July 13, 2010

Time for efficiency in fighting AIDS: Bill Gates

By Maggie Fox, Health and Science Editor

Tue Jul 13, 2010 5:48pm EDT

WASHINGTON (Reuters) - No big influxes of new money are coming to fight the AIDS pandemic, but some smarter targeting and using approaches that have been shown to work can still save lives, Microsoft founder and philanthropist Bill Gates said on Tuesday.

Focusing more treatment on women in Africa, drug users in places where needles drive the epidemic and on gay and bisexual men where that is appropriate can go a long way to fighting the virus, Gates told reporters.

"We can focus our prevention efforts. We can look at where there is the most impact," Gates said.

Gates, whose Bill & Melinda Gates Foundation spends a large chunk of its $34 billion endowment on fighting AIDS, is influential in directing other spending as well. He has pushed governments, non-profit groups and other philanthropies to join efforts he supports.

One big goal is to extend treatment to more people. An estimated 33.4 million people worldwide are infected with the human immunodeficiency virus that causes AIDS. Only about five million people get drugs that can keep patients healthy and reduce the risk they will infect someone else.

"With treatment, the challenge is the financing," Gates told reporters in a preview of a keynote speech next Tuesday at the International AIDS Society conference in Vienna. The conference is a gathering of AIDS researchers, activists, patients and advocates held every two years.

"We want to broaden treatment. The only way to do that is efficiency," Gates said, noting that no one has the money to treat everyone who needs it.

"Clearly we are facing a major challenge in terms of funding because the global economic downturn has a lot of governments looking hard at their budgets," he said.

He noted that intense pressure had persuaded drug makers such as GlaxoSmithKline to provide inexpensive drugs to poor countries and to allow generic pharmaceutical companies to make cheap copies in countries such as India.

"Now we need to look at delivery costs, personnel costs and administration costs," Gates said.

"It is clear from some countries where treatment costs are quite low that if we take best practices and spread those around, we can really do a lot better there."

While treatment saves lives and prevents new infections, it is not the only way to prevent the spread of the disease, Gates said. "Other prevention efforts continue to be very important, like male circumcision, like pushing for behavior change, including condom use."

Gates has also pressed for development of a microbicide -- a gel, cream or device that women, and perhaps men, can insert to protect themselves from sexual transmission of the virus.


Patients With Haemophilia Co-Infected With HCV/HIV Derive Liver Benefits From HAART: Presented at Haemophilia 2010

By Thomas R. Collins

BUENOS AIRES -- July 13, 2010 -- Patients with haemophilia who are co-infected with hepatitis C virus (HCV) and HIV have a higher incidence of serious liver problems, but treatment with highly-active antiretroviral therapy (HAART) can reduce the risk associated with HCV, according to an analysis presented here at the Hemophilia World Congress 2010.

"It is well established that patients who are co-infected with HIV have a faster progression to end-stage liver disease and hepatocellular carcinoma," said Olga Katsarou, MD, National Reference Center for Bleeding Disorders, Athens, Greece, on July 12. "The introduction of highly active antiviral treatment in 1996 has dramatically modified the natural history of HIV infection by reducing the morbidity of AIDS-related causes and increasing the overall survival."

But the impact of HAART in the progression of hepatitis C remains controversial and unclear, she added, although there have been signs of a beneficial effect.

A total of 324 patients were enrolled in the study, with 164 having HCV alone and 160 infected with both HCV and HIV.

Seventy-seven patients received HCV treatment -- 57 in the HCV group and 20 in the HCV/HIV group. Sixty-five of the patients in the HCV/HIV group received HAART treatment of at least 3 months.

A total of 34 patients suffered serious liver-related events -- 12 in the HCV group and 22 in the HCV/HIV group.

Those with HCV and HIV were found to have a nearly 10-fold chance of having a serious liver-related event (hazard ratio [HR] = 9.6) compared with those with only HCV (HR = 1; P < .001).

But the chances that those with both viruses who received treatment with HAART would have a serious liver-related event were 5 times lower than the HCV/HIV group overall (HR = 1.7).

Those receiving HCV treatment had a nearly 40% reduction in risk of such an event (HR = .62), compared with the HCV-alone group, but this finding was not statistically significant.

"In our study, we found that the cumulative incidence of the development of a serious liver-related event in HCV-infected patients is higher when they are infected with HCV," Dr. Katsarou said. "The concerns that we had at the beginning that HAART could have a negative impact due to liver toxicity, it seems, to the contrary, that it can reduce the risk for the progression to end-stage liver disease in HIV co-infected haemophiliacs."

