can be treated with drugs.

Hepatitis C problem at a glance
Patients at risk of hepatitis C infection from blood transfusions in neonatal ICUs at Alaska Native Medical Center and Providence Alaska Medical Center before 1992, by the numbers:

• Number of transfusion recipients 1975 to 1992: 1,786
• Now dead: 237
• Couldn't be contacted: 898
• Found and sent notices: 651
• Found and tested: 215
• Positive for hepatitis C: 7

Daily News reporter Julia O'Malley can be reached at jomalley@adn.com  or 257-4325.

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Drugs found effective against hepatitis C
http://www.centredaily.com
By Bob Lamendola - South Florida Sun-Sentinel

Combination of meds works as cure for some

FORT LAUDERDALE, Fla. -- Doctors and researchers almost never use the word "cure," but they came as close as they ever do Monday when describing a combination of two drugs used to treat the severe liver disease hepatitis C.

Among some patients, the drug cocktail of pegylated interferon and ribavirin completely kills the virus that causes hepatitis C, and keeps it from coming back, doctors said in reporting their new study at a Digestive Disease Weekly conference in Washington.

The catch is, the drug combo does not work in about half of people with hepatitis C, and researchers still are not sure why it works so completely for some but fails in others. Also, the combo has difficult side effects.

"I call it a cure. It doesn't work for everyone but it has the ability to eradicate this virus, and this study is the best evidence to prove that," said Dr. Eugene Schiff, director of the center for liver diseases at the University of Miami medical school, who was attending the conference but not involved in the study.

The findings of the six-nation study, headed in the United States by Virginia Commonwealth University, solidifies the drug combination as the top treatment for the virus, which has infected about 4 million here.

The virus spreads only via direct contact with infected blood. Most cases stem from blood transfusions before 1992 and intravenous needle use, but the virus also can occasionally be passed through sex.

Long-term infection of hepatitis C has caused a leap in the incidence of liver cancer and liver damage and is the leading cause of people needing liver transplants.

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Baraclude (Entecavir) Treatment Demonstrated Greater Viral Load Reduction Compared to Adefovir at 48 Weeks in Study of Antiviral-Naive Chronic Hepatitis B E-Antigen Positive Patients
http://pharmalive.com/

WASHINGTON, May 21, 2007/PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company (NYSE: BMY) today announced new data from study ETV-079, which showed that treatment with Baraclude (entecavir) demonstrated greater viral load reduction than adefovir at 48 weeks -- a result that was also seen at weeks 12 (primary endpoint) and 24. These data from an open-label, randomized viral kinetics study of 69 antiviral-naive chronic hepatitis B e-antigen (HBeAg) positive patients were presented at the annual Digestive Disease Week(R) meeting.

Study ETV-079 evaluated the antiviral activity of BARACLUDE and adefovir, and enrolled patients who had a high viral load at study entry (HBV DNA greater than or equal to 10(8) copies/mL). In this study, 58 percent of BARACLUDE-treated patients and 19 percent of adefovir-treated patients achieved undetectable viral load at 48 weeks.

"The study results show that BARACLUDE produced greater viral load reductions than adefovir at all time points analyzed -- from the earliest at 12 weeks to this latest analysis at 48 weeks," said Nancy Leung, M.D., of the Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.

The safety profile was comparable between the treatment groups. One patient treated with adefovir discontinued due to adverse events. No deaths were observed in either treatment group. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were back pain, headache, influenza, nasopharyngitis, fever, upper respiratory tract infection, and urinary tract infection.

About the Study
Study ETV-079 was a randomized, open-label, comparative viral kinetics study of antiviral-naive chronic HBeAg-positive patients evaluating antiviral activity as measured by mean reduction in viral load, or levels of hepatitis B virus (HBV DNA) in the blood. HBeAg or e-antigen, is a viral protein associated with hepatitis B infections, and is found in the blood only when there is virus present.

The primary endpoint for the study was mean reduction in HBV DNA levels at week 12. Viral load reduction was also measured at weeks 24 and 48 of the follow-up. Patients received 0.5 mg of BARACLUDE(R) (entecavir) once daily (n=33) or 10 mg of adefovir once daily (n=32).

Patients in the BARACLUDE treatment group had a mean baseline viral load of 10.26 log(10) copies/mL. Patients in the adefovir treatment group had a mean baseline viral load of 9.88 log(10) copies/mL. Data Results

Week 48

* BARACLUDE-treated patients achieved a mean change in viral load of -7.28 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -5.08 log(10) copies/mL (95 percent Confidence Interval -2.69, -1.03)

* 58 percent of BARACLUDE-treated patients and 19 percent of adefovir-treated patients had undetectable viral load (HBV DNA <300 copies/mL, measured by a common assay -- polymerase chain reaction, or PCR)

Week 24

* BARACLUDE-treated patients achieved a mean change in viral load of -6.97 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -4.84 log(10) copies/mL (95 percent Confidence Interval -2.51, -1.20)

* 45 percent of BARACLUDE-treated patients and 13 percent of adefovir- treated patients had undetectable viral load (HBV DNA <300 copies/mL)

Week 12

* BARACLUDE-treated patients achieved a mean change in viral load of -6.23 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -4.42 log(10) copies/mL (p < 0.0001)

* 12 percent of BARACLUDE(R) (entecavir)-treated patients and 9 percent of adefovir-treated patients had undetectable viral load (HBV DNA <300 copies/mL)

Adverse events in study ETV-079:

* Seventy-eight percent (n=28/36) of patients taking BARACLUDE and 82 percent (n=27/33) of patients taking adefovir experienced an adverse event. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were back pain, headache, influenza, nasopharyngitis, fever, upper respiratory tract infection, and urinary tract infection.

