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Week Ending: April 1st, 2006
Alan Franciscus
Editor-in-Chief
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March 27th, 2006
Combination Algorithms Improve Diagnosis of Fibrosis in Hep C
SourceURL:http://www.gastrohep.com/
The most recent issue of the Journal of Hepatology finds that stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic Hepatitis C, and reduces the need for liver biopsy.
Chronic Hepatitis C, biopsy is the gold standard for assessment of liver fibrosis.
Non-invasive markers have been proposed but their use is limited by diagnostic accuracy.
Dr Giada Sebastiania and colleagues from Italy assessed the diagnostic performance of non-invasive markers of liver fibrosis.
The investigative team combined the non-invasive markers in sequential algorithms.
The team evaluated 190 patients with chronic Hepatitis C.
Aspartate aminotransferase to platelets ratio, Forns' index, and Fibrotest at the time of liver biopsy were measured.
A stepwise combination algorithm was developed and validated prospectively in 100 additional patients.
The team developed 3 algorithms.
The need for liver biopsy is reduced by 50 to 70% – Journal of Hepatology
The first algorithm included significant fibrosis identified with high diagnostic performance using aspartate aminotransferase to platelets ratio as a screening test.
This was followed by a fibrotest in aminotransferase to platelets ratio non-classified cases.
The first algorithm was also identified by restricting liver biopsy to patients classified F0 to F1 by non-invasive tests.
The second slightly modified algorithm had a similar performance when applied to Hepatitis C carriers with normal alanine aminotransferase.
In the third algorithm, cirrhosis was identified using a dedicated algorithm with a different cut-off, reducing the liver biopsies needed by 60 to 70%.
Dr Sebastiania's team concluded, "Stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic Hepatitis C. "
"Need for liver biopsy is reduced by 50 to 70% but cannot be completely avoided."
J Hepatol 2006: 44(4): 686-93
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Health Department Releases Report on Hepatitis B and C
SourceURL:http://www.region.durham.on.ca
WHITBY, ON, March 27, 2006 - Durham Region Health Department has released a new report entitled "Snapshot on Hepatitis B&C" which examines local trends in the occurrence and health consequences of hepatitis B and C.
Hepatitis B and C are infectious diseases that can progress to cirrhosis of the liver or liver cancer. While there is a vaccine available to prevent hepatitis B, currently there is no vaccine available for hepatitis C.
"Annually, Durham Region only sees about two cases of hepatitis B each year," said Kathy Moran, an epidemiologist with the Health Department, "however, for hepatitis C, over 230 cases are reported each year. In addition, rates of infection for hepatitis B and C were found to be consistently higher in males than in females."
The reason for the differences between males and females may be related to how hepatitis B and C are spread. High risk sexual behaviours such as having unprotected sex with multiple partners or men having sex with men, the sharing of syringes, needles or other drug paraphernalia and having procedures such as tattooing and body piercing are known risk factors for hepatitis B and C.
A vaccine for hepatitis B has been available free of charge to all grade 7 students in Ontario since 1994. Through its school-aged immunization program, the Health Department provides annual hepatitis B vaccination clinics for grade 7 students across Durham Region. During the 2004-05 school year, 91 per cent of eligible grade 7 students received the required two doses of the hepatitis B vaccine.
For more information about hepatitis B and C or to obtain a copy of the report, please call Durham Region Health Department at 905-668-7711 or 1-800-841-2729.
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Jack Slater, 1946-2006: "I Don't Want to Be Missed. I'd Rather Be Celebrated"
http://seattletimes.nwsource.com
By Cara Solomon
Seattle Times reporter
In all the years he was sick, Jack Slater had plenty of time to wonder why.
He could have gotten stuck on the question, first as he was waiting for the liver transplant, and later as he was living with the results.
But early on, Mr. Slater came to a conclusion.
"The answer is there is no answer," he wrote in The Seattle Times. "Just suffering and, if you are lucky, meaningful work, good friends, a few opportunities to love, and time to plant tomatoes."
Mr. Slater, a teacher, actor, writer, artist and Ballard resident who led Times readers through the story of his liver transplant in a series called "Life on the Waiting List," died Friday, a year and a half after the operation. He was 59.
He was surrounded by friends and family at the University of Washington Medical Center. By Mr. Slater's side was his wife, Deborah Swets, whom he once described as his dream.
Mr. Slater died of complications from hepatitis C, the blood-borne virus that destroyed his liver, then attacked the liver he received in a September 2004 transplant operation.
For two years, Mr. Slater brought wit and wisdom to the story of his sickness, his wait for a liver transplant and his life after the operation.
Hundreds of readers e-mailed after his first installment, subtitled "Diary of a Transplant," ran in October 2003. Some said they put him in their prayers. One woman offered her own liver. Another wrote just two words: thank you.
"Sure all of this makes me feel exposed," Mr. Slater later wrote. "But it also makes me feel a little less alone."
There was another advantage to writing: Mr. Slater loved the stage. The articles gave him another forum to say what he saw in the world now that he was sick.
He handled it with humor and honesty. He laid his anger bare, along with his fear. He talked about sickness the way other people talk about the weather.
Mr. Slater was thankful for the work. "It gave him meaning and purpose," said Swets, 57.
John Slater Jr. was born Sept. 10, 1946, in Chicago but grew up in Lake Worth, Fla., the first of three children born to John and Delle Slater. He made friends wherever he went.
Polio at age 5 left Slater with a slight limp, but he played sports anyway. Baseball was his favorite. He wrote in The Times that he wanted to be laid in a hammock when he died, his hands folded behind his head, a ball game on the radio.
He always held originality in high esteem. "If someone else did it, or said it, he wasn't going to repeat it," said his brother, Stephen Slater of Hawaii. Mr. Slater painted animals and other scenes onto plywood. He published a volume of poetry. He let his creativity loose in the garden. A friend gave him 100 daffodil bulbs two years ago. Mr. Slater planted them all around the house. They are in bloom now.