[Presentation title: Incidence of Liver-Related Morbidity in a Cohort of Haemophilia Patients: The Impact of HAART on HCV Progression. Abstract 16FP04]


Ryan sets sail for smoother seas with liver transplant

SMOOTH SAILING: Ryan Agnew with his dog Bailey
 and his ship, "Ryan's Challenge." A 16-foot version of the ship was
 the centerpiece to the St. Peter's Church vacation Bible camp.

by Meg Ryan
Jul 13, 2010

Ryan Agnew, a fifth grader at John Brown Francis School, has remained buoyant in stormy seas throughout his courageous struggle back to health.

Everything changed for Ryan last fall. An active – healthy child who enjoys playing hockey and soccer, as well as the guitar and piano, Ryan became very sick on Columbus Day of last year.

Ryan turned jaundice and started vomiting after playing a soccer game. His parent took him to Hasbro Children’s Hospital, but doctors there assessed the situation as dire and he was transferred to the care of Dr. Sukru Emre at Yale Children’s Hospital in Connecticut.

Then came the tidal waves. Over the course of the next two weeks he rapidly declined to critical condition. After countless blood tests and biopsies, Dr. Emre diagnosed Ryan with an untypical hepatitis, which caused liver failure.

“Our family was devastated,” recalls Ryan’s mom, Connie Agnew.

It was easily the darkest time in Ryan’s young life.

“I was going through rough waters. I couldn’t go outside. My entire school was going to come and sing to me on my front lawn, but I had to go back to the hospital. I would say the hardest part of my journey was the very first blood draw. I had hundreds, but I will never forget my first one,” says Ryan.

Dr. Emre and the other medical professionals at Yale Children’s Hospital began giving Ryan a series of liver function tests, which scanned his blood enzymes and proteins, which indicate liver disease. Ryan’s numbers were extremely high – a surefire sign of liver disease, if not outright failure.

Unfortunately in Ryan’s case, it was the latter. By the end of October, Ryan’s liver had failed completely.

Things were grim.

But fortunately for Ryan, however, some good fortune was finally on the horizon. The brave and generous family of a girl in a diabetic coma stepped forward and donated her liver to Ryan.

On October 26, Dr. Emre performed a dual surgery – a procedure that saved Ryan’s life. Dr. Emre split the donor child’s liver in half and gave the right lobe to Ryan and the left to an infant named Alvir. Both surgeries were successful.

After the surgery, and many prayers from friends and family members, Ryan began the long road back to a full recovery.

In June, he participated in the St. Peter’s Vacation Bible School Camp for the third consecutive year – this year as a counselor.

Margaret Andreozzi, the camp’s director, who had gotten to know Ryan over the last three years, felt as if the camp’s theme, “high seas”, coincided closely with Ryan’s tribulations over the past year.

She had already asked her brother-in-law, Robert Adams, of Assonet, Mass., to build a 16-foot model clipper ship.

So at the closing ceremony two weeks ago, Andreozzi and Adams decided to present the ship as “Ryan’s Challenge” in honor of his journey.

It was then given to St. Peter’s School’s principal, Mrs. Joan Sickinger, to be used as a float in Warwick’s 2011 Gaspee Day Parade. Father Roger C. Gagne presented Ryan with his own smaller replica of the ship to commemorate the event.

“I [couldn’t] stop crying,” said Connie, referring to the ceremony.

“It certainly was Ryan’s challenge, and he conquered it. We never would have gotten through it without the support of our parish, family, friends and community.”

Ryan is doing well, but the recovery is still very much an ongoing journey. He takes life saving drugs twice daily and maintains a strict diet. Ryan still has to refrain from any strenuous activities and therefore hasn’t returned to his active lifestyle. But if his heroic recovery over the better part of the last year is any indication, he will sooner than later.

In the meantime, Ryan has taken his suffering and turned it into something positive. He has devoted himself to working as an organ transplant spokesman in Rhode Island and Connecticut. Ryan spoke at the Transplant Awareness Fair at Yale University on May 15 where Billy Joel performed, and over a thousand people gathered to learn more about organ transplants.

Ryan has also spoken at fundraisers for the Ronald McDonald House, where he also spent time recovering. He will speak at an upcoming fundraiser at Mohegan Sun this November.

For more information about organ transplants or to learn how you can become a donor visit http://www.donatelifenewengland.org/ today.


