• Hepatitis Test Awaited in Taser Death

• Mullen: An Unusual Love Story Ends Sadly

• VCAM-1 Plays Central Role in the Pathogenesis of Vasculitis

• Cancer in Patients with Hepatitis C

• Fighting a Hidden Menace

• Canadian Scientists May Have Found why Hepatitis C Triggers Chronic Infection

• Hidden Epidemic of Hepatitis C Threatens to Overwhelm NHS with 500,000 Liver Patients

• Aethlon Medical to Initiate Hepatitis-C Trials

• Scientists Replicate Hepatitis C Virus in Laboratory

• Coagulation Tests Unlikely to Reflect Thrombin Generation in Cirrhosis

• Lamivudine for Hepatitis B with Advanced Fibrosis

• Taxpayers Stuck with Hepatitis Bills

• Roche's Pegasys Gets EU Approval for Chronic Hepatitis B Treatment

• Increased Risk of Hepatocellular Carcinoma with Transjugular Shunt

• FDA Approves Pegasys and Copegus as the Only Hepatitis C Treatment for HIV Patients

February 20th, 2005

Vaccine against Hepatitis E Soon: Scientist
SourceURL:http://news.newkerala.com/

[India News]: New Delhi, Feb 20 : Vaccine against hepatitis E virus, the most common cause of viral hepatitis in adults in India, may soon be possible with several samples being developed worldwide while one by US scientists has shown high degree of efficacy during trials, a researcher said here.

Successful vaccines for prevention of hepatitis A and hepatitis B, the two other important pathogens found in developing countries, have been developed and licensed and both have had an impact on the incidence of viral hepatitis when used appropriately, Robert H Purcell from the Laboratory of Infectious Diseases, US' National Institutes of Health (NIH) told a symposium on viral hepatitis.

"There is also need for A vaccine against hepatitis E. Candidate vaccines have been developed by expressing truncated forms of the virus coat proteins in bacteria or insect cells," he said. These vaccines use "highly conserved and highly imunogenic" region "ORF2" of virus.

"One recombinant hepatitis E vaccine has been developed by our laboratory. It has successfully completed pre-clinical trials in rhesus monkeys," he said.

It has advanced through phase II/II clinical trials and tested for efficacy by the US army in a field trial in Nepal, he said, adding the pre-clinical trials demonstrated that the vaccine has 100 per cent efficacy in monkeys.

The results of the human clinical trials have not been disclosed yet and are being analysed. But preliminary evidence suggests a high degree of efficacy for this vaccine, he said. PTI.

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Hepatitis Test Awaited in Taser Death
SourceURL:http://www.chron.com

Harris County officials are awaiting results from blood tests taken on a 52-year-old man who died after being shocked by a Taser gun late Friday.

Harris County Precinct 1 Constable deputies used the Taser while attempting to serve the man with a mental health commitment warrant. Joel Casey, 52, had been scheduled to enter a local drug and alcohol treatment facility when he struggled with deputies.

Houston Police Homicide Sgt. Mike Peters said the incident is under investigation.

The deputies were unaware the man had a history of heart problems and had Hepatitis B, Chief Deputy J.C. Mosier said.

"It is a tragedy," Mosier said Saturday. "We feel terrible about this."

Mosier said deputies tried to revive Casey, and administered mouth-to-mouth resuscitation. "Our deputies are very, very upset and also somewhat frightened," by Casey's reported case of hepatitis, Mosier said.

The blood test results will show whether that was true, he said, adding that the deputies relied on health information about Casey from the drug treatment center.

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Mullen: An Unusual Love Story Ends Sadly SourceURL:http://www.sltrib.com
By Holly Mullen, Tribune Columnist

Richard Bentley reaches into his hip pocket, pulls out a tattered leather wallet bulging with bits of notepad paper, receipts, a few dollar bills. He fumbles for a driver license that bears a photo of Rebecca Case Bentley, his wife of 26 years.

We are walking together late Friday near the campus for Salt Lake City's homeless population, at 200 South and 500 West. Richard has a bed at the men's homeless shelter until April 4. In her driver license picture, Rebecca is smiling. She has long brown hair and wears a clean denim shirt.

On the street, people know her as Becky. She and Richard were together one last time on the morning of Feb. 13. Becky had slept the night before at the overflow shelter across the street from Richard. He met her out front. They walked to the McDonald's at 210 W. 500 South for breakfast. They ate. Richard went to refill her coffee, and Becky used the restroom.

She died in there. A police report gives her age and few details. She was 45. When Richard ran in to try to revive her, Becky, he says, "was purple." Salt Lake City police Detective Dwayne Baird says a lifetime of drug addiction and related medical problems were the likely cause of death. An autopsy report is pending.

As a result of decades of intravenous drug use, Becky had hepatitis C. Richard, too. Heroin has been their drug of choice. Richard, who is 52, says Becky was fighting pneumonia before she died. One of her fingers was badly infected.

This is a love story of the street. People who live free of addiction may not understand it. The Bentleys' love was fueled by shooting drugs and shared hopelessness. It did not start that way.

"I met Becky one week before her 19th birthday. She was a nice girl," Richard says. "She spent a lot of time as a girl with her cousins in Altamont, near Roosevelt. She loved it there.

"We were co-dependent together, that's for sure," Richard tells me. "But we loved each other, too." His eyes are moist. Minutes after Becky's death, he says, "I told her, 'Your suffering is over. I'll get myself better and join you someday.' I just spoke from my heart."

They made three children together. Richard had been a diesel mechanic's apprentice. Becky was a community college student. They smoked marijuana and drank a bit. Richard says both were gateway drugs. He started using heroin. A couple of years later Becky wanted to join him. Richard says he tried to talk her out of it.

"She did it anyway. The last 15 years have been turmoil."

In 1991 the Bentleys' parental rights were terminated. Their children, ages 11, 6 and 1 at the time, were adopted. Richard has not spoken to them since.

Anyone who works or lives among the homeless knows Richard and Becky Bentley. They worked  street corners and parking lots, holding signs and panhandling change. They combined their proceeds. Some days, they made up to $100, which Richard says covered both their habits for one day.

It became about staying well. Always. Shortly after an addiction takes hold, shooting up is no longer about getting high. It's about trying not to be sick, preventing nausea and vomiting and joint and muscle aches and a body wracked with chills.

This is why a homeless woman dying in a fast-food bathroom holds no mystery for Ed Snoddy.

"We know someday a person like Rebecca is just not going to wake up," says Snoddy, who drives a homeless outreach van for Volunteers of  America. "Our mission is just to make their journey a little softer."

Richard bought Becky a long black skirt, pink blouse and butterfly jewelry for her burial. Her body will rest in the Altamont town cemetery.

