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Week Ending: January 13th , 2007
Alan Franciscus
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January 6th , 2007
Caregiving: Lawford Says Get Tested – 3
http://www.upi.com
By ALEX CUKAN
UPI Health Correspondent
ALBANY, N.Y., Jan. 4 (UPI) -- Many don't get tested for hepatitis C, or HCV, because of the stigma of the way many contract the disease -- illegal drugs, sex with more than 10 partners, tattoos.
But there are other ways to catch the disease.
Because HCV is transmitted blood-to-blood, a person can also be infected by: blood transfusion, blood products, or organ transplant prior to HCV screening in 1992; unsterilized dental equipment that might contain blood; shared personal equipment that may contain blood like a razor and recreational sports injuries.
But judging from the mail this series of columns on HCV has generated, quite a few people in healthcare are insensitive, rude or downright insulting when a patient discloses he or she has HCV.
No one knows better than I that someone can get hepatitis via unexpected routes. In college, I was part of a group of seven students who served in student government at the University of Buffalo. We were very close. We saw each other every day and spent our evenings and weekends together.
Rick said he was tired a lot and not feeling well for most of our senior year. It slowed him down, but he didn't miss school or any big event. But who wasn't tired?
Rick was checked by doctors and nothing was found; his condition was chalked up to the rigors of applying to law school. He did very well on the LSATs and was accepted to Georgetown Law School.
When he went to Washington in the fall, he wrote me a letter each week and he didn't complain much about feeling ill. That next summer I saw him several times and while he looked skinnier, he seemed OK. It was at spring break of his second year in law school that I was shocked to see that he was very thin and looked jaundiced. Something was clearly wrong.
He was later diagnosed with liver cancer. Rick died the next spring. Rick had no risk factors for HCV of hepatitis B.
While many have said that baby boomers were party animals and "everyone was experimenting with drugs and alcohol" back then, our little group did not. We did not take drugs, did not have sex and no one had a tattoo. We drank a few beers and ate potato chips in Rick's basement for his end-of-semester party twice a year. His parents and grandparents were upstairs. Looking back, we seem to have bypassed much of the excesses of the '60s and '70s. What we did not understand is why someone age 23 would die of liver cancer.
Rick might have had hepatitis B or C -- both can lead to liver cancer, but my guess is was hepatitis C. He had a summer job in the county medical examiner's office and it's my guess he had some contact with contaminated blood. This was before AIDS and universal precautions and before HCV was confirmed in 1988.
But it really doesn't matter how a person gets infected; once infected treatment should be sought -- because you can die from this.
Christopher Kennedy Lawford had risk factors for HCV, which he details in his memoir, "Symptoms of Withdrawal: A Memoir of Snapshots and Redemption."
The 51-year-old actor and author tested positive for HCV in 2001 some 15 to 20 years after he had been infected -- the disease can lie dormant for a couple of decades.
He is sharing his experience of being diagnosed and successfully treated for HCV as part of a national education campaign called Hep C STAT! for Stop, Test And Treat. The campaign encourages individuals to stop and consider their own risk factors, get tested and, if infected, talk to a liver specialist about available treatment options.
Lawford suggests getting tested if a person has a risk factor, but a reader who leads a support group for people with HCV thinks everyone should get tested.
I agree. Since it is believed that the transmission of HCV may be possible through the inhaling of illegal drugs such as cocaine and crank when straws are shared among users, it is possible that a one-time use of cocaine in the 1980s could cause an infection 20 years later.
Although the majority of cases of HCV are believed to be contracted through illegal drug use, sex and tattoos, it doesn't really matter how a person gets infected, it matters that they get treatment and that they get treated with dignity and respect.
There wasn't much treatment for Rick, but today those with HCV have options.
Next: What treatment involves
Alex Cukan is an award-winning journalist, but she always has considered caregiving her real work. UPI welcomes comments and questions about this column. E-mail: consumerhealth@upi.com
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10,000 People Exposed to Hep C in Dublin
http://www.irishmedicalnews.ie
The Blood Borne Virus Forum has called for a regional hepatitis C strategy developed in 2004 to be published and rolled out nationally.