A graduate of Calvin College in Michigan, Mr. Slater worked as a community activist and teacher before turning to acting. He spent about 20 years, mostly in Los Angeles, working on movies, commercials and television shows. He also wrote and produced plays.
Mr. Slater was involved in rallies against the Vietnam War and against American involvement in Nicaragua. He always rooted for the underdog.
In 1991, he moved to Seattle to be with Swets. He taught at the King County Jail, and later at Franklin High School.
In 1997, during a routine physical, Mr. Slater discovered he had hepatitis C. Five years passed before the symptoms – exhaustion, weight loss, muscles losing their power – really hit. Mr. Slater went on medical leave from Franklin High in 2002.
The Times approached Mr. Slater about writing about waiting for a liver transplant, and what followed was a mix of practical advice and inspiration, laced with humor.
At one point, Mr. Slater joked about the things conspiring against his getting a liver: a drop in gang violence, lower speed limits in Montana, people mellowing out through meditation and yoga, automobile air bags and the Department of Homeland Security.
He wrote that laughter kept him sane. "I laugh at this rotten disease and curse it, rip out its throat and kick it down the stairs," he wrote. "And then I laugh some more."
Mr. Slater did much of the laughing with his wife. She was the woman, he wrote, who saved his life every day, in a hundred ways. She was his note-taker during doctor's visits, his helper at home, his face full of optimism when life looked so grim.
Mr. Slater got a new liver Sept. 21, 2004, in an operation that lasted 7-½ hours and was considered a success. He was soon sneaking ice cubes behind the nurse's back, sharing a naughty joke and saying he felt "like a million bucks."
But it was a tough recovery. Significant complications set in after three months.
Mr. Slater tried to balance the bad with work on a book, "Hepatitis C, Blah Blah Blah." On good days, Swets said, he would play with the neighborhood children, wearing a red clown's nose and trying to spray water on them.
"Being almost sick, or almost better, is my new normal," Mr. Slater wrote in October.
In recent months, the virus seriously damaged his new liver. This week, his kidneys shut down, and fluid in his belly became infected. Thursday, he told his brother he was ready to die.
Dozens of visitors came to the hospital this week, people who had supported Mr. Slater and Swets all these years, paying parts of their insurance premiums, bringing them homemade meals. One friend placed a red clown's nose over Mr. Slater's oxygen mask. Another played the viola for him, everything from Bach to Simon and Garfunkel.
From his bed, in a lucid moment, Slater made a request.
"Play something humorous," he said.
In addition to his wife and brother, Mr. Slater is survived by his parents of Lake Worth, Fla. A sister, Jane Slater of Bellingham, died in 2004.
Cara Solomon: 206-464-2024 or csolomon@seattletimes.com
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Iron Overload Does Not Affect HCV Genotype and Response to Interferon and Ribavirin Therapy
http://www.therapeuticsdaily.com
Hepatitis Weekly - Mar. 27, 2006
2006 MAR 27 - (NewsRx.com) -- Research from Brazil has reported that iron overload does not affect hepatitis C virus (HCV) genotype and response to interferon and ribavirin therapy.
"The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy," wrote R.M. Souza and colleagues, Universidade Federal da Bahia.
They continued, "Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload."
The authors observed, "Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (p=.906). There was a significant difference in fibrosis stage between groups (p=.005).
"In group I (N=30), one patient had stage F0/F1 of fibrosis, while in group II (N=65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II."
"Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (p=.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis," reported the scientists.
The investigators concluded, "There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy."
Souza and colleagues published their study in Brazilian Journal of Medical and Biological Research (Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection. Braz J Med Biol Res, 2006;39(1):79-83).
For additional information, contact L.G.C. Lyra, Servico de Gastro-Hepatologia, Hospital Prof. Edgard Santos, Universidade Federal da Bahia, Av Juracy Magalhaes Jr, 1855-501, BR-41940060 Salvador, BA, Brazil.
The publisher's contact information for the Brazilian Journal of Medical and Biological Research is: Association Bras Divulg Cientifica, Faculdade Medicina, Sala 21, 14049 Ribeirao Preto, Sao Paulo, Brazil.
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AAP Endorses Cdc's Hepatitis B Recommendations for Infants, Children, and Adolescents
http://www.immunize.org
The American Academy of Pediatrics (AAP) recently published an article, "Academy endorses CDC's hepatitis B recommendations," in the online version of its publication AAP News. It concerns ACIP's new hepatitis B recommendations, which covers immunization of infants, children, and adolescents. The online AAP News article is reprinted below in its entirety.
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The Academy has endorsed the Centers for Disease Control and Prevention (CDC) recommendation for hepatitis B vaccine, "A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States."
The CDC recommends that all newborns receive a birth dose of hepatitis B vaccine before leaving the hospital unless a physician provides a written order to defer the birth dose. CDC also recommends that all children age 19 and younger receive the vaccine series.
DELAY IN 'RARE CIRCUMSTANCES'
"On a case-by-case basis and only in rare circumstances," the birth dose may be delayed until after hospital discharge, according to the new recommendation. This exception applies only to infants who weigh at least 2,000 grams and whose mothers are known to be HBsAg negative during the current pregnancy. When a decision is made to delay the birth dose, a physician's order to withhold the birth dose and a copy of the original laboratory report indicating that the mother was HBsAg negative during this pregnancy must be placed in the infant's medical record.
In infants who do not receive a first dose before hospital discharge, the first dose should be administered no later than 2 months of age.
CDC recommendations also state that the birth dose should not be delayed if the infant's mother engaged in high-risk sexual or drug-using practices during pregnancy (e.g., having had more than one sex partner during the previous six months or an HBsAg-positive sex partner, evaluation or treatment for an STD, or recent or current injection-drug use) or in situations of expected poor compliance with follow-up to initiate the vaccine series.