"Someday," Richard says, "I'll be buried next to her."

hmullen@sltrib.com

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February 22nd, 2005

VCAM-1 Plays Central Role in the Pathogenesis of Vasculitis
SourceURL:http://www.gastrohep.com

Findings in February’s issue in the Journal of Hepatology indicate that vascular cell adhesion molecule-1 is mainly involved in the pathogenesis of Hepatitis C mixed cryoglobulinemia vasculitis and may be a potential therapeutic target.

Dr Kaplanskiab and colleagues from France aimed to better characterize the molecules involved in leukocyte tissue infiltration during Hepatitis C-mixed cryoglobulinemia associated vasculitis.

The researchers evaluated the involvement of endothelial cell leukocyte adhesion molecule-1, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1.

The team included 36 patients with Hepatitis C- mixed cryoglobulinemia associated vasculitis.

The investigative team used 3 different approaches including ELISA analysis, and tissue expression by immunohistochemistry on patients nerve biopsies.

There are elevated concentrations of soluble vascular adhesion molecule-in patients with Hepatitis C mixed cryoglobulinemia vasculitis – Journal of Hepatology

The investigators also used endothelial expression by analysis on cells activated in vitro by cryoprecipitates purified from patients with Hepatitis C mixed cryoglobulinemia associated vasculitis.

The researchers found elevated concentrations of soluble vascular adhesion molecule-in patients with Hepatitis C mixed cryoglobulinemia vasculitis compared to Hepatitis C vasculitis patients without mixed cryoglobulinemia, with the highest concentrations in severe vasculitis.

The researchers detected vascular cell adhesion molecule-1 expression on blood vessels from nerve biopsies performed in patients with severe vasculitis.

The investigators found that cryoprecipitate induced vascular cell adhesion molecule-1, endothelial cell leukocyte adhesion molecule-1 and intercellular cell adhesion molecule-1 expression in patients with Hepatitis C mixed cryoglobulinemia vasculitis when added to endothelial cells in vitro.

The team thought this was possibly through a mechanism due to the C1q complement fraction interaction with endothelial cells.

Dr Kaplanskiab reports that, “Vascular cell adhesion molecule-1 is mainly involved in the pathogenesis of Hepatitis C mixed cryoglobulinemia vasculitis associated severe vasculitis and may be a potential interesting therapeutic target.”

Journal of Hepatology 2005: 42(3): 334-340

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Cancer in Patients with Hepatitis C
Source: www.eurekalert.org

Association noted between certain non-liver cancers and hepatitis C in Sweden

People infected with the hepatitis C virus (HCV) have a higher risk of developing non-Hodgkin's lymphoma and multiple myeloma, according to a recent study of the Swedish population. These findings are published in the March 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc, the journal is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

Previous studies have shown that people with HCV have a higher risk of developing cirrhosis and liver cancer, however, studies of the association between HCV and other malignancies have yielded varied and conflicting results. In Sweden, a cluster of four cases of non-Hodgkin's lymphoma in 554 HCV patients raised the question of an association between those two diseases and other related cancers in the country's population.

To evaluate this possibility, researchers, led by Ann-Sofi Duberg of Örebro University Hospital in Sweden, gathered data from the Swedish Institute for Infectious Disease Control and the Swedish Cancer Registry to examine the incidence of non-Hodgkin's lymphoma, multiple myeloma, chronic lymphatic leukemia, acute lymphatic leukemia, Hodgkin's lymphoma and thyroid cancer in the country's entire cohort of HCV patients.

For 27,150 HCV patients, the researchers modelled the date of HCV infection based on age and mode of transmission. They then collected data on the relevant cancer diagnoses among these patients for the time period from 1990 to 2000, excluding those whose HCV diagnosis was within 3 months of their cancer diagnosis. Lastly, they performed statistical analyses to compare these patients' cancer rates to those of the entire Swedish population.

They found that the risk of both non-Hodgkin's lymphoma and multiple myeloma were significantly higher compared to the general population ­ 1.99 and 2.54 times higher, respectively. Their risk of chronic lymphatic leukemia and thyroid cancer were not significantly higher, and the incidence of both acute lymphatic leukemia and Hodgkin's lymphoma was too low to be included.

"The majority of the non-Hodgkin's lymphoma and multiple myeloma patients were estimated to have been infected more than 15 years, which is consistent with the theory that lymphomagenesis is a slow process and non-Hodgkin's lymphoma develops after a long influence," say the authors. They suggest that the risk for HCV-related malignancy increases with time of HCV infection.

As in many countries, Sweden has had an increase in the incidence of malignant non-Hodgkin's lymphoma in recent years. As most Swedish HCV patients were born after 1950, the cancer increase might be related to long-lasting HCV infection.

In conclusion, "this is the first study of the incidence of non-Hodgkin's lymphoma, multiple myeloma, chronic lymphatic leukemia, acute lymphatic leukemia, Hodgkin's lymphoma and thyroid cancer in a nationwide cohort of HCV-infected persons," the authors report. "Although the delayed diagnosis of hepatitis C most probably has made us underestimate the risk, this study showed that the risk of B-cell non-Hodgkin's lymphoma and multiple myeloma were significantly increased."

Article: "Non-Hodgkin's Lymphoma and Other Nonhepatic Malignancies in Swedish Patients With Hepatitis C Virus Infection," Ann-Sofi Duberg, Marie Nordström, Anna Törner, Olle Reichard, Reinhild Strauss, Ragnhild Janzon, Erik Bäck, and Karl Ekdahl, Hepatology; 41:3; March 2005 (DOI: 10.1002/hep.20608).

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Fighting a Hidden Menace SourceURL:http://www.northjersey.com
By ABIGAIL LEICHMAN, STAFF WRITER

Delores Cox swallows two pills each morning and three at night. Once a week, she gets an injection. She's been on this regimen since August, hoping that it will keep her liver from succumbing to the deadly effects of the hepatitis C virus she contracted years ago.

Hepatitis C is the most common blood-borne viral infection in the United States and the leading cause of chronic liver disease and liver transplants. Somewhere between 4 million and 5 million Americans are infected, with 30,000 new infections occurring yearly - about 3,000 of them in New Jersey.

"A large number of people have this potentially serious disease and don't know it," said Dr. George Abdelsayed, director of the Hepatitis C Clinic at Barnert Hospital in Paterson. "We're not even treating 250,000 of them. We obviously have a lot of work to do, finding and treating and educating."

That's not easy. Because the virus quietly does its damage over 20 to 30 years, most people don't suspect they have chronic liver disease until it's nearing its last stages.

Resources:

• Hepatitis C Clinic at Barnert Hospital, Paterson, (973) 977-6736 or (973) 977-6657.

• Hepatitis Treatment Center at Hackensack University Medical Center, (201) 996-3196.

• Hepatitis C support group at Christ Hospital, Jersey City, (201) 795-1230.

• Hepatitis support group at Mountainside Hospital, Montclair, (973) 429-6856.

