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Week Ending: October 6 th , 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
September 29th, 2007
HCV Advocate Launches HepC NewsFeed
http://www.hcvadvocate.org/Feeds/HepCNews.xml
Stay informed with the latest news and reviews from the HCV Advocate. You can now subcribe (free) to our Newsfeed and either view it through your browser or have the HepCNews feed across your screen with Netsplorer, a free RSS reader. To view the HCV Advocate Newsfeed, go to the HCV Advocate site and click on the "RSS HepC News" button at the top of the right hand button column on our front page. Or you can just click here.
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My good friend and the foolish war on drugs
http://www.aspentimes.com
By John Colson
I have a good friend who smokes more pot than anyone I've ever known, and he does it legally, at least when he's in his home state of California.
Toby [can't give you his real name, those assholes at Homeland Security might be reading this] is one of those guys who lives to laugh, and whose laugh goes far beyond infectious.
When we walk through desert canyons - one of our favorite activities - and Toby starts to laugh, you expect the rocks to chuckle right along, or at least crack a smile.
When he's in a room full of people, forget about it. If he starts in laughing, anyone nearby had better put down their glass or their plate and just give in to the mirth. Saves on carpet cleaning bills that way.
But ol' Toby's got his serious side. He hates war, despises corporations for their dehumanizing effect on American politics and society, is a tree-hugger and an animal rights activist and proud of it. One of his favorite activities, besides getting stoned and walking in the desert, is going to political rallies and protests and sticking his thumb in the eye of whichever establishment baddie is the subject of the day.
He's a teacher at a metropolitan college, has been for decades, and although I've never been in his classroom, I can imagine his students like him almost as much as I do. I've known him since high school, and can't imagine life without him on the planet somewhere, laughing.
Oh, did I mention he's got Hepatitis C?
That's a blood-born disease that can cause liver failure, is mighty tough to cure, and is one of those maladies that nobody likes to talk about. That's because it can be contracted through the use of intravenous drugs, which may be how Toby caught it in his wild, tempestuous youth, while he was learning to laugh.
Anyway, the Hep-C complication is why Toby can smoke pot legally in California (and in Colorado, for that matter), thanks to a voter approved initiative legalizing the medical use of marijuana to manage pain and other symptoms. He buys it at a local dispensary, which is a lot like a pharmacy only the wares are kept in sealed jars, and the place smells like a warren of very active skunks, thanks to all the high-grade pot. He says the marijuana prescription has helped him fend off the disease, stay active in all his pursuits and keep up a relatively cheerful outlook on life, even though he is in constant anxiety about his own mortality.
And now to the nut of this tale. This week we were treated to televised images of Drug Enforcement Administration storm troopers busting dispensaries in southern California. The agents were basically spitting in the eyes of all those voters who concluded that someone smoking pot to ease pain and discomfort was not a threat to national security or anyone else's well-being.
The scenes, repeated on TV news shows across the spectrum of cable channels, got me thinking.
The voters have passed these laws, presumably while in their right minds without any coercion from wild-eyed, gun-toting pot dealers lurking in the shadows of their voting booths. It's generally presumed that somewhere between 5 and 10 percent of Americans use pot with some regularity, and that many more have tried it at least once, and they seemed to have generally survived the exposure.
But our federal watchdogs have decided we, the voters in several states, don't know what we're doing when it comes to deciding which substances we consider beneficial or at least therapeutic, despite a growing body of evidence that we are right.
You see, the war on drugs, which has been estimated to cost more than $40 billion in 2003 and which is getting more expensive every year, has become an industry unto itself. And it guarantees its own survival by setting up a never-ending struggle with the drug cartels, who benefit from our insane drug laws because they keep drugs in the "contraband" category, allowing them to continue to make money. It's a lovely little dance they have going, isn't it?
Meanwhile, people's lives are made worse by all this foolishness. Toby faces pain and misery if he can't get the one drug that truly helps him. Neighborhoods face street wars and urban blight because the thugs and the cops are engaged in this endless ballet of bullets and jail cells, all paid for by our taxes.
What is wrong with this picture? You tell me.
John Colson can be reached at jcolson@aspentimes.com.
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September 30th, 2007
Hep C tests offered at city store
http://news.bbc.co.uk
Screening for the potentially-fatal virus hepatitis C is being offered in the high street in Nottingham.
People can drop in for testing and confidential advice at the Boots store in the Victoria Centre on Monday.
The project is part of World Hepatitis Awareness Day and was instigated by the late Dame Anita Roddick, who contracted the virus through a blood transfusion.
It has been organised by the Hepatitis C Trust, Nottingham University Hospitals NHS Trust and Boots.
The free tests will be carried out by nurses from the city's Queen's Medical Centre.
There will also be an exhibition to raise awareness of the virus at the Broadmarsh shopping centre.
Charles Gore, chief executive of the Hepatitis C Trust, said: "Dame Anita Roddick instigated this project.
"She herself had hepatitis C but it was undiagnosed for 30 years, so she was passionate about encouraging anyone at risk to get tested."
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Students ignorant of virus
http://news.scotsman.com
HALF of Scottish university students are unwittingly exposing themselves to the risk of the deadly hepatitis C virus, according to research published today.
Students risk their health by sharing banknotes or straws when snorting drugs, getting tattoos or piercings and sharing razors and toothbrushes.
The survey, conducted during fresher's week at Edinburgh University, also found that around two-thirds of students knew little about hepatitis C.
Charles Gore, chief executive of the Hepatitis C Trust, said: "These findings are shocking. Young people are putting themselves at risk and they seem completely unaware of the dangers."
The disease, which affects more than 50,000 people in Scotland, attacks the liver.
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Family curse destroys liver
http://www.stuff.co.nz/
RUTH HILL - The Dominion Post
Donald Bethune is one of 12 children of whom five are infected with an accidental family curse.
The Wainuiomata man's mother contracted the potentially deadly hepatitis B virus from a blood transfusion. Of he and his four siblings, Mr Bethune was the worst affected, requiring a liver transplant four years ago when he was 49.
"They said without it, I would have only had two weeks to live, I had only 3 per cent liver function left ..."
Today is World Hepatitis Awareness Day and the Hepatitis Foundation is encouraging people to get blood tests.
More than 200 New Zealanders die prematurely from chronic hepatitis B and related conditions each year.
An estimated 110,000 people in New Zealand are chronic carriers, while a further 40,000 are thought to be infected with hepatitis C.
It is estimated that hepatitis C will cost the health system $400 million during the next 10 to 15 years.
When he was 18 Mr Bethune discovered he was infected. But it was not till after his transplant that he learnt that four of his siblings were also carriers.
The curse ends with Mr Bethune - his three children and his wife all have "good antibodies".
"It's a miracle really because it's highly infectious."
Last month Hepatitis C claimed the life of Dame Anita Roddick, who founded the Body Shop empire. She contracted the disease in a blood transfusion in 1971 after giving birth.
Hepatitis Foundation chief executive John Hornell said most people infected with hepatitis did not know they had it. Only about a quarter have actually been screened and diagnosed.
"There's been a vaccine for hepatitis B available for 20 years, a relatively cheap vaccine, yet people are still dying from this preventable disease."
There is no cure for hepatitis B, which kills about a quarter of the people infected.
The disease is most prevalent among Maori, Pacific Islanders and Asians.
Unlike the hepatitis B virus, there is no vaccine for hepatitis C.
Associate Professor Ed Gane, the chief hepatologist and liver transplant physician at Auckland City Hospital, said hepatitis C was curable in 70 per cent of cases.
It is now the leading cause of referral for liver transplant and second-leading cause of liver cancer in New Zealand.
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October 1st, 2007
Could You Have Hepatitis? New Report Shows That the Majority of Europeans With Hepatitis C Remain Undiagnosed
http://www.prnewswire.co.uk
BRUSSELS, Belgium, October 1 /PRNewswire/ --
- European Liver Patients Association Urges People at Risk to get Tested!
A report(1) released today by the Eurasian Harm Reduction Network (EHRN)(i) highlights the significant inconsistencies that exist in hepatitis C (HCV) diagnosis and treatment across Europe and beyond. In recognition of World Hepatitis Awareness Day, patient groups around the globe are united in their call for action.
The report indicates that in some European countries it is estimated that more than 90% of people who are infected with HCV have not been diagnosed (Germany 90%; Poland 98%)(ii). Not only does this put many people at risk of long-term liver damage, it also means that they may unknowingly transmit the virus to others.
"It is alarming that in the twenty-first century there are European countries where up to 98% of people with chronic hepatitis C may not even know they are infected", says Nadine Piorkowsky, President, European Liver Patients Association (ELPA). "The peak of hepatitis C related mortality is still to come. If we want to flatten it, policymakers in Europe will have to act now. We are therefore calling on the EU and national governments to urgently recognise hepatitis C as a major public health threat."
Stephen Hughes, Member of European Parliament, agrees: "The European Union has a crucial role in identifying best practice with regard to hepatitis C screening in order to address existing health inequalities."
Hepatitis C and, specifically, the under-diagnosis of HCV infection are not unique to Europe; rather, HCV is a global health issue and the rates of diagnosis are a problem around the world. In fact, HCV is much more common than HIV, the virus that causes AIDS, with more than four times as many people living with hepatitis C than with HIV.(2) According to the World Health Organization (WHO), an estimated 53,700 deaths globally each year are directly attributable to HCV. The WHO also reports that more than 308,000 deaths annually are likely to be due to liver cancer caused by HCV and associated with a significant proportion of the 785,000 deaths due to cirrhosis.(3) This suggests that, globally, HCV may cause up to 500,000 deaths a year, and possibly even more. With many undiagnosed cases of HCV, it is likely these numbers will rise in the near future.