Announcing the National HIV/AIDS Strategy

Posted by Jeffrey Crowley on July 13, 2010 at 12:45 PM EDT

Today, I am pleased to announce the release of the National HIV/AIDS Strategy for the United States. The release of the strategy reaffirms President Obama’s commitment to fighting this domestic epidemic.

From the time that we first heard about the human immunodeficiency virus (HIV) thirty years ago through today, HIV has become a global pandemic with more than 33 million people living with HIV around the world. In the United States, approximately 56,000 people become infected each year, more than 1.1 million Americans are living with HIV, and nearly 600,000 Americans have been lost to this disease. Unless we take bold actions, we anticipate a new era of rising infection rates and even greater challenges in serving people with HIV.

President Obama believes that we must re-focus public attention on ending the domestic HIV epidemic. The vision for the National HIV/AIDS Strategy is simple:

The United States will become a place where new HIV infections are rare, and when they do occur, every person, regardless of age, gender, race/ethnicity, sexual orientation, gender identity, or socio-economic circumstance will have unfettered access to high-quality, life-extending care, free from stigma and discrimination.

To make this a reality, the Obama Administration is launching a comprehensive plan for fighting HIV in our country. The strategy has three primary goals:
  • Reducing the number of new infections;
  • Increasing access to care and optimizing health outcomes for people living with HIV; and
  • Reducing HIV-related health disparities.
Today, Secretary Sebelius also announced that $30 million of the Affordable Care Act’s Prevention Fund will be dedicated to the implementation of the NHAS. This funding will support the development of combination prevention interventions. It will also support improved surveillance, expanded and targeted testing, and other activities.

Since taking office, the Obama Administration has taken extraordinary steps to engage the public to evaluate what we are doing right and identify new approaches that will strengthen our response to the domestic epidemic. The Office of National AIDS Policy hosted 14 HIV/AIDS Community Discussions with thousands of Americans across the U.S., we reviewed suggestions from the public via the White House website, we organized a series of expert meetings on several HIV-specific topics, and we worked with Federal and community partners who organized their own meetings to support the development of a national strategy.

To develop the Strategy, we convened a panel of Federal officials from across government to assist in reviewing the public recommendations, assessing the scientific evidence for or against various recommendations, and making their own recommendations for the Strategy.

The Strategy provides a roadmap for moving the Nation forward in addressing the domestic HIV epidemic. It is not intended to be a comprehensive list of all activities to address HIV/AIDS in the United States, but is intended to be a concise plan that will identify a set of priorities and strategic action steps tied to measurable outcomes.

The release of the National HIV/AIDS Strategy is just beginning. The job of implementing this strategy does not fall to the Federal government alone. Success will require the commitment of all parts of society, including State and local governments, businesses, faith communities, philanthropy, the scientific and medical communities, educational institutions, people living with HIV, and others. We are appreciative of the high level of engagement we have received from so many stakeholders to date.

Please visit WhiteHouse.gov/ONAP or AIDS.gov to learn more about the strategy and how you can get involved in the fight against HIV and AIDS.

Jeffrey Crowley is the Director of the Office of National AIDS Policy


FDA Drug Safety Communication: New boxed warning for severe liver injury with arthritis drug Arava (leflunomide)

Safety Announcement

[07-13-2010] The U.S. Food and Drug Administration (FDA) is adding information on severe liver injury to the Boxed Warning of Arava (leflunomide) – a drug used to treat rheumatoid arthritis - to highlight the risk of severe liver injury in patients using this drug and how this risk may be reduced. FDA previously required a Boxed Warning stating that leflunomide was contraindicated in pregnant women, or women of childbearing potential who were not using reliable contraception.

The information on severe liver injury now being added to the Boxed Warning states:
  • Patients with pre-existing liver disease should not receive leflunomide.
  • Patients with elevated liver enzymes (ALT greater than two times the upper limit of normal) should not receive leflunomide.
  • Caution should be used in patients who are taking other drugs that can cause liver injury.
  • Liver enzymes should be monitored at least monthly for three months after starting leflunomide and at least quarterly thereafter.
  • If the ALT rises to greater than two times the upper limit of normal while the patient is on leflunomide – leflunomide should be stopped, cholestryamine washout begun to speed the removal of leflunomide from the body and follow-up liver function tests conducted at least weekly until the ALT value is within normal range.
Although a bolded warning statement on severe liver injury was added to the leflunomide drug label in 2003, FDA determined that information on severe liver injury should be included in the Boxed Warning to highlight the importance of appropriate patient selection before starting treatment, and monitoring once treatment has begun.