• Hepatitis C Association in Scotch Plains, (866) 437-4377, offers educational programs and online emotional support for patients and caregivers (hepcassoc.org).

• Hepatitis Help Line Call Center, (800) 522-HEPC (Monday through Friday).

• Hepatitis C Caring Ambassadors Program, (877) 737-4372. Studies alternative therapies to complement medical treatment and handle its side effects. The third edition of "Hepatitis C Choices" is available for free download at hepcchallenge.org.

• National Hepatitis C Advocacy Council, hepcnetwork.org.

"If you got infected in 1970, you may not have started to show symptoms till the '90s," Abdelsayed said. "In many cases, you find successful, middle-aged people with hepatitis C that they contracted from a needle they used in college, from getting a tattoo, or from snorting cocaine." Most cases are discovered during routine blood tests.

As the disease progresses, its signs include extreme fatigue, muddled thinking and problems with hand-eye coordination. Eventually, untreated liver disease leads to bleeding, coma and death. In the late stages, treatment may not work.

But if it's caught early enough, the infection can be wiped out in about 70 percent of cases, and treatment also reduces the risk of liver cancer by 80 percent. "We don't have a magic bullet, but we do cure it better than we did before," said Abdelsayed.

The course of treatment, which lasts six months to a year, consists of weekly injections of pegylated interferon and daily oral doses of ribavirin. Abdelsayed said some patients resist treatment because they've heard the medications can cause unpleasant side effects including depression - which can be managed with antidepressants - and don't always get rid of the virus.

"People are waiting for better therapies, but I can tell you we are looking at a minimum of five to 10 years before that will happen," he said. "If you get treatment and you don't hit a home run, you're still a winner, because it will slow the progression."

Cox, 52, declined treatment when Abdelsayed diagnosed the disease a couple of years ago. "At first, I didn't feel comfortable with the idea of the shot," she said.

But after learning more about the disease and the medications, she has become what Abdelsayed calls an ideal patient. "She has incredible determination and willpower," he said, "because she understands the consequences of non-treatment."

Advocates across the country are hoping to reach many more potential patients like Cox. In December, Congress hosted hearings to assess its efforts since 1998, when hepatitis C was first recognized as an epidemic. Advocates are hoping legislators will pass a 2003 initiative that would fund a federal program for hepatitis C counseling, testing, surveillance, education, training and research.

Already, the Centers for Disease Control and Prevention has placed hepatitis C coordinators at every state health department. In New Jersey, nurse-practitioner Sandra Van Sandt took that position a year and half ago. She has been developing recommendations for educating health-care providers and the public.

"One thing we'd like is to provide programs for internists and family practitioners so that they can educate and test [at-risk] patients," she said.

Experts say much more needs to be done. "The hepatitis C crisis poses a grave threat to the public health of Americans," said Dr. Tina St. John, medical director of the Hepatitis C Caring Ambassadors Program. "Dire long-term consequences of this crisis must be addressed immediately at the federal level with dedicated funding and a workable plan of action."

E-mail: leichman@northjersey.com

What is hepatitis?
Hepatitis is an inflammation of the liver, a vital organ that rids the body of toxins, metabolizes drugs and produces proteins and blood-clotting factors. If hepatitis progresses to the chronic stage, it can lead to cirrhosis (scarring) of the liver or liver cancer. Hepatitis A, B and C are caused by three different viruses.

Hepatitis A

• Most commonly spread through: Contaminated food or water.

• How serious: It does not lead to chronic liver disease and generally resolves within a couple of months without treatment.
• How many infected each year: About 150,000, 150 in New Jersey.
• Vaccine: Yes, recommended for people visiting countries with poor sanitation or in high-risk professions (such as day-care workers).
• Prevention: Wash hands with soap and water after using the bathroom; avoid eating undercooked shellfish and drinking untreated water.

Hepatitis B

• Most commonly spread through: Intravenous drug use and sex with multiple partners.
• How serious: Most cases resolve themselves, but treatment with interferon or lamivudine for chronic liver disease is needed in about 10 percent of cases.
• How many infected each year: 200,000 Americans, 200 in New Jersey.
• Vaccine: Yes; required since 2001 for all New Jersey schoolchildren.
• Prevention: Avoid sharing toothbrushes, razors, needles and other personal care items.

Hepatitis C

• Most commonly spread through: Intravenous drug use.
• How serious: About 85 percent of those infected will develop chronic liver disease and need medical treatment. Liver failure caused by chronic hepatitis C infection is the leading cause of liver transplants in the United States. Hepatitis C leads to 8,000 to 10,000 deaths per year.
• How many infected each year: 30,000 Americans, 3,000 in New Jersey. Between 4 million and 5 million Americans are infected.
• Vaccine: No.
• Prevention: Avoid sharing toothbrushes, razors, needles and other personal care items; avoid intravenous drugs or those inhaled through a straw or sharp object that can break the skin; use only reputable practitioners for tattooing or body piercing.
• Determine if you should be tested

Who should be tested for hepatitis C?

The Centers for Disease Control and Prevention and the New Jersey Health Department recommend that these individuals be tested for hepatitis C infection:

• Anyone who injected illegal drugs, even once or a few times many years ago.
• Anyone who was ever on long-term hemodialysis, received clotting factor concentrates produced before 1987 or has persistently abnormal liver tests.
• Anyone who received a transfusion or organ transplant prior to July 1992.
• Health-care, emergency medical and public-safety workers after needle sticks or mucosal (eye or mouth) exposures to hepatitis C-positive blood.
• Children born to hepatitis C-positive women.
• Veterans of the U.S. armed forces.
• Women who underwent a Caesarian section or premature delivery before 1990.
• People who have received invasive cosmetic procedures, including piercing and tattooing.
• People with a history of multiple sexually transmitted diseases or multiple sex partners.

Canadian Scientists May Have Found why Hepatitis C Triggers Chronic Infection SourceURL:http://www.canada.com
Helen Branswell, Canadian Press

TORONTO (CP) - A team of Canadian researchers believes it has unravelled the mystery of how hepatitis C evades the human immune system to cause chronic disease in about three-quarters of the people who become infected.

Their discovery provides a bright ending to the personal tragedy of the hepatitis C patient whose blood they studied, a man who became infected through a medical error in a hospital clinic.

The researchers report that the virus escapes detection because its external coat mimics immunoglobulin, one of the immune system's warriors. Further, the virus may evolve to maintain or improve its camouflage as time goes on, they suggest.

Because the immune system is set up to attack only things it considers foreign, it does not attempt to destroy the virus.

"If you want to hide in a forest, it's often good to look like a tree," explained Dr. Earl Brown, a virologist at the University of Ottawa and senior author of the paper.

The team came to its conclusions by studying blood drawn from the first infected blood donor caught by heightened screening methods put in place after Canada's tainted blood scandal. The man was so newly infected with hepatitis C that his immune system hadn't yet responded to it. As a consequence, the scientists were able to chart that response over time.