* Six percent (n=2/36) of patients taking BARACLUDE and 15 percent (n=5/33) of patients taking adefovir experienced a Grade 3-4 adverse event.

* Three percent (n=1/36) of patients taking BARACLUDE experienced a serious adverse event (elevated ALT that resolved with continued treatment). Nine percent (n=3/33) of patients taking adefovir experienced a serious adverse event (one patient had elevated ALT that resolved with continued treatment; one patient had acute hepatitis with ALT flare [ALT flare defined as greater than two times baseline and greater than 10 times the upper limit of normal]; one patient was involved in a motor vehicle accident).

* There were no deaths in either arm and one patient discontinued treatment due to an adverse event.

About BARACLUDE(R) (entecavir)Discovered at Bristol-Myers Squibb, BARACLUDE(R) (entecavir) is a nucleoside analogue indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication with either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. BARACLUDE has been approved in more than 60 countries and regions around the world.

Important Information About BARACLUDE(R) (entecavir) 0.5mg/1mg Tablets

BARACLUDE(R) (entecavir) is a prescription medicine used for chronic infection with hepatitis B virus (HBV) in adults where the virus is multiplying and damaging the liver. BARACLUDE does not cure HBV or stop the spread of HBV to others.

People should not take BARACLUDE if they are allergic to it or any of its ingredients. BARACLUDE has not been studied in children and is not recommended for anyone less than 16 years of age.

People taking BARACLUDE(R) (entecavir) should tell their healthcare provider right away if they feel very weak or tired, have unusual muscle pain, have trouble breathing, have stomach pain with nausea and vomiting, feel cold -- especially in their arms and legs, feel dizzy or lightheaded, or have a fast or irregular heartbeat, as they may be signs of a serious condition called lactic acidosis (buildup of an acid in the blood).

Lactic acidosis is a medical emergency and must be treated in the hospital. Some people who have taken medicines like BARACLUDE have developed serious liver problems called hepatotoxicity. This may occur with liver enlargement (hepatomegaly) and fat in the liver (steatosis).

People should call their healthcare provider right away if they get any of the following signs of liver problems: yellowing (jaundice) of the skin or the white part of the eyes, darkening of the urine, lightening in the color of bowel movements (stools), not feeling like eating food for several days or longer, feeling sick to the stomach (nausea), or having lower stomach pain. Lactic acidosis and hepatotoxicity have happened in some people taking medicines like BARACLUDE.

In some people, hepatitis B symptoms may get worse or become very serious when they stop taking BARACLUDE. People should not stop BARACLUDE without talking to their healthcare provider. Healthcare providers will need to follow their patients and do blood tests to check the liver when BARACLUDE is stopped. People should tell their healthcare provider if they have or develop kidney problems because their healthcare provider may want to do tests to see if a lower dose is needed or a different dose schedule.

Because BARACLUDE is removed from the body through the kidneys, a lower dose or a different dose schedule may be required. Healthcare providers may want to perform tests to determine whether a patient needs a lower dose or should take BARACLUDE less often than once a day.

It is not known if BARACLUDE is safe to use during pregnancy. It is not known if BARACLUDE helps to prevent a pregnant mother from passing HBV to her baby. A pregnant woman and her healthcare provider will need to decide if BARACLUDE is right for her. A woman should not breastfeed if she is taking BARACLUDE.

People should discuss with their healthcare provider all prescription and non-prescription medicines, vitamins, herbal supplements, and other health preparations they are taking or plan to take. BARACLUDE(R) (entecavir) may interact with medicines that leave the body through the kidneys. The most common side effects of BARACLUDE in clinical studies were headache, tiredness, dizziness, and nausea.

This list of side effects is not complete at this time because BARACLUDE is still under study. People should report any new or continuing symptom to their healthcare provider. BARACLUDE should be taken once daily on an empty stomach (at least two hours after a meal and two hours before the next meal). To learn more about BARACLUDE and for Full Prescribing Information, including boxed WARNINGS, please visit www.bms.com .

Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.

BARACLUDE(R) (entecavir) is a trademark of Bristol-Myers Squibb Company.

Full prescribing information for BARACLUDE, including boxed WARNINGS, is available at www.bms.com .

SOURCE  Bristol-Myers Squibb Company

CONTACT: Ken Dominski, Communications, +1-609-252-5251, +1-609-273-9656,
or ken.dominski@bms.com , or John Elicker, Investor Relations, +1-212-546-3775,
or john.elicker@bms.com , both of Bristol-Myers Squibb Company/
Web site:  http://www.bms.com/

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The Optimal Liver for Transplant in Hepatitis-C Patients? Presented at DDW
http://www.docguide.com/
By Bruce Sylvester

WASHINGTON, DC -- May 22, 2007 -- New research suggests that hepatitis-C- (HCV) infected patients receiving livers from HCV-infected donors have a slower rate of fibrosis progression at 1 year than those receiving uninfected livers.

The findings were presented at a press briefing here at the Digestive Diseases Week (DDW).

"The implications are potentially highly important," said presenter and investigator Paul Kwo, MD, associate professor of medicine and medical director of liver transplantation, Indiana University School of Medicine, Indianapolis, United States.

"Many people live 'peacefully' with hepatitis C infection, but when they die of other causes, their livers have not been considered to be eligible for transplantation. Our study suggests that survival rates for recipients are at least as good with cadaveric hepatitis-C-infected, noncirrhotic livers as with uninfected livers. This could mean the availability of many more cadaveric livers for transplant, where there is a critical shortage now," said Dr. Kwo.

