SARS Vaccine Caused Liver Damage in Animal Testing
By HELEN BRANSWELL SourceURL:http://cnews.canoe.ca
TORONTO (CP) - A SARS vaccine designed by Canadian scientists triggered severe liver inflammation when tested in ferrets - an unexpected problem that should give pause to others working to develop a vaccine against the disease.
The team, which reported its findings in the Journal of Virology, stumbled upon the problem by accident when one of the scientists insisted on running unplanned blood chemistry tests on the vaccinated ferrets.
The director of the Canadian SARS Research Network says the results are a red flag to all working on vaccines for the disease.
"This is really important because it really is saying: proceed cautiously in people," said Dr. Mark Loeb, an infectious disease specialist at Hamilton's McMaster University. Loeb was not involved in the work.
The team was drawn from the Canadian Science Centre for Human and Animal Health, the Winnipeg complex which houses the National Microbiology Laboratory and the National Centre for Foreign Animal Disease.
Research scientist Jingxin Cao constructed the recombinant vaccine by genetically modifying a pox virus to produce a protein - called the spike protein - which is made by the SARS coronavirus. The spike protein is the key protein on the SARS virus that triggers an immune response.
Cao chose the modified pox virus, called MVA, because it has been widely - and safely - used in development of other vaccines.
"It's really safe, even in the so-called immune compromised, like AIDS patients," he said in an interview.
The team then put the vaccine to the test, vaccinating ferrets, which are believed to suffer disease similar to that experienced by humans who contract SARS. They then waited to see whether the animals developed antibodies to the virus when they were exposed to SARS in what's called a challenge test.
On that front, things went smoothly.
"We had quite nice antibody levels against this protein," said Hana Weingartl, head of special pathogens in the centre for foreign animal disease.
But then colleague Markus Czub insisted on running the blood chemistry tests and found evidence of severe hepatitis - inflammation of the liver. Autopsies on the animals confirmed the finding.
And there was another hitch. Their control ferrets - the unvaccinated animals - didn't show signs of disease, leading the team to wonder whether they are indeed a good model for human SARS.
"They certainly do replicate the virus but they did not get sick," Weingartl said.
That isn't the experience of another Canadian researcher working on a SARS vaccine.
Brett Finlay, a molecular biologist at the University of British Columbia, said ferrets his team tested developed symptoms similar to human SARS.
"They got sick; they got lung disease, just like people do," said Finlay, whose team worked on different kinds of vaccines, including one based on a killed coronavirus and another on a modified adenovirus.
"You crack open the lungs and it's all inflamed and yucky, just like you see in SARS."
His team's results are not yet published, so they haven't been confirmed by outside experts through a scientific journal's peer review process. But he says they did not see liver inflammation - and they checked.
"We did not see what they saw. We'd heard about that, so we were looking."
Finlay agreed with Loeb that all teams working on a SARS vaccine will have to check for liver inflammation from now on.
"We'd be dumb not to," he insisted.
As for the Winnipeg team, they cannot say whether the problem they saw relates strictly to their vaccine or is indicative of a wider challenge to the development of a SARS vaccine.
"We don't know whether or not this association of vaccination with enhanced hepatitis is only related to the MVA base," Cao said. "Could be if you tried a different way - for example, adenovirus-based, another virus based - you won't see this. We don't know."
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Doctor Hears from Patients Who Say University Broke Law
By TONY MESSENGER
SourceURL:http://www.columbiatribune.com/
Physician Paul King has a prescription for what ails his soon-to-be former employer.
The care plan starts with a heavy dose of thinking before taking hasty actions, and it ends with a continuing treatment of putting patients before profits.
King is a gastroenterology specialist who has worked as a doctor at University Hospital for 15 years. His specific area of emphasis is liver disease. He is one of the only specialists in Mid-Missouri in treatment of patients with hepatitis C, a potentially fatal disease that attacks the liver. He’s respected in his field. In 2000, he was named the Outstanding Young Physician by the University of Missouri-Columbia Medical Alumni Association.
Lately, though, King has been discouraged by what he sees at University Hospital. As the hospital system has climbed out of its financial crisis with the help of The Hunter Group, cuts have been made to certain areas of service. While profits are rising, the quality of care, in some cases, is not, King says.
That’s why he decided to leave to start a private practice. King thought he was leaving on good terms with no hard feelings. Then he started hearing from his patients.
King was shocked when he found out what had happened. His former boss, Kevin Dellsperger, chairman of internal medicine, had given a list of about 800 of King’s former patients, along with their phone numbers, to a home-health-care provider from Cape Girardeau. A woman from the company had been calling the patients, King says, trying to sell home health-care services, including a $3,000-a-month drug that he says many of the patients didn’t need.
"She was making cold calls, asking people about their hepatitis C," he says. "Most of the people on the list have hepatitis C. Not all of them do. I got a call from one lady frantic over the phone call. “I don’t have hepatitis C,” she told me. “What’s this all about?” Whoever was making the calls had no way of knowing if these people were sick, if they have cirrhosis, if they’re still using. She’s just making phone calls to get people on treatment. That is scary."