The decision to add information on severe liver injury to the Boxed Warning was based on FDA’s 2010 review of adverse event reports which identified 49 cases of severe liver injury, including 14 cases of fatal liver failure, between August 2002 and May 2009. In this review, the greatest risk for liver injury was seen in patients taking other drugs known to cause liver injury, and patients with pre-existing liver disease (see Data Summary below).

Healthcare professionals should be aware of the risk for severe liver injury with this drug, and ensure appropriate patient selection and monitoring (see Additional Information for Healthcare Professionals below).

Patients should know that severe liver injury is a rare, but serious side effect of this drug. Patients who experience itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools should contact their healthcare professional right away—these may be signs of severe liver injury (see Additional Information for Patients below).

Additional Information for Patients
  • Be aware that cases of severe liver injury have been reported in people taking leflunomide.
  • Contact your healthcare professional if you develop itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools. These may be signs of liver injury.
  • Talk to your healthcare professional about any concerns you have with this medication.
  • Report any side effects with leflunomide to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

Additional Information for Healthcare Professionals
  • Cases of severe liver injury, including fatal liver failure, have been reported in patients using leflunomide.
  • Only patients for whom the anticipated therapeutic benefit is expected to outweigh the risk of severe liver injury should be considered for leflunomide treatment.
  • Patients with pre-existing liver disease (acute or chronic infection with hepatitis B or C virus), or those with serum ALT greater than 2 times the upper limit of normal before initiating treatment, should not be treated with leflunomide.
  • Caution should be used when leflunomide is given with other drugs that have the potential to cause liver injury.
  • ALT levels should be monitored at least monthly for three months after starting leflunomide and at least quarterly thereafter.
  • If the ALT rises to greater than 2 x the upper limit of normal while the patient is being treated with leflunomide – leflunomide should be stopped, cholestryamine washout begun, and follow-up liver function tests conducted at least weekly until normalization.
Data Summary

In 2003, a bolded warning statement about the risk of severe liver injury and a recommendation to monitor liver function tests every 6 to 8 weeks were included in the professional prescribing information for leflunomide. In 2009, based on continued reports of severe liver injury, FDA conducted an updated review of severe liver injury and leflunomide and identified 49 cases, 36 which required hospitalization, reported between August 2002 and May 2009.

The estimated duration of leflunomide treatment before the occurrence of severe liver injury ranged from 9 days to 6 years, with the majority of patients developing severe liver injury within the first 6 to 12 months of treatment.

Of the 49 cases, there were 14 deaths. An additional five patients required a liver transplant and nine patients experienced a life-threatening event. Twenty-three reports described jaundice at the time of diagnosis, 11 reported coagulopathy (clotting disorder), and five reported encephalopathy. Other presenting symptoms in these cases included vomiting, rash and or itching, abdominal pain, and fever. Seventeen cases reported normal liver enzymes prior to starting leflunomide.

Forty-six of the 49 patients were also taking other medications that have been associated with liver injury, including methotrexate, TNF-α blockers, hydroxychloroquine, acetaminophen, non-steroidal anti-inflammatory drugs, and statins. In addition, 14 patients had pre-existing liver disease such as active or chronic hepatitis, and/or a history of alcohol abuse. Although many patients who developed severe liver injury were also taking other drugs that can damage the liver, or had pre-existing liver disease, FDA concluded that use of leflunomide was associated with the development of severe liver injury in these patients.

To highlight the importance of appropriate patient selection and monitoring in reducing the risk of severe liver injury, the agency decided that specific recommendations to ensure safe use of leflunomide needed to be added to the Boxed Warning.

-Related Information
Leflunomide (marketed as Arava) Information


India's patent regime hurting across Asia-Pacific

Priyanka Golikeri / DNA
Tuesday, July 13, 2010 2:04 IST

Mumbai: Sitting in a first-floor room of a nondescript school building off Thakurdwar Road at Charni Road in south Mumbai, Eldred Tellis is a picture of frustration and agony.

As the founder director of Sankalp Rehabilitation Trust, which works with HIV/AIDS patients, Tellis is confronted with the challenge of providing affordable treatment for patients of hepatitis C, a liver disease that affects almost 95% of users of injectable drug.

Unless hepatitis C is treated, no effort to save AIDS patients would suffice.

“Hepatitis C medicines are incredibly expensive. We just can’t treat patients,” says Tellis.