The investigators compared transplant outcomes for liver recipients from HCV-infected donors to those for standard, nonextended criteria (ECD) donors. They analysed data from 38 liver recipients and 76 ECD donors, data extracted from a transplant center registry, UNOS (United Network for Organ Sharing), and original on-site donor data charts.

Thirty percent of all donors met non-ECD criteria (standard donors) and were included as potential matches for the case-control study. The researchers matched each HCV-positive liver donor recipient to 2 standard donor recipients

They then analysed recipient data for graft survival and patient survival at 3 months, 1 year, and 2 years. They also noted perioperative death, HCV recurrence, and 4-month and 1-year fibrosis.

The researchers discovered that when HCV-positive livers were used, there was no difference in survival rates compared with patients receiving uninfected livers. And they reported that the rate of fibrosis appeared to be slower in recipients of HCV-infected livers.

"The use of HCV-positive donors may be considered as a first-line therapy to increase the available donor pool of organs in those undergoing OLT for HCV-related cirrhosis," the authors concluded.

"We need more organ options for hepatitis-C patients," added press briefing moderator John Vierling, MD, professor of medicine, chief of hepatology, and director of Baylor Liver Health, Baylor University College of Medicine in Houston, Texas, United States. "This could go a long way to meeting the need for more donors."

[Presentation title: Use of Hepatitis C-infected Donors in Liver Transplantation: A Case-Control Study]

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May 23rd, 2007


Reversibility of Hepatic Fibrosis and Cirrhosis--Is it all Hype?
http://www.medscape.com/
Scott L Friedman

Now that the idea that hepatic fibrosis is reversible is taking root, many clinicians are beginning to ask why, if fibrosis is reversible, is there so little progress in the clinical setting, and will patients ever really benefit from antifibrotic therapies? Underlying such questions is a subtle cynicism that the reversibility of fibrosis and cirrhosis has been overhyped – yet another example of the medical media 'spin machine' giving false hope to desperate patients. The situation has been fueled by the actions of ambitious institutional press relations officers. One such example is the worldwide media focus on the use of sulfasalazine to treat hepatic fibrosis, with claims that half of all liver deaths could be avoided[1] even though the drug's reported efficacy was based on a single study in rodents.

So what is the truth, and how do we maintain perspective? First of all, progress has been tremendous. The mere idea that fibrosis can regress when the initial disease is controlled or cured is exciting, given the decades of dogma that suggested scar formation was a unidirectional pathway. Ample evidence that fibrosis regresses with control of hepatitis B, hepatitis C, or other chronic liver diseases[2] attests to the tremendous regenerative power of the liver, and the rapid progress made in the development of targeted antiviral and disease-specific treatments. Without such advances a discussion of reversibility would have been moot, but this discussion has raised some semantic issues that sow controversy and obscure continued progress. Specifically, use of the term 'reversal' implies a complete return to normal histology, whereas a better term would be 'regression'—a more accurate and relevant term that indicates improvement in fibrosis without necessarily a return to normal histology. Of equal importance, stasis of disease or delayed progression are clinically meaningful, as they might prevent the development of cirrhosis, which is the only stage of chronic liver disease associated with significant and predictable complications.[3] A related issue is the failure of some clinical studies to distinguish between cirrhosis, which connotes distinct architectural and structural changes (including nodules of fibrosis that encapsulate hepatocytes), and advanced fibrosis, which lacks these features.

We are approaching a situation with hepatic fibrosis somewhat like that observed for cancer, where progress in curing disease in rodent models has been far more rapid than in humans. What is so different about hepatic fibrosis in rodents? The answer could lie primarily in the speed of disease progression, which in rodents occurs in weeks after toxin administration (e.g. carbon tetrachloride, thioacetamide, dimethylnitrosamine) or bile-duct occlusion, whereas in humans it typically requires decades. During that protracted interval in humans, there is ample time for collagen crosslinking by tissue transglutaminase, septal thickening, and progressive acellularity, features associated with less-reversible disease in animal studies.[4] Fibrosis resolution in rodent models occurs through conversion of micronodular to macronodular cirrhosis and thinning of septae.[4] Micronodularity and thickened septae in humans might, therefore, reflect advanced, less-reversible disease, a conclusion underscored by the finding that these features correlate with increased severity of portal hypertension in patients with cirrhosis.[3]

This observation raises another challenging paradigm shift brought about by the growing evidence of fibrosis regression, namely that not all cirrhosis is the same; in fact, patients with cirrhosis can experience a widely variable clinical course. Our current staging methods do not, however, discriminate sufficiently between different degrees of cirrhosis. This oversight is understandable because until the past decade it hardly mattered whether a patient had 'early' or 'late' cirrhosis – their only viable option would be liver transplantation, indicated solely when hepatic decompensation occurred. Moreover, of the several histologic scoring methods, only the Ishak staging system has two cirrhosis stages rather than one, and it has been unclear whether these two stages correlate with different clinical outcomes or risk of deterioration.[3, 5] Indeed, given the significant sampling variability of liver biopsies[6], standard fibrosis scoring systems might never be adequate to predict clinical outcomes. Other approaches to stage the extent of liver injury and fibrosis are, therefore, being developed, such as assessment of the number of activated stellate cells by smooth-muscle actin staining,[7] determination of tissue elasticity using a noninvasive probe,[8] quantifying metabolic activity by a breath test[5] or multiplex serum marker panels.[9] Alone or in combination, these tests will substantially improve our ability to predict prognosis, enabling us to select patients for optimum antifibrotic or disease-specific treatments, or liver transplantation. In fact, assessing fibrosis histologically could become obsolete unless we develop methods that can be used to quantify the chemical or structural reversibility of the hepatic scar that correlates with response to therapy and reversibility, for example by assessing the extent of collagen crosslinking.