It’s also, King believes, a clear violation of the recently enacted federal privacy law, the Health Insurance Portability and Accountability Act, or HIPA. The law severely restricts hospitals’ and doctors’ ability to share private information about patients, including names and phone numbers, without consent from the patient. There are specific rules that guide the use of information for marketing, unless the other medical party already has some relationship to the patient.
What complicates the privacy concern in this case is the nature of hepatitis C patients. Most, King says, are middle-age folks who contracted the disease from youthful indiscretions in the 1960s and ’70s. Some got it from blood exposure or bad needles, possibly from drug use, others got it from bad blood transfusions before 1990 when procedures were improved.
"Most of the time," King says, "People don’t even know they have it."
King thinks Dellsperger gave out the list, in part, because the university will be unable to serve his patients. There are no other doctors in the internal medicine department who have the specific liver focus that he does. And the hospital already had made a decision to cut back in terms of nurses, some of which are key in caring for hepatitis C patients. Like chemotherapy for cancer patients, treatment for hepatitis C can be physically and mentally devastating, and the nurses are key to the patient’s well-being.
Many of his patients, King says, were planning to follow him to his private practice, and the university acted to try to cut its losses. Losing revenue is not part of the hospital’s new fiscal plan.
"It really looks like an attempt to keep patients from going with me," King says.
University officials deny that charge, but they acknowledge there were problems with the way King’s list of patients was handled.
"Our belief is that" Dellsperger "was doing everything possible to make sure there was no lapse in the patients’ care," says Mike Lynch, director of corporate compliance for the university. That said, the phone calls from the Cape Girardeau company have stopped, and the list is being returned to the university. Lynch says an investigation into whether a HIPA violation occurred is ongoing.
"I think it’s safe to say nobody’s going to receive any more phone calls," he says.
One patient who did receive phone calls isn’t satisfied the university is doing enough to protect his privacy.
The liver transplant patient, who does have hepatitis C, asked that I not use his name. He said he was shocked when he received a call from the Cape Girardeau company, but what really made him mad was his conversation with Dellsperger and his secretary.
"I kept asking how my name ended up on the list, and she wouldn’t tell me," he says. Dellsperger "told me they gave names to the company because they didn’t have anybody qualified to deal with our condition."
He says Dellsperger admitted the action was a mistake, but that was no consolation.
"I’ve already lost my privacy," he says.
Dellsperger couldn’t be reached for comment.
Hospital spokeswoman Joann Wait agreed a mistake was made. Patients should have been called before their information was passed to a third party, she says. "That’s what we should have done."
For now, hospital officials are going through the list themselves, calling every patient and trying to determine whether a violation of federal law occurred.
King says there’s no doubt.
"Any spin you put on it," he says, "it shouldn’t have happened this way."
Tony Messenger is a columnist at the Tribune. His column appears on Sunday and Tuesday through Thursday. He can be reached at 815-1728 or by e-mail at tmessenger@tribmail.com.
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November 29th, 2004
Gilead Licenses Hepatitis C Compounds
SourceURL:http://biz.yahoo.com
Associated Press
Gilead Sciences Licenses Hepatitis C Compounds from Achillion Pharmaceuticals
FOSTER CITY, Calif. (AP) -- Biotechnology company Gilead Sciences Inc. said Monday that it is licensing certain experimental hepatitis C treatments from privately held Achillion Pharmaceuticals.
Under the agreement, Gilead will pay $5 million up front, buy $5 million of equity and provide the bulk of research funding in exchange for worldwide rights to the research, development and commercialization of certain Achillion compounds designed to treat the liver disease. Achillion could also receive up to $100 million in payments as certain milestones are reached and will receive royalties on any sales. Gilead said payments to Achillion could be significantly higher if multiple related compounds are developed.
The compounds are small-molecule inhibitors which seem to block replication of the hepatitis C virus through an action involving its protease enzyme.
New Haven, Conn.-based Achillion will continue to develop the compounds through a proof-of-concept clinical study in patients who are infected with the hepatitis C virus. Gilead said it will provide partial funding for this research and take on all subsequent research costs.
Achillion chief executive Michael Kishbauch said that the deal will advance development of the hepatitis C compounds while freeing up Achillion's resources to advance its HIV and anti-bacterial programs.
Hepatitis C, a viral liver disease which often leads to scarring of the liver and cancer, is the leading cause of liver transplantation in the United States, the company said.
Shares of Gilead were up 6 cents at $34.57 in morning trading on the Nasdaq.
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Hygiene Risk for Dental Patients
ANDREW DENHOLM
POLITICAL CORRESPONDENT
SourceURL:http://news.scotsman.com/
DENTAL patients across Scotland are being put at risk of infection from blood diseases such as HIV and hepatitis because of poor standards of hygiene.
Dr Mac Armstrong, the Chief Medical Officer for Scotland, has written to all dentists calling for urgent action to improve basic sterilisation techniques. Dr Armstrong has also written to all GPs and health boards calling on them to ensure high standards are maintained.