Preterm infants weighing less than 2,000 grams and born to HBsAg-negative mothers should have their first vaccine dose delayed until one month after birth or hospital discharge, whichever comes first. For these infants, a copy of the original laboratory report indicating that the mother was HBsAg negative during this pregnancy should be placed in the infant's medical record.
The recommendations call for physician follow-up in infants whose birth dose is delayed.
CATCH-UP
Hepatitis B vaccination is recommended for all children and adolescents 19 years of age and under. Children and adolescents who have not previously received hepatitis B vaccine should be vaccinated routinely at any age with an appropriate dose and schedule, but all children aged 11-12 years should have a review of their immunization records and should complete the vaccine series if they were not previously vaccinated or were incompletely vaccinated.
[The CDC recommendation is online at http://www.cdc.gov/mmwr/PDF/rr/rr5416.pdf or see the Dec. 23, 2005, Morbidity and Mortality Weekly Report (MMWR. 2005;54(RR-16):1-23)].
Additional information about hepatitis B is available in the 2003 edition of the AAP Red Book (pages 318-336) and on the Red Book Online Web site: http://aapredbook.aappublications.org.
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Time for Britain to Adopt Universal Hepatitis B Immunisation
SourceURL:http://www.medicalnewstoday.com
It's time for Britain to adopt universal hepatitis B immunisation, say senior doctors in an editorial published online by the BMJ today.
The United Kingdom is one of the few developed countries that have not implemented universal immunisation. Instead, it follows a policy of selective immunisation of high-risk groups, and screening all women attending antenatal clinics.
But this approach has come in for some criticism. So, is the British selective programme effective and should the UK now adopt universal immunisation against hepatitis B, ask the authors?
Although the UK has one of the lowest incidences of hepatitis B infection worldwide, the Health Protection Agency estimated that only 44% of infections are potentially preventable under the current programme.
Of particular importance is the average net immigration of about 6,500 people with chronic hepatitis B infection each year between 1996 and 2000, say the authors. This total is cumulative, and therefore the pool is increasing.
For example, in Ireland, the incidence of hepatitis B infection increased markedly between 1997 and 2003, in part reflecting migration from countries with high rates of infection.
However, they warn that targeting vaccination at immigrants could be seen as stigmatising and divisive. Instead, they suggest that, as population movements increase, control of infectious diseases must be supported by regional and global strategies.
Several European countries now include hepatitis B vaccine in their infant immunisation programmes. Alternatively, vaccinating adolescents has been shown to be acceptable and effective.
Would universal vaccination against hepatitis B in the United Kingdom be too costly?
Most cost benefit studies were done before prices were influenced by global markets, say the authors. The full economic burden of hepatitis B still needs to be established but, if direct costs can be reduced by negotiated tendering, there can no longer be a financial argument against adopting a universal immunisation strategy against hepatitis B in the United Kingdom, they conclude.
Contact: Emma Dickinson
edickinson@bmj.com
BMJ-British Medical Journal
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Novartis: Telbivudine Better Than Epivir
SourceURL:http://www.redorbit.com
Novartis said Monday study results show telbivudine, a potential hepatitis B drug, works better than GlaxoSmithKline's Epivir.
Novartis, which is developing telbivudine with Idenix, said the one-year phase 3 study results were included in its recent regulatory submission to Chinese health authorities. The study results also were presented Monday at the International Liver Congress in Shanghai.
These data suggest that telbivudine, if approved in China, may become an important new treatment option for the millions of Chinese patients with this potentially life-threatening disease, Dr. Jinlin Hou, a principal investigator in the study and director of the hepatology unit at Nanfang Hospital, Southern Medical University, Guangzhou, China, said in a statement issued by Novartis and Idenix.
The trial, which is an ongoing two-year treatment study, found that after one year of treatment the telbivudine group showed greater anti-viral and clinical efficacy than the Epivir group, Novartis and Idenix said.
The telbivudine group experienced a greater reduction in hepatitis B virus levels. In addition, a higher percentage of the telbivudine group showed normalization of liver enzymes and HBeAg loss (an indication of durable response to treatment).
Source: United Press International
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March 28th, 2006
Immunosuppression without Steroids in Liver Transplants Is Safe
SourceURL:http://www.gastrohep.com
The latest issue of the Journal of Hepatology finds that immunosuppression without steroids is safe, reduces infection and metabolic complications, with good 6-month survival rates.
Dr Laura Lladóa and colleagues from Spain evaluated the efficacy of a steroid-free immunosuppression protocol.
The team randomized 198 liver-transplant patients between 2001 and 2004.
The patients in Group1 received immunosuppression with Basiliximab and cyclosporine, along with prednisone.
The patients in Group2 received immunosuppression with Basiliximab and cyclosporine, but without prednisone.
The primary end points were acute rejection, and patient and graft survival.
The secondary end points were infection, metabolic complications, and Hepatitis C-virus recurrence.
The overall rejection rate was 15%, with no differences between the groups – Journal of Hepatology
The team found that the overall rejection rate was 15%, with no differences between the groups.
Infection rate was similar in both groups, at 51% in Group1 vs 47% in Group 2.
The researchers observed that diabetic patients in Group 2 had a significantly higher rate of bacterial infections.
The 6-month protocol biopsies showed Hepatitis C recurrence in 90% of patients, without differences between groups.
Hypertension was more frequent in Group 1 occurring in 44% vs 25% in Group 2.
De novo diabetes rate was higher in Group 1, at 29% vs 18% in Group 2, presenting with higher glycated hemoglobin levels.
The research team noted that 6-month survival rates were similar between the 2 groups.
Dr Lladóa's team concluded, "Immunosuppression without steroids is safe and reduces infection and metabolic complications."