Two key hepatitis C medicines—pegylated interferon alpha 2a and pegylated interferon alpha 2b — both patented in India, cost between $16,000 and $18,000 (Rs 7.5-8.4 lakh) for a 48-week course of treatment.

Same is the case with patented HIV/AIDS medicines like raltegravir, which costs Euro 2000 (Rs 1.2 lakh) per year in India, and etravirine priced internationally (no separate pricing for developing countries) at about $8000 (Rs 3.7 lakh) per year.

Other than the patent-holders, no other company can manufacture the medicines till the patents expire.

“The older medicines for HIV/AIDS are given by the government, but the newer ones, which are patented, are just unaffordable. With competition, prices come down. But that’s not possible in case of patented drugs. Hence, patients are left to God’s mercy,” says Loon Gangte, president of Delhi Network of Positive People, which works with HIV/AIDS patients.

The sentiments of Gangte and Tellis are reflected across Asia Pacific, in countries that depend on India for supply of low-cost off-patent (generic) medicines.

Estimates suggest that 200 million people around the world are infected with hepatitis C, while a report by the World Health Organisation (WHO), Unicef and UNAIDS, shows that at the end of 2008, about 5 million HIV/AIDS patients were not having access to treatment.

“We are seeing several deaths due to hepatitis C across Asia-Pacific, although no specific numbers are available. India is the pharmacy of the world. Patients look forward to cheap medicines from India, but as key HIV/AIDS and hepatitis C medicines hold patents in India, its a huge setback for patients in our region,” says Giten Khwairakpam, programme coordinator, Coalition of Asia Pacific Regional Network on HIV/AIDS, which works in Vietnam, Malaysia, Papua New Guinea, East Timor, Myanmar, etc.

Abdullah Denovan from Indonesia, who is the national coordinator of Indonesian Network of HIV Infected Persons, also echoes Khwairakpam’s views. “In 2009, there were over 15,000 hepatitis C cases in Indonesia. Estimates show that, from the 1980s to September 2009, Indonesia had about 18,442 HIV/AIDS sufferers. There may be many more unreported cases. There are no generics from India due to the patents.”

Manipur-based Deepak Leimapokpam, a user of injectable drugs who is afflicted by both HIV and hepatitis C is one of the very few who has managed to source funds from friends and relations abroad.

“99% of hepatitis C patients across India, specially in states like Manipur, Mizoram, Nagaland, are bereft of treatment. Of the more than 300 people with Hepatitis C whom I know, just two- three are on treatment,” says Leimapokpam, who is with the Manipur Network for Positive People in Imphal.

Leimapokpam says he spends about Rs 14,000-15,000 for a vial of the medicine per week. “Patients with both hepatitis C and HIV need to take the hepatitis C treatment for a year, and Rs 14,000 per week is just unimaginable.”

Five years after India adopted the product patent and 20-year patent regime, in accordance with the trade related aspects of intellectual property rights agreement (Trips) of the World Trade Organisation (WTO), the adverse effects of the regime are rubbing salt into the wounds of patients across countries.

“Local manufacturing in developing countries is not developed. Hence we have to depend on India,” says Kannikar Kijtiwatchakul, coordinator, health consumer protection programme, Chulalongkom University in Thailand.

Apart from Thailand, Indonesia, less developed countries like Lesotho, buy nearly 95% of all anti-retrovirals from India. Moreover, international humanitarian aid organisation Medecins Sans Frontieres, which provides treatment to 140,000 HIV/AIDS patients in 30 countries, buys more than 80% of its HIV/AIDS drugs from India. Also, about half the essential medicines that Unicef distributes and 75% medicines distributed by the International Dispensary Association in developing countries come from India.

Industry estimates suggest, that by 2015, when the Indian pharmaceutical market would be worth $20 billion, about 15% of total drugs would be patented molecules.

Anuradha Salhotra, managing partner at intellectual property law firm Lall, Lahiri & Salhotra, says the minute Trips came into effect, patent filings rose and will continue going up.

“That is frightening for all patients dependent on India. If key medicines are patented, it would allow patent holders to charge whatever they want and would push millions below poverty line,” says Khwairakpam.


New Way to Expand Donor Pool for Transplant Organs?

Dr. Noel Carter.
(Credit: Image courtesy of University of Sunderland)

ScienceDaily (July 12, 2010) — New research could have an "incredible" impact on the numbers of people being saved through the organ donor system, experts claim.

As demand for organ transplants continues to outstrip supply, a team of scientists from the University of Sunderland are hopeful they may have found a way to expand the donor pool.