Another parallel between advances in fibrosis research and in cancer research lies in their incremental nature, such that progress can best be appreciated in hindsight. One need only look to the examples of breast, prostate and hematological malignancies to appreciate how significantly their outcomes have improved through sensitive detection and improved therapies based on a clear understanding of their pathogenesis. Similarly, without effective antiviral drugs for hepatitis B and hepatitis C, liver fibrosis reversibility would never have been imagined. Now, however, the challenge is to prove that fibrosis can be reversed by a direct attack on the pathways of fibrogenesis and matrix degradation, instead of therapy directed only to the primary cause of liver disease. Ample therapeutic targets have been identified and there are many drugs in development that could establish a 'proof of concept' provided that clinical trials are thoughtfully designed and of sufficient duration, end points of efficacy are sensitive and robust, and cohorts are appropriately stratified based on disease risk. To accomplish appropriate stratification, genetic risk markers are being uncovered that should enable clinical trials to distribute patients of comparable fibrosis progression risk equally into both treatment and control groups.[10] In addition to genetic markers of disease progression, improved antiviral therapies could allow us to define genetic rather than histological markers of disease regression, because an increasing fraction of patients will be able to clear or suppress their chronic HCV or HBV infections, thereby enabling fibrosis to regress.

So, hindsight indeed provides ample evidence of gratifying progress in hepatic fibrosis. Continued evolutionary development that changes our thinking about fibrotic liver disease and its prognosis is likely in the future. Revolutionary advances would certainly be welcome, but slow and steady gains should still justify hope without provoking hype.

Reprint Address
SL Friedman. Box 1123, Mount Sinai School of Medicine, Room 11-70C, 1425 Madison Avenue, New York, NY 10029-6574, USA. Email: scott.friedman@mssm.edu

References

1. British Broadcasting Corporation, London (2006) Drug 'may reverse liver disease'. [http://news.bbc.co.uk/2/hi/health/5382172.stm] (accessed 22 March 2007)
2. Bonis PA et al. (2001) Is liver fibrosis reversible? N Engl J Med 344: 452–454
3. Nagula S et al. (2006) Histological–hemodynamic correlation in cirrhosis – a histological classification of the severity of cirrhosis. J Hepatol 44: 111–117
4. Issa R et al. (2004) Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 126: 1795–1808
5. Herold C et al. Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C. Liver 21: 260–265
6. Ratziu V et al. (2005) Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128: 1898–1906
7. Gawrieh S et al. (2005) Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation. Liver Transpl 11: 1207–1213
8. Foucher J et al. (2006) Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 55: 403–408
9. Ngo Y et al. (2006) A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C. Clin Chem 52: 1887–1896
10. Huang H et al. (2006) Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C. Gastroenterology 130: 1679–168

Author Information
SL Friedman is Fishberg Professor and Chief of the Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.

Disclosure: The author has declared associations with the following companies/organizations: Angion Biomedica, Intercept, Conatus, XTL, Stromedix, Breath ID, Biogen Idec, Genzyme, Gilead, Glaxo Smith Kline, Novartis and Pro-Pharmaceuticals.

Nat Clin Pract Gastroenterol Hepatol.  2007;4(5):236-237. 

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New HCV Protease Inhibitor Effective Against Hepatitis C
www.medscape.com
Reuters Health

NEW YORK (Reuters Health) May 15 - A new, oral HCV protease inhibitor, SCH 503034, is well tolerated and may be effective against hepatitis C (HCV) genotype 1 that is refractory to interferon treatment, according to a report in the April issue of Gastroenterology.

SCH 503034 is a specific inhibitor of NS3 protease, which plays an essential role in the replication of HCV, the authors explain.

Dr. Christoph Sarrazin from Saarland University Hospital, Hamburg, Germany and associates evaluated the safety and tolerability of SCH 503034, alone and in combination with pegylated interferon-alpha-2b (IFN), in 26 patients with chronic HCV infection that had not responded to treatment with IFN with or without ribavirin.

Both as monotherapy and in combination with IFN, SCH 503034 was generally well tolerated, the authors report.

One week of treatment with SCH 503034 alone resulted in a mean maximal reduction in HCV RNA of 1.08 log10 at 200 mg 3 times daily, and 1.61 log10 at 400 mg 3 times daily, the investigators say.

Combination therapy with SCH 503034 and IFN resulted in greater decreases in HCV RNA than with IFN alone, the researchers note. The best results (a mean decrease in HCV RNA of 2.68 log10 after 2 weeks) were seen with the combination of SCH 503034 400 mg 3 times daily and IFN.

"Evaluation of virologic response during monotherapy and combination therapy suggests that combination SCH 503034 plus IFN was associated with anti-HCV activity in these patients who had previously not responded to IFN with or without ribavirin," the authors report.

"Phase II clinical trials with HCV genotype 1 nonresponders are underway to determine the optimum dosing and exposure levels for this potentially important therapeutic regimen," the researchers add.

"Novel oral antiviral approaches are exciting and fashionable," writes Dr. Jean-Michel Pawlotsky from Hopital Henri Mondor, Creteil, France in a related editorial. "The spectacular antiviral efficacy of some of these drugs should not, however, be allowed to mask the specific new problems they raise."