J Hepatol 2006: 44(4): 710-16
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Medivir: Medivir's Antiviral MIV-210 (FLG) Inhibits Hepatitis B Virus (HBV) Which is Resistant to Currently Marketed Antivirals
SourceURL:http://www.redorbit.com
The March edition of Antimicrobial Agents and Chemotherapy features a report by Professor Fabian Zoulim and his colleagues at INSERM in Lyon, France that Medivir's antiviral MIV-210 (FLG) in laboratory assays is active against lamivudine- and adefovir-resistant HBV. Lamivudine and adefovir are currently used in treatment of HBV patients, but both lead to the development of resistance, thereby losing their therapeutic efficacy. The newly published results therefore show that HBV which has developed resistance against both lamivudine and adefovir is inhibited by MIV-210 (FLG). Several HBV antivirals in clinical development give the same resistance profile as lamivudine.
The newly published results indicate that the two polymerase inhibitors MIV-210 (FLG) and adefovir block the HBV polymerase by different mechanisms. The authors consider that MIV-210 (FLG) should be suitable both for treatment of drug-resistant HBV, but also as first-line therapy together with e.g. adefovir in order to minimize the risk of resistance development and to enhance the therapeutic efficacy.
In previously published trials, chronically HBV-infected woodchucks have been treated with lamivudine, adefovir or MIV-210 (FLG), and MIV-210 (FLG) has shown superior antiviral efficacy.
Hepatitis B is a very common form of jaundice, in need of better treatment alternatives than those currently available. Sales of HBV pharmaceuticals are growing strongly and are expected to reach USD 1 billion annually by the year 2010. MIV-210 (FLG) is also active against HIV which has a polymerase which resembles the HBV polymerase. Phase IIa clinical trials with MIV-210 (FLG) are currently underway in HIV patients. These trials are shortly expected to be ready for result evaluation, as a basis for the project's future clinical strategy. MIV-210 is one of the projects whose outlicensing or divestment is administered by Medivir HIV Franchise AB.
About Medivir
Medivir develops pharmaceuticals for widely prevalent diseases with proteases as the target enzyme. The goal is to become a self-sustaining, profitable, research-based pharmaceutical company with proprietary products on the market. The company is located in Huddinge, Sweden and Chesterfield Research Park, Essex, England.
The group comprises Medivir AB, subsidiary Medivir UK Ltd, Medivir HIV Franchise AB and Medivir Personal AB. At the end of December 2005, the Group had 133 employees. In 1996 Medivir was listed on the O list at the Stockholm Stock Exchange (Stockholmsborsen). Medivir's research portfolio embraces projects on hepatitis C, labial herpes, osteoporosis, rheumatoid arthritis (RA), asthma, multiple sclerosis (MS). Medivir has seven individual projects in development, of which one is entering phase III.
Medivir HIV Franchise AB is focused on the development and divestment of HIV/HBV projects and examining the clinical strategy for shingles drug MIV-606.
Medivir AB (publ.), Lunastigen 7, SE-141 44 Huddinge, Sweden.
Phone (switchboard): +46 (0)8 5468 3100.
This information was brought to you by Waymaker http://www.waymaker.net
Source: Business Wire
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DNA Vaccine in Development
SourceURL:http://www.redorbit.com
By BRIAN DONNELLY
A NEW type of vaccine for mass immunisation against killer diseases such as hepatitis B, cancer, and HIV is being developed by Scottish scientists.
The Moredun Research Institute, near Edinburgh, has developed a vaccine that could replace all conventional methods, and potentially prevent the world's most serious diseases from developing.
Dr John March and his team are developing a vaccine made from genetic instructions, or DNA, rather than using the disease organism itself, which is what conventional vaccines rely upon.
Dr March said: "To date, we have produced a vaccine against hepatitis B. Theoretically, there is no reason why the vaccines should not perform equally well against other conditions such as cancer, HIV, malaria, and rabies."
The DNA vaccine is placed inside a bacterial virus, known as a bacteriophage, with special genetic instructions so that the vaccinated host, or patient, can make the vaccine itself by reading this DNA. In this way, the patient produces the vaccine.
Source: Herald, The; Glasgow (UK)
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March 29th, 2006
PowderMed's Therapeutic DNA Vaccine for Chronic Hepatitis B Enters Phase I Clinical Trials in Patients
SourceURL:http://biz.yahoo.com
OXFORD, United Kingdom--(BUSINESS WIRE)--March 29, 2006--PowderMed, the immunotherapeutics company focused on the development and manufacture of DNA-based vaccines for viral diseases and cancer, has announced that its dual-antigen encoding immunotherapeutic for Hepatitis B (HBV) has received US IND approval together with approval from the Singapore, Hong Kong and Taiwanese Regulatory Authorities and has entered Phase I Clinical Trials. The study will primarily evaluate the safety and tolerability of the HBV immunotherapeutic, pdpSC18, administered by PMED(TM), PowderMed's needle-free delivery technology, in patients with chronic Hepatitis B infection, both in combination with lamivudine and as monotherapy. Additionally, assessments of immunogenicity and clinical response will be made.
Worldwide HBV affects 350 million people and there are no commercially available therapeutic vaccines for the treatment of chronic HBV infection. Chronic infection occurs in 98% of newborn children infected by vertical transmission from the mother (the most common means of transmission in Asia-Pacific), and in 5% of individuals infected after 2 years of age. About 25% of these patients will progress to cirrhosis and 20% of this subgroup will develop hepatocellular carcinoma - one of the most common cancers worldwide.
Welcoming this study and the potential for a novel therapeutic vaccine to HBV, Dr Antonio Bertoletti, of the Center for Molecular Medicine, Singapore, said:
"Patients with chronic Hepatitis B show a state of relative hypo-responsiveness of HBV-specific T-cells compared with that demonstrated in patients who control the virus replication after acute infection. Therapeutic induction and/or activation of the T-cell response for HBV core and surface proteins may have the potential to control infection. It has been shown that Hepatitis B surface (HBsAg) and core antigen (HBcAg) induces envelope-and core specific CD4+ and CD8+ T-cell responses and that the response against the Hepatitis B core antigen (HBcAg), is often associated with viral control. The combination of these two genes in PowderMed's pdpSC18 HBV therapeutic DNA vaccine, thus provides a potential mechanism to both clear the virus via the CD8+ response and to overcome unresponsiveness in chronically infected patients via the CD4+ response."