"The EHRN report on HCV prevalence in Europe highlights the need for more in-depth studies in order to increase awareness and ensure an evidence-based approach to this disease", says Jeffrey Lazarus, World Health Organization Regional Office for Europe.
The report shows that the availability and quality of national, regional and global HCV reporting, resourcing and screening varies dramatically from country to country. For example, even the official data from the United Kingdom illustrates that almost two-thirds of estimated HCV cases are undiagnosed (88,337 diagnosed, 192,663 undiagnosed), which, sadly, is a significantly better rate of diagnosis to undiagnosis than most countries. In contrast, in Poland the estimated number of cases in the general population is 750,000, while only 20,000, or 2%, of cases have been diagnosed.
Ms Piorkowsky recognises the importance of awareness campaigns: "Today, on World Hepatitis Awareness Day, we draw attention to the ongoing needs in the hepatitis C battle globally, and call on people who may be at risk to get tested!"
France is a clear example of the positive impact public awareness campaigns can have. Due to government-led campaigns, hepatitis awareness in that country has increased substantially. Currently, an estimated 56% of those infected know that they have the infection, compared with 24% in 1994. In contrast, the EHRN report indicates that in northern Spain, only 16% of people who tested positive for HCV were aware of their status.
Globally, 180 million people are infected with hepatitis C; many others are infected and do not know it.(4) Could you be one of them? Get tested.
Risk Factors for Hepatitis C
- Have tattoos or body piercings
- Had a blood transfusion before screening was introduced (in most countries, before 1992)
- Shared equipment for injecting drugs or cocaine straws/bank notes
- Had medical or dental interventions in countries where equipment is not adequately sterilised
- Had needle stick injuries (especially emergency services and healthcare workers)
- Shared a toothbrush or a razor (very low to medium risk)
About World Hepatitis Awareness Day
Now in its fourth year, World Hepatitis Awareness Day, which takes place on 1 October 2007, aims to increase awareness about hepatitis B and C. This year, ELPA and other international patient organisations are working together to promote this important educational initiative and encourage those at risk to "Get Tested'". Alarmingly, many people are unaware that they are infected and remain undiagnosed. Left untreated, both forms of viral hepatitis can lead to cirrhosis, liver cancer and liver transplantation, yet hepatitis B can be prevented through immunisation and, in many cases, hepatitis C can be cured. The EHRN report on prevalence of hepatitis C in Europe illustrates the situation of undiagnosed cases (available at http://www.hepatitisday.info). ELPA has been supported by unrestricted grants from Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Gilead, Novartis and Schering-Plough.
About the European Liver Patients Association (ELPA)
ELPA emerged from a desire amongst European liver patient groups to share their experiences of the very different approaches to liver disease adopted in different countries. In June 2004, 13 patient groups from 10 European and Mediterranean countries created the association. ELPA was formally launched in Paris on 14 April 2005, during the annual conference of the European Association for the Study of the Liver (EASL) and now has 20 members from 17 countries. ELPA's aims are to promote the interests of people with liver disease and, in particular, to highlight the size of the problem. This involves promoting awareness and prevention, addressing the low profile of liver disease compared with other areas of medicine such as heart disease, sharing experience from successful initiatives and working with professional bodies such as EASL and with the EU to ensure that treatment and care are harmonised across Europe to the highest standards.
Further information about hepatitis can be found on:
http://www.hepatitisday.info
http://www.elpa-info.org
For broadcast-standard video supporting this press release, please visit http://www.thenewsmarket.com/elpa. If you are a first-time user, please take a moment to register. Questions may be directed to: journalisthelp@thenewsmarket.com.
References:
(1). Eurasian Harm Reduction Network (EHRN). Comparative analysis of HCV prevalence across selected countries of Europe and the Mediterranean area; 1 October 2007.
(2). World Health Organization. AIDS Epidemic Update. 2006. (Accessed February 27, 2007, at http://www.who.int/hiv/mediacentre/
2006_EpiUpdate_en.pdf.)
(3). World Health Organization. Department of Measurement and Health Information. (December 2004).
(4). World Health Organization. Initiative for Vaccine Research, Viral Cancers, Hepatitis C. 2006. (Accessed July 24, 2006, at http://www.who.int/vaccine_research/diseases
/viral_cancers/en/index2.html.)
(i) EHRN: Formerly known as the Central and Eastern European Harm Reduction Network (CEEHRN)
(ii) EHRN data: Percentage calculated by subtracting diagnosed cases from estimated number of cases in general population
Distributed by PR Newswire on behalf of European Liver Patients Association (ELPA)
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Judge acquits 4 doctors in Canada's tainted blood trial
http://www.cbc.ca/
CBC News
Four doctors and a U.S. drug company were found not criminally negligent on Monday in the distribution of an HIV-tainted blood-clotting product that left many infected in one of Canada's biggest public health disasters.
After an 18-month trial, Superior Court Justice Mary Lou Benotto acquitted former officials from the Canadian Red Cross Society, Health Canada and New Jersey-based Armour Pharmaceutical Co. of criminal negligence causing bodily harm and common nuisance endangering the public.
Dr. Roger Perrault, former national medical director of the Canadian Red Cross Society, former Health Canada officials Dr. John Furesz and Dr. Donald Boucher, and former Armour Pharmaceutical Co. executive Dr. Michael Rodell were charged with one count each of criminal negligence causing bodily harm and common nuisance endangering the public after patients were given an HIV-infected blood-clotting product in 1986-87. Armour Pharmaceutical faced the same charges.
The judge called the events "tragic, but to assign blame where none exists would compound the tragedy," the CBC's Kas Roussy reported from outside the Toronto courthouse.
The ruling in Canada's first criminal trial reflects only one small part of the tainted blood scandal, which is considered Canada's worst preventable public health disaster. Twenty-thousand people contracted hepatitis C and more than 1,000 were infected with HIV through the transfusion of blood and blood products in the 1980s and 1990s.
It's not clear how many people have died as a result, but in 1997 the death toll was 3,000.
In 1993, Ontario Justice Horace Krever looked into what went wrong with the nation's blood supply during the 1980s and recommended at the conclusion of the inquiry that all victims of the tainted blood tragedy be compensated, not just those covered by Ottawa's original package.
But this is the first criminal trial connected to the scandal. A second criminal trial faces Perrault later this year in Hamilton, where he faces several charges stemming from allegations that the Red Cross and senior officials failed to take adequate measures to screen donors.
In May 2006, the Red Cross apologized to tens of thousands of Canadians infected with HIV or hepatitis C.
The Crown withdrew charges of criminal negligence causing bodily harm and common nuisance against the charity in exchange for a guilty plea under the federal Food and Drugs Act.
The Red Cross accepted responsibility, paying a $5,000 fine and dedicating $1.5 million to a scholarship fund and research project aimed at reducing medical errors.
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Weight-based dosing of ribavirin improves outcomes for patients with hepatitis C
http://www.eurekalert.org/
New treatment protocol benefits African-American patients with HCV genotype 1
Patients with hepatitis C treated with combination therapy of pegylated interferon and ribavirin had better outcomes when taking a weight-based dosage of ribavirin compared to a flat dosage. This treatment technique also improved the response rates of African American patients, whose outcomes have lagged behind those of Caucasian patients. These findings are in the October issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The articles and an accompanying editorial are also available online at Wiley Interscience (http://www.interscience.wiley.com/journal/hepatology).
Combination therapy of pegylated interferon and ribavirin is the standard of care for patients with chronic hepatitis C, allowing more than half to achieve a sustained viral response. However, previous studies have suggested that a weight-based dose of ribavirin might lead to even better results. To examine this possibility, researchers, led by Ira Jacobson of Cornell University, conducted a large, multi-center, randomized, prospective, open-label study between December 2000 and June 2005.
They enrolled 5,027 patients with hepatitis C from more than 200 centers around the country. All participants were 18 to 70 years old, weighed less than 125 kg, had detectable HCV RNA in their blood, and had never been treated for it. They were randomly assigned to receive interferon and a flat dose of ribavirin (800 mg/day), or interferon and a weight-based dose of ribavirin, which started at 800 mg/day for patients weighing under 65 kg, and increased by 200 mg/day for up to each additional 20 kg of weight up to a maxiumum dose of 1400 mg. Those with HCV genotype 2 or 3, which is more responsive to interferon-based therapy, also tested treatment durations of 24 and 48 weeks. Each patient was followed up for 24 weeks after treatment.
“A sustained viral response was achieved by significantly more patients who received a weight-based dose (44.2 percent) than fixed dose (40.5 percent) ribavirin,” the authors report. “Overall, response rates decreased as weight increased when a fixed dose was used but remained unaltered with a weight-based dose.” Discontinuation rates and reported adverse events did not differ significantly between the two treatment schemes, and relapse rates were lower for patients who had received weight-based dosing. The researchers also found that 48 weeks of treatment offered no additional benefit compared to 24 weeks for patients with genotypes 2 or 3..
Another group of researchers from the same study, also lead by Jacobson, used the study data to understand the impact of weight-based ribavirin with peginterferon alfa-2b in African American patients with HCV genotype 1. Genotype 1 is the hardest to treat, and it afflicts African Americans disproportionately.
Three hundred eighty seven African American patients with genotype 1 were included in the analysis: of those weighing 65 kg or more, and therefore receiving different doses of ribavirin in each arm, 188 had received flat-dose ribavirin, and 174 had received weight-based dosing. Significantly fewer patients in the flat-dose group (10 percent) attained a sustained virological response, compared to 21 percent in the flat-dose group. Relapse rates were 30 percent and 22 percent, respectively.