Addressing the Joint Oireachtas Health Committee, the Forum said some 10,000 people in Dublin are exposed to hepatitis C at present and people across the country are at risk of contracting the virus because they are not aware of the risks.
According to Mr Thomas Cumberton, a community development worker with Donore Community Drug Team in Dublin, people using straws and banknotes to snort cocaine are not aware of the risks of contracting hepatits C through blood to blood infection, through nosebleeds on to notes or straws.
He said: “they are astounded when I make them aware of the risks because they do not see themselves as drug users. When they use cocaine only at weekends, they do not see themselves as drug users because they do not take it every day or do not inject heroin.
“However, they are sharing the paraphernalia in toilets in pubs and nightclubs.”
Ms Jean Flanagan, a hepatitis C nurse specialist with the HSE in north Dublin, said there are approximately 14,000 drug users in Dublin and “statistical projections are that between 70 per cent and 80 per cent will be infected with hepatitis C if they inject longer than six months. This means that approximately 10,000 people in Dublin are exposed to hepatitis C at present. She told the committee, however, that there is “momentum within the prisons” for change to occur.
According to a study done by the Forum in 2000, some 37 per cent of prisoners were exposed to hepatitis C through antibodies and “we noticed up to 81 per cent prevalence in injecting drug users in prison”.
She added that people with a history of drug use who are recommended for treatment present problems since “they have many complex needs and these cannot often be met at hospital level as it requires more in-depth service provision. This is not currently available. We are seeking to develop support services to enable people to fully access treatment”.
Patients are not supposed to wait more than an hour in any outpatient setting or any more than two weeks to be seen by a specialist and, according to the Forum, this State-devised strategy is comprehensive.
However, Ms Flanagan said “no definitive policy or strategy is in place to deal with prevention and management of hepatitis C for the remaining majority (those who either do not know how they were infected through certain risk-taking or were infected through sharing drug-use equipment)“.
No allocated budget was made for the largest prevalence group making it difficult to develop services, she said.
According to Ms Flanagan there are services available to people who become infected, “however, more definitive needs such as counselling services and community supports are not available because no identifiable budget or strategy is in place. They use separate clinics to those infected by blood and blood produce and must wait.”
Treatment of one hepatitis C patient can cost approximately E16,500. One uncomplicated transplant can cost between E28,000 and E56,000 and the Forum envisages large numbers in the future.
As regards awareness, the Forum said there are currently only two community workers in the country providing information and delivering workshops to the community on hepatitis C and HIV.
Ms Flanagan added that some GPs are not very aware of the issues relating to hepatitis C “and it may not be high on their lists of priorities as so many illnesses exist.
“Patients may receive a diagnosis but may not have comprehensive information for follow-up and may not understand how chronic and serious a condition hepatitis C is.”
According to the Forum a regional hepatitis C strategy was drawn up in 2004 through the former ERHA and is currently under review again.
“As there is such a high prevalence of hepatitis C in Ireland, managing it and reducing future infection will require quite a lot of effort from many departments. We are looking at significant service developments. Harm reduction programmes are always controversial,” Ms Flanagan said.
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ELAD(R) Bioartificial Liver Trial in China Achieves Significance at Halfway Point
http://www.drugnewswire.com
SAN DIEGO and BEIJING, Jan. 4 /PRNewswire/ -- Vital Therapies, Inc. (VTI) announced today that it has completed the interim analysis of the first 45 patients enrolled in its controlled, randomized, two-center, single-treatment trial in China for the ELAD(R) (Extracorporeal Liver Assist Device) System. The trial is studying a bioartificial liver treatment in patients with chronic liver disease at Beijing Youan and 302 Military Hospitals in Beijing. The preliminary data indicate that ELAD has already achieved statistical significance in the endpoint of transplant-free survival.