"We watched it (the virus) walk into the forest," Brown said, continuing with his metaphor.

The blood donor had become infected in an Alberta hospital in the spring of 2000 while receiving intravenous antibiotics. Now living in southeastern British Columbia, he's pleased his misfortune may help science figure out how to foil the virus.

"It was such a bizarre sequence of events that I wanted to see some good come out of it," said Randy, 47, who asked that his surname not be made public.

"This might be something that could potentially lead to a cure or a better treatment for a lot of people. And that kind of drives you along on this," said Randy, who was cleared of infection in 2003 after two courses of treatment with expensive anti-viral drugs.

However, Brown said the findings - reported in this week's issue of the journal Virology - suggest a vaccine for hepatitis C may be an elusive, even dangerous target that could backfire by prompting the immune system to attack itself.

The team, which also involves scientists from Canadian Blood Services and the Alberta provincial laboratory of public health, compared the genetic codes for the virus's envelope with those of some components of the immune system, finding areas where the virus appeared to be mimicking the body's defenders.

The findings will influence future research into not just hepatitis C but other viruses that don't provoke an extended immune response, Brown said.

"It's going to change the way (scientists) think in hepatitis C (research) for sure, and probably a bunch of other diseases. It's impossible for it not to."

Others interpreted the findings more cautiously.

"It's an intriguing hypothesis but I think at this point it's really only a hypothesis," said Dr. Jake Liang, chief of the liver diseases branch of U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Liang, an expert in viral hepatitis, said the study was well done. But he and others believe the whole notion of viral "mimicry" is overhyped.

"A lot of these hypotheses are based on very weak evidence. It does have some appeal to it. Sounds good. But very few of them have ever been proved to be causal," Liang said.

Dr. Mel Krajden of the British Columbia Centre for Disease Control said he doubted the mechanism identified is the full answer to why some hepatitis C infections become chronic.

"I'm sure it's more complex than just this," said Krajden, who heads the centre's hepatitis service.

It is estimated that about 240,000 Canadians are infected with hepatitis C, which causes inflammation of the liver that can lead to cirrhosis or liver cancer.

It spreads from person to person via contact with infected blood. Shared drug paraphernalia - needles, pipes and straws - are currently the main vehicle of transmission, though prior to changes in blood screening methods, blood transfusions were also a key source of infection. The virus can also be transmitted during sex with an infected person, although the risk is low.

In about 20 or 25 per cent of cases, people will spontaneously clear the virus. The remainder are chronically infected, though treatment with anti-viral drugs appears to cure some - though not all - cases.

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February 23rd, 2005

Hidden Epidemic of Hepatitis C Threatens to Overwhelm NHS with 500,000 Liver Patients SourceURL:http://news.independent.co.uk/
By Maxine Frith, Social Affairs Correspondent

Britain is facing an epidemic of hepatitis C, with the number of cases likely to be double that of official estimates, The Independent has learnt.

More than 500,000 people in the UK may be infected with the virus, a study by doctors at Southampton University has found. Experts said that the government figure of 250,000 cases was a "gross underestimate", and warned that the NHS was facing a time-bomb of potentially fatal liver disease as a result of ministerial failures to tackle the problem.

Professor William Rosenberg, a liver disease expert at Southampton University, said: "We are seeing twice the number of cases that we would expect if the official estimates were right.

"The tragedy is that if nothing is done, in the next 10 or 20 years we are going to end up with tens of thousands of people needing liver transplants, with hospital wards overflowing with patients with end-stage, untreatable disease and liver cancer. The cost to the NHS and public health could be absolutely disastrous."

Hepatitis C is a blood-borne virus that causes inflammation and damage to the liver.

The majority of people experience no symptoms for many years, but an estimated 30 per cent of patients will develop fatal cirrhosis of the liver if the disease is left untreated for more than 20 years. New drugs for hepatitis C have up to a 90 per cent cure rate, yet less than 1 per cent of infected people have access to them.

Government figures, supplied by the Health Protection Agency (HPA) and based on random testing of blood samples in hospitals, have assumed that 250,000 people in the UK are infected with the disease.

But experts say that the HPA estimates do not accurately reflect the large number of people who would be considered at "high risk" of infection.

The main causes of infection are through intravenous drug use, dirty tattooing kits and contaminated blood products prior to 1991, when screening was introduced.

Professor Rosenberg said: "The problem is that many people look at these risks and don't think it applies to them. But there is a huge cohort of people who 20 or 30 years ago may have dabbled in drugs, even just once at a party, who could be infected.

"They are judges, businessmen, lawyers. They are the ones who could have had the virus for 20 or 30 years now and could soon start developing end-stage liver disease."

Professor Rosenberg said that because the HPA estimate is based solely on random testing of blood samples in hospitals, it is not representative of the scale of high-risk groups.

Testing of hospital blood samples does not take into account the high rates of infection among drug users, who tend not to use health services, as well as ignoring the fact that the majority of those infected are otherwise healthy and often have no need to visit a hospital.

The statistical modelling by the Southampton University team used new estimates of high-risk groups, including current drug users, prisoners and people who have previously experimented with intravenous drugs. The figure tallies with the most comprehensive study of hepatitis C prevalence, carried out in France, which estimated that about 1.2 per cent of the general population was infected, compared with the 0.4 per cent assumed by the HPA.

Out of the estimated 500,000 infections, just 60,000 people have been diagnosed and only 3,000 are receiving treatment.

Almost 6,000 new cases are diagnosed each year, and last year the Government launched a hepatitis C strategy to tackle the issue and raise public awareness of the virus.

Charles Gore, chief executive of the Hepatitis C Trust, said: "There is a firestorm that is starting to brew in hepatitis C and nothing is being done about it. The Government promised a big campaign but we have seen very little action. I am extremely disappointed, and very concerned that we are going to be engulfed by an epidemic of liver disease very soon."

The Department of Health insisted yesterday that it was taking the issue seriously.

A spokeswoman said: "Our hepatitis C awareness-raising campaigns for health professionals and the public are in their early stages.

"We will evaluate progress and review whether the scope of the campaign needs to be extended.

"Current information suggests that the current level of chronic hepatitis C infection is around 0.4 per cent of the population, or about 200,000 people. This estimate has been made by the Health Protection Agency, which provides authoritative advice on infectious diseases and co-ordinates national surveillance".

Public health experts are concerned that the stigma surrounding hepatitis C and a widespread assumption that it is a "low-life" disease discourage people from seeking a test. They want a campaign on the scale of the HIV/Aids health warnings in the 1980s to publicise the threat.