The move follows a Scottish Executive study which found that dental surgeries routinely failed to meet basic hygiene standards.
According to the study, three quarters of practices do not change the water in their sterilisers on a daily basis.
Half do not have a dedicated sink for the cleaning of drills, probes and tweezers, while 70 per cent have no record of staff training for sterilisation techniques. A further 60 per cent have no instruction manuals for sterilising equipment.
Deadly viruses, including HIV, hepatitis C and vCJD, the human form of mad cow disease, can all be spread through contact with infected blood.
In September, a helpline was set up for 3,500 patients of an Inverness dentist after claims he failed to sterilise equipment.
Dr Armstrong said yesterday that standards had slipped due to a combination of ignorance and complacency.
And while he stressed that there was no evidence that any hepatitis infections had taken place as a result of poor hygiene, he said that without higher standards there was always a risk of such cross-contamination.
"We have written to all dentists, GPs and health boards in Scotland to highlight the concerns identified in this study and to make clear that we expect action on ten priority areas as a matter of urgency," he said.
"It is the legal and professional responsibility of all dentists, doctors and nurses working with re-usable instruments in primary care to ensure that this happens."
The Chief Dental Officer, Ray Watkins, echoed the concerns and highlighted a £150,000 training programme which has been set up for the profession.
"We have now set up an expert group to take this forward," Mr Watkins said.
"As well as providing training for staff in their practices, it will provide clear and consistent information and help them systematically audit their decontamination practices.
"We have asked NHS Boards to provide us with action plans detailing how they plan to address any shortcomings identified through this process."
The British Dental Association said: "Infection control is a core element of dental practice and the BDA fully supports its members in achieving excellence in this area.
"We provide both written and one-to-one guidance on infection-control issues and work closely with the relevant government departments to ensure the profession has the most appropriate and up-to-date advice."
A spokeswoman for the British Medical Association added: "We support the aims of the chief medical officer in highlighting this issue to all GPs."
The Executive report was carried out by the Glennie Group, chaired by John Glennie, chief executive of NHS Borders. The report was commissioned after concern in the 1990s that CJD could be transmitted via surgical instruments.
While dental procedures are categorised as low risk for such transmissions, there remains a risk for HIV, hepatitis B and C and other bacterial and viral infections.
"The survey has highlighted that the cleaning of instruments has several shortcomings and is poorly controlled," states the report. "The problem is compounded by the lack of clear instructions from manufacturers on the use of dental devices."
That could lead to disposable instruments being used more than once, the report added.
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Nearly 20% of HIV Patients Infected with Hepatitis C
SourceURL:http://asia.news.yahoo.com
(Kyodo) _ Nearly 20 percent of the HIV patients in Japan are also infected with the hepatitis C virus or HCV, while almost all of the HIV patients infected through blood products are infected with the HCV, according to results of a health ministry survey obtained by Kyodo News.
The survey by a study group of the Health, Labor and Welfare Ministry was conducted in January and covered major HIV/AIDS treatment facilities nationwide of which 176 or 48 percent responded. The survey covered 4,877 HIV patients treated at the 176 facilities.
Of 811 HIV patients infected through tainted blood products, 786, or 96.9 percent, tested positive in an antibody test for HCV, the survey showed.
It also showed that 19.2 percent of all the HIV patients surveyed also tested HCV-positive.
Of 20 HIV patients infected through sharing needles used in drug injection, nine, or 45 percent, tested HCV-positive, while 4.2 percent of the 2,730 HIV patients infected through male-to-male sexual contact were HCV-positive.
The main source of HCV infection is blood contact. There are an estimated 1.5 million people with HCV in Japan.
People infected with HCV may develop liver cirrhosis or liver cancer unless appropriately treated.
Currently, the onset of AIDS is brought under control by combining a number of medications in the early stages of infection, but more than half of the HIV patients are dying due to hepatic disease such as liver cirrhosis, some surveys show.
Kazuhiko Koike, a professor at the University of Tokyo's medical department who led the ministry survey, said, "It's important to let doctors and patients know of the treatment of hepatitis and take emergency action against the disease as the hepatitis symptoms of HIV patients tend to deteriorate rapidly. We shouldn't think lightly of such patients' symptoms of hepatitis by paying attention only to HIV."
According to a survey by the Japanese AIDS Foundation for AIDS Prevention, annual deaths of HIV patients decreased to 11 in 2002 after peaking at 69 in 1994. Of those who died in 2002, no patients showed AIDS symptoms while six died of hepatitis.
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News from NIH: Action Plan for Liver Disease Research
SourceURL:http://www.gastrohep.com
After a Congressional request asking for more focus on NIH-funded liver disease research, the NIH has developed a trans-NIH Action Plan with the aim of decreasing the burden of liver disease in the United States, reports a recent statement by the NIH.
Liver disease is an important cause of morbidity and mortality in the United States, affecting persons of all ages, but most frequently individuals in the productive years of life, between the ages of 40 and 60 years.
Liver disease also disproportionately affects minority individuals and the economically disadvantaged.