"We have been very pleased with the clinical response we have seen in patients suffering from an acute exacerbation of chronic liver disease," said Duan Zhong-Ping, M.D., lead investigator and professor of Beijing Artificial Liver Treatment & Training Center and vice president, Beijing Youan Hospital. "Our center has treated a large number of patients with other mechanical and bioartificial liver treatments, and although the data with ELAD is preliminary, none has looked more promising than ELAD to impact a patient's long-term survival from a single treatment. The response of ELAD treated patients is best explained by regeneration of the liver since the improvement continues long after ELAD is discontinued."
ELAD augments the metabolic functions of a patient's liver, thereby enabling a bridge to transplant or liver recovery. The system differs from the mechanical filtration systems in development by using an immortalized line of human liver cells which, in addition to processing and removing blood toxins, can also supply to the patient metabolites synthesized by the liver, such as blood clotting proteins.
The statistics for the 42 evaluable patients showed that, at this point in time, the endpoint of transplant-free survival has already achieved statistical significance. The Kaplan Meier survival curves showed a p value for the difference between the treated and control groups of 0.03 (Wilcoxon basis). A p value of 0.05 and below is generally accepted as the standard for statistical significance in such a trial.
"While the p values will change as data continues to be generated, it is encouraging to be achieving these kinds of values halfway through the trial," added Dr. Duan.
Consistent with the recoveries that have been noted by the physicians among the patients in the trial, other measures also indicate the success of the trial to date, such as:
- 8 of 14 (57 percent) controls have either died or had to be transplanted versus 7 of 28 (25 percent) treated patients.
- Biochemistry measures such as bilrubin, INR, Albumin and MELD scores, and clinical observations such as ascites, appetite and fatigue are also showing expected improvements in treated patients versus controls.
"VTI is grateful to its outstanding staff in San Diego and in China for the smooth implementation of the trial," said Terry E. Winters, Ph.D., VTI chairman and CEO. "We are also grateful to the tireless staff at the hospitals for treating the patients and to the Chinese authorities for their cooperation in importing ELAD into China to treat these very sick patients. We have received positive clinical response and strong support from our clinical trial physicians as well as our Clinical Advisory Board. Additionally, we are thrilled at the flawless scale up of manufacturing and the logistics of providing ELAD cartridges to China. This has given us the confidence to be able to provide commercial quantities of ELAD cartridges to China from our plant in San Diego starting with the planned market launch in late 2007."
These data were reviewed internally with the Vital Therapies Clinical Advisory Board (CAB), which includes eight prominent U.S. and European clinical experts in the field of hepatology and liver transplant surgery. CAB Chairman, J. Michael Millis, M.D., professor of Surgery and chief, Section of Transplantation University of Chicago, said: "This is clearly the most promising data on artificial livers ever generated. This experience in China and these data will provide the knowledge to enable the CAB to assist in developing an excellent protocol for the phase 3 U.S. FDA studies, which the company plans to begin in late 2007."
VTI is now seeking a Series C private equity financing in the United States and China for both the commercial launch in China as well as the implementation of phase 3 studies in the United States.
About the Study
This study is a controlled, randomized, two-center, single-treatment trial in China for the ELAD(R) (Extracorporeal Liver Assist Device) System. The trial is being run at Beijing Youan and 302 Military Hospitals in Beijing and will continue enrolling until the planned 90 patient total is achieved. The first patient was enrolled in March, and the analysis covers the nine months through November 30. At that time, 26 of the 42 patients had either completed the 84 day trial, died or been transplanted. Patient enrollment criteria included seriously ill patients with acute on chronic liver failure who were estimated to have a 50 percent probability of mortality in 30 days.
There have been no significant safety issues attributable to ELAD. The sole serious adverse event was not attributed to ELAD. Thrombocytopenia, which was expected in this patient group, was handled with platelet transfusions. The live C3A cell cartridges for this trial have been grown at VTI's production facility in San Diego and shipped to China within a 24 hour window to treat each patient.
This trial has been conducted in China under an allowance from the State Food and Drug Administration (SFDA). At the conclusion of the trial, the results will be submitted to the SFDA and may also be submitted to regulatory authorities in other countries as part of the basis for allowance of pivotal trials.