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Aethlon Medical to Initiate Hepatitis-C Trials SourceURL:http://biz.yahoo.com/

Clinical Programs in India to Be Managed in Conjunction with HIV/AIDS Studies

SAN DIEGO--(BUSINESS WIRE)--Feb. 23, 2005--Aethlon Medical, Inc. (OTCBB:AEMD - News) announced today that it plans to initiate clinical trials to treat patients infected with the Hepatitis-C Virus (HCV) in India. According to the World Health Organization, HCV is a global disease with approximately 170 million persons or 3% of the world's population infected. It is estimated that up to 50% of the infected population is not responsive to treatment with current drug regimens.

Sunil Sawhney, the former Director of Boston Scientific India, and other regulatory advisors from Qualtran, LLC will manage the HCV trials in India, as well as trials related to the treatment of HIV, the AIDS virus. Site selection for both trials is underway, and patient enrollment is expected to begin in the coming months.

Aethlon CEO James A. Joyce stated, "Initiating studies to treat humans infected with Hepatitis-C is a natural progression of our science. Especially when considering the pre-clinical evidence that our Hemopurifier(TM) treatment technology has multi-pathogen binding capabilities, including the simultaneous capture of both HCV and HIV from the blood of infected patients."

About Aethlon Medical

Aethlon Medical is pioneering the development of viral filtration devices to treat HIV/AIDS, Hepatitis-C (HCV), and pathogens that are mass casualty biological warfare candidates. Each treatment application employs the use of a proprietary technology known as the Hemopurifier(TM), which is designed to rapidly reduce the presence of infectious disease and toxins in the body. The Hemopurifier converges the established scientific principals of affinity chromatography and hemodialysis as a means to augment the immune response of clearing viruses and toxins from the blood before cell and organ infection can occur. More information on Aethlon Medical and the Hemopurifier technology is available at www.aethlonmedical.com.

Certain of the statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the ability of the Company to obtain FDA and other regulatory approvals permitting the sale of its products, the Company's ability to manufacture its products and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings.

Contact:
Aethlon Medical, Inc.
James A. Joyce, 858-459-7800 x301
jj@aethlonmedical.com

or

Investor Awareness, Inc.
Tony Schor/Kevin Dudley, 847-945-2222
info@investorawareness.com

Source: Aethlon Medical, Inc.

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Scientists Replicate Hepatitis C Virus in Laboratory SourceURL:http://www.eurekalert.org

New in vitro model system will allow study of therapeutics and virus life cycle

For the first time, scientists have replicated hepatitis C virus (HCV) in the laboratory. The ability to replicate HCV in cell culture will allow researchers to better study the life cycle and biology of this virus and to test potential antiviral compounds, which may lead to new therapies for the liver disease that results from infection with HCV. Scientists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the National Institutes of Health (NIH), conducted the study, which appears in the Feb. 15, 2005 issue of Proceedings of the National Academy of Sciences (PNAS).

"Until recently, research on this infectious disease has suffered from the lack of a robust in vitro model system," says T. Jake Liang, M.D., Chief of the Liver Diseases Branch of the NIDDK and co-author of the study. "Our model system produced viral particles that have all the properties of the whole virus. This evidence together with an analysis of the replicated viral RNA supports a conclusion of viral replication and production."

The NIDDK group used a strain of HCV that would have applications to the greatest number of people – genotype 1, the major type of HCV of human infections worldwide and the type most resistant to current therapies. They constructed an HCV replica using a DNA copy of the original HCV single-strand RNA genome. They placed the DNA copy between two ribozymes, RNA molecules that have enzymatic function and can cleave RNA sequence at specific locations. These two ribozymes were designed to generate the correct ends of the HCV genome and to act as start and stop buttons to gene activity. The construct was "naked," meaning that it contained only nucleic acids, the genetic material of the virus, and did not have the HCV viral envelope, a protective shell of lipids and proteins that surrounds the viral RNA in fully-formed HCV. The naked HCV construct was then placed into human liver cells in a cell culture medium.

The NIDDK scientists found evidence of HCV proteins and HCV RNA within the human liver cells in the culture. Electron microscopy showed evidence of high levels of viral particles resembling fully-formed HCV outside of the human liver cells in the culture medium. The researchers believe that the HCV construct contained within the human liver cells behaved like a true HCV infection by producing fully formed copies of the virus and releasing them from the host cell into the culture medium. Further testing is needed before the researchers can determine if the viral particles produced in this system are in fact infectious. Also, this system only represents the tail end of the viral life cycle—viral replication, assembly and release from host cells. Another HCV model system is needed to show the beginning stages of the viral life cycle—viral entry into host cells and viral activity in the host cell before replication.

"With this cell-based system, we can screen compounds with a cell-based assay to look for inhibitors of virus replication," says Liang. "We can also apply this technique to develop model systems for other similar viruses."

HCV is a small, enveloped, single-stranded RNA virus in the family Flaviviridae. HCV is a major cause of liver disease in the United States and the world. One in a series of hepatitis viruses, HCV accounts for about 15 percent of acute hepatitis cases, 60 to 70 percent of chronic hepatitis cases, and up to 50 percent of cases of cirrhosis, end-stage liver disease, and liver cancer. Almost 4 million Americans, or 1.8 percent of the U.S. population, have antibodies to HCV indicating ongoing or previous infection with the virus. Approximately 10,000 to 12,000 deaths each year in the United States are due to HCV.

Heller, Theo; Jonathan Auerbach; Tarice Williams; Tzivia Rachel Moreen; Allison Jazwinski; Brian Cruz; Neha Jeurkar; Ronda Sapp; Guangxiang Luo; and T. Jake Liang. "An in vitro model of hepatitis C virion production." Proceedings of the National Academy of Sciences, Vol. 102, No. 7, pp. 2579-2583.

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February 24th, 2005

Coagulation Tests Unlikely to Reflect Thrombin Generation in Cirrhosis SourceURL:http://www.gastrohep.com

Findings in March’s issue of Hepatology show that bleeding in patients with cirrhosis is mainly due to the presence of hemodynamic alterations so that conventional coagulation tests are unlikely to reflect the coagulation status of these patients.

Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests

The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear, partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo.

Conventional coagulation tests include prothrombin time and activated partial thromboplastin time.

Dr Tripodi and colleagues from Italy propose that these are inadequate to explore the physiological mechanism regulating thrombin, because they do not allow full activation of the main anticoagulant factor, protein C, whose levels are considerably reduced in cirrhosis.

The researchers used a thrombin generation test to investigate the coagulation function in patients with cirrhosis.

Reduced procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, leaving the coagulation balance unaltered. – Hepatology

The team showed that thrombin generation without thrombomodulin was impaired, which is consistent with the reduced levels of procoagulant factors typically found in cirrhosis.

However, when the test was modified by adding thrombomodulin, the protein C activator operating in vivo, patients generated as much thrombin as controls.

Hence, the team observed that the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, leaving the coagulation balance unaltered.

The researchers found these results to help clarify the pathophysiology of hemostasis in cirrhosis.

In addition, the researchers suggested that bleeding is mainly due to the presence of hemodynamic alterations.