This Phase I, First Time in Human Study will enroll patients at seven sites in SE Asia (Singapore, Taiwan, Hong Kong) and the USA. Since the immunological response and hepatic tolerability of the Hepatitis B immunotherapeutic would be expected to differ considerably between non-infected subjects and subjects with active Hepatitis B disease, the Phase I clinical study will enroll subjects with active Hepatitis B disease in order to specifically address both safety and immunogenicity in the most predictive manner possible. Each subject will participate in the study for a period of up to 27 weeks, plus a 4-week run-in and screening period. Allowing for the planned safety reviews between dosing cohorts and a 4-month recruitment window, results can be expected during 2007.
Commenting on the trial, Dr John Beadle, PowderMed's Chief Medical Officer, said:
"Given the limitations of the currently available treatment regimens for chronic Hepatitis B, a regimen, either as a monotherapy or combination, that could provide enhanced clearance of virus, seroconversion, a reduction in resistant strains or a reduction in post-treatment exacerbations of hepatitis would be highly desirable. The concept of a novel DNA therapeutic vaccine to boost the immune response to the virus and promote viral clearance is thus an attractive and timely novel therapeutic strategy in an area of substantial unmet medical need."
Phase I clinical trials of a prophylactic DNA Vaccine containing only the HBsAg gene (pPWRG7128) in 95 subjects, showed that vaccination via PMED(TM) was generally well tolerated both locally and systemically, and resulted in seroprotective levels of antibodies and measurable cell-mediated immune responses.
About PowderMed Ltd - www.powdermed.com
PowderMed is a private immunotherapeutic company based in Oxford, UK. The Company is focused on the clinical development and manufacture of therapeutic and prophylactic DNA-based vaccines for viral diseases and cancer. The company has 4 clinical and 3 pre-clinical stage projects. The lead clinical programme has shown positive Phase I results in the treatment and prevention of human influenza. This technology is uniquely and easily adaptable to treat avian flu and to address the pandemic threat. PowderMed also has a product for the treatment of genital herpes in Phase I trials, and two partnered Phase I programmes in Cancer (Ludwig Institute for Cancer Research) and HIV/AIDS (Glaxo SmithKline). PowderMed vaccines are delivered using PMED(TM) (Particle mediated epidermal delivery), a needle-free, painless delivery system that requires minimal medical training, allows self-administration and requires no refrigeration for stockpiling. Specifically, PowderMed's technology delivers DNA to the epidermal layer of the skin where it is presented to the cells of the immune network, thereby creating immunity and thus facilitating both treatment and prevention of disease.
The Company has a highly experienced management team that has a combined 160 years of experience, with Rolf Stahel as the chair of the board. The Company has sufficient funds through to the end of 2006 having raised GBP 20 million in venture financing to date, with an additional GBP 5 million available from its existing investor syndicate that comprises Abingworth Management, Advent Venture Partners, Isis College Fund, Oxford Bioscience Partners and SV Life Sciences.
PowderJect® Particle Mediated Epidermal Delivery (PMED(TM)) technology
Using the PowderJect device, DNA precipitated onto microscopic gold particles is propelled by pressurised helium gas at near supersonic speeds into the epidermis. The microscopic gold particles (mean particle diameter 1 - 3 microns) are used as the carrier because they have the appropriate size and density needed to deliver the DNA directly into the immunologically active antigen presenting cells (APCs) of the epidermis. These cells have a mean diameter of 20 microns and thus the microscopic gold can easily enter the cell. Studies have shown that once inside the nuclei of APCs, the DNA elutes off the gold and becomes transcriptionally active, producing the encoded protein that, when presented by the APCs to lymphocytes, triggers strong T-cell mediated immune responses. It is this ability of PMED to produce a robust and reproducible T-cell mediated immune response to a broad range of viral and cancer antigens, that provides PowderMed with its unique competitive advantage in the field of DNA-based vaccines.
Chronic Hepatitis B in Man
Hepatitis B virus (HBV) is responsible for the most common form of parenterally transmitted viral hepatitis. Approximately 350 million people worldwide are persistent carriers of the virus. 75 percent of all carriers are of Asian origin and the disease is endemic in these regions. It is a major cause of acute and chronic infections of the liver with significant associated morbidity and mortality. HBV is a non-cytopathic virus and liver injury is mainly mediated by the host immune response against virus-infected liver cells and by the production of inflammatory cytokines. A vigorous T cell response is believed to be responsible for the elimination of the hepatitis B virus.
There are no commercially available therapeutic vaccines for the treatment of chronic HBV infection. Treatment for chronic hepatitis B infection is limited to immunomodulators (Interferon alpha (IFN-(alpha))) and antiviral agents.
Immunisation seeks to exploit the adaptive immune response either by inducing protective immune responses prior to infection (prophylactic immunisation) or by representing antigenic components of persistent infectious organisms to revitalise immune responses that are insufficient to effect clearance of the pathogen (therapeutic immunisation).
Contact:
Media enquiries:
In Europe ROW
Northbank Communications Ltd
Sue Charles, +44 (0)20 7886 8150
powdermed@northbankcommunications.com
or
In USA:
Schwartz Communications, Inc.
Erik Clausen, +1 781 684.6606
PowderMed@schwartz-pr.com
or
PowderMed Ltd
Dr Clive Dix, +44 (0)1865 501 549
CEO
clive.dix@powdermed.com
Source: PowderMed
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Substance Misusers with Hep C Are Treated Less Often Than Non-Users
SourceURL:http://www.gastrohep.com
The latest Journal of Viral Hepatitis shows that Hep C-infected veterans with mental illness or substance abuse are treated less often than those without such co-morbidities, even though therapy completion rates are similar.
Hepatitis C virus infection is more frequent in veterans than in nonveterans.
Up to 85% of Hepatitis C-infected veterans have psychiatric and/or substance use co-morbidities.