“An unexpected finding of our study was the increase in efficacy with an increase in ribavirin dose in heavier patients,” the authors report. That is, sustained viral response rates increased as body weight increased, suggesting that “ribavirin distribution may be more complex than realized and body weight may only approximate the marker for size required to dose RBV consistently,” the authors say.
In conclusion, weight-based dosing of ribavirin offered a significant advantage in efficacy of treatment for African American patients, however, the rate of sustained viral response in this population remains low. “Further studies are needed to elucidate the fundamental basis for the impaired responsiveness in this population,” they say.
In an accompanying editorial, Steven-Huy Han, MD and Jason Smith, PharmD of Los Angeles, report that this study adds significantly to our understanding of interferon therapy in African American patients. It will change the approach to ribavirin dosing and will benefit a difficult-to-treat population.
They suggest that the larger question of whether true weight-based dosing of ribavirin is superior to the currently approved standard dosing schemes still awaits head-to-head studies to answer. “At the minimum,” they conclude, “the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients.”
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Article: “Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial.” Jacobson, Ira; Brown, Robert; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul; Santoro, John; Becker, Scott; Wakil, Ed; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauley, Mary Pat; Griffel, Louis; Brass, Clifford A. Hepatology; October 2007; (DOI: 10.1002/hep.21932).
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How To Fight Treacherous Hepatitis B
http://www.sciencedaily.com/
Science Daily — One in four people who are chronically infected with hepatitis B will die from its impact if untreated, but a team of researchers at the Stanford University School of Medicine has identified the most cost-effective way of fighting this treacherous infection.
Those infected with hepatitis B often don't know it, because they can go without symptoms for years. Looking at adults in the U.S. group most likely to be infected with hepatitis B - Asians and Pacific Islanders - the Stanford researchers created a mathematical model that found the most effective strategy is to screen this group to identify those who are chronically infected.
Those who are infected require lifelong management, including screening for liver cancer and possible treatment with antiviral medication.
Hepatitis B is 100 times more infectious than AIDS and about 10 times more prevalent worldwide, striking Asia particularly hard. One out of every 250 people in the United States has chronic hepatitis B infection, but studies estimate that among foreign-born Asians, the rate is one in 10.
"I don't want to tell any more 30-year-olds that they are going to die and there is nothing I can do," said Samuel So, the Lui Hac Minh Professor and a professor of surgery, one of the study authors.
Chronic hepatitis B infection often has no symptoms until it causes liver cancer or, after years of attack by the patient's immune system, causes so much scarring of the liver that it fails. And the infection often strikes young, otherwise healthy adults. About 60 to 80 percent of liver cancer worldwide is caused by chronic hepatitis B infection, according to World Health Organization estimates.
So founded the Asian Liver Center at Stanford more than a decade ago to educate, vaccinate and screen thousands of people vulnerable to hepatitis B infection in the San Francisco Bay Area, nationwide and in the Philippines and China.
Although current U.S. policy calls for newborns to be vaccinated against hepatitis B, So wanted to identify the best ways to protect those who missed their childhood vaccinations, especially the many foreign-born Americans from areas where hepatitis B is endemic, such as Africa, Eastern Europe and Asia.
So teamed up with Margaret Brandeau, PhD, a Stanford professor of management science and engineering, and a graduate student in her department, David Hutton, to develop a model to explore the costs and benefits of vaccination and screening.
"He knows so much about hepatitis B and we know a lot about mathematical modeling and cost-effectiveness analysis," said Hutton, who is the lead author of the publication. "When you put the two together, it seemed like a really great fit."
This analysis built on results published earlier this year by So and Stanford medical student Steven Lin. They screened more than 3,000 Asian-Americans at community-based events and clinics in the San Francisco Bay Area, and found that two out of three Asian Americans who are chronically infected with hepatitis B were not even aware of it. So said that demonstrated for the first time the importance of routine hepatitis B screening, and he wanted to find the most cost-effective way to do that.
"Initially we were just going to look at vaccination, and we almost stumbled upon this idea of screening and treatment," said Hutton. A quick blood test can determine if a person is infected, and is the only way to identify patients early for treatment.
The interesting thing, the authors said, is that identifying those who are chronically infected - rather than vaccinating all adults - turned out to have the most benefit.
"In retrospect, it makes sense that you want to identify the people who are chronically infected by screening," said Brandeau, the senior author of the study. Adults' immune systems are well-developed, so they run much less risk of acquiring chronic hepatitis B than do newborns and children. "But we didn't know that going in, and that was a real benefit of using a model," she said.
Their model also found, once a chronically infected individual is identified, there was a large benefit from vaccinating family members and others who have close contact to prevent the spread of the infection.
The model's estimate for the scenario of screening, treating those infected, and vaccinating close contacts was $39,903 per year of quality-adjusted life gained. "Quality-adjusted life" is a way of quantifying the benefit of a medical intervention by measuring added years lived, adjusted by the quality of those years. To put that number in perspective, So said, the cost-effectiveness of screening for hepatitis B is similar to the cost-effectiveness of HIV screening in the American adult population, which the U.S. Centers for Disease Control and Prevention has recently recommended.
"All of the evidence is falling into place," So said. "We have big ambitions to form a global hepatitis B initiative to eradicate hepatitis B from the face of the Earth." This study shows that to make that work, it is critical to screen adults from endemic areas to find those who are chronically infected and give them appropriate medical management so they won't die from it.
With So's leadership, the Asian Liver Center has advocated and helped to introduce legislation in California and in Congress that would support hepatitis B screening and immunization, and increase research that would improve detection and treatment options. So also consults for the CDC on policy advisories.
His ambitions fit right in with what Brandeau and Hutton want to do. Their next modeling project is with So, looking at the cost-effectiveness of the various catch-up vaccination strategies to protect the approximately 400 million children in China from hepatitis B.
In his biggest effort yet, So is also launching a campaign in a distant corner of China this fall, partnering with public health professionals and the government to vaccinate half a million children against the virus. China has the greatest burden of chronic hepatitis B and liver cancer in the world, So said. He was in Qinghai, a province neighboring Tibet, in early September to watch the first group of school children get vaccinated.
"It's a no-brainer," So said. "If we could vaccinate everyone, in 10 years we could have no new infections - it's just so simple."
Brandeau and Hutton hope to show the effectiveness of such a strategy with their mathematical skills. "I really want to create models that can influence policy, using operations research, systems analysis, and mathematics for the public good," said Brandeau. "We have the same goals."
Their findings will be published in the Oct. 2 issue of Annals of Internal Medicine.
Note: This story has been adapted from material provided by StanfordUniversityMedicalCenter.
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Transgene Extends Therapeutic Vaccine Candidate TG4040 Development Program Against Chronic Hepatitis C
http://biz.yahoo.com/
Treating Patients Who Have Relapsed After Standard Treatment
STRASBOURG, France, October 1 /PRNewswire-FirstCall/ -- Transgene S.A. (Eurolist Paris: FR0005175080) announces today that the first patients have been enrolled in a Phase I trial in Canada of its therapeutic vaccine candidate TG4040 (MVA-HCV). The trial is expected to treat approximately 24 patients that are chronically infected with the Hepatitis C Virus (HCV) and who have relapsed after standard treatment of Ribavirin and Pegylated-Interferon Alpha. The trial is sponsored by the University of Montreal and supported by the Canadian Network for Vaccines and Immunotherapies.
Patients will receive one subcutaneous injection of TG4040 per week over a 3-week period together with a boost injection at Month 6. Dosing will be escalated in several cohorts from 106 to 108 pfu per injection. The trial's primary endpoint is safety whereas secondary endpoints are immune response to the vaccination and effect on viral load. Availability of safety data as well as preliminary viral and immunological data is planned by end of 2008.
Another Phase I study of TG4040 is currently being conducted in France on 15 HCV patients who have never received any other therapy for their condition. Preliminary results are expected at the end of 2007.
"We are very pleased to initiate this second Phase I trial of our therapeutic HCV vaccine", said Philippe Archinard, Chief Executive Officer of Transgene. "Addressing a different patient population will provide us with additional and valuable data to assess the potential of our vaccine."
About chronic hepatitis C:
Hepatitis C currently represents a major public health concern. The number of persons chronically infected with HCV in the world is estimated at 170 million to 200 million and hepatitis-C-related deaths at approximately 470 000 annually. Peak of incidence of HCV-related diseases is expected to occur in 2025-2030 in developed countries. HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma which are the prime reason for liver transplants. The current standard of care for patients infected with the HCV genotype 1 (a combination of Pegylated-Interferon Alpha and Ribavirin), effective in 50% of patients completing therapy, is lengthy and often poorly tolerated. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong need for new alternative approaches, including combination therapies.
About TG4040:
Transgene's TG4040 product candidate is based on the MVA virus carrying and expressing non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus. The MVA vector is a highly attenuated strain of vaccinia virus that combines an extensive history of safety with the ability to stimulate a strong immune response to antigens.
About Transgene:
Transgene is a France-based biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The company has one product which has completed Phase II trials (TG4001/R3484), two compounds in Phase II trials (TG4010 and TG1042) and one compound in Phase I studies (TG4040). Transgene has concluded a strategic partnership agreement with Roche for the development of its TG4001/R3484 therapeutic vaccine to treat HPV-mediated diseases. Transgene has bio-manufacturing capacities for viral-based vectors and technologies available for out-licensing. Additional information about Transgene is available on the Internet at http://www.transgene.fr.