The team also noted that conventional coagulation tests are unlikely to reflect the coagulation status of these patients.

Dr Tripodi concluded, “Generation of thrombin is normal in cirrhosis.”

“For a clinical validation of these findings, a prospective clinical trial is warranted where the results of thrombin generation in the presence of thrombomodulin are related to the occurrence of bleeding.”

Hepatology 2005: 41(3): 533-558

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Lamivudine for Hepatitis B with Advanced Fibrosis SourceURL:http://www.rednova.com/

Clinical Question: Is lamivudine safe and effective for the treatment of hepatitis B infection in patients with advanced liver disease?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: The authors identified adults with chronic hepatitis B infection who were hepatitis B e antigen (HBeAg) positive or HBeAg negative with detectable hepatitis B virus DNA and who had histologic evidence of advanced liver fibrosis (i.e., an Ishak fibrosis score of 4 or more on a scale of 0 to 6). Exclusion criteria included hepatocellular carcinoma, a serum alanine transaminase level more than 10 times the upper limit of normal, hepatic failure, autoimmune hepatitis, co-infection with hepatitis C or human immunodeficiency virus, anemia, leukopenia, and thrombocytopenia. Allocation appeared to have been concealed through a central randomization process (although no details were given), and analysis was by intention to treat. Outcomes were assessed by a committee masked to treatment assignment. Most of the patients were men (85 percent) and almost all were Asian.

Participants were randomized to receive lamivudine in a dosage of 100 mg per day (n = 436) or placebo (n = 215) and were supposed to be followed for five years. However, the study ended prematurely once the benefit of lamivudine become apparent. The primary end point was a combined outcome called "time to disease progression," and included an increase in the Child-Pugh score of two or more points, spontaneous bacterial peritonitis with sepsis, renal insufficiency, variceal bleeding, hepatocellular carcinoma, or death caused by liver disease.

After a median treatment duration of 32 months, 34 patients in the lamivudine group and 38 patients in the placebo group had reached the primary combined end point (7.8 versus 17.7 percent; P = .001; absolute risk reduction = 9.9 percent; number needed to treat [NNT] = 10). Most of the benefit was attributed to fewer patients with an increased Child-Pugh score (3.4 versus 8.8 percent; P = .02; NNT = 18) and fewer cases of hepatocellular carcinoma (3.9 versus 7.4 percent; P = .05; NNT = 29). After reaching an end point, patients had the option of receiving lamivudine during an open- label continuation phase of the study.

During the double-blind phase, two deaths occurred in the lamivudine group compared with none in the placebo group. Serious adverse events were similar between groups (12 percent for lamivudine versus 18 percent for placebo; P = .09). However, when the open-label phase of the trial is included, more deaths occurred in the lamivudine group (12 versus four; statistical significance not reported). Approximately one half of the patients in the lamivudine group developed the YMDD mutation during treatment, thought to be caused by lamivudine. These patients were more likely to reach the primary end point than those who remained negative (11 versus 4 percent) and were more likely to die of hepatocellular carcinoma, but they still did better than patients receiving placebo.

Bottom Line: For every 10 patients with chronic hepatitis B infection and advanced liver disease who take lamivudine instead of placebo for 2.5 years, one fewer patient experiences progression of liver disease. Long-term use of lamivudine often triggers the YMDD mutation, and the benefit is attenuated in these patients. (Level of Evidence: 1b)

Study Reference: Liaw YF, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med October 7, 2004;351:1521-31.

Source: American Family Physician

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Taxpayers Stuck with Hepatitis Bills SourceURL:http://www.omaha.com
BY NICHOLE AKSAMIT, WORLD-HERALD STAFF WRITER

Who ultimately will pay for the largest hepatitis C outbreak of its kind in the United States?

Hold onto your wallet and hope for good health. If you receive medical services, provide health care or pay taxes in Nebraska, it may be you.

As many as 63 of the 92 malpractice lawsuits related to the 2000-01 outbreak in Fremont, Neb., have been settled. Details are sealed under a judge's order, but there's little doubt that damages will total in the millions.

The lawsuits involve dozens of cancer patients who contracted hepatitis C while undergoing chemotherapy. At least one died after developing liver disease.

But Dr. Tahir Javed - the oncologist whose clinic was linked to 99 hepatitis C infections, who lost his Nebraska and New York medical licenses and was named in all those lawsuits - is serving as a provincial minister of health in his native Pakistan and probably won't pay a dime.

Based on how malpractice cases typically are handled in Nebraska, L. Tim Wagner, director of the Nebraska Department of Insurance, said any settlements or jury awards would come from malpractice insurance companies and from the state-administered Excess Liability Fund, which functions as a sort of supplemental insurance.

A Lancaster County District Court judge ruled in October that Javed is not personally liable for damages above his malpractice insurance limits and under the state's liability cap.

So, where do Nebraskans' health and wallets come in?

Malpractice insurance companies and the Excess Liability Fund are supported by fees paid by health care providers and facilities.

The approximately 80 percent of Nebraska health providers who participate in the fund have to buy more malpractice insurance this year because legislators upped the requirements - a move intended to bolster the fund and prompted in part by the Javed cases.

More coverage means most doctors are paying higher premiums and larger payments to the fund. And higher overhead for them could mean higher costs or reduced services for you.

"I don't know that the medical community can simply absorb those costs," Wagner said.

Sandy Johnson, executive vice president of the Nebraska Medical Association, said doctors usually aren't able to pass extra costs directly to patients because patients' insurance companies reimburse doctors at set rates.

Dr. Peter Whitted, an Omaha ophthalmologist and attorney who heads the Nebraska Medical Association's professional liability committee, said the resulting squeeze on doctors interferes with the quality of and access to care for patients.

"It's getting tougher to make ends meet (as a physician)," he said. "To make an office go, you've got to see so many more patients. You can't spend as much time with each one."

He said higher overhead cost may prompt doctors to stop performing procedures that aren't adequately reimbursed or steer more toward private-pay patients. It also means fewer people may choose to enter the profession.

"Ultimately, we pay in an indirect way," said Whitted. "When your mom gets sick, you don't get the kind of care you need."

And then there's Medicaid and Medicare - tax-supported programs for the elderly, the poor and the disabled that help with medical bills that exceed court-approved damages.

"If you don't get enough settlement because you have a cap on damages, then the money's got to come from someplace for medical expenses," said Dan Cullan, the Omaha doctor and trial lawyer who won one of the state's largest malpractice awards.

"The taxpayers are going to get stuck for the difference through Medicare or Medicaid. And then there will probably be some private insurance companies that get stuck for it, too."

In the final analysis, said Wagner, the public pays.

"Javed will not pay from his personal accounts. The nurses will not pay from their private accounts. In all likelihood, the hospital will not pay from its personal accounts," he said.

"It's a system, and the system pays. And the public is part of the system."