Medical research on liver disease is critically important and further progress in research promises to bring under control the major toll of liver disease on human health and well-being.
Indeed, the last 25 years of medical research in liver disease has resulted in major improvements in the survival and quality-of-life of patients with liver disease.
Action Plan for Liver Disease Research is set up to advance research on liver disease with the aim of decreasing the burden of liver disease in the USA—NIH
The next 25 years should bring even more profound and important changes.
To address the burden of liver diseases in the United States, the National Institutes of Health is developing an Action Plan for Liver Disease Research.
NIH created a Liver Disease Research Branch (LDRB) in the NIDDK and established a Liver Disease Subcommittee of the Digestive Diseases Interagency Coordinating Committee.
This is a congressionally mandated committee responsible for coordination of digestive disease research activities among components of the NIH and other federal agencies.
Their mission statement:
The goal of the Action Plan for Liver Disease Research will be to advance research on liver disease with the aim of decreasing the burden of liver disease in the United States.
NIH; 2004: online statement
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Response to Percutaneous Ablation Predicts Survival
SourceURL:http://www.gastrohep.com
A study in December's Hepatology reports that initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function.
Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival.
Dr Bruix and colleagues from Barcelona in Spain undertook a study on 282 cirrhotic patients with early nonsurgical HCC.
The participants were treated with percutaneous ablation during a 15-year period.
The researchers found single tumors in 244 patients, and 2 to 3 nodules were seen in 38 patients.
Initial complete response to percutaneous ablation is associated with improved survival in Child-Turcotte-Pugh class A and B patients with nonsurgical HCC—Hepatology
The researchers noted initial complete response in 192 patients and it was independently related to the size of the main tumor and tumor stage (2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2-3 nodules, 46%).
At the end of follow-up, the research team recorded that 80 patients presented with a sustained complete response.
The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%, respectively.
The researchers found that the independent predictors of survival were Child-Turcotte-Pugh class and initial complete response.
Child-Turcotte-Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller.
Dr Bruix concluded, "Our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child-Turcotte-Pugh class A and B patients with nonsurgical HCC."
"Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function."
Hepatology: 2004;40:1352-1360
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AIDS Takes its Toll, Despite Advances
BY NANCY DOOLING
Press & Sun-Bulletin
SourceURL:http://www.pressconnects.com
HIV, Hepatitis C to Be Subject of Conference
Acquired immune deficiency syndrome, and the human immunodeficiency virus that causes it, continue to kill quietly, despite enormous strides in treatment.
Being diagnosed with HIV or AIDS is no longer an immediate death sentence. Drug treatment has allowed victims to live 15 and even 20 years with the illness, experts said.
Gone are the images of the horrific ravages the disease inflicted on its victims in the early 1980s, when the virus surfaced among gay men, killing them in a matter of months.
Now, AIDS and HIV sufferers live longer, more anonymous lives. But there's a flip side to effective treatment. Because people are living longer with the disease, they need special services over longer periods of time, said Ron Siwiec, director of development at the Southern Tier AIDS Program in Johnson City.
"We have to help a larger group of people who are living with disease," said Siwiec, who has been involved at STAP for a decade.
A new trend Siwiec and caseworkers at STAP are seeing is an explosion of patients with both HIV and Hepatitis C. About 25 percent of STAP's clients have both viruses, Siwiec said. STAP will host a regional conference on HIV and Hepatitis C issues on Dec. 6 and 7 in Binghamton.
In the Binghamton region, including Broome, Chenango and Tioga counties, 106 people have HIV, and 144 individuals live with AIDS, statistics from the Centers for Disease Control and Prevention indicate. Overall, 324 people were diagnosed with AIDS between 1995 and 2001 in the region, CDC figures show. That number does not include prisoners.
In New York, male-to-male sex remains overwhelmingly the way the disease is transmitted, followed by intravenous drug use. That has remained the trend in all Western countries.
In the developing world, especially Africa, the illness is primarily transmitted between men and women having sex, CDC numbers show. However, advocates say the number of women infected with HIV and AIDS in the United States is growing.
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Preventing the Spread of Hepatitis C
SourceURL:http://www.wlns.com
11/29/04- It's a silent killer, now new research shows Hepatitis C is 4 times more prevalent than HIV, and now considered a major threat to public health. Nearly 4 million Americans have Hepatitis C and many aren't even aware they have it.
Doctors says it's the leading cause of cirrhosis, liver transplants and liver cancer in the US, and the problem is only growing. Infectious disease specialist Doctor Peter Gulick has seen 3 patients with liver cancer in just 1 month, but he says that's not alarming. Liver cancer is increasing at the fastest rate of any other cancer, and more than half of people with the disease have Hepatitis C.
Dr. Peter Gulick, infectious diseases: "It's difficult to treat, not a lot of treatment options with chemo or radiation and it has to be monitored."
Liver cancer is not the only health problem associated with Hepatitis C, it causes significant liver damage, and as a result, every year more and more people have to have a liver transplant.
Dr. Peter Gulick: "It's the #1 reason for transplants in the U.S. Hepatitis C. It's going to be a major drain on the health care system soon because we will not have enough livers to transplant."