Cautionary note regarding forward-looking statements
This press release contains forward-looking statements referring to the planned clinical testing and development of one of Transgene's therapeutic vaccine candidates. However, clinical testing and successful product development depend on a variety of factors, including the timing and success of future patient enrolment and the risk of unanticipated adverse patient reactions. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Trangene's Document de reference on file with the French Autorite des marches financiers on its website at http://www.amf-france.org and Transgene's website at http://www.transgene.fr
Source: Transgene S.A.
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Vertex hep C drug shows real promise, limitations
http://news.yahoo.com
By Bill Berkrot
NEW YORK (Reuters) - A closely watched hepatitis C drug being developed by Vertex Pharmaceuticals Inc continues to promise improvement over current treatments, according to analysts who have viewed brief summaries of data from highly anticipated clinical trials.
The summaries, known as abstracts, of data to be presented in full next month at the American Association for the Study of Liver Diseases annual meeting also suggest some limitations and side effects from the drug, telaprevir, analysts said.
"The incremental information provided by Vertex and the (study's) investigators continues to suggest that telaprevir will deliver a sustained virological response (SVR) of 70 percent, or thereabouts, in real world efficacy," Geoff Porges, an analyst with Sanford Bernstein, wrote in a research note.
Other analysts also said the available data appears to add up to an SVR of at least 70 percent in the clinical trial known as PROVE-2. An SVR rate higher than 50 percent is considered to be positive and 75 percent would be viewed as a major success, analysts have said.
SVR is a measure of patients in whom the hepatitis C virus has reached undetectable levels and appears to have been cleared from the system.
The studies are also attempting to show that by adding telaprevir to standard therapy of pegylated interferon and ribavirin there would be a lower relapse rate and significantly shorter treatment duration than without the Vertex drug.
"These results continue to show the potential that telaprevir has to enhance the efficacy of the current standard of care and provide a higher cure rate for patients with hepatitis C virus," said Jason Kolbert, an analyst for Susquehanna Financial Group.
Kolbert did note a potentially worrisome higher patient dropout rate with the PROVE-2 trial than in the earlier PROVE-1 study - 12.5 percent versus 10.9 percent - and the persistence of a troublesome rash seen with many patients who receive the Vertex drug.
Porges said data in the abstracts appear to debunk Vertex assertions that telaprevir could be effectively used without ribavirin, and that ribavirin was the cause of the rash seen in earlier combination studies.
Based on available PROVE-2 data, Porges said, within 12 weeks 25 percent of patients in the telaprevir-plus-interferon group saw the virus rebound from previously low levels compared with 4 percent in the triple-therapy group.
"This means that pegylated interferon with telaprevir but without ribavirin is a non-starter as a regimen for further study," Porges said.
He added that from further analysis of the data, "it is now clear that telaprevir, not ribavirin, was the cause of the rash observed in combination treated patients in PROVE-1."
The limitations "do leave the window open for competitors to enter the market" but do not affect telaprevir's immediate market potential, Porges said.
Vertex shares were up 56 cents, or 1.5 percent, at $39.00 in early afternoon trade on Nasdaq.
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Victims outraged by tainted blood trial acquittals
http://www.ctv.ca
CTV.ca News Staff
An Ontario judge has acquitted all defendants in the tainted blood scandal, angering victims of the worst public health disaster in Canadian history.
Ontario Superior Court Justice Mary Lou Benotto delivered her verdict Monday afternoon in a Toronto courtroom, ending the 18-month long trial.
Former Canadian Red Cross chief Dr. Roger Perrault, three other doctors and the New Jersey-based Armour Pharmaceuticals Co. were all acquitted.
"There was no conduct that showed wanton and reckless disregard," said Benotto.
She then went on to say: "The conduct examined in detail over one and a half years confirms reasonable and responsible and professional actions and responses during this difficult time. The allegations of criminal conduct on the part of these men and this corporation were not only unsupported by the evidence, they were disproved."
Defence lawyer Eddie Greenspan, who represented Perrault, said the ruling has restored his client's reputation.
"Today's absolute vindication, and his complete exoneration, is something we've been expecting for the last 10 years," he told reporters outside the court building.
"But he's not a happy man. He's spent 10 years of his life trying to get his reputation back, although I've no doubt that this has done it."
More than 20,000 Canadians contracted HIV or hepatitis C from tainted blood products administered in the mid-1980s.
All defendants had pleaded not guilty to criminal negligence charges. Lawyers for three of the accused doctors had argued the Crown lacked a substantial amount of evidence to prove its case.
It was alleged the defendants were criminally negligent in the distribution of an Armour HIV-infected blood-clotting product between July 1986 and December 1987.
James Kreppner, a hemophiliac who contracted HIV through contaminated blood products, watched the trial closely, both as a lawyer and advocate for fellow victims.
"I'm not out for revenge but I want the truth told as well, and I think the initial inquiry into the blood system told the truth," he told reporters. "And I expected something to happen as a result of those facts."
Another victim, Mike McCarthy, was blunt in his reaction to Monday's verdict.
"It's a shock, the verdict, and I think every tainted blood victim is going to feel there is no closure here. We feel it's been a miscarriage of justice."
But in delivering her ruling, Benotto cautioned against continued blame for the scandal.
"The events were tragic. However, to assign blame where none exists is to compound the tragedy," she said.
The Globe and Mail journalist Andre Picard, who also followed the trial, wrote a book about the blood scandal called "The Gift of Death." Picard told CTV's Canada AM that the criminal trial is a small part of a much larger tragedy.
"It's important legally because it's the first case and it's important symbolically but it's not an indictment of the tainted blood tragedy, that's not possible to do in a court of law," Picard said Monday.
"We're looking at a very specific case, to make an example of people, I think, is a better way of putting it."
A second criminal trial for Perrault -- dealing more specifically with how the Canadian Red Cross and senior health officials failed to prevent the spread of disease through donated blood -- is set for Hamilton, Ont.
"They're both important cases, but I have to emphasize that you can't put tainted blood in a criminal context," Picard said.
The Canadian Red Cross is no longer involved in blood distribution. In 1998, that responsibility was transferred to Canadian Blood Services and Hema-Quebec.
In May 2006, the Canadian Red Cross apologized and pleaded guilty to violating the Food and Drug Regulation Act by distributing tainted blood products. The Crown withdrew charges of criminal negligence causing bodily harm and common nuisance against the charity in exchange for the guilty plea.
The Red Cross agreed to pay a $5,000 fine and allotted $1.5 million for a University of Ottawa scholarship fund and research project aimed at reducing medical errors.
As of 1997, the death toll for those who received tainted blood products was 3,000. It's unclear how many others have died since then.
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Summaries for Patients: Antiviral Therapy for Chronic Hepatitis B
http://www.annals.org
Annals of Internal Medicine
4 December 2007 | Volume 147 Issue 11
Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.
Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians.
The full report is titled "Treatment of Hepatitis B e Antigen-Positive Chronic Hepatitis with Telbivudine or Adefovir: A Randomized Trial" It is in the 4 December 2007 issue of Annals of Internal Medicine (volume 147). The authors are H.L.Y. Chan, E.J. Heathcote, P. Marcellin, C.-L. Lai, M. Cho, Y.M. Moon, Y.-C. Chao, R.P. Myers, G.Y. Minuk, L. Jeffers, W. Sievert, N. Bzowej, G. Harb, R. Kaiser, X.-J. Qiao, N.A. Brown, and the 018 Study Group.
What is the problem and what is known about it so far?
Hepatitis B is an inflammation of the liver that is caused by a virus. The virus spreads through contact with infected body fluids. Most people who get hepatitis B recover within a few months, but some develop chronic infection. Chronic infection increases one’s risk for liver failure and liver cancer. Persons with chronic infection often have viral-related protein substances in their blood (called hepatitis B surface antigens and e antigens) for many years. When an e antigen is present, it usually means that the person has very active liver disease and a lot of virus present. Doctors often treat these patients with powerful antiviral drugs. However, some patients develop viral forms (mutants) that are resistant to 1 or more antiviral drugs. To help suppress virus levels, prevent resistance, and improve outcomes, doctors might use different types of antiviral drugs or switch drugs during treatment. Few studies have assessed the benefits and harms of switching among different antiviral therapies for chronic hepatitis B.
Why did the researchers do this particular study?
To see which of the following 3 treatment regimens best suppresses virus levels in patients with chronic hepatitis B: telbivudine (a thymidine nucleoside analogue), adefovir (an adenosine nucleotide analogue), or adefovir followed by a switch to telbivudine.
Who was studied?
135 adults with chronic hepatitis B who were e antigen positive. Their average age was about 33 years. Most were Asian men. None were coinfected with hepatitis C or D virus or HIV.
How was the study done?
The researchers recruited patients with e antigen–positive chronic hepatitis B from 16 international, academic, gastroenterology clinics. Patients were randomly assigned to telbuvidine for 52 weeks, adefovir for 52 weeks, or adefovir for 24 weeks followed by a switch to telbivudine for 28 weeks. Telbuvidine was taken as 3 daily pills (600 mg total) and adefovir as a single daily pill (10 mg). The researchers asked patients about side effects and tested blood for evidence of actively multiplying virus (HBV DNA levels) several times during follow-up. They then compared the amounts of virus over time in the groups.
What did the researchers find?