Nebraska's hepatitis C malpractice cases

How much money?

Estimate of medical bills: Patients' situations vary widely, but an attorney representing several said in 2003 they faced a minimum of $100,000 each; $100,000 x 92 patients = $9.2 million.

Maximum settlements: $1.25 million (legal cap for each defendant who participated in the Excess Liability Fund) x 92 cases x 3 main defendants = $345 million

Average claim paid by the fund: $312,000 x 92 cases x 3 defendants = $86.1 million

Change in the fund so far: About $17 million more in "anticipated liabilities" now than before the Javed cases.

Who pays directly?

Malpractice insurance companies for defendants: Up to $200,000 per incident or $600,000 a year for an individual or $200,000 per incident and $1 million a year for a hospital.

The Excess Liability Fund: Up to $1.25 million per defendant, less the amount paid by malpractice insurance.

Medicaid, Medicare and private health insurers, which may cover some medical expenses in cases for which settlements don't cover the bills.

Who pays indirectly?

Health care providers who are members of the fund. They paid an estimated $34 million in malpractice premiums and excess liability fees in 2004. They will pay 30 percent to 50 percent more this year - a result of inflation and legislative changes prompted in part by the hepatitis cases.

Patients, who may receive less face time with doctors, have access to fewer procedures and pay higher insurance premiums to help offset costs.

Nebraska taxpayers, whose taxes support Medicaid and Medicare.

Sources: L. Tim Wagner, director, Nebraska Department of Insurance; Omaha attorney Dan Cullan; Omaha ophthalmologist Dr. Peter Whitted; World-Herald archives and calculations.

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February 25th, 2005

Roche's Pegasys Gets EU Approval for Chronic Hepatitis B Treatment SourceURL:http://uk.biz.yahoo.com

ZURICH (AFX) - Roche Holding AG (Virt-X: ROG.VX - news) said that its Pegasys drug has been approved by the EU Commission for treatment of chronic hepatitis B.

'Pegasys is well-known to physicians as a highly effective treatment for chronic hepatitis C and we are glad the EU Commission has recognised the benefits it also offers to patients with chronic hepatitis B,' the Swiss drugmaker said.

Approval in the US is expected this year.

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Increased Risk of Hepatocellular Carcinoma with Transjugular Shunt SourceURL:http://www.gastrohep.com

Findings in the recent issue of Hepatology suggest the need for a strict hepatocelullar carcinoma surveillance program for patients, especially if they are not expected to undergo a liver transplantation.

A trend toward a higher incidence of hepatocelullar carcinoma in patients with cirrhosis treated with bare-stent transjugular intrahepatic portosystemic shunt has been observed in previous studies.

Dr Bañares and colleagues from Spain assessed the influence of transjugular intrahepatic portosystemic shunt as a risk factor for developing hepatocelullar carcinoma.

The researchers compared the incidence of hepatocellular carcinoma in 2 retrospective cohorts of patients.

The research team included in the transjugular intrahepatic portosystemic shunt cohort patients with cirrhosis who underwent transjugular intrahepatic portosystemic shunt placement for the treatment of portal hypertension-related complications (n= 138).

The team used a non- transjugular intrahepatic portosystemic shunt control group composed of patients admitted at the hospital at the same time of transjugular intrahepatic portosystemic shunt insertion group.

Hep C is a predictor of hepatocelullar carcinoma in patients without transjugular intrahepatic portosystemic shunt - Hepatology

The researchers ensured that the groups were individually matched 1:1 according to age, sex, Child-Turcotte-Pugh class, and cause of cirrhosis.

A stratified Cox model was used by the researchers to assess risk of hepatocelullar carcinoma development.

The investigators found that he median time of follow-up was similar in transjugular intrahepatic portosystemic shunt and non- transjugular intrahepatic portosystemic shunt cohorts; 30.3 and 31.4 months, respectively.

The researchers also showed that the probability of developing hepatocelullar carcinoma at 1, 3, and 5 years was 3%, 24%, and 34% for the transjugular intrahepatic portosystemic shunt cohort and 1%, 6%, and 25%, for the control, respectively, with a hazard ratio of 1.52.

Hepatitis C virus infection and age were independent predictors of hepatocelullar carcinoma development in patients without transjugular intrahepatic portosystemic shunt.

Dr Bañares concluded, “Patients with cirrhosis who are treated with transjugular intrahepatic portosystemic shunt may have a higher incidence of hepatocelullar carcinoma.”

“This observation suggests the need for a strict hepatocelullar carcinoma surveillance program for these patients, especially if they are not expected to undergo a short- or medium-term liver transplantation.”

Hepatology 2005: 41(3): 566-571

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FDA Approves Pegasys and Copegus as the Only Hepatitis C Treatment for HIV Patients
Source: www.roche.com

-- Pegasys combination offers the only FDA-approved option against a leading cause of death in people with HIV--

Nutley, NJ –February 25, 2005 – Roche announced today that the U.S. Food and Drug Administration (FDA) has approved Pegasys Ò (peginterferon alfa-2a) and Copegus Ò (ribavirin, USP) for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. Pegasys combination therapy is the first and only regimen FDA-approved for hepatitis C treatment in patients with HIV.

Pegasys, the most prescribed hepatitis C medication in the U.S., was approved in 2002 by the FDA for use alone and in combination with Copegus for the treatment of adults with chronic hepatitis C.

“For the first time, the 300,000 Americans who are coinfected with hepatitis C and HIV have an FDA-approved hepatitis C treatment option. This is a very important advance for the HIV community,” said Jeffery Smith, Director, Clinical Research, American Foundation for AIDS Research (amfAR). “Hepatitis C has become one of the leading killers of people with HIV because advances in HIV treatment are helping patients live longer and because hepatitis C progresses much more quickly to liver failure in people with HIV.”

Hepatitis C and HIV are the two most prevalent blood-borne infections in the United States. It is estimated that approximately 30 percent of Americans with HIV are also coinfected with the hepatitis C virus. Research has shown that hepatitis C is more resistant to treatment in people with HIV. Recent guidelines by the National Institutes of Health and Centers for Disease Control and Prevention recommend that people with HIV be screened for hepatitis C and that all patients with chronic hepatitis C, including those with HIV, be considered for treatment.

“The risks and benefits of medications can be very different for people with HIV, and research has suggested that this is true for hepatitis C therapies as well,” said Douglas Dieterich, MD, Professor of Medicine, Mount Sinai School of Medicine, New York City. “Studies have shown that hepatitis C and HIV coinfected patients treated with Pegasys combination therapy had response rates that were three times higher than those treated with conventional interferon combination therapy.”

“Making decisions based on evidence is particularly important for HIV patients given the unique and complex medical challenges that they face,” said Salvatore Badalamenti, MD, Medical Director, Roche. “The safety and efficacy results from the APRICOT study and in our label can only be applied to Pegasys combination therapy.”