About Liver Disease
According to the World Health Organization (WHO), severe liver disease annually affects approximately 12 million patients worldwide. In China, hepatitis is the third most prevalent disease, over 140 million people are infected with a hepatitis virus and 32 million people have active viral liver disease. In China, over 400,000 people die each year from liver disease. Official estimates suggest that China's yearly medical expenses for liver disease infections are more than $12 billion.
About ELAD(R)
The ELAD(R) system provides important metabolic support for patients with severe liver failure, thereby enabling a bridge to recovery or transplant depending on the type and severity of liver disease. The system consists of four cartridges containing cells that function like a normal human liver by metabolizing toxins and removing waste products while delivering essential proteins back into the plasma. These cartridges are incorporated into a blood pumping system at the patient's bedside and enable continuous patient treatment for up to 12 days. The key to the performance of ELAD is its utilization of a proprietary human hepatocyte cell line, C3A, an immortalized cell line that can be grown, stored and shipped worldwide.
About Vital Therapies, Inc.
Vital Therapies, Inc. (VTI) is a private San Diego-based liver therapy company. VTI is developing the first human-liver cell-based system, ELAD(R) (Extracorporeal Liver Assist Device), which provides important metabolic support for patients with severe liver failure. For more information, please visit: www.vitaltherapies.com
Source: Vital Therapies, Inc.
CONTACT: investors, Aron Stern of Vital Therapies, Inc.,
+1-858-673-6840, or astern@vitaltherapies.com; or media, Kelly McKenna of
MS&L, +1-415-293-2808, or Kelly.mckenna@mslpr.com, for Vital Therapies, Inc.
Web site: http://www.vitaltherapies.com/
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Impact of Infection with both HIV and Hepatitis C Virus
http://www.emaxhealth.com
Although many individuals infected with the hepatitis C virus (HCV) are naturally able to control levels of the virus with their immune systems, those who also become infected with HIV, the virus that causes AIDS, may lose that ability. In a report in the December issue of PLOS Medicine, a group of researchers from the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH) report one of the first studies of how HIV infection impacts immune system functions involved with HCV control. Their findings suggest that beginning antiretroviral therapy earlier than is generally recommended may help preserve HCV control in patients infected with both viruses.
"The global burden on health of chronic viral infections is immense, and HCV and HIV are chief among culprit viruses," says Arthur Kim, MD, of PARC-MGH, co-first author of the PLOS Medicine report. "Due to shared routes of transmission, infection with both viruses is common. Unfortunately, HCV behaves as an opportunistic infection in the presence of HIV and is becoming a leading cause of illness and death in persons with HIV."
In order to examine immune system factors associated with spontaneous control of HCV and how that control is altered by HIV infection, the researchers enrolled four groups of participants: 60 were infected with both viruses, and half of those had low HCV levels upon entering the study. The other two groups of 17 participants were infected with HCV only, with one group successfully controlling viral levels. Spontaneous HCV control is known to rely on the activity of CD4 helper T cells specifically targeted against the virus, and destruction of CD4 cells by HIV underlies the immune deficiency that characterizes AIDS. Therefore the researchers measured participants' T cell response to HCV at the outset of the study and at two- to six-month intervals during the study period.
The results showed that those individuals able to maintain low HCV levels in spite of HIV coinfection had stronger virus-specific responses for both CD4 T cells and the CD8 "killer" T cells than did those with elevated HCV counts. Not surprisingly, participants infected only with HCV had even more powerful antiviral T cell responses. About a quarter of those infected with both viruses who originally controlled HCV levels lost control during the two-and-a half-year study period, and their increased virus levels corresponded with an overall drop in CD4 T cells. None of the viral controllers who were infected with HCV alone had any increase in viral levels during the study period. Loss of protective responses and susceptibility to recurrent HCV infection may help to explain the higher rates of persistent HCV observed in subjects who are HIV/HCV coinfected, compared to those with HCV alone.