"Although adjunction of an oral HCV inhibitor may give interesting results, other options are already available for the treatment of chronic hepatitis C, including optimization of the current pegylated IFN-alpha-ribavirin combination," the editorial concludes. "All these options should be explored, as they may benefit patients in the near future."

Gastroenterology 2007;132:1270-1278,1611-1615

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Many Hemophilia Patients With Chronic Hepatitis C Develop End-Stage Liver Disease
www.medscape.com
Reuters Health

NEW YORK (Reuters Health) May 14 - Nearly one-fifth of hemophilia patients with chronic hepatitis C virus (HCV) infection will eventually develop end-stage liver disease (ESLD), according to a report in the May 1st issue of Blood.

Dr. Eveline P. Mauser-Bundschoten from University Medical Center Utrecht, The Netherlands, and associates explain that many patients with inherited bleeding disorders were infected with HCV before 1990 through replacement therapy with inadequate virus-inactivated clotting factor products.

The team assessed the occurrence of ESLD in 847 such patients who were infected with HCV between 1961 and 1990 and were followed until 2005.

After a median follow-up of 27 years, 19% of the patients had spontaneously cleared HCV and 81% remained chronically infected, the authors report. A quarter of the patients were coinfected with HIV.

After 35 years of infection, the cumulative incidence of ESLD was 17.1% of all patients with chronic HCV infection, the results indicate, compared with only 2.1% of patients who spontaneously cleared HCV.

The cumulative incidence of ESLD was far higher in patients coinfected with HIV (35.1%) than in HIV-negative patients (11.5%), the researchers note.

Of the 70 patients with chronic HCV infection who developed ESLD, 58 had never been treated with anti-HCV therapy and 12 were unsuccessfully treated.

During follow-up, 199 patients died, including 73 from HIV/AIDS, 55 from liver disease, and 71 from other causes.

Dr. Mauser-Bundschoten and colleagues conclude that, with longer duration of HCV infection, the risk of ESLD is emerging in patients with inherited bleeding disorders. "Future studies must be performed to study the effect of interferon-based regimens on the development of ESLD," the investigators say.

Blood 2007;109:3667-3671.

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Nurses say many may have hepatitis C and not know it
http://www.milforddailynews.com
By Jennifer Lord/Daily News staff

In their years treating patients at MetroWest Medical Center, nurses Kelly Lindebald and Lynn Dempsey have learned there is no such thing as a typical hepatitis C patient.

Drug users who have shared needles may have it. So might a suburban stay-at-home mom who had a blood transfusion before 1990.

"It's the most common blood-borne illness in the country - more than 4 million are infected," said Dempsey, coordinator for the hospital's hepatitis C clinic.

"And most don't know," added Lindebald, the co-coordinator. "There are probably many more people walking around that have absolutely no idea they have it."

Hepatitis C is a virus that causes inflammation of the liver, leading to chronic liver disease and cirrhosis. It is the most common cause of liver transplants. The virus is transmitted when blood from an infected person enters the body of a person who is not infected, most commonly through sharing drug needles, needle sticks in health workers or from mother to child during childbirth.

Some patients may have contracted hepatitis C by getting a tattoo or a body piercing under non-hygenic conditions or even sharing a razor or toothbrush with an infected person. Sexual transmission is also possible but considered rare.

"About 10 percent of the population doesn't even know how they got it," Lindebald said. "They're starting to suspect snorting drugs may be a risk factor as well. Anything that can transfer blood-to-blood."

To help determine who might be infected with hepatitis C, the hospital is offering free testing tomorrow beginning at 2:30 p.m. as part of an all-day hepatitis C awareness event. The test requires a simple blood draw and results will be sent to patients' primary care doctors or the hospital's clinic if the patient does not have a main doctor.

"A lot of people don't find out (they have it) until they give blood and get a letter in the mail," Lindebald said. "It's a horrible way to find out."

Symptoms typically don't appear until 10 to 20 years after infection and about 80 percent never have signs or symptoms. Some symptoms may include jaundice, fatigue, dark urine, abdominal pain, loss of appetite and nausea.

Unlike hepatitis A and B, there is no vaccine against hepatitis C and it is considered incurable, although treatment with interferon and ribavirin can bring the viral load down to an undetectable level, Dempsey said.

The number of new infections each year declined from an average of 240,000 in the 1980s to about 26,000 in 2004, the latest year for which statistics are available. The number of hepatitis C-related deaths could increase to 38,000 a year by 2010, surpassing annual HIV/AIDS deaths, according to the U.S. Centers for Disease Control and Prevention.

While the typical patient is over the age of 40, figures released recently by the state Department of Public Health found hepatitis C cases on the upswing among 15- to 25-year-olds, rising from 254 in 2001 to 784 in 2005. The jump was attributed to an increase in young people experimenting with injectable drugs.

"It's important to say it's not passed on by casual contact," Dempsey said. "Hepatitis C carries the same kind of stigma as HIV - in fact, hepatitis C and HIV often go hand-in-hand."

(Jennifer Lord may be reached at 508-626-3880 or jlord@cnc.com.)

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Government refusing to release thousands of blood scandal document - Willott
http://www.libdems.org.uk

The Government has been accused by the Liberal Democrats of obstructing an inquiry into a blood products scandal by refusing to release key documents relating to how thousands of NHS patients were infected with HIV and Hepatitis C.

Lord Archer is conducting a non-Government backed inquiry into how thousands of haemophiliacs during the 1970s and 1980s were infected with HIV and Hepatitis C from NHS treatment.

Ahead of the second public hearing of evidence to the inquiry tomorrow, key documents have still not been released by the Government.