Dr. Gulick says Hepatitis C may not show up for 20 to 30 years, that's why it's critical if you're at risk to get checked out.
Dr. Peter Gulick: "There's new treatment coming out in the next 3-5 years that could be effective, but if you don't know you have it and wait, the only thing you're looking at is a liver transplant."
The best protection is prevention. With that in mind, the Michigan Department of Community Health along with local physicians and community leaders are working to develop programs to address this growing concern.
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November 30th, 2004
Waning Immunity to Hepatitis B Vaccine: Booster Needed
SourceURL:http://www.gastrohep.com
Findings suggest that 1 or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma-derived HB vaccine, reports the December's issue of Hepatology.
Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however, more needs to be learned about the duration of protection and indications for boosters.
Dr Huang and colleagues from Taiwan undertook a study to measure antibody to HB core antigen (anti-HBc), HB surface antigen (HBsAg), and pre- and postbooster titers of HBsAg antibody (anti-HBs).
The researchers included 2 cohorts of 15 year-year-old children and observed them 15 years after primary neonatal immunization with plasma-derived HB vaccines.
Group A consisted of 78 children who were born to HB e antigen-positive HBsAg carrier mothers and had developed protective levels of anti-HBs antibodies (10 mIU/mL) following HB immunization.
Group B consisted of 113 apparently healthy children whose anti-HBs titers after vaccination were unknown.
The researchers were unable to identify anti-HBs (antibody titer <10 mIU/mL) in 29.9% of Group A and 62.4% of Group B.
The research team detected anti-HBc in 33.3 % of Group A and 4.4 % of Group B.
Single booster augments the serological response to the vaccine in most but not all subjects—Hepatology
The researchers found that after a single booster dose of HB vaccine, 2.7% in group A and 3.3% in group B remained anti-HBs-negative.
A blunted serological response was noted in approximately 20% in both groups.
The research group noted that there was 1 HBsAg carrier in group A (1.3%) and 4 in group B (3.5%).
The researchers found that 15 years after neonatal immunization with plasma-derived HB vaccine, a large proportion of children exhibited waning immunity.
This poses the risk of breakthrough infection.
The team found that a single booster augmented the serological response to the vaccine in most but not all subjects.
Dr Huang concluded, "Our findings suggest that 1 or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma-derived HB vaccine".
Hepatology 2004;40:1415-1420
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Medivir AB enters into License and Research Collaboration Agreement on Hepatitis C
SourceURL:http://uk.biz.yahoo.com
HUDDINGE, Sweden, Nov. 30, 2004 (PRIMEZONE) -- Medivir AB (Stockholm: MVIRb.ST - news) today announced that it has signed a license and research collaboration agreement on Hepatitis C with Tibotec Pharmaceuticals Ltd, a subsidiary of Johnson & Johnson (NYSE: JNJ - news) .
The goal of the research collaboration is to discover and develop orally active protease inhibitors of the NS3/4A protease of HCV. Medivir has developed a novel series of potent HCV NS3/4A protease inhibitors. These HCV inhibitors exhibit antiviral properties in a cell-based assay and have drug-like properties.
Tibotec will be responsible for the global clinical development of these compounds and has acquired exclusive, worldwide marketing rights, except for in the Nordic countries, which have been retained by Medivir. The product will be commercialized in the non-Nordic countries by the Tibotec, Ortho-Biotech or Janssen Cilag operating companies of Johnson & Johnson. Under the terms of the agreement, Tibotec will make an upfront payment of Euro 6.5 million and, based on successful achievement of pre-specified scientific, clinical and regulatory milestones, payments of up to Euro 62 million. In addition, upon reaching a specific clinical milestone, Medivir has the right to receive a product that achieves certain predefined commercial criteria for marketing in the Nordic region or an additional payment. Medivir will receive royalties on product sales. The agreement also includes research funding.
"We are pleased to enter this collaboration and see this as evidence of Medivir's competence within protease research. Hepatitis C is the hot spot of antiviral research today. This collaboration takes Medivir another important step further on its journey towards becoming a profitable, integrated pharmaceutical company", says Medivir's CEO Lars Adlersson.
Hepatitis C is a form of hepatitis caused by an RNA virus (HCV). According to the WHO 3% of the global population are infected with hepatitis C (HCV) amounting to 200 million people. In the US 1.8% of population are infected amounting to 3.9 million people. Presently there are approximately 2 million patients diagnosed for HCV in the western world. In more than 60% of cases, infection with HCV leads to long-term disease and disability. It is the most common cause of chronic liver disease, hepatocellular carcinoma, and the most frequent reason for liver transplantation. The HCV market is today dominated by interferon-based treatment regimes which have both limitations in efficacy and tolerability. The market is according to Datamonitor expected to grow rapidly from today's 3.5 bn USD to 9 bn USD in 2010.