In analyzing factors that might be associated with the loss of HCV control in those infected with both viruses, the researchers made a surprising discovery. The factor most powerfully associated with maintaining HCV control was not the CD4 T cell count upon entering the study but the lowest previously recorded or 'nadir' CD4 count. That finding suggests that, for individuals infected with both viruses, beginning antiretroviral treatment before CD4 levels drop too low to maintain HCV responses may be desirable.
The researchers also found that, among those whose HCV levels rose, individuals who maintained some T cell responses had lower viral levels than did those with little or no T cell response. This suggests that the immune system retains a level of secondary immunity against HCV - the kind of 'memory' response against a previously encountered pathogen seen in many infections.
"Currently a nationwide trial is recruiting people for a study examining whether earlier treatment of HIV will improve hepatitis C treatment outcomes," Kim says. "Part of this study will investigate how earlier treatment may affect immune responses. It also will be important to follow the impact of loss of HCV control on liver disease, since this will probably have important consequences for patients with HIV." Kim is an instructor in Medicine at Harvard Medical School.
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Risk Factors for Diabetes Following Liver Transplant
http://www.docguide.com/
HOBOKEN, NJ -- January 4, 2007 -- A new study on risk factors of new-onset diabetes mellitus (NODM) following liver transplant found that a history of obesity, impaired fasting glucose and hepatitis C infection (HCV) paired with the use of a particular immunosuppressant are associated with an increased risk of NODM. Since all of these factors can be detected prior to undergoing a transplant, treatment should be tailored to the patient's risk.
The results of this study appear in the January 2007 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS).
The development of NODM after a liver transplant is associated with increased cardiovascular disease and death, a higher incidence of rejection, more infections and reduced quality of life. It is therefore likely that the survival rate following liver transplant could be improved by reducing the incidence of NODM. However, the exact incidence of NODM is not clear because existing studies have used varying criteria. In addition, no definitive risk factors have been clearly established.
Immunosuppressive drugs are known to contribute to diabetes, although this effect varies depending on the drug; calcineurine inhibitors are less likely to cause diabetes than steroids.
Led by Faouzi Saliba, MD, of the Hôpital Paul Brousse in Villejuif, France, the study included 211 patients from 10 transplant centers in France who had undergone a liver transplant between October 2003 and June 2004. Patients' clinical records were reviewed and their fasting blood glucose levels were recorded 3, 6, 12 and 18 months after undergoing the transplant. For those with NODM, the date of diagnosis was noted, along with the immunosuppressive treatment and diabetes management they had received.
The results showed an incidence of NODM of 22.7 percent, with the majority of the cases diagnosed within three months of transplant. In addition, 12.4 percent of the patients with normal glucose levels pre-transplant developed impaired fasting glucose (IFG). The risk factors for developing NODM included HCV infection (especially when combined with the immunosuppressant tacrolimus), IFG prior to the transplant, and a history of clinical obesity. In addition, the presence of at least two cardiovascular risk factors and a history of either gestational diabetes or having given birth to a baby weighing over 4 kilograms also increased the risk of NODM.
The authors note that since abnormal glucose regulation prior to transplantation has been implicated as a possible risk factor of NODM and IFG emerged as a strong predictor of the condition in the current study, pre-transplantation glucose screening may be important in helping to predict NODM.
"Our study suggests that it may eventually be possible to derive a composite risk factor equation for the development of NODM following liver transplantation with appropriate weighing for each variable, perhaps similar to the risk assessment instruments developed for the primary prevention of cardiovascular disease," the authors conclude.
In an accompanying editorial in the same issue, Paul J. Thuluvath, MD, FRCP, of the Johns Hopkins University School of Medicine in Baltimore notes that the study confirms that a significant number of patients develop NODM after liver transplantation, however almost all of them were on steroids and developed the disease within 3 months of transplant.
A previous study showed that 24 of 88 patients were found to have diabetes mellitus at the end of the first year post-transplant, but by the end of the second year only 8 of them had the condition.