A potential source of organs is from donors who have suffered heart attacks. In such cases organs are starved of oxygen and damage can occur making them unsuitable for transplantation.

But work to preserve these organs is taking place at Sunderland where research has shown that by rapidly cooling the kidneys you minimise the damage and preserve organs.

This research has led to the development of new medical devices to allow the rapid cooling of the organs, which have been approved by the NHS and are now used in clinical practice.

With three people dying every day while waiting for an organ, the news this week -- in National Transplant Week (July 5-11) -- could give hope to thousands of UK transplant patients.

The university's biomedical sciences department has been collaborating with Professor David Talbot, a visiting Professor at the University of Sunderland and a consultant transplant surgeon at Newcastle's Freeman Hospital, and an early pioneer of this research.

Dr Noel Carter, senior pharmacy lecturer in the Faculty of Applied Sciences and is part of the research group, said: "The primary aim of our research is to expand the donor pool. If we can achieve this then the benefits will be incredible.

"One of our PhD students Alex Navarro, who graduates next week, has based his thesis on the development of new medical devices to allow the rapid cooling of the organs."

Historically most donors are from either "living donors" such as family members or 'heart beating donors', where a patient is declared brain dead following an injury.

But the university research group has been focusing on 'non-heart beating donors', these are cases where patients have suffered a heart attack either in intensive care, Accident & Emergency or outside the hospital environment, and there has been an extended period of time in which the body is warm and there is no oxygen being supplied to the organs.

Dr Carter said: "Our research focuses on minimising the damage to the tissue and on regenerating it before you get the organ working again and transplant it into a recipient.

"One of our strategies has been to cool the organ as quickly as possible, to minimise damage.

"We use a type of fluid or perfusate to do this, these can be artificial salt solutions, designed specifically to be physiological. We are working with a company called Aquix who have produced a perfusate that could help regenerate the organ before transplantation."

Dr Carter said 'non-heart beating' donation is now being taken seriously by the medical profession, as the number of transplants in the UK has remained static over the last 10 years, while the waiting list has risen.

Further research is due to take place at the university, as two Masters students test a warm oxygenated approach -- instead of cooling the organs, warm fluid with oxygen is pumped through them to prevent tissue damage prior to transplantation.

The biomedical science team is also collaborating with a German pharmaceuticals company to set up human clinical study to assess the use of an anti-inflammatory drug to supplement the perfusate.

Dr Carter said: "Adding drugs to the perfusates is just another tool to help preserve the organs, and is the research of another one of our PhD students."

Much of the funding for the research has come though the Northern Counties Kidney Research Fund, a local charity funding kidney transplant research.

Dr Carter added: "All this research is vitally important, but ultimately the decision always comes down to consent from the family in order for these organs to be used.

"So the more we can promote transplantation in general, the more likely people will give their consent."

This, and other types of applied research, are expected to grow considerably with the opening later this year of the University of Sunderland's new £7.5m sciences complex.

The new facility, which opens in December, will deliver research with 'real world' impact -- research that quickly transfers from the laboratory into the public domain, be it new drugs and therapies, improved health practices or benefits to the environment.

The university will work closely with businesses and organisations in the health sector to allow them access to leading science experts and some of the most up-to-date facilities in the UK.

The theme of National Transplant Week, which runs until Sunday, is about taking time to have a 'Heart to Heart', asking people to find time to sit down with their friends and relatives and talk about the issue.

Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Sunderland, via AlphaGalileo.


Funds boost for liver transplant hospital

July 14, 2010

EXTRA funding will allow Melbourne's Austin Hospital to form a second dedicated surgical team to do more liver transplants - including split liver transplants where one organ is used to save the lives of both an adult and child.

The Austin is the only provider of liver transplants in Victoria, Tasmania and southern New South Wales. It carried out 54 transplants last financial year.

However, more than 200 new patients are added to the transplant list annually, with 20 per cent dying before receiving a new liver.

Health Minister Daniel Andrews yesterday announced an extra $1.4 million a year in recurrent funding for liver transplants, which will allow the Austin to form the second, dedicated surgical team. And this will enable the service to perform more of the split liver transplants.

The Austin team performed the operation in a Victorian-first living transplant two years ago when a young mother donated a segment of her liver to save the life of her one-year-old son.

It has performed occasional split liver transplants from deceased donors for some years, but is sometimes unable to muster a second surgical team at short notice.