Tests at 24 weeks after treatment showed that viral amounts (HBV DNA levels) were reduced more with telbuvidine than with adefovir. At 52 weeks, HBV DNA levels were similar among patients initially treated with telbivudine and among those switched to telbivudine. These levels were lower than those among patients treated continuously with adefovir. Similar types and numbers of side effects were reported across groups.
What were the limitations of the study?
Both the researchers and the patients knew which therapies the patients received. Long-term drug resistance and clinical outcomes were not assessed. We do not yet know whether the findings are generalizable to other geographic areas and populations. Only 2 of several available antiviral agents were tested.
What are the implications of the study?
Telbivudine alone and switching from adefovir to telbivudine both suppressed viral levels more than adefovir alone in adults with e antigen–positive chronic hepatitis B.
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Medivir: Phase Ia Data on TMC435350 to be Presented at AASLD
http://home.businesswire.com
STOCKHOLM, Sweden--(BUSINESS WIRE)--Regulatory News:
Medivir (STO:MVIRB) announced that their abstracts for the 58th Annual Meeting of the American Association for Study of Liver Diseases (AASLD) have been published today and are available on Hepatology web site (AASLD).
The two abstracts summarize the results from a phase I clinical trial and further preclinical data that will be presented by Medivir and Tibotec, on their investigational compound TMC435350, a hepatitis C protease inhibitor, at AASLD in Boston, Massachusetts, USA on November 6th, 2007. The two posters are titled “Results of a phase I placebo-controlled trial in healthy volunteers to examine safety, tolerability and PK of the protease inhibitor TMC435350 after single and repeated dosing” and “In vitro activity and preclinical PK of a potent HCV NS3/4A serine protease inhibitor, TMC435350”.
Data from the phase Ia clinical trial show that TMC435350 was well tolerated in single doses up to 600 mg and in 5 days of dosing up to 400 mg once-daily.
The project has advanced to phase Ib trials, where its ability to suppress virus in patients infected with Hepatitis C is being investigated following once-daily oral dosing.
“The successful outcome of the phase Ia clinical trial is the single most important milestone for Medivir so far this year” comments Lars Adlersson, CEO & President at Medivir.
Chronic infection with the hepatitis C virus (HCV) leads to liver diseases. According to the WHO, 3% of the global population is infected with HCV, which means 200 million individuals. In the USA, 1.8% of the population is infected, that is 3.9 million people. In more than 60% of these cases, the HCV infection leads to chronic liver disease, cirrhosis and liver tumors. It is the most common reason for liver transplant. The HCV market is currently dominated by interferon-based treatments.
Medivir, please see the company website www.medivir.se
This information was brought to you by Cision http://newsroom.cision.com
Contacts
Medivir AB
Rein Piir, CFO & Vice President Investor Relations
Tel. +46 708 537292
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October 2nd, 2007
Blood system has more checks since scandal
www.ctv.ca
Helen Branswell, The Canadian Press
TORONTO -- Canadians who need blood or blood products are safer as a consequence of measures taken in the aftermath of the tainted blood scandal, a tragedy which led to the revamping of the blood collection and transfusion system in this country, the head of the agency responsible for the blood service said Monday.
"The legacy of the tainted blood scandal has been very profound, in this country and even internationally," Dr. Graham Sher, CEO of Canadian Blood Services, said in an interview from Ottawa.
Sher wouldn't comment on an Ontario Superior Court ruling acquitting Dr. Roger Perrault, the former national medical director of the Canadian Red Cross, and three other doctors of criminal charges related to the scandal.
But he stressed that there are many more checks in place today to protect recipients of blood transfusions or blood products from bloodborne disease agents, known and unknown.
Still, there is no way to ensure that donated blood is risk-free. Sher insisted: "We've never claimed that it's risk free."
"Our job is to make that risk as low as possible and we've been extremely successful at that," he said.
"And then the physician must always counsel his or her patient before a transfusion in terms of what are the risks and what is the benefit. And you don't get a transfusion unless you absolutely need one."
Sher said both Canadian Blood Services and Hema-Quebec, its Quebec equivalent, follow the recommendations of the Krever Inquiry and use what's known as the precautionary principle when making decisions about blood safety issues.
In essence, the precautionary principle means that when there are two or more possible courses of action, the choice should be the option that affords the greatest safety - even in the face of small risk.
When the blood services learned that the West Nile virus could be transmitted in blood they worked with the pharmaceutical industry to ensure rapid development and deployment of tests. This summer - the worst ever for West Nile infections in this country - Canadian Blood Services found and removed from the blood system 70 blood donations contaminated with the virus.
A second layer of tests has been put in place for HIV and hepatitis B and C, Sher added.
And when scientists at the Public Health Agency of Canada discovered that simian foamy virus can be transmitted through blood, the blood services added a question to their blood clinic screening questionnaire aimed at excluding would-be donors who work with or have contact with primates.
There is currently no test for simian foamy virus, a retrovirus from the same class of viruses as the human immunodeficiency virus (HIV). Common in some primates, the virus isn't believed to cause disease in humans. But diseases caused by retroviruses can take a long time to develop, and the blood services don't want to take chances, Sher said.
"That's a very good example of where we've applied the precautionary principle. In fact . . . we're the only two blood systems in the world - the two Canadian blood services - that have a measure in place to ask donors about exposure to certain types of primates."
The agencies are currently studying the potential threat posed to the blood system by Chagas disease, caused by a parasite rarely found in Canada but more commonly found in Central and South America. The agency believes it may have a test in place for Chagas in 2008.
As another precaution, Canadian Blood Services filters white cells out of the blood donated to it. White blood cells are immune system soldiers and can harbour pathogens. They aren't needed for blood products, Sher said, and it is safer to remove them.
"It's one way of lowering the risk to the recipients," he said, noting the agency is one of few in the world that takes this added step.
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Tassie turns blind eye to hep C
http://www.news.com.au
MICHELLE PAINE
A NATIONAL poll shows Tasmanians are dangerously ignorant about hepatitis C, says the Tasmanian Council on AIDS, Hepatitis and Related Diseases.
TasCAHRD said the State Government continued to bury its head in the sand, with no funding for an agreed program on the virus.
"The results of this poll demonstrate a disturbing lack of hepatitis awareness in our community," said TasCAHRD chief executive officer Kevin Marriott.
"More than 3400 Tasmanians have been exposed to the virus yet we continue to be ignorant about simple things like how the virus is transmitted, how it affects the body and treatment options."
The poll found 45 per cent of Tasmanians surveyed had no idea how hepatitis C affected the body.
Only 11 per cent were aware hepatitis C was curable.
Hepatitis C is spread via blood-to-blood contact and, untreated, can cause liver failure and liver cancer in some people. Symptoms include debilitating fatigue, abdominal pain, loss of appetite, nausea and vomiting, fever, skin rashes, joint and muscle pains, feelings of isolation and depression, brain fog, irritability and mood swings.
Mr Marriott said Tasmania continued to be the only state not funding community-based prevention, care and support programs, despite the development of the Sexually Transmitted Infections and Blood Borne Virus Action Plan.
"We have a good action plan that (Health) Minister (Lara) Giddings' office has signed off on, but it cannot be fully implemented unless it is appropriately funded," he said.
"The Tasmanian Government has its head in the sand on the issue of hepatitis."
Mr Marriott said people should consider being tested if they had injected illicit drugs even once, had an unsterile tattoo or body piercing, had come from or had undergone medical treatment in a country with high rates of hepatitis C, or had received blood or blood products before 1990.
Tasmanian public health physician Kelly Shaw said the Government's action plan aimed to address education, prevention, diagnosis, treatment and support.
A project officer had been appointed to promote education and prevention programs for people at increased risk and to spread the message in schools.
Dr Shaw said the Government was addressing the major risk factor through ongoing investment in the needle and syringe program.
Hepatitis C can be diagnosed with a blood test through GPs.
See www.hepatitisaustralia.com for more information.
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Cases of hepatitis C on rise in ČR
http://www.praguemonitor.com
By ČTK
Prague, Oct 1 (CTK) - The Czech State Health Institute registered 1022 cases of hepatitis C in 2006, which was over 200 more than in 2005, but Petr Husa from the Czech Hepatology Society says the real may be even markedly higher, he told CTK Monday.
Husa said hepatitis C has almost no symptoms at first, although it may result in cancer or liver cirrhosis.
The number of Czechs infected by hepatitis C has been gradually growing in the last ten years.
The most risky group are drug addicts using needles, since 35 percent of them get infected with hepatitis C on average.
While one can be vaccinated against hepatitis A and B, vaccination against hepatitis C is impossible. The only protection is prevention and lowering risks, such as exchanging new injection needles for old ones by drug addicts.
"We provided nearly four million needles last year in the Czech Republic, one-third of them in Prague," Martina Richterova Teminova from the Sananim anti-drug group said.
Until last year, another way of lowering the incidence of hepatitis were quick tests. Based on new regulations, the tests need to be certified by the Health Ministry, but none of them has received the certificate yet.
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Pharmasset Commences Dosing in Phase 3 Registration Studies of Clevudine for HBV
http://www.therapeuticsdaily.com
From the PharmaLive.com News Archive - Oct. 01, 2007
Two 48-week Superiority Studies versus Hepsera in Patients with Chronic Hepatitis B
PRINCETON, N.J., October 1, 2007 /PRNewswire-FirstCall/ -- Pharmasset, Inc. has commenced dosing in Phase 3 registration clinical trials of clevudine for the treatment of chronic hepatitis B virus (HBV) infection. Clevudine is an oral, once-daily pyrimidine nucleoside analog that has previously been evaluated in 14 clinical trials in more than 800 individuals. The current Phase 3 studies will be conducted in 856 nucleoside treatment- naive patients with chronic HBV at approximately 140 global clinical sites to support the registration of clevudine in the Americas and Europe. Pharmasset licensed these territories from Bukwang Pharmaceuticals, who recently received South Korean regulatory approval and began marketing clevudine in South Korea under the brand name Levovir. As a result of the initiation of these studies, Pharmasset will pay Bukwang a $1.0 million milestone payment.