"This may suggest that many patients in the cohort studied by Saliba et al. may not have diabetes with longer follow up especially when steroid is discontinued," the author states.
He adds that the increased incidence of NODM in patients with HCV is noteworthy and confirms the trends seen in previous studies, although the mechanisms of how this happens remain unclear.
"It is probable that NODM will have an impact on long-term survival, and therefore it is important to continue to study the impact of NODM and its intervention on long-term graft and patient survival in patients with and without HCV," the author concludes. "As we develop newer immunosuppressive drugs, we now have the ability to improve the diabetic control by tailoring and manipulating the medications in liver transplant recipients."
The journal Liver Transplantation is published on behalf of the societies by John Wiley & Sons, Inc.
REFERENCES:
Article: "Risk Factors for New-Onset Diabetes Mellitus Following Liver Transplantation and Impact of Hepatitis C Infection: An Observational Multicenter Study," Faouzi Saliba, Mohamed Lakehal, Georges-Philippe Pageaux, Bruno Roche, Claire Vanlemmens, Christophe Duvoux, Jérome Dumortier, Ephrem Salamé, Yvon Calmus, Didier Maugendre, Liver Transplantation; January 2007 (DOI: 10.1002/lt.21010).
Editorial: "Is There a Link Between Hepatitis C Virus and New Onset of Diabetes Mellitus After Liver Transplantation?" Paul J. Thuluvath, Liver Transplantation; January 2007 (DOI: 10.1002/lt.21024).
SOURCE: John Wiley & Sons, Inc.
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Liver Cell Created from Subcutaneous Fat
http://www.yomiuri.co.jp/
The Yomiuri Shimbun
A team of doctors has succeeded in creating a hepatic cell out of subcutaneous fat, a development that might lead to a regenerative medicine technique that would enable patients with hepatitis or cirrhosis to have their livers repaired.
More than 3.5 million people in Japan suffer from the diseases, and clinical application of the team's findings is being eyed for sometime in the next few years.
According to the National Cancer Center Research Institute and the International Medical Center of Japan, the doctors used a cell called mesenchymal stem cell that accounts for about 10 percent of the subcutaneous fat tissue of a human body, believing the cell has the potential to change into different cells that make up various organs or other tissues. In the research, five grams of subcutaneous fat was taken from each of seven patients who underwent abdominal surgery at the International Medical Center of Japan, and the mesenchymal stem cells were extracted from the fat tissues.
The researchers added three types of proteins that prompt growth to the stem cells, and incubated them for about 40 days.
As a result, nearly all cells turned into hepatic cells, according to the doctors.
At least 14 types of proteins, including albumin--one of the major components of blood--and drug-metabolizing enzyme, that are known to be synthesized only in the human liver, were detected in the incubated cells, the doctors said. Then the researchers injected about 1 million incubated cells into lab mice that were artificially made to develop liver malfunctions.
The ammonia level in the mice, which had been rising before injection, dropped to a normal level in one day, the doctors said.
Regenerated subcutaneous fat cells have already been used in some clinical practices such as breast reconstruction, but this is the first time in the world that more than one function for the human liver has been observed in the regenerated cells, according to the research team.
While the most highlighted technique in regenerative medicine is embryo-stem cell development, it has been criticized because it utilizes fertilized egg cells.
The use of subcutaneous fat cells, on the other hand, faces fewer obstacles in terms of life ethics, and are advantageous because they can be taken from patients' own bodies to eliminate the risk of rejection, the doctors said.
Takahiro Ochiya, head of the Section for Studies on Metastasis Research at the National Cancer Center Research Institute, who led the team of researchers, said: "I would give 60 out of 100 if I were to grade the hepatic cells we made from subcutaneous fat for their performance. They barely pass the test at the moment, but we would like to go on working to make cells that perform like real hepatic cells."