Pegasys is the only pegylated interferon supported by published studies including U.S. patients for the treatment of hepatitis C in hepatitis C and HIV coinfected patients.

Pivotal Study

The FDA approval of Pegasys combination therapy for the treatment of HCV/HIV coinfected patients is based on results from APRICOT (AIDS Pegasys Ribavirin International Coinfection Trial), the largest-ever study to date evaluating chronic hepatitis C treatment in patients coinfected with hepatitis C and HIV. The results showed that 40 percent of patients treated with Pegasys and Copegus achieved a sustained virological response. Sustained virological response refers to a patient’s continued undetectable hepatitis C levels in the blood 24 weeks after finishing a course of treatment.

The randomized, partially blinded international trial enrolled a total of 860 HCV/HIV coinfected patients in 19 countries, including the United States. All patients were HCV positive, had compensated liver disease, a CD4+ count greater than 100 cells/mL, and stable HIV disease, with or without antiretroviral therapy. Patients were randomized to 48 weeks of treatment with interferon alfa 2a 3MIU three times a week plus 800 mg/day of ribavirin, 180 mcg of Pegasys once weekly plus placebo, or 180 mcg of Pegasys once weekly with 800 mg/day of Copegus. Sustained virological response (SVR) was assessed at the end of 24 weeks of treatment-free follow up (week 72).

The adverse event profile of coinfected patients treated with Pegasys and Copegus was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%) and mood alteration (9%).

About Pegasys

Pegasys, a pegylated alpha interferon, and Copegus were approved by the FDA in December 2002 for use in combination for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis.

The FDA is currently reviewing an indication for Pegasys for the treatment of chronic hepatitis B.

Pegasys is dosed at 180mcg as a subcutaneous injection taken once a week. Copegus is available as a 200mg tablet, and is administered orally two times a day as a split dose.

Roche has backed Pegasys with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients coinfected with hepatitis C and HIV, African Americans, patients with cirrhosis, patients with normal ALT levels, and patients who have failed to respond to previous therapy.

Data from six Pegasys studies, including APRICOT, have been published in The New England Journal of Medicine.

About Roche – More Than a Century in the U.S. and the World

Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is one of the world’s leaders in diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on many fronts to improve people’s health and quality of life. Roche employs roughly 65,000 people in 150 countries, including approximately 15,000 in the United States.

Roche’s U.S. operations celebrate their American Centennial in 2005. In another milestone this year, Roche was named in January to Fortune magazine’s list of Best Companies to Work for in America. One of an increasingly rare breed of major healthcare companies that still bear their original name, Roche today has more than a dozen U.S. sites located in California, Colorado, Indiana, New Jersey and South Carolina, as well as in Puerto Rico. Roche has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Roche’s Pharmaceuticals Division offers a portfolio of leading medicines in therapeutic areas including cancer, HIV/AIDS, hepatitis C, transplantation, dermatology and influenza. Roche’s Diagnostics Division supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our worldwide and U.S. websites (Global: www.roche.com and U.S.: www.roche.us).

Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus

Indication

Pegasys®, a pegylated alpha interferon, alone or in combination with Copegus® (ribavirin, USP) is indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that is clinically stable (e.g. antiretroviral therapy not required or receiving stable antiretroviral therapy).

Dosing and Administration

Pegasys, a premixed solution, is dosed at 180mcg as a subcutaneous injection once a week. Copegus, available as a 200mg tablet, is administered at 800 to 1200mg taken twice daily as a split dose. The two products are sold separately.

Combination Therapy Clinical Studies

The two combination therapy pivotal study findings for patients without HIV:

Study 5, published in the March 2, 2004 Annals of Internal Medicine, including 1,284 patients receiving medication, showed that patients with certain genotypes (strains) of the hepatitis C virus should be treated with different dosing regimens of Pegasys and Copegus. The treatment regimens and resulting sustained virological response rates for these groups treated with Pegasys and Copegus therapy were:

Genotype 1: 48 week duration with 1000 – 1200mg Copegus: 51 percent

Genotype non-1: 24 week duration with 800mg Copegus: 82 percent

Study 4, published in the September 26, 2002 New England Journal of Medicine, including 1,121 patients receiving medication, showed that Pegasys and Copegus combination therapy is a more effective treatment for chronic hepatitis C than interferon alfa-2b and ribavirin. The sustained virological response rate in the Pegasys and Copegus treated patients was 53 percent compared to 44 percent in the interferon alfa-2b and ribavirin group. Sustained virological response refers to a patient’s continued undetectable serum hepatitis C RNA levels 24 weeks after finishing a course of treatment.

Combination therapy pivotal study findings for patients with HIV:

Study 6, published in the July 29, 2004 New England Journal of Medicine, including 868 HIV patients receiving medication, showed that Pegasys and Copegus combination therapy is a more effective treatment for chronic hepatitis C in patients with HIV than Pegasys monotherapy and more effective than interferon alfa-2a and ribavirin. The sustained virological response rate in the Pegasys and Copegus treated patients was 40 percent compared to 11 percent in patients treated with interferon alfa-2a and ribavirin and 20 percent in patients treated with Pegasys monotherapy.

Adverse Events

Alpha interferons, including Pegasys, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping Pegasys therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

Use with Ribavirin. Ribavirin, including Copegus, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in worsening of cardiac disease. Ribavirin is genotoxic, mutagenic, and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

Pegasys is contraindicated in patients with hypersensitivity to Pegasys or any of its components, autoimmune hepatitis, and hepatitic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. Pegasys is also contraindicated in hepatitis decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic chronic hepatitis C patients coinfected with HIV before or during treatment. Pegasys is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. Pegasys and Copegus therapy is additionally contraindicated in patients with a hypersensitivity to Copegus or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the six months after treatment has concluded. Routine monthly pregnancy test must be performed during this time. If pregnancy should occur during treatment or during six months post-therapy, the patient must be advised of the significant teratogenic risk of Copegus therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during six months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.

Chronic hepatitis C patients with cirrhosis are at risk of hepatitic decompensation and death when treated with alpha interferons, including Pegasys and Copegus. Cirrhotic chronic hepatitis C patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) appear to be at increased risk for the development of hepatitic decompensation compared to monoinfected patients. During treatment, patients’ clinical status and hepatic function should be closely monitored, and Pegasys treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed.

The most common adverse events reported for Pegasys and Copegus combination therapy, observed in clinical trials (n=451), were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%). The adverse event profile of coinfected patients treated with Pegasys and Copegus was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%) thrombocytopenia (8%) weight decrease (16%) and mood alteration (9%).

Serious adverse events include neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections, bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including psoriasis and lupus), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemiccolitis), pancreatitis, and opthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).

The complete package inserts for Pegasys and Copegus are available at www.pegasys.com, or by calling 1-877-PEGASYS.

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