"Based upon prior 24 week treatment results, we are optimistic that clevudine will demonstrate superiority to Hepsera in its ability to suppress HBV DNA and normalize liver enzyme levels after 48 weeks of treatment," stated Dr. Michelle Berrey, Pharmasset's Vice President, Clinical Development & Chief Medical Officer. "We also expect to build upon the results from earlier studies that demonstrated clevudine's ability to provide a sustained virologic response, or SVR, for chronic HBV infection. If we are able to demonstrate SVR for HBV in these studies, clevudine could offer patients and their physicians an important new disease management option that might reduce the need for further therapeutic intervention after a defined treatment period."
Registration Studies for New Drug Application (NDA)
The clevudine Phase 3 registration program includes two 48-week clinical trials designed to demonstrate the superiority of clevudine 30mg over Hepsera (adefovir dipivoxil) 10mg, each administered once-daily as monotherapy. Clevudine Study 305 will enroll approximately 376 chronic hepatitis B e-antigen positive patients (HBeAg+), and clevudine Study 306 will enroll approximately 480 chronic hepatitis B e-antigen negative patients (HBeAg-). Pharmasset plans to submit the 48-week data from these studies to the FDA as the basis for clevudine marketing approval.
The primary endpoint for the registration studies is a composite endpoint measuring the proportion of patients with both undetectable serum HBV DNA and normalized liver enzyme (ALT) levels following 48 weeks of monotherapy. The registration studies will also assess improvement in liver histology, hepatitis B e-antigen (eAg) seroconversion, decreases in the reservoir of HBV hepatic cccDNA, and quantitative eAg and surface antigen (sAg). The clevudine registration studies will be conducted in the United States, Canada, Brazil, the United Kingdom, Spain, Greece, Turkey, Romania, Czech Republic, Australia, New Zealand, Singapore, Hong Kong and Taiwan. Please see www.clinicaltrials.gov or e-mail for more information about the clevudine registration studies. clinicaltrials@pharmasset.com
Assessment of SVR for HBV
After the primary registration data have been obtained at week 48, the Phase 3 studies will continue to week 96 to gather additional safety and efficacy data, as well as to assess clevudine's sustained virologic response (SVR) rate for HBV. SVR is a measure of undetectable virus 24 weeks after stopping therapy, which clevudine previously demonstrated in Bukwang's South Korean registration studies.
At week 72, HBeAg- patients in Study 306 who have been treated with clevudine and have suppressed HBV DNA and normalized ALT levels will be randomized to continue active clevudine or switch to placebo. The purpose is to determine the proportion of patients who sustain a virologic response 24 weeks after stopping clevudine treatment at week 96. HBeAg+ patients in Study 305 that have been treated with either clevudine or Hepsera and undergo eAg seroconversion (loss of eAg with suppressed HBV DNA and normalized ALT) will discontinue therapy at week 72. SVR will be assessed in these HBeAg+ patients for clevudine and Hepsera 24 weeks after stopping treatment at week 96.
South Korean Registration Studies for Clevudine
Bukwang received marketing approval for clevudine from the South Korean FDA based on two 24-week, randomized (3:1), double-blind, placebo-controlled, multi-center South Korean Phase 3 registration trials in 337 patients. Study 301 enrolled 248 HBeAg+ patients who received clevudine 30 mg or a placebo once-daily, and Study 302 enrolled 89 HBeAg- patients who received clevudine 30 mg or a placebo once-daily. All patients were evaluated for an additional 24 weeks of follow-up care without clevudine treatment.
After 24 weeks of clevudine treatment, 59% of HBeAg+ patients achieved undetectable HBV DNA (<300 copies/mL) and 92% of HBeAg- patients achieved undetectable HBV DNA. These results were statistically significant compared to placebo. In addition to the potent antiviral suppression, 16% of the HBeAg- patients who received clevudine demonstrated a sustained virologic response (SVR) 24 weeks after stopping therapy, versus 0% of the patients who had received the placebo. In Study 303, a South Korean open-label, follow-on study of clevudine, Bukwang observed similar findings to those noted above for Studies 301 and 302. Twelve weeks after completing a 48-week course of therapy, 80% of HBeAg- patients had undetectable HBV DNA.
Clevudine was generally safe and well-tolerated by patients with chronic HBV. Serious adverse events during treatment in Studies 301 and 302 and during follow-up indicated that a higher percentage of placebo-treated patients had seriously elevated liver enzyme levels. Otherwise, there was no meaningful difference between clevudine and placebo in the incidence of serious adverse events.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
Pharmasset is currently developing three product candidates. Clevudine, for the treatment of chronic HBV infection, is in Phase 3 clinical trials for registration in the Americas and Europe. Clevudine is already approved for HBV in South Korea and marketed by Bukwang Pharmaceuticals in South Korea under the brand name Levovir. R7128, an oral treatment for chronic HCV infection, is in a Phase 1 clinical trial through a strategic collaboration with Roche. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial.
Hepsera is a registered trademark of Gilead Sciences, Inc.
Contact
Alan Roemer, Vice President
Investor Relations & Corporate Communications
Office: (609) 613-4125
alan.roemer@pharmasset.com
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding our business that are not historical facts are "forward-looking statements" that involve risks and uncertainties, including without limitation the risk that adverse events could cause the cessation of the Phase 3 studies and/or our development of clevudine, the risk that the registration clinical trials of clevudine will not be successful or will not provide meaningful data, the risk that the on- going or anticipated clinical trials for any one or more of our product candidates will not be successful and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of these risks and uncertainties, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section of our Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 filed with the Securities and Exchange Commission entitled "Risk Factors" and discussions of potential risks and uncertainties in our subsequent filings with the Securities and Exchange Commission.
CONTACT: Alan Roemer, Vice President, Investor Relations & CorporateCommunications of Pharmasset, +1-609-613-4125, alan.roemer@pharmasset.com
Web site: http://www.pharmasset.com/ http://www.clinicaltrials.gov/
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Effects of Portal Hypertension in Rats Reversed by Combination Therapy, Promising Implications for Human Patients
http://www.medicalnewstoday.com
A combined treatment with rapamycin and Gleevec might reverse the effects of portal hypertension in patients with chronic liver disease, according to the results of a new study on rats. The study is in the October issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience.
Portal hypertension is a serious complication of chronic liver disease, and a leading cause of liver transplantation and mortality. It develops when a blockage in the blood flow through the liver causes the body to develop new blood vessels to develop (through a process called angiogenesis) across the esophagus and stomach. These new vessels drain into the portal vein, worsening the portal blood pressure and contributing to the formation of life-threatening complications like esophageal varices. Prior studies have suggested that anti-angiogenic treatment might help prevent the progression of the portal hypertension syndrome.
Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are crucial to angiogenesis, so researchers, led by Mercedes Fernandez of the IDIBAPS in Barcelona, examined the effects of VEGF and PDGF inhibitory drugs on rats with established portal hypertension, to best mimic the typical human patient. They treated portal vein-ligated rats with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor) or both simultaneously, and determined the effects on hyperdynamic splanchnic circulation and portosystemic collateralization.
In rats whose portal hypertension was fully developed, the combined therapy significantly reduced splanchnic neovascularization and pericyte coverage of neovessels. The rats experienced a 40 percent decrease in portal pressure, along with a 30 percent decrease in superior mesenteric artery blood flow and a 63 percent increase in superior mesenteric artery resistance. This was "a significant reversal of the hemodynamic changes provoked by portal hypertension in rats," the authors report.
They found that the magnitude of the effects of the combination treatment was superior to the addition of the effects of either drug alone, suggesting that the two worked together to mediate the maintenance of the vascular and circulatory abnormalities observed in rats with portal hypertension.
This is the first study to show that portal hypertension development is associated with a progressive overexpression of PDGF as well as VEGF. It also revealed that anti-angiogenic therapy could not merely prevent, but also revert, abnormalities associated with portal hypertension which would be a very helpful for treating patients with portal hypertension, because they are typically only diagnosed when their condition causes clinical problems. Furthermore, both drugs tested in this study have already been broadly used to treat human malignancies.
"Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchic neovascularization and portosystemic collaterization is regulated by VEGF and PDGF in portal hypertensive rats," the authors conclude. "An extended anti-angiogenic strategy (i.e. targeting VEGF/endothelium and PDGF/pericytes) may represent a novel approach in the treatment of portal hypertension."
Article adapted by Medical News Today from original press release.
Article: "Reversal of Portal Hypertension and Hyperdynamic Splanchnic Circulation by Combined Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Blockade in Rats." Fernandez, Mercedes; Mejias, Marc; Garcia-Pras, Ester; Mendez, Raul; Garcia-Pagan, Juan Carlos; Bosch, Jaime. Hepatology; October 2007; (DOI: 10.1002/hep.21785).
Source: Amy Molnar
John Wiley & Sons, Inc.
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October 3rd, 2007
Sneak a Peek at Promising Hep C Stocks
http://www.thestreet.com
By Adam Feuerstein
Senior Writer
BOSTON -- Research abstracts of data set for unveiling at next month's big hepatitis C meeting were published over the weekend, offering another glimpse at experimental drugs from Vertex Pharmaceuticals (VRTX) and Gilead Sciences (GILD) , among others.