The director of the Austin's liver transplant unit, Professor Bob Jones, said splits were becoming more viable with growing surgical experience and better drugs. He said that with the second surgical team ''we can get most of these kids now if we do everything right''.

Split livers can help children aged up to about one, growing with them as they develop.

The medical director of the liver transplant unit, Professor Peter Angus, said demand for adult transplants was growing due to increased incidence of liver diseases, including chronic hepatitis B and C.

While the extra surgical resources will help make the most of donor organs, Mr Andrews said Australia, with one of the lowest rates of donation in the developed world, also needed more donors.


Response at Week 8 Accurately Predicts Sustained Response to Pegylated Interferon plus Ribavirin for Hepatitis C

SUMMARY: Virological response to interferon-based therapy at week 8 is as likely to accurately predict which chronic hepatitis C patients will go on achieve sustained response as the usual 12-week stopping algorithm, according to a study published in the May 2010 Journal of Viral Hepatitis. Using this earlier cut-off for treatment discontinuation could spare patients the side effects and cost of additional futile therapy.

By Liz Highleyman

Early virological response (EVR) -- an HCV viral load decline of at least 2 logs 12 weeks after starting pegylated interferon plus ribavirin -- is typically used as a "stopping rule" to predict which hepatitis C patients are likely to achieve sustained virological response (SVR) as measured 24 weeks after completing treatment. Individuals who have not demonstrated significant viral load decline by week 12 are unlikely to do so later, and are often advised to discontinue therapy at this time.

E. Lukasiewicz and colleagues with the international DITTO-HCV Study Group performed an analysis to assess whether treatment response before week 12 would also accurately predict sustained response, thereby sparing patients additional weeks of futile therapy.

The investigators used a technique called longitudinal discriminant analysis to build and validate mathematical models that included patient characteristics and HCV RNA measurements at 4, 8, or 12 weeks of treatment. They calculated a partial area under the curve (PA) index for each time point, comparing their accuracy of prediction in the range of high negative predictive values.

  • Failure to achieve sustained virological response was best predicted before week 12 by a single HCV viral load measurement at week 8, together with patient sex, age, and body mass index (PA index 0.857).
  • The week 8 model was not inferior for predicting SVR compared with models that included a week 12 HCV RNA measurement (PA index 0.831).
  • The best model using only viral load measurements up to week 4, however, was inferior to the week 8 model (PA index 0.796).
These results, the study authors concluded, "indicate that lack of sustained viral response is best predicted after 8 weeks of treatment and that waiting until 12 weeks does not improve the prediction."

Investigator affiliations: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel; Faculty of Industrial Engineering and Management, Technion, Technion City, Haifa, Israel; Gertner Institute for Epidemiology, Sheba Medical Center, Tel Hashomer, Israel; Department of Virology, INSERM U635, Henri Mondor Hospital, University of Paris XII, Creteil, France; Department of Hepatology and Gastroenterology, University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands; Division of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Universitätsklinikum des Saarlandes, Homburg, Saarland, Germany.



E Lukasiewicz, M Gorfine, LS Freedman, and others (DITTO-HCV Study Group). Prediction of nonSVR to therapy with pegylated interferon-alpha-2a and ribavirin in chronic hepatitis C genotype 1 patients after 4, 8 and 12 weeks of treatment. Journal of Viral Hepatitis 7(5): 345-351 (Abstract). May 2010.


Asian Patients Respond as Well as Whites to Interferon-based Therapy for Chronic Hepatitis C

SUMMARY: Asian-American and white patients with genotype 1 or 2/3 chronic hepatitis C have a similar likelihood of achieving sustained response to pegylated interferon plus ribavirin, according to a California study described in the May 2010 American Journal of Gastroenterology. Investigators suggested that seemingly higher Asian response rates seen in previous studies were due to misclassifying easier-to-treat HCV genotype 6 as genotype 1.

By Liz Highleyman

It is well known that race/ethnicity influences response to interferon-based combination therapy for chronic hepatitis C virus (HCV) infection. Numerous studies have shown that people of African descent -- and possibly Hispanics/Latinos, though data less inconsistent -- do not respond as well as Caucasians; some research has found that Asians may respond better than any other group.

Philip Vutien from Stanford University Medical Center and colleagues compared sustained virological response (SVR) rates among Asian-American and Caucasian patients accurately classified as having HCV genotype 1 or genotypes 2/3 using viral core sequencing.