Commenting, Liberal Democrat MP for Cardiff Central, Jenny Willott who has campaigned on this issue, said:

"This is a shameful obstruction of justice. The Government is using every trick in the book to keep hidden the full facts of how thousands of haemophiliacs came to be infected with Hepatitis C and HIV under the NHS.

"The Department of Health’s internal review is very disappointing. After waiting for nearly a year, all we have is a summary of just a tiny number of documents - less than 2% of the total they hold - and only those that relate to Hepatitis C from 1970-85.

"Over 1,000 haemophiliacs were infected with HIV under NHS treatment, so why haven’t the 2,000 documents on AIDS been released?

"I have written to the Department of Health calling for a review and the release of all the documents it now holds on this issue. Without the disclosure of all the relevant documents, Lord Archer’s inquiry will never be able to get to the bottom of this scandal."

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May 24th, 2007


Hepatitis C victims dying while compensation stalled
http://www.thepeterboroughexaminer.com
Editorial

The thousands of Canadians suffering from hepatitis C incurred outside the previously-recognized compensation window of 1986-1990 applauded in their hearts and minds last July 25 when then-new Prime Minister Stephen Harper said in an address in Cambridge, "... because these victims have waited long enough for what is due to them, our government is going to do everything in its power to ensure that matters are moved ahead as quickly as possible..."

Those sufferers who rejoiced last July after that momentous announcement and who still remain with us might today be ruminating about the speed with which Canadian governments historically provide redress when the perpetuation of an injustice is finally recognized.

Discussions were launched concerning options for extending the compensation practice for hepatitis C patients as of Nov. 22, 2004. Five months later the House of Commons unanimously supported a motion which effectively called for the immediate compensation of the "pre-1986/ post 1990 class." Seven months after that our government entered into a "memorandum of understanding" which committed it to compensate those Canadians, leaving only the amounts and categories of compensation to be negotiated. The federal government agreed it would place nearly $1 billion into a trust fund to expedite the compensations with fairness and compassion. This distribution would be based upon the principle of parity with the compensation schedule with the "'86-'90 class." Class members read last July that they would receive their entire sum for their compensation up front.

Almost 10 months later, those fortunate enough to still be around await only final agreement by courts in four jurisdictions, Ontario's the largest among them, and the creation of an administrative structure to evaluate applications and ultimately to forward payments. The July 2006 report concluded that we could all rest assured that the federal government would be (will be?) working as hard as it can and as quickly as possible to provide compensation to the class. We look for signs the government is doing this hard work.

Given that a diagnosis of hepatitis C is effectively a death sentence and that sufferers quickly lose both the ability and the energy to work (and commensurately the ability and the energy to persevere in organizing among themselves to pressure governments to provide compassion and support and promised redress through compensation), it must seem like an elusive goal indeed to await the day when the prime minister's promises of last summer actually materialize into their deteriorating lives and the broken lives and dreams of their families and loved ones.

CHRISTIN McKAY RR 2, Lakefield

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Biolex Therapeutics Raises $30 Million to Advance Its Hepatitis C Drug Candidate and Other Pipeline Programs
http://www.marketwire.com/

PITTSBORO, NC -- (MARKET WIRE) -- May 24, 2007 -- Biolex Therapeutics, a privately held biopharmaceutical company, announced today the closing of a $30 million Series C financing. The financing was led by Investor Growth Capital of New York and included the participation of two other new investors, JP Morgan Securities, Inc. and Easton Capital. The financing was oversubscribed and included strong participation from existing shareholders including Quaker BioVentures, Polaris Venture Partners, Intersouth Partners, Mitsui & Co. Venture Partners, Johnson & Johnson Development Corporation and Dow Venture Capital. The funds will be used primarily to advance Biolex's lead drug candidate Locteron™ into Phase 3 clinical development in hepatitis C, and to advance the Company's other drug candidates.

The Company also announced that Sunny Sharma, M.D., Vice President with Investor Growth Capital, has joined the Biolex Board of Directors.

"The response to this financing was outstanding and we believe that the additional expertise and resources of our new investors will complement the strong investor group that has supported the advancement of Biolex to date," said Jan Turek, Biolex's President and Chief Executive Officer. "We welcome Dr. Sharma to our Board of Directors and look forward to his contribution to this very experienced group that has been a great resource to Biolex."

"We are pleased to be a part of the Biolex story, which has some very interesting product and platform attributes," said Sunny Sharma, M.D. "Locteron has the potential to be a best-in-class interferon for the treatment of hepatitis C. We are also very excited about the Company's glycosylation optimization technology and its application in various product opportunities."

About Biolex Therapeutics
Biolex Therapeutics is developing and commercializing therapeutic proteins based on the LEX System(SM), its patented expression system that enables the production of hard-to-make proteins and the optimization of monoclonal antibodies. The Company is developing a proprietary pipeline of products that rely upon known mechanisms of action to provide a reduced risk profile while targeting large, proven pharmaceutical markets. Biolex's lead clinical candidate, Locteron™, is being developed as a best-in-class controlled-release interferon alfa for the treatment of hepatitis C and is currently in Phase 2 testing. The Company's second product candidate, BLX- 155, is a direct-acting thrombolytic, designed to break up clots in certain diseases such as acute peripheral arterial disease, deep vein thrombosis and catheter occlusion. In addition, the unique capabilities of the LEX System have led to collaborations with Centocor, Medarex, Genmab and other leading pharmaceutical/biotech companies. Biolex is a venture capital- backed company located in the Research Triangle region of North Carolina, United States. For additional information, please visit Biolex's web site at www.biolex.com.