The Liver Meeting, sponsored by the American Association for the Study of Liver Diseases, is the biggest gathering of liver disease experts and researchers in the U.S. This year's event, Nov. 2-6 in Boston, will be the focus of investors and analysts interested in the development of new, potentially blockbuster, drugs for the treatment of hepatitis C.
The October issue of the AASLD medical journal Hepatology was made available to association members last weekend and contained detailed data abstracts ahead of next month's meeting. Some of these abstracts contain new, albeit limited, information about a slew of hepatitis C drugs.
The really important data, however, won't be publicly disclosed until the meeting begins.
But for those hepatitis C junkies who can't wait a month, here's a quick summary of some of the research abstracts. Full public access to the abstracts should be available starting Tuesday and can be found here:
I've written extensively about Vertex and its hepatitis C drug telaprevir, a protease inhibitor that, so far, has shown very promising direct antiviral activity against the hepatitis C virus. (For that background, look here and here.)
The Liver Meeting is a big event for Vertex because for the first time, researchers will be presenting phase II data from a U.S. study detailing rates of sustained virologic response (SVR) for hepatitis C patients taking telaprevir-containing regimens.
In layman's terms, SVR is a cure for hepatitis C, so the data will provide the most important measure of the drug's efficacy and safety to date.
As I wrote last week, investor expectations for the telaprevir SVR rate in the U.S-based phase II trial, known as Prove 1, are in the low-60% range.
There isn't any new information in the abstracts that shed light on the Prove 1 study, but there is some new data from the European-based phase II study known as Prove 2.
Specifically, 79% of patients taking a telaprevir-containing regimen in Prove 2 reported having an undetectable level of virus after 12 weeks.
That compares to a 12-week undetectable rate of 70% in the Prove 1 study. It's expected that the efficacy data from Prove 2 will be a bit better than Prove 1. Historically, European hepatitis C patients perform better than their U.S. counterparts.
The Liver Meeting will be the clinical debut for Gilead's experimental polymerase inhibitor GS 9190, the company's first big push into the hepatitis C market.
A single-dose study of GS 9190 shows a median viral load reduction of 0.5 to 1.5 log, depending on the dosage, according to the abstract. (Generally speaking, viral load changes are measured in "log" -- a log 1 reduction is considered a good level of efficacy at this stage of development.)
That's a respectable showing of efficacy for a single dose. There were also no unusual or worrisome toxicities detailed in the abstract.
The second part of this phase I study is more important and will dose patients over eight days. Data from this portion of the study will be presented at the meeting.
Swiss drug maker Roche has garnered some attention for its polymerase inhibitor RS 1626, which in previous studies has shown very good efficacy. There are, however, some worries about the drug's toxic effects, which include anemia.
Roche will present some early data next month on RS 1626 used in various combinations with standard-of-care drugs pegylated interferon and ribavirin. Some of this data is contained in the abstract, and it's quite interesting.
A 1,500-milligram dose of RS 1626 plus standard of care resulted in 81% of patients reporting undetectable levels of virus after four weeks. By comparison, only 5% of patients given the standard of care alone had undetectable virus levels.
There were some serious adverse events reported in the abstract, including grade 4 neutropenia, or low white blood cell counts. The rates of toxicity increase with higher doses of RS 1626. There is no mention of anemia in the abstract, although that could be reported at the meeting.
Last month, Pharmasset (VRUS) released positive preliminary results from a phase I study of its polymerase inhibitor R7128 when dosed by itself for 14 days in patients with hepatitis C. The best data was from a 1500-mg dose of R7128 given twice a day, which resulted in a 2.7 log reduction of viral load.
Pharmasset and its partner Roche have already announced plans for new phase II studies of R7128 in combination with standard of care. Additional data from the phase I study will be presented at the meeting.
Adam Feuerstein writes regularly for TheStreet.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships.
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Diabetes Tied To Recurrence of HCV-Related Liver Cancer
http://www.cancerpage.com
By David Douglas
NEW YORK OCT 02, 2007 (Reuters Health) - Diabetes is a predictor of poor outcome in patients who have hepatocellular carcinoma related to hepatitis C virus infection (HCV), Japanese investigators report in the September issue of the American Journal of Gastroenterology.
As senior investigator Dr. Shuichi Kaneko told Reuters Health, "Diabetes is a risk factor not only for development of hepatocellular carcinoma, but also for recurrence after operation."
Dr. Kaneko and colleagues at Kanazawa University retrospectively studied 90 patients with hepatitis B and/or C who had undergone surgical treatment for hepatocellular carcinoma. Of this group, 30 had diabetes and the remaining 60 were diabetes-free.
In all, 49 patients had recurrence after surgery. Of these, 22 were from the diabetic group (73.3%) and 27 (45.0%) were from the non-diabetic group. Mean time to recurrence was 32.8 months.
The researchers found that there was no significant difference in survival between diabetic patients and non-diabetic patients with hepatitis B-related hepatocellular carcinoma.
However, comparison of diabetic and non-diabetic patients with HCV-related disease showed that survival rates at 3 years and beyond were significantly lower in the diabetic group than among the non-diabetics. Survival rates at 5 years, for example, were 43.8% versus 82.6%, respectively.
Given these findings, concluded Dr. Kaneko, diabetic patients "should be closely followed for this carcinoma."
SOURCE:
Am J Gastroenterol 2007;102:1939-1946.
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Pharmasset Commences Dosing in 28-Day Combination Study of R7128 with Pegasys(R) plus Copegus(R) for Hepatitis C
http://biz.yahoo.com
PRINCETON, N.J., Oct. 3 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS - News) has commenced dosing in a Phase 1 study of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in up to 75 treatment-naive patients chronically infected with hepatitis C virus (HCV) genotype 1. R7128 is a prodrug of PSI-6130, an oral cytidine nucleoside analog polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. The purpose of this study is a preliminary evaluation of safety, tolerability, pharmacokinetics and antiviral activity of R7128 in the clinically-relevant setting of combination therapy with the current standard of care for chronic HCV infection.
The study will include two to three oral doses of R7128 (500 mg to 1500 mg) that will be administered twice-daily with Pegasys plus Copegus for 28 days. There will be 25 patients in each dose cohort with 20 patients randomized to receive R7128 and 5 patients randomized to receive placebo, all administered in combination with the standard of care. After completing 28 days of the triple combination regimen and a follow-up period of 4 weeks of Pegasys plus Copegus, all patients will then receive 40 weeks of open-label standard of care dosing under a separate protocol. Please see www.clinicaltrials.gov or e-mail clinicaltrials@pharmasset.com for more information.
"We are excited about the rapid pace of development of R7128, and the opportunity to evaluate its safety and potency in combination with the standard of care," stated Dr. Michelle Berrey, Pharmasset's Vice President, Clinical Development & Chief Medical Officer. "The 28-day endpoint will provide meaningful data on early viral kinetics and the proportion of patients who have undetectable HCV RNA by the end of this treatment period. We look forward to sharing the preliminary results of this combination study in the first quarter of 2008 and making plans for future studies of R7128."
About Pharmasset
Pharmasset is a clinical stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
Pharmasset is currently developing three product candidates. Clevudine, an oral treatment for chronic HBV infection, is in Phase 3 clinical trials for registration in the Americas and Europe. Clevudine is already approved for HBV in South Korea and marketed by Bukwang Pharmaceuticals in South Korea under the brand name Levovir. R7128, an oral treatment for chronic HCV infection, is in a Phase 1 clinical trial through a strategic collaboration with Roche. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial.
About R7128
R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a pyrimidine nucleoside analog inhibitor of HCV RNA polymerase. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.
R7128 Phase 1 Study Overview
The Phase 1 clinical trial is a multiple center, observer-blinded, randomized and placebo-controlled study to investigate the pharmacokinetics, pharmacodynamics, safety, tolerability and food effect of R7128 in healthy volunteers and in patients chronically infected with HCV genotype 1. This adaptive Phase 1 study is comprised of three parts:
Part 1 is a single ascending dose study of R7128 conducted in 46 healthy volunteers. The primary objective of Part 1 is to assess the safety, tolerability and pharmacokinetics of R7128 following single ascending doses under fasting conditions. The secondary objective of Part 1 is to explore the effect of food on the pharmacokinetics of R7128. Results from the single ascending dose portion of the study indicated that all doses of R7128 studied (500 mg to 9000 mg) were generally safe and well-tolerated. All patients completed the study, and none experienced gastrointestinal adverse events or serious adverse events during the study. No hematological or laboratory abnormalities of clinical significance were noted.
Part 2 is a multiple ascending dose study of R7128 conducted in 40 patients chronically-infected with HCV genotype 1 who previously failed interferon therapy. The primary objective of Part 2 is to assess the safety, tolerability and pharmacokinetics of R7128 after once-daily (QD) or twice- daily (BID) dosing for 14 days. The secondary objective is to assess antiviral activity by measuring the change in HCV RNA. Preliminary data from the multiple ascending dose portion of the study indicated that R7128 demonstrated potent, dose-dependent antiviral activity in four patient cohorts receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. Patients receiving 1500 mg BID demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of viral rebound in any dose cohort during the 14 days of dosing. R7128 was generally safe and well tolerated. There were no serious adverse events, no adverse events requiring dose modification, no dose-related gastrointestinal adverse events and no clinically significant changes in hematologic or other laboratory parameters.