Prior to the 2002 National Institute of Health Consensus Conference, the co-morbidities included relative contraindications to antiviral therapy, assuming a poor adherence.
Dr Garcia-Tsao and colleagues compared eligibility, completion and response to antiviral therapy in Hepatitis C-infected veterans with and without these comorbidities.
Veterans who were anti-Hepatitis C-positive and had been seen at least once in a liver clinic between 1999 and 2002 were identified.
Records were reviewed for patient demographics and status of liver disease.
The team also assessed treatment eligibility, type of therapy, completion of therapy and virological response.
Sustained virological response did not differ significantly between groups – Journal of Viral Hepatitis
The research team compared patients with active mental illness or substance abuse with those without these comorbidities.
Of 697 anti-Hepatitis C-positive-patients, 647 Hepatitis C-RNA-positive patients were included.
Of these, 294 had mental illness or substance abuse and 353 controls.
The team reported that patient demographics, viral and liver disease characteristics were comparable between groups.
Patients with mental illness or substance abuse were considered ineligible for therapy more frequently and were treated less frequently than controls.
However, the team noted that completion of therapy and sustained virological response did not differ significantly between groups.
Hepatitis C-infected veterans with mental illness or substance abuse are being offered therapy and treated less often than those without such co-morbidities.
However, the researchers noted that therapy completion and sustained virological response rates are similar.
Dr Garcia-Tsao's team commented, "These findings challenges the perception that adherence is poorer in this patient population."
J Vir Hep 2006: 13(4): 235
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Novartis Licenses Hep C Drug
SourceURL:http://www.redherring.com
The Swiss pharma giant agrees to promote Idenix' experimental hepatitis C drug.
Novartis said Wednesday it has licensed a late-stage compound developed by Idenix Pharmaceuticals to treat the liver infection hepatitis C, marking an ambition move by the Swiss pharmaceutical giant to enter an already competitive market.
Idenix has received $25 million under the terms of the collaboration agreed in May 2003, and may receive up to $45 million more from Novartis as the drug, valopicitabine, hits final stage trial milestones.
If it is eventually approved in the U.S., Europe, and Japan, Idenix will get up to $455 million more and the two companies will co-promote the drug in the United States, United Kingdom, Spain, France, Italy, and Germany. Novartis will market the drug elsewhere.
"We remain optimistic for NMC283's [Valopicitabine's] prospects given the size of the combination-therapy market it addresses and assume estimated 2010 sales of $300 million," wrote Deutsche Bank analysts Mark Purcell and Paul Mann.
Others, however, were less enthusiastic.
"We believe this project will not reach the market until 2009 at best," wrote Natexis Bleichroeder analysts Florent Cespedes and Laure-Hélène Mercier.
They describe the project as ambitious, given the market size already shared between two major pharma players: Roche and Schering-Plough.
Roche makes a $1.38-billion combination treatment for the disease called Pegasys/Copegus. Schering-Plough makes Peg-Intron/Rebetol, worth $1.1 billion a year.
Valopicitabine is a pill intended to be taken once a day and work by inhibiting an enzyme critical in the hepatitis C virus' reproduction.
It is aimed at one genetic type of the virus, the most prevalent form, in which the current standard treatment has limited efficacy. More than 170 million people worldwide are affected by hepatitis C.
"Valopicitabine complements our current hepatitis pipeline and represents an important step forward in our mission to bring more effective and safer drugs to patients suffering from hepatitis C," said Novartis Pharma CEO Thomas Ebeling.
Novartis and Idenix are also working on two experimental drugs for hepatitis B, another virus that causes liver damage leading to liver scarring (cirrhosis) and liver cancer.
One of these is called telbivudine, in final stage clinical trials. The other drug, valtorcitabine, is in mid-stage human testing.
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Adrenal Insufficiency in Cirrhosis Is Related to Increased Mortality
SourceURL:http://www.gastrohep.com
Adrenal insufficiency in patients with cirrhosis and severe sepsis is related to disease severity, and is associated with hemodynamic instability, renal dysfunction, and increased mortality, reports the latest Hepatology issue.
Patients with cirrhosis are susceptible to bacterial infection.
This can result in circulatory dysfunction, renal failure, hepatic encephalopathy, and a decreased survival rate.
Severe sepsis is frequently associated with adrenal insufficiency, which may lead to hemodynamic instabity and a poor prognosis.
Dr Cheng-Shyong Wu and colleagues from Taiwan evaluated adrenal function using short corticotropin stimulation test.
The research team assessed 101 critically ill patients with cirrhosis and severe sepsis.
Adrenal insufficiency occurred in 52% of patients.
The patients with adrenal insufficiency had a higher hospital mortality rate when compared with those with normal adrenal function, at 81% vs 37%.
Survival with adrenal insufficiency was 15% vs 63% with normal adrenal function – Hepatology
The team observed that the cumulative survival rates at 90 days were 15% and 63% for the adrenal insufficiency and normal adrenal function groups, respectively.
The team found that the hospital survivors had a higher cortisol response to corticotropin.
The cortisol response to corticotropin was inversely correlated with various disease severity, Model for End-Stage Liver Disease, and Child-Pugh scores.
Acute physiology, age, chronic health evaluation III score, and cortisol increment were independent factors to predict hospital mortality.
The researchers noted that mean arterial pressure on the day of SST was lower in patients with adrenal insufficiency.
In addition, the team found a higher proportion of these patients required vasopressors.
Mean arterial pressure, serum bilirubin, vasopressor dependency, and bacteremia were independent factors that predicted adrenal insufficiency.
Dr Wu's team concluded, "Adrenal insufficiency is common in critically ill patients with cirrhosis and severe sepsis."
"It is related to functional liver reserve and disease severity and is associated with hemodynamic instability, renal dysfunction, and increased mortality."