The Medivir Group Medivir is an innovative, specialist research corporation that develops drugs with the objective of becoming a sustaining and profitable pharmaceuticals corporation. Medivir is located in Huddinge, Sweden and near Cambridge, UK. Medivir's research is oriented on developing new drug compounds based on polymerases and proteases as target enzymes. The group consists of Medivir AB, its subsidiary Medivir UK Ltd. and Medivir Personal AB. As of 30 September 2004, the group had 125 employees. Medivir was listed on the Stockholm Exchange O-list in 1996. Medivir's research portfolio includes projects against HIV, jaundice, shingles, cold sores, osteoporosis, RA (rheumatoid arthritis), asthma and MS (multiple sclerosis). Medivir has five projects in clinical development phases, each with a unique clinical profile. The company's broad-based preclinical research portfolio houses six defined projects and nearly ten activities in various preclinical phases.
Medivir AB (publ), Lunastigen 7, SE-141 44 Huddinge, Sweden, tel (switchboard): +46 (0)8 5468 3100
This information was brought to you by Waymaker http://www.waymaker.net
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December 1st, 2004
New Push against Hepatitis
SourceURL:http://www.eveningnews24.co.uk
DRUG users and people who have had blood transfusions are being targeted in a bid to halt the spread of potentially fatal Hepatitis across Norfolk.
Norwich Primary Care Trust is one of six trusts in the county which is stepping up its screening facilities and increasing awareness of the disease, often referred to as the "silent epidemic".
It is suspected there are thousands of people who are unaware they are infected with Hepatitis C which, if left untreated, can cause serious liver disease including cirrhosis and liver cancer.
People most at risk of contracting the illness are intravenous drug users and those who had blood transfusions or an organ transplant before 1991, when donor safety checks were introduced.
Other vulnerable groups are people who have regular sex with an infected partner and babies whose parents have the disease.
At a meeting between Norwich PCT, MPs and other healthcare professionals and patient groups, an action plan on dealing with Hepatitis C in Norfolk was established, including increasing awareness in schools and more screening for prison inmates and other high risk users.
It is estimated there are around 2,500 known sufferers in Norfolk, with 95 per cent being current or previous drug users.
Director of Public Health for Norwich, Peter Brambleby, said the PCT would be targeting people at risk through four main methods—prevention, screening, treatment and support.
"Prevention is the most important aspect at this stage," he told the Evening News. "We are going to increase screening in high risk areas and target people who have no knowledge of the disease.
"There are people who could be infected and they know nothing about Hepatitis C at all. There has been a rise in injected users both in the community and in prisons. These are the people we most want to target," Mr Brambleby added.
Michael Colyer, from Colman Road, Norwich, was one of the main players in getting the meeting off the ground and has wanted an awareness campaign for the disease for years.
A Hepatitis C sufferer himself, the 53-year-old claims there are thousands of people who are undiagnosed. He said he hoped the strategy would prevent further infections and enable undiagnosed victims to get treatment.
"I have spent nine years trying to get the Government to recognise the illness and it is good to see something finally coming together," he said.
He was infected with the virus after receiving contaminated blood products through the NHS.
Norwich MP Ian Gibson said he welcomed the move. "We are sitting on edge of a time bomb," he said. "Many people are taking huge risks with their lives and we have to recognise this is a major problem in Norwich.
"Hepatitis C should be equated with the same concern shown over AIDS. This is a great move forward and I congratulate everyone concerned for starting off this process."
Symptoms of Hepatitis C include abdominal discomfort tiredness and nausea. The virus is transmitted via blood to blood contact.
If you want to be screened for Hepatitis C or need more information, call the Hepatitis C Trust on 0870 200 1200 or log onto www.hepc.nhs.uk
Has your life being touched by Hepatitis C? Call Sarah Hall on (01603) 772426 or e-mail sarah.hall2@archant.co.uk
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Clinical Trial: Leuprorelin and Flutamide in Male Patients with Hepatocellular Carcinoma Treated with Tamoxifen
SourceURL:http://www.gastrohep.com
A study published in December's issue of Hepatology finds that there is no benefit in survival with antiandrogenic treatment in male patients with advanced hepatocellular carcinoma.
The growth of hepatocellular carcinoma (HCC) is thought to be dependent on androgens, as androgen receptors are present in most of these tumors.
The aim of this multicenter trial was to assess the effect of antiandrogens in patients who have advanced hepatocellular carcinoma.
Male patients with advanced HCC were randomized into 2 groups treated with (1) leuprorelin (3.75 mg/mo subcutaneously), flutamide (750 mg/d orally), and tamoxifen (30 mg/d orally) or (2) tamoxifen alone (30 mg/d orally) administered until death. Survival was the main end point (log-rank test).
The required sample size was 375 patients (alpha, 5%; beta, 10%; 1-year survival, 45% in treated group and 30% in controls).
Between February 1994 and January 1998, 376 male patients (mean age, 66 years; treated group, n = 192; control group, n = 184) were included.
No baseline imbalance was found between the groups.
At the reference date (January 1, 2003), 183 deaths (95.3%) were observed in the treated group and 177 deaths (96.2%) were observed in controls.
13 patients were lost to follow-up.