Part 3 is a multi-center, observer-blinded, within-cohort randomized, placebo-controlled study being conducted in up to 75 treatment-naive patients with genotype 1 hepatitis C virus. The primary objective is to assess the safety, tolerability and pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The secondary objective of Part 3 is to evaluate the short-term change in HCV RNA. The study will include two to three oral doses of R7128 (500 mg to 1500 mg) that are being administered twice-daily with Pegasys plus Copegus for 28 days.
Pegasys and Copegus are registered trademarks of Roche.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost four million people in the United States have been infected with HCV, of whom 2.7 million are chronically infected.
Contact
Alan Roemer, Vice President
Investor Relations & Corporate Communications
alan.roemer@pharmasset.com
Office: (609) 613-4125
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding our business that are not historical facts are "forward-looking statements" that involve risks and uncertainties, including without limitation the risk that adverse events could cause the cessation of the Phase 1 study and/or our development of R7128, the risk that our collaboration with Roche will not continue or will not be successful, the risk that the on-going or anticipated clinical trials for any one or more of our product candidates will not be successful or will not provide meaningful data and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of these risks and uncertainties, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section of our Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 filed with the Securities and Exchange Commission entitled "Risk Factors" and discussions of potential risks and uncertainties in our subsequent filings with the Securities and Exchange Commission.
Source: Pharmasset, Inc.
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Imaging May Lessen Liver Biopsies to Diagnose Fibrosis
http://www.medpagetoday.com
By Michael Smith, Senior Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
ROCHESTER, Minn., Oct. 3 -- Many liver biopsies to diagnose liver fibrosis and cirrhosis may soon be supplanted by non-invasive imaging techniques, researchers here said.
Action Points:
- Explain to interested patients that liver fibrosis is a serious consequence of many forms of liver disease, so that tools to diagnose the extent of fibrosis are needed.
- Point out that the gold standard for diagnosis is the liver biopsy, which is painful, and can cause morbidity and mortality.
- Explain that researchers are seeking new ways to diagnose fibrosis without the need for biopsies, using various imaging techniques.
New methods of evaluating fibrosis are highly accurate, according to three papers in the October issue of Clinical Gastroenterology and Hepatology.
Two of the studies evaluated new diagnostic methods, while the third was a meta-analysis of research on ultrasound-based transient elastography, the method that has received the most research attention.
The method involves using an ultrasound generator to send a wave through the organ, wrote Jayant Talwalkar, M.D., of the Mayo Clinic College of Medicine, and colleagues.
The wave moves faster through stiffer tissue, allowing clinicians to gauge the extent of fibrosis, Dr. Talwalkar and colleagues said.
All told, the researchers found nine published studies comparing the results of ultrasound-based transient elastography to standard biopsies as a diagnostic tool for patients with stage IV fibrosis, or frank cirrhosis.
Seven of them also allowed comparison for patients with stages II, III, and IV fibrosis.
For the cirrhosis patients, the researchers said, the pooled sensitivity estimate for the nine studies was 87%, while the pooled specificity estimate was 91% -- results that qualified as "excellent."
The results were "consistent with values seen among tests considered to provide strong diagnostic evidence in clinical decision making," the researchers said.
The estimates were lower for patients with less advanced disease, with a pooled sensitivity estimate of 70% and a pooled specificity estimate of 84%.
Although the studies used differing cutoff points, so that the analysis could not pin down true accuracy, "ultrasound-based transient elastography appears to be a clinically useful test for detecting cirrhosis," the researchers concluded.
A second Mayo team, led by Richard Ehman, M.D., Ph.D., investigated a variation on ultrasound-based transient elastography -- this time using magnetic resonance to create mechanical shear waves in the liver.
The researchers studied the technique in 35 normal volunteers and 50 patients with chronic liver disease and found that the average liver stiffness (measured in kilopascals) was 2.2 for normal volunteers and 5.8 for those with liver disease.
The degree of stiffness was significantly correlated with the degree of fibrosis (P<0.001), Dr. Ehman and colleagues reported.
The technique had a sensitivity of 98% and a specificity of more than 99% for differentiating any stage of liver fibrosis from normal liver tissue, the researchers said.
The study also showed that hepatic steatosis had no effect on the diagnostic power of the technique, the researchers said.
Finally, another technique -- this one analyzing blood flow in the liver -- also proved useful in evaluating the extent of fibrosis and cirrhosis in patients with chronic hepatitis C, according to Chen-Hua Liu, M.D., of the National Taiwan University Hospital in Taipei, and colleagues.
The researchers prospectively evaluated consecutive hepatitis C patients between January, 2003 and December, 2006, and enrolled 503 of them. Duplex Doppler ultrasonography was used to assess splanchnic vascular hemodynamics before a liver biopsy.
In multivariate logistic regression analyses, two hemodynamic characteristics -- the mean portal vein velocity and the splenic artery pulsatility index -- significantly predicted (P<0.001) patients with hepatic fibrosis up to and including cirrhosis, Dr. Liu and colleagues found.
But the splenic artery pulsatility index was more accurate, the researchers said.
On the other hand, they added, because of variations among observers and equipment, obtaining reproducible results might be difficult. It's also not clear how well the technique will work in patients with other types of underlying disease, so more research is needed, they said.
"The studies are the wave of the future," said journal editor C. Mel Wilcox, M.D., of the University of Alabama.
"Using Doppler ultrasound and MRI, these investigators found these modalities to be accurate and reproducible in detecting fibrosis and cirrhosis," he said in a statement.
"Look for more studies using these non-invasive imaging studies, and perhaps others in the future."
Dr. Ehman's study was supported by the NIH. Dr. Ehman and co-author Phillip Rossman hold patents related to the technology and have a potential financial interest in this research.
Dr. Liu's study was supported by the National Taiwan University Hospital, the National Science Council, and the Taiwan Department of Health. The authors reported no conflicts.
For the meta-analysis, Dr. Talwalkar and colleagues reported no conflicts.
Additional Hepatitis Coverage
- Primary source:
Clinical Gastroenterology and Hepatology
- Source reference:
Talwalkar JA et al. "Ultrasound-Based Transient Elastography for the Detection of Hepatic Fibrosis: Systematic Review and Meta-analysis." Clin Gastroenterol Hepatol 2007; 5: 1214-20.
- Additional source:
Clinical Gastroenterology and Hepatology
- Source reference:
Liu C-H et al. "Noninvasive Diagnosis of Hepatic Fibrosis in Patients With Chronic Hepatitis C by Splenic Doppler Impedance Index." Clin Gastroenterol Hepatol 2007; 5: 1199-1206.
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October 4th, 2007
Canada pulls Novartis's Prexige on hepatitis fears
http://news.yahoo.com
TORONTO (Reuters) - Canada said on Thursday it has stopped the sale of Novartis Pharmaceuticals Canada Inc's anti-inflammatory drug Prexige and will cancel its market authorization due to the risk of serious liver-related effects, mainly hepatitis.
It said there have been four cases internationally, including two cases in Canada, of hepatitis associated with the 100 mg dose.
The decision to withdraw the drug came following a review of information from Novartis, which the government's health department, Health Canada, requested after Australia pulled Prexige from its market in August after it was linked to liver diseases at doses of 200 mg and 400 mg.
Prexige, a Cox-2 selective inhibitor non-steroidal anti-inflammatory drug, has been marketed in Canada since November 2006 for the treatment of osteoarthritis in adults at a maximum daily dose of 100 mg.
Health Canada recommended that patients using the drug contact their doctors for alternative treatments.
Late last month, the U.S. Food and Drug Administration rejected Prexige, giving the drug a "non-approvable letter." At the time, Novartis said it would continue talks with the FDA. The drug is still available in Europe.
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Hepatitis on the Rise in Hawaii
http://www.khon2.com
By KHON News
Hawaii has the highest rate of liver cancer in the country. Liver cancer can be caused by Hepatitis, a viral infection that will eventually lead to death.
Death from liver cancer is the highest form of cancer death for native Hawaiian, Filipino, and Chinese men in Hawaii; the primary cause is hepatitis.
Pamela Anderson, Naomi Judd and Jim Nabors...all of these people have one thing in common; they are each diagnosed with hepatitis.
Here in Hawaii...
"We're infected our island is infected with hepatitis C and B, we're the worst in the United States," says Eddie Ochoa, prison and outreach educator.
"Its something that doesn't make people sick for years and years and years sometimes people can have it for 10, 20, 30, decades," says Dr. Alan D. Tice, consultant in infectious diseases.
Hepatitis B or C is found in 1 out of 20 people in Hawaii; the majority of the people who have it don't even know or don't know anything about it.
"A while back I went to the doctor and he did a blood test on me and he said that I had hepatitis I knew I had it but I didn't know what it was," says Ochoa.
Hepatitis is a disease caused by a virus that attacks the liver. Without being vaccinated the virus can be transmitted through intravenous drug use, unprotected sex, sharing razors, tooth-brushes and from mother to child.
"The Philippines for example, in Micronesia and many parts of Asia, China they didn't have the vaccines," continues Tice.
Homeless and inmates in Hawaii prisons have the highest infection rate of hepatitis.
"I go into the prison, in OCCC, I do module one and two, the psych wards and I share with them," says Ochoa.
He shares with inmates the knowledge to learn about Hepatitis and how to live with it.
"I share in the jail or the hospital is the message of hope," continues Ochoa.
"I don't have very long either my liver's not going to last forever but while its still there I will be doing this, "says Ochoa.
Hepatitis is expected to continue to cause liver disease and increase up to up to 200% in the next two years. A hepatitis symposium will be held on Oahu at the Queens Medical Center, Conference Center, 510 S. Beretania Street on October 27 from 8a.m. to 4p.m.
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