Contacts:
Media:
Michelle Linn
Linnden Communications
508-419-1555

Investors:
Dale Sander
Chief Financial Officer
858-663-6993

SOURCE:  Biolex Therapeutics

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May 25th, 2007


Hepatitis B patients' understanding of infection and treatment deficient
http://www.eurekalert.org

Many patients with chronic hepatitis B are deficient in their understanding of the lifelong disease and often do not comply with the drug regimens necessary to control it, according to a new UCLA survey that suggests improved patient involvement in disease management decisions could be the key to fixing this problem.

The national survey — funded by Idenix Pharmaceuticals and Novartis Pharma AG and presented May 20 during the annual Digestive Diseases Week conference in Washington, D.C. — indicates that patient involvement in disease management decisions need to be improved, which could result in better adherence to drug regimens and improved clinical outcomes.

“The results of this study are very compelling and are a wake-up call to physicians caring for hepatitis B patients that we need to educate our patients more about risk factors, modes of transmission and expectations regarding antiviral therapy,” said Dr. Steven-Huy Han, associate clinical professor of medicine and surgery in the division of digestive diseases at the David Geffen School of Medicine at UCLA and a consultant for both Idenix and Novartis.

The study was based on responses from 301 adult chronic hepatitis B patients on antiviral therapy. Of those, 24 percent were on interferon treatment. Most of these patients were males between the ages of 31 and 50, with about half being of Asian descent. In addition, 64 percent were from the mid-Atlantic or Pacific regions of the United States. The study was based on Internet interviews, supplemented by telephone interviews, conducted between September and November 2006.

Among the findings:

• 36 percent of respondents mistakenly thought the virus could be spread through sharing utensils.
• 80 percent were aware of the long-term consequences of the hepatitis B virus.
• Half of the respondents erroneously believed a cure existed for the chronic virus, though just more than 60 percent had been in treatment for about a year.
• 31 percent said they knew specific names of hepatitis B virus tests, but only half knew what the tests measured.
• 85 percent felt that measuring virus levels was important, though 27 percent didn’t know if their physicians took those measurements.
• 37 percent did not discuss treatment goals with their physicians, yet 88 percent of these respondents felt they should be doing this.
• 51 percent felt involved in treatment decisions.
• 54 percent were unsure why the drugs they were taking had been chosen.

Respondents also admitted frequently missing doses or taking them at the wrong time. For instance, 12 percent admitted not complying once per month; 7 percent once every two weeks; 7 percent once a week; 7 percent two to three times per week; 1 percent four to six times per week; and 4 percent once per day. Also, 9 percent thought that missing one or two doses didn’t matter.

###
Other researchers on this study were Lisa Griffith of Idenix Pharmaceuticals and Tzvetelina Westphalen of Novartis Pharma AG.

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Scientists Model Hepatitis C Virus
http://www.physorg.com

One of the most common life-threatening viral infections in the United States today is hepatitis C virus (HCV). The standard treatment is successful in only about 50 percent of treated HCV chronic patients, with no effective alternative treatment for those who fail to clear the virus.

Recently, scientists at Los Alamos National Laboratory, in collaboration with researchers from the Center for HCV Research at Rockefeller University, developed the first mathematical model of intracellular HCV replication. The model is designed to help scientists and medical researchers develop a better understanding of the dynamics of replication, as well as the mechanisms of drugs currently being used to treat HCV. This new understanding may eventually lead researchers to a more successful treatment for the virus.

In research published recently in the Journal of Virology, Los Alamos theoretical biophysicist Harel Dahari and his colleagues describe how they leveraged recent advances in HCV cell culture replication to provide the quantitative data necessary for creating a computer model of the dynamic interplay between host and virus during replication of the virus in Huh-7 (human liver) cells.

"With more than 200 million people in the world infected with HCV and half of those not responding to treatments," said Dahari, "our model can be an important tool for understanding the HCV replication mechanisms. Perhaps more importantly, it may prove useful in designing and evaluating new antivirals for use in combating the virus."

According to the researchers, the next step will be to incorporate virus production and infection into one comprehensive model of the complete HCV life cycle.

Dahari, Ruy Ribeiro and Alan Perelson from Los Alamos and Charles Rice from Rockefeller University collaborated in this research, which was funded by the National Institutes of Health.

Source: Los Alamos National Laboratory

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Further evidence that HIV/hepatitis C coinfected patients have poorer immunological response to HIV therapy
www.aidsmap.com
Michael Carter

Hepatitis C coinfection is associated with lower CD4 cell counts and CD4 cell percentages in HIV-positive patients who are fully adherent to their antiretroviral treatment regimens, a US study published in the May edition of Alcoholism: Clinical and Experimental Research has found. The investigators believe that their findings have important clinical implications for the timing of both anti-hepatitis C treatment and antiretroviral therapy in coinfected individuals.

A significant number of HIV-positive individuals are coinfected with hepatitis C virus, with estimates in the US ranging from 15% to 30%. The impact of hepatitis C virus on HIV disease progression is a controversial subject. Although data from the large Swiss HIV cohort indicated that coinfected individuals experienced more rapid HIV disease progression, this finding was not supported by a large US study.

Investigators therefore wished to test the hypothesis that hepatitis C infection had an adverse effect on CD4 cell count, CD4 cell percentage and HIV viral load in a cohort of HIV-positive individuals taking antiretroviral therapy who had alcohol problems. The study involved 396 patients who were assessed at baseline and then at six monthly intervals for 42 months.