Median survival time was estimated to be 135.5 days (95% CI, 112-189) and 176 days (95% CI, 141-227) in treated and control groups, respectively (P = .21).
Crude and adjusted relative risks of death in the treated group were estimated at 1.14 (95% CI, 0.93-1.40) and 1.08 (95% CI, 0.87-1.33; P = .48) respectively.
Premature interruption of treatment was more frequent in the treated group (n = 45) than in controls (n = 22; P = .0045), mainly because of digestive side effects.
In conclusion, no benefit in survival was found with antiandrogenic treatment in male patients with advanced HCC.
Hepatology;2004: 40 (6): 1361 – 1369
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Hepatitis B Virus Reactivation in Breast Cancer Patients
SourceURL:http://www.gastrohep.com
Results published in December's issue of Liver International support the preemptive use of lamivudine for prevention of HBV reactivation in patients who need short-term chemotherapy.
Recent data suggest that hepatitis B virus (HBV) reactivation develops in 41% of breast cancer (BC) patients carrying HBV after chemotherapy.
Dr Chao and colleagues in Taipei, Taiwan undertook a study that aimed to determine the role of preemptive use of lamivudine in BC patients undergoing chemotherapy.
The researchers included a total of 11 female patients with BC who were seropositive for hepatitis B surface antigen (HBsAg) in the test group.
The research team treated 10 of these patients in an adjuvant setting and 1 for metastatic disease.
The researchers gave lamivudine from the start of chemotherapy and this was maintained until 1 month after the last infusion of chemotherapy.
Serum ALT remained unchanged without rebound hepatitis after cessation of chemotherapy and withdrawal of lamivudine—Liver International
The control group consisted of 9 historical breast cancer patients carrying hepatitis B virus and the researchers gave them similar systemic chemotherapy without preemptive lamivudine.
The research team monitored variables including HBsAg, HBV envelope antigen, anti-HBV envelope antibody, serial serum alanine transaminase (ALT), quantitative HBV viral DNA analysis, and HBV-DNA precore promoter and precore sequence.
The researchers performed a test for the emergence of mutant strains, notably nucleotide 550, 6 months after the completion of chemotherapy.
The researchers found that all patients tolerated lamivudine well without development of evident HBV reactivation or overt hepatitis.
In addition, the team noted that serum ALT remained unchanged without rebound hepatitis after cessation of chemotherapy and withdrawal of lamivudine.
No emergence of lamivudine-selective resistant strain (so-called tyrosinemethionineaspartateaspartate mutations) was observed.
Dr Chao concluded, "Our results encourage preemptive use of lamivudine for prevention of HBV reactivation in patients who need short-term chemotherapy."
Liver International; 2004: 24 (6): 540
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December 2nd, 2004
SourceURL:http://www.gastrohep.com
Combination pegylated interferon with ribavirin is effective therapy in hepatitis C Virus recurrence and in hepatitis C virus nonresponsive to interferon and ribavirin, reports the most recent issue of Transplantation.
The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective.
Dr Slapak-Green and colleagues from Miami, America undertook a retrospective review of liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin.
Participants received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) and therapy intended for at least 48 weeks.
The researchers then recorded complications, including neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression.
The research team determined a diagnosis of hepatitis C virus recurrence by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test.
28% of patients who were naive to therapy and 21% of nonresponders were HCV nondetectable at the end of 48 weeks of therapy—Transplantation
The researchers included a total of 57 liver-transplant recipients in the study.
The participants were separated into Group 1 , 29 participants naive to therapy and Group 2, 28 nonresponders.
The research team administered at least 6 months of interferon and ribavirin therapy.
The researchers observed that 8 (28) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy.
In addition, the research team noted that ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2.
Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim.
Dr Slapak-Green concluded, "Combination pegylated interferon with ribavirin appears to be effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin."
She added, "This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy."
Transplantation; 2004: 78(9):1303-1307
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SourceURL:http://www.gastrohep.com
The significant ethnic and sex differences in the prevalence of hepatic steatosis may have a profound impact on susceptibility to steatosis-related liver disease, suggests a study in December's issue of Hepatology.
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined.
Dr Hobbs and colleagues from Texas, America undertook a study in order to examine and compare the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects.
The researchers took a multiethnic, population-based sample (32% white, 48% black, and 18% Hispanic) and used proton magnetic resonance spectroscopy to evaluate HTGC.
The research team noted that HTGC varied over a wide range (0.0%-42%; median, 4%) in the population.
Almost 1/3 of the population had hepatic steatosis, and most subjects with hepatic steatosis had normal levels of serum alanine aminotransferase (79%).
Frequency of hepatic steatosis varied significantly with ethnicity:
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45% in Hispanics
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33% in whites
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24% in blacks
—Hepatology
The researchers found that the frequency of hepatic steatosis varied significantly with ethnicity (45% in Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white women).
In addition, the team observed that the higher prevalence of hepatic steatosis in Hispanics was due to the higher prevalence of obesity and insulin resistance in this ethnic group.