Hepatol 2006: 43(4): 673-81
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March 30th, 2006
Hep C Genotype Determines Sustained Viral Response in Black Patients
www.gastrohep.com
Black patients with Hep C genotype 1, but not 2 or 3, have a lower sustained viral response rate than non-Blacks, and this is not explained by more frequent dose reductions of interferon and ribavirin, reports the latest Journal of Viral Hepatitis.
In previous Hepatitis C virus treatment studies, Black patients had a lower sustained viral response rate to interferon and ribavirin than non-Black patients.
In addition, Black patients had a higher frequency of Hepatitis C virus genotype 1 infection.
Dr Bräu and colleagues conducted a community-based study.
The research team determine whether Black patients have a lower sustained viral response rate independent of genotype. The team prospectively enrolled 785 patients, of which 25% were Black, 72% were White, and 3% were of other ethnic groups.
Patients with genotype 2 or 3 received interferon alpha-2b 3 MU 3 times weekly plus ribavirin of 1000 to 1200 mg/day for 24 weeks.
In patients with genotype 1, this treatment regime was given for 48 weeks. The researchers found that Black patients were more commonly infected with genotype 1.
The team also noted that these patients had a sustained viral response less frequently compared with non-Black patients.
50% with genotype 2/3 had sustained viral response vs 6% with genotype 1 – Journal of Viral Hepatitis
Within genotype 1, Black patients had a lower sustained viral response rate of 6% compared to 14% for non-Black patients.
However, this was not the finding within genotype 2 or 3, where 50% of Black patients had a sustained viral response rate vs 37% in non-Black patients.
The team observed that Black patients had lower baseline hemoglobin levels, and neutrophil counts. The Black patients required more frequent dose reductions of ribavirin, and interferon. However, the team found that dose reductions were not associated with lower sustained viral response rates while early treatment discontinuations were.
Independent predictors of sustained viral response were genotype 1, Black race, and advanced fibrosis, stages 3 and 4.
Dr Bräu and team concluded, "Black patients infected with Hepatitis C virus genotype 1, but not 2 or 3, have a lower sustained viral response rate than non-Black patients."
"This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions."
J Vir Hep 2006: 13(4)
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Comparing Endoscopic Treatments of Acute Gastric Variceal Hemorrhage
SourceURL:http://www.gastrohep.com/
The most recent Hepatology issue shows that the efficacy of endoscopic band ligation to control active gastric variceal hemorrhage is similar to N-butyl-2-cyanoacrylate injections, but the injection is associated with a lower rebleeding rate.
Progression of gastric variceal hemorrhage is poorer than esophageal variceal bleeding.
However, data on its optimal treatment are limited.
Dr Ming-Chih Hou and colleagues from Taiwan designed a prospective study comparing the efficacy of endoscopic band ligation and endoscopic N-butyl-2-cyanoacrylate injection.
The investigative team included liver patients with cirrhosis with or without concomitant hepatocellular carcinoma.
The team also assessed patients presenting with acute gastric variceal hemorrhage.
The patients were randomized into 2 treatment groups.
There were 48 patients in Group 1 who received endoscopic band ligation, and another 49 patients in Group 2 receiving N-butyl-2-cyanoacrylate injections.
The investigators found that both treatments were equally successful in controlling active bleeding.
The team noted that more patients who underwent endoscopic band ligation had rebleeding.
Rebleeding with endoscopic band ligation occurred in 2% vs 27% with injections – Hepatology
The 2-year and 3-year cumulative rate of rebleeding were 63% and 72% for endoscopic band ligation, and 27% for both periods with the injection.
The investigative team observed that rebleeding risk of endoscopic band ligation was sustained throughout the entire follow-up period.
Multivariate Cox regression showed concomitance with hepatocellular carcinoma, and the treatment method as independent predictors of rebleeding.
There was no difference in survival between the 2 groups.
The investigators noted that severe complications attributable to these 2 treatments were rare.
Dr Hou's team commented, "The efficacy of endoscopic band ligation to control active gastric variceal hemorrhage appears not different to N-butyl-2-cyanoacrylate injection, but the injection is associated with a lower rebleeding rate."
Hepatol 2006: 43(4): 690-7
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Hepatitis Program Bill Heads to Governor
SourceURL:http://www.desmoinesregister.com
Legislation calling for creation of a public health program on viral hepatitis is headed to Gov. Tom Vilsack for his expected signature.
The goal of the program is to distribute information and provide assistance with medical referrals to Iowans who are considered at higher risk for exposure to hepatitis C. The program would make available hepatitis A and hepatitis B vaccinations, as well as hepatitis C testing. House File 2493 was approved 47-0.
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Advocates Slam 'Racist' Drug Trial
SourceURL:http://www.nj.com
BY GEORGE E. JORDAN
Star-Ledger Staff
Schering-Plough defends hepatitis C test exclusion
Two patient advocacy groups yesterday accused Schering-Plough of racial discrimination for excluding African-Americans from a clinical trial of its new hepatitis C treatment.
They claim African-Americans, classified as "hard to treat" because they do not respond well to traditional hepatitis treatment regimens, were excluded so the clinical trial would generate high success rates.
"The bottom line is that African-Americans have been left out of this study to make the drug look good," said Judith Dillard of the Community HIV/AIDS Mobilization Project, or CHAMP, who de cried "the racist exclusion."
The Kenilworth-based company said its new treatment is for patients who do not respond to the standard combination therapy of interferon and ribavirin.
"It doesn't make any sense," said Bob Consalvo, a Schering- Plough spokesman, of the advocacy groups' criticism.
He said there were scientific reasons for excluding African- Americans from the Phase II clinical trial currently under way. That trial involves 300 patents worldwide to establish dosage ranges for the new protease inhibitor, code named SCH 503034. He said African-Americans would be included in another branch of the Phase II trail, which involves testing high dosages.
African-Americans, who make up a significant portion of the nonresponders, are an important part of the $3 billion hepatitis market. About 4 million Americans have been infected with hepatitis C, which is spread by contact with blood. It can be transmitted to babies at birth and by drug addicts sharing hypodermic needles.