Data were gathered on demographics, HIV risk behaviours, and alcohol and drug use. Patients were also asked about their adherence to antiretroviral therapy. Those who did not report 100% adherence to their treatment in the last three days were considered non-adherent. Blood samples were obtained to measure CD4 cell count, CD4 cell percentage, and HIV viral load.

At baseline, individuals were also tested for hepatitis C virus, with just over 50% (199 individuals) having evidence of hepatitis C virus infection using RNA viral load tests.

The mean age was 43 years, 75% were men, 41% were African American, median CD4 cell count was 403 cells/mm3 and median HIV viral load was a little under 1,000 copies/ml with 31% of patients having an undetectable viral load. The mean period since HIV diagnosis was nine years and individuals had been taking antiretroviral therapy for a mean of seven years.

Of the patients who were assessed as being fully adherent to antiretroviral therapy (total 185, of which 99 were coinfected), CD4 cell counts were a mean of 46 cells/mm3 lower in coinfected patients, a statistically significant difference (p = 0.03). In non-adherent patients, no significant difference was seen in CD4 cell counts those patients who were coinfected and those who were not.

The investigators also found that adherent coinfected patients had significantly lower CD4 cell percentages than patients who only had HIV and who were also fully adherent (mean difference, 2%, p < 0.01). Once again, there was no difference between non-adherent patients regardless of their coinfection status.

HIV viral load did not differ significantly between coinfected patients and patients only infected with HIV, irrespective of their adherence.

Alcohol consumption did not affect the investigators findings, nor did their findings change after they controlled for time since antiretroviral therapy was initiated.

“Determining whether HCV coinfection affects HIV disease progression is important for understanding the optimal timing and sequencing of therapies for these infections”, write the investigators.

They add, “the observation of a lower CD4 cell count in patients with HCV infection that were receiving and adherent to antiretroviral therapy is of particular interest” as it is consistent with the findings from the Swiss HIV cohort that found that individuals with hepatitis C infection had a blunted recovery in CD4 cell count after initiating HIV therapy compared to those without hepatitis C. The investigators speculate that hepatitis C may have a direct effect on CD4 cells.

“This study’s findings have important implications for understanding the optimal management…for coinfected patients”, and the investigators believe that they “strengthen the argument to initiate HCV therapy early in the course of HIV disease. These findings may also support the earlier induction of antiretroviral therapy in coinfected individuals to both offset the negative impact of HIV on HCV disease progression and the potentially negative impact of HCV on CD4 cell recovery.”

Reference

1. Cheng DM. Impact of hepatitis C on HIV progression in adults with alcohol problems. Alcohol Clin Exp Res 31: 829 – 836, 2007.
2. Greub et al. Clinical progression, survival and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV cohort study. The Lancet 356: 1800 – 1805, 2000.
3. Sulkowski MS et al. Hepatitis C and progression of HIV disease. JAMA 288: 199 – 206, 2007.

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Investigative Eltombopag Shows Promise for Thrombocytopenia in Hepatitis C Patients: Presented at DDW
http://www.docguide.com
By Bruce Sylvester

WASHINGTON, DC -- May 25, 2007 -- Investigative eltrombopag increases platelet counts in hepatitis C patients prior to myelosuppressive pegylated interferon alpha (PEG-IFN/ribavirin) therapy and helps maintain healthy counts during the first 12 weeks of antiviral treatment, averting the need for PEG-IFN avoidance or dose modification in the majority of patients, researchers report.

The Phase II findings were presented here at the Digestive Diseases Week (DDW) annual meeting.

As background to this study, presenter and investigator Dickens Theodore, MD, Director of Clinical Development, Oncology Group, GlaxoSmithKline, Research Triangle Park, North Carolina, United States, said, "For a certain group of people with hepatitis C, those with low platelet counts, physicians have some anxiety about initiating pegylated interferon treatment, and this is based on FDA warnings. We wanted to see if this drug could increase platelet counts before pegylated interferon treatment started and then maintain platelet counts in hepatitis C patients during the first crucial first 12 weeks of treatment, allowing that treatment to continue at optimal dosing levels. "

The authors added, "There is an unmet need for a safe and effective treatment of disease and INF-associated thrombocytopenia in HCV-infected patients to help facilitate optimal treatment."

The investigators enrolled 74 HCV-positive subjects with compensated cirrhosis and platelet counts of 20-70,000 micro-units per liter.

During the 4-week induction phase of the trial, the subjects were randomised (1:1:1:1) to receive 30 mg, 50 mg, 75 mg eltrombopag or placebo once daily.

Subjects who achieved platelet counts of >70,000 micro-units per liter in the induction phase were allowed to initiate PEG-IFN therapy along with study drug for the 12 week maintenance phase.

Of the 74 subjects in the induction phase, 49 successfully entered the maintenance phase and initiated PEG-IFN treatment.

The investigators compared baseline platelet counts to those made at the completion of PEG-IFN treatment (study day 113).

The authors reported, "Eltombopag effectively maintained platelet counts above 50,000 micro-units per liter in up to 81% of patients during the first 12 weeks of antiviral treatment, counteracting the myelosuppressive effects of PEG-IFN. And eltrombopag use avoided the need for PEG-IFN dose modification in approximately 90% of patients during the first 12 weeks of antiviral treatment."

They noted that the findings warrant further research into long-term (48-week) use of eltombopag in patients with HCV-associated thrombocytopenia.

The research was supported by GlaxoSmithKline.

[Presentation title: Eltrombopag Maintains Platelet Counts During Myelosuppressive Pegylated Interferon Alpha Treatment of Chronic Hepatitis C Virus Infection. Abstract T1044]

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