In some prior studies, Asian patients with genotype 6 -- which responds better to interferon -- were inaccurately classified as having genotype 1 using the less sensitive INNO-LiPA assay, leading to falsely high reported genotype 1 response rates. HCV genotype 6 is predominant in Southeast Asia but rare in the U.S. and Europe.

The researchers analyzed data from a cohort of 269 treatment-naive chronic hepatitis C patients with genotypes 1 or 2/3 treated with pegylated interferon plus ribavirin between 2001 and November 2007 at 4 community-based gastroenterology clinics in Northern California; 157 were Caucasian and 112 were of Asian descent.


Antivirals Are Poorly Tolerated, Largely Ineffective Against HCV After Liver Transplantation

Authors and Disclosures

Lara C. Pullen, PhD
President, Environmental Health Consulting, Oak Park, Illinois

July 13, 2010 (Hong Kong, China) — Results from a new study suggest that antiviral therapy should be used more judiciously in patients with hepatitis C virus (HCV) infection who have undergone liver transplantation.

Specifically, these patients should not be started on antiviral therapy in the first postoperative year unless there is clear evidence of histologic recurrence of HCV infection, investigator Michael Charlton, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, told attendees here at the International Liver Transplantation Society 16th Annual International Congress.

The most common indication for liver transplantation in North America is HCV-related end-stage liver disease. Most of these transplant recipients go on to experience virological recurrence, which is a major cause of morbidity and mortality. Cirrhosis is diagnosed in 20% to 40% of patients in the 5 years after transplantation, Dr. Charlton noted during an interview with Medscape Medical News.

"I think the study highlights the difficulties we face in treating HCV infection in liver transplant recipients with our current tools — peginterferon and ribavirin. Most patients don't tolerate treatment and most of those who do tolerate treatment don't respond to it."

In the PHOENIX study, the Mayo Clinic team looked at the safety, tolerability, and safety of prophylactic peginterferon alfa-2a plus ribavirin therapy after liver transplantation in 115 patients randomized to treatment (55 patients) or observation (60 patients) 10 to 26 weeks after transplantation. The mean age in the prophylaxis group was 51.0 years (range, 35 to 68 years) and in the observation group was 53.5 years (range, 38 to 66 years). Patients in the prophylaxis group received peginterferon alfa-2a (135 µg/week for 4 weeks followed by 180 µg/week for 44 weeks) and ribavirin (initially dosed at 400 mg/day and escalated to 1200 mg/day).

Dr. Charlton reported sustained virologic response in 22% of the patients in the prophylaxis group and 21% of those in the observation group, who were treated if histologic recurrence was demonstrated.

When analyzed at 120 weeks on an intent-to-treat basis, the frequency of histologically confirmed HCV recurrence was similar in both groups (P = .725).

Prophylactic antiviral therapy had no effect on patient or graft survival. Antiviral therapy was poorly tolerated, and only 55.6% of the prophylaxis group and 28.6% of the observation group were able to tolerate more than 80% of the intended antiviral dosing.

Dr. Charlton added: "I hope the results will provoke new studies of strategies to improve the tolerability and efficacy of posttransplant antiviral therapy. The near-term advents of IL28b testing and the addition of protease inhibitors are eagerly awaited."

Brian B. Borg, MD, MHSc, from the Ochsner Multi-Organ Transplant Institute in New Orleans, Louisiana, added that after liver transplantation, "patients are on multiple immune suppressive regimens, especially in the early posttransplant period, and are prone to other comorbidities making them less optimal candidates for treatment. The treatment response is not as good as in pretransplant patients and adherence to current combination therapy is poor because of side effects and potential complications." Dr. Borg is not affiliated with the study, but spoke with Medscape Medical News about the implications of the research.

Other transplantation centers have found alternative strategies for dealing with this problem. Luca Cicalese, MD, from the Texas Transplant Center at the University of Texas Medical Branch in Galveston, told Medscape Medical News that "at the Texas Transplant Center, we start treatment for hepatitis C after liver transplant only when there is evidence of active infection. We are also using a particular immunosuppressive protocol (to reduce the risk of rejection) that is particularly designed to reduce the risk of recurrence of hepatitis C posttransplant in our patients, which has drastically reduced such occurrence." Dr. Cicalese was not involved with the study.

Dr. Charlton's study was funded entirely by Roche/Genentech, the makers of peginterferon alfa-2a and ribavirin.
Dr. Borg and Dr. Cicalese have disclosed no relevant financial relationships.

International Liver Transplantation Society (ILTS) 16th Annual International Congress: Abstract 0-162. Presented June 19, 2010.