For reasons researchers do not fully understand, a statistically significant percentage of African-Americans do not respond to traditional hepatitis C treatments. Further complicating the matter is that African-Americans who contract hepatitis C tend to have other health complications.
Brian Klein of the Hepatitis C Action & Advocacy Coalition said advocates held a March 16 conference call with Schering-Plough officials, including Clifford Brass, a top researcher.
"Schering-Plough has offered no valid safety reason for the exclusion," Klein said in a statement. "It is clear to us that Schering-Plough chose to exclude an entire racial group from the study to achieve the best efficacy results possible on the road to marketing the drug."
Consalvo, who participated in the conference call, said Schering-Plough scientists were concerned about the public perception of excluding African-Americans from the Phase II dosing trials.
"It was something, at first blush, that causes concern," he said. "We absolutely had the same concern."
After consultation with peer review boards and other hepatitis researchers, he said, the drug maker concluded it was "more prudent and scientific valid" to limit African-American participation until Phase III. That's when the range of dosages established in Phase II of the clinical trial can be tested to determine which is most efficacious treatment for the full range of patient groups.
In a statement, Dillard, who is black, dismissed Schering- Plough's explanation, and the addition of African-Americans to a high-dose test group.
"People of African descent are allowed into the trial as long as they are not African-Americans," she said. "My community needs equal access to early research so we can find treatments that work for us, not just a few token people brought in later for the high dose arm to try to cover up this racist exclusion."
George E. Jordan may be reached at gjordan@starledger.com or (973) 392-1801.
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March 31st, 2006
Safety of Nation's Blood Supply a Prime Concern for Hemophiliacs
SourceURL:http://www.belleville.com
BY DEBORAH L. SHELTON
St. Louis Post-Dispatch
ST. LOUIS - The first people hurt when the nation's blood supply gets tainted are likely to be those whose lives depend on transfusions.
That's why blood safety is a major concern of the more than 400 people with hemophilia and other clotting disorders who are attending a national conference in St. Louis starting today.
Since the 1980s, blood contaminated with HIV or hepatitis C has infected about 7,500 of the estimated 20,000 people with hemophilia living in the United States, said Carl Weixler, president of the Hemophilia Federation of America, which is hosting the two-day conference at the Sheraton West Port.
Of those, about 5,500 have died, he said.
Most were infected before a blood test was developed to screen for the viruses.
As of 2004, about 9,500 people in the United States have developed AIDS through exposure to contaminated blood products or tissue, according to the Centers for Disease Control and Prevention.
About 300,000 people in the United States with hepatitis C acquired their infection through a blood transfusion, according to the CDC.
"We say it's the worse medically induced holocaust ever," said Weixler, 44, who lives in Kentucky. Weixler learned in 1987 that he had been infected with HIV from a tainted transfusion. The following year, he learned he had hepatitis C.
Today, the chance of becoming infected with either HIV or hepatitis C is about 1 in 2 million, according to the CDC.
In recent years, newly emerging diseases such as West Nile virus and the human variant of mad cow disease have posed new challenges for blood safety.
"The things we do as a community to safeguard the blood supply will protect the entire country," Weixler said. "We are the canaries in the coal mine."
Hemophilia is a clotting disorder that causes excessive and painful bleeding during or after an injury. Bleeding can occur in joints, muscles, the abdominal cavity, the brain or other organs, or spill outside the body.
Kathy Seward MacKay said it's important to keep the issue of blood safety alive. Her husband, David, died from complications of hepatitis in 1997 at 33. He had hemophilia, and was infected with HIV and hepatitis C transmitted through a transfusion.
"The universal message is that we need to be vigilant in protecting the blood supply because we are all just one car accident away from relying on a transfusion," MacKay said. "There are still cases of HIV that slip through, not a lot, but it happens. And we don't know what the next bloodborne virus will be."
Before 1985, the Food and Drug Administration screened blood for only two diseases - syphilis and hepatitis B. Before tests for HIV were developed, rules were put in place in 1983 to prevent people from donating blood if they fell into one or more groups considered at higher risk of being infected, an FDA spokesman said.
The FDA licensed the first test for HIV in 1985 and the first test for hepatitis C in 1992.
After it was learned in 2003 that West Nile virus, which entered the country in the late 1990s, could be transmitted by blood, a test was developed in 2005 to screen for it.
Now there are new screening tests, and advances in technology have made the tests more likely to detect diseases.
"We have tests on top of tests now for hepatitis C and HIV," said Dr. Jerry Squires, senior medical officer for the national office of the American Red Cross.
The Red Cross provides about 45 percent of the nation's blood, the single largest supplier.
Some people with hemophilia now are transfused with a genetically engineered nonblood, or recombinant, product.
However, "a significant percentage is still dependent on the blood supply," Weixler said.
Corey Dubin, president of the Committee for Ten Thousand, an advocacy group for people with hemophilia, has been infected with HIV for 23 years and hepatitis C for 38 years. He said blood safety has improved greatly but he remains concerned about implementation of national standards.
The Red Cross has operated under an FDA consent decree since 1993, which stemmed from inspections that revealed persistent and serious violations of blood safety rules.
Today, there is growing concern about blood transmission of Creutzfeldt-Jakob disease, the human variant of mad cow disease. There is no screening test for it.
Three suspected cases have been identified in the United Kingdom, Squires said. Eating meat products contaminated with mad cow disease has been linked to more than 150 deaths worldwide from variant Creutzfeldt-Jakob disease, a rare and fatal nerve disease.
Anyone who has spent three months or more in the United Kingdom from 1980 through 1996, or who has spent five years in Europe from 1980 to the present, is asked not to donate blood in the U.S.
"We have people within the Red Cross, Association of American Blood Banks and other blood centers who spend a lot of their time looking at what new types of diseases might be transmitted by blood_what's on the horizon_what's the next virus, next bacterium that we have to worry about, that we will have to have a test for or donor deferral criteria for," Squires said.
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