However, the researchers could not explain the lower frequency of hepatic steatosis in blacks by ethnic differences in body mass index, insulin resistance, ethanol ingestion, or medication use.
The research team found that the prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics.
The ethnic differences in the frequency of hepatic steatosis in this study mirror those observed previously for NAFLD-related cirrhosis (Hispanics > whites > blacks).
Dr Hobbs concluded, "The significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis-related liver disease."
Hepatology; 2004: 40 (6): 1387 – 1395
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SourceURL:http://www.gastrohep.com
ALT levels usually dropped during follow-up and although severe hepatic lesions can be found in asymptomatic blood donors, mild hepatic damage is the rule, states a report in December's issue of Liver International.
Alanine aminotransferase (ALT) elevation in blood donors can be related to many variables such as viral hepatitis, overweight and ethanol consumption.
Dr Torezan-Filho and colleagues from Sao Paulo in Brazil designed a study in order to define factors associated with ALT elevation in candidates for blood donation.
The researchers evaluated ALT levels during follow-up, and aimed to establish a histological diagnosis of hepatic disease.
The research team enrolled 119 subjects in the study.
All participants were hepatitis B surface antigen/anti-hepatitis C virus negative and had been rejected as blood donors as a result of elevated ALT (>1.5 times the upper normal limit (UNL) in two determinations).
The researchers investigated alcoholism, obesity, drug-induced liver disease, diabetes, hemochromatosis and 1-anti-trypsin deficiency in all of the 119 participants (113 males, six females, aged 33.4±8.4 years).
Obesity and alcoholism were most frequently associated with ALT elevation—Liver International
During follow-up, the research team determined ALT every 8 weeks and liver biopsy was recommended in cases with persistently elevated ALT levels.
The researchers found that obesity (30%) and alcoholism (29%) were most frequently associated with ALT elevation.
In 9% of cases no association was found.
The research team also noted that ALT levels decreased significantly, regardless of the associated factor.
Liver histology in 40 patients showed steatosis (35%), steatohepatitis (30%), non-specific reactive hepatitis (13% of cases), normal liver (15% of cases) and alcoholic cirrhosis, hemochromatosis and non-specific portal fibrosis in three cases.
Dr Torezan-Filho concluded, "ALT levels usually dropped during follow-up and although severe hepatic lesions can be found in asymptomatic blood donors, mild hepatic damage is the rule."
Liver International; 2004: 24 (6): 575
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December 3rd, 2004
SourceURL:http://home.businesswire.com
EMERYVILLE, Calif.--(BUSINESS WIRE)--Dec. 3, 2004--Chiron Corporation (Nasdaq:CHIR) and Laboratory Corporation of America(R) Holdings (LabCorp(R)) announced today that they have signed a licensing agreement for Chiron's hepatitis C virus (HCV) intellectual property for nucleic acid testing (NAT). The agreement gives LabCorp, including its subsidiary National Genetics Institute (NGI), a semi-exclusive license to use Chiron's patented HCV NAT technology in screening plasma donations in the United States, subject to existing licenses and certain conditions. As part of the licensing arrangement, LabCorp has also agreed not to challenge the validity or enforceability of certain Chiron HCV patents. Financial terms of the agreement were not disclosed.
"This license agreement and settlement attests to the significant scientific breakthrough Chiron scientists made by discovering the elusive virus responsible for hepatitis C. To date, Chiron has licensed more than 15 companies with its HCV technology, enabling these companies to find new ways to address the burden of HCV infection," said Gene Walther, acting president, Chiron Blood Testing. "We continue to work to enable companies to develop and market products that will reduce the toll from this life-threatening disease and prevent its transmission."
About Chiron
Chiron delivers innovative and valuable products to protect human health by advancing pioneering science across the landscape of biotechnology. The company works to deliver on the limitless promise of science and make a positive difference in people's lives. For more information about Chiron, please visit www.chiron.
This news release contains forward-looking statements, including statements regarding sales growth, royalties, product development initiatives, new product indications, new product marketing, acquisitions, and in- and out-licensing activities that involve risks and uncertainties and are subject to change. A full discussion of the company's operations and financial condition, including factors that may affect its business and future prospects, is contained in documents the company has filed with the SEC, including the form 10-K for the year ended December 31, 2003, and the form 10-Q for the quarter ended September 30, 2004, and will be contained in all subsequent periodic filings made with the SEC. These documents identify important factors that could cause the company's actual performance to differ from current expectations, including the outcome of clinical trials, regulatory review and approvals, manufacturing capabilities, intellectual property protections and defenses, litigation, stock-price and interest-rate volatility, and marketing effectiveness. In particular, there can be no assurance that Chiron will increase sales of existing products, successfully develop and receive approval to market new products, or achieve market acceptance for such new products. There can be no assurance that Chiron's out-licensing activities will generate significant revenue, nor that its in-licensing activities will fully protect it from claims of infringement by third parties. In addition, the company may engage in business opportunities, the successful completion of which are subject to certain risks, including shareholder and regulatory approvals and the integration of operations.
We do not undertake an obligation to update the forward-looking information we are giving today.