Yasuyuki Sakai, associate professor of the Center for Disease Biology and Integrative Medicine at the University of Tokyo, hailed the team's findings as a "remarkable achievement," but pointed out that several issues need to be addressed before clinical application. "To achieve a certain level of therapeutic effect from a patient with liver disease, more than 10 billion hepatic cells have to be implanted into his or her liver. To reach the goal of clinical application, researchers must develop a technique to more efficiently make hepatic cells from a large amount of subcutaneous fat," Sakai said.
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January 8th, 2007
Phynova Obtains FDA Approval of its IND to Enter Into a Clinical Trial of PYN17 for the Treatment of Chronic Hepatitis C
http://www.pharmalive.com
OXFORDSHIRE, England, Jan. 8, 2007-Phynova Group PLC (AIM: PYN), a developer of pharmaceuticals derived from Chinese botanical drugs targeting viral and metabolic diseases and cancer, is pleased to announce that its first drug candidate will shortly enter into clinical trials in the US.
The Group has received approval from the US Food and Drug Administration (FDA) for an Investigational New Drug (IND) application in respect of its lead drug candidate PYN17, to proceed to the clinical trial phase. This trial will evaluate 40 patients in the USA with chronic hepatitis C (CHC).
Phynova's trial is expected to begin in Q2 2007 and will investigate the effect of PYN17 on safety and efficacy parameters. These include the key symptoms associated with CHC such as fatigue, poor concentration and abdominal pain leading to a marked deterioration in an individual's quality of life. There are no treatments currently available to effectively manage these disease symptoms.
PYN17 is a botanical drug derived from Chinese medicinal plants with a long history of safe use in humans.
Hepatitis C is a major viral disease with over 200 million sufferers worldwide including over four million in the USA.
Phynova's drug pipeline includes PYN18, an anti-viral drug for the treatment of hepatitis C and PYN22, an anti-obesity drug. In both cases patents have been filed to support these drug programmes.
Robert Miller, the CEO of Phynova said "This is a major milestone for us, validating our business model to shorten the time it takes to progress new drug candidates into human trials by developing products derived from Chinese
medicines which have a long history of use in humans. The US is the largest pharmaceutical market in the world and this approval sets us on the path to targeting that market."
Phynova
Phynova was founded in July of 2002 to develop drugs that satisfy unmet therapeutic needs in areas such as: infectious disease, metabolic disease and cancer. The Company's headquarters are located in the Long Hanborough near Oxford and it has a laboratory at Warwick Horticultural Research Institute.
Phynova is developing Drug Candidates which are mainly derived from botanical medicines and have proved effective and safe in clinical use in China. The Chinese have been using botanical medicines for thousands of years and over that time have built up a wealth of knowledge and expertise in the medicinal use of plants. In a number of areas these medicines are used in China in circumstances where there is an unmet therapeutic need in the West. Since all of Phynova's Drug Candidates are derived from plants, its drugs will be produced from sustainable resources.
For further information, please contact:
Phynova Group PLC
Robert Miller, Chief Executive
01865 784880
Buchanan Communications
Diane Stewart/ Tim Anderson
020 7466 5000
Nabarro Wells & Co. Limited
Marc Cramsie
020 7710 7400
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Kaiser Health Disparities Report: A Weekly Look at Race, Ethnicity and Health
http://www.kaisernetwork.org
Studies Examine Increasing Black Physician Population, Incidence of Hepatitis C-Related Condition Among Blacks, Whites
The following summarizes news coverage of studies on black physician recruitment and hepatitis C in blacks and whites.
Black physicians: An increase in the number of black physicians nationwide would improve health outcomes in black communities and among the poor, according to a study published in the journal Health Services Research, the Kansas City infoZine reports. Lead researcher Daniel Howard from the Institute for Health, Social, and Community Research at Shaw University and colleagues found that while many blacks are visiting black physicians, some of those providers are retiring and often are being replaced by foreign-born physicians, who might not be as familiar with black culture. Previous research has found a connection between improved outcomes and access to care and the availability of black physicians, who often better understand cultural and social contexts of illnesses and treatment preferences in the black community, infoZine reports. Researchers recommend that the health care workforce policy be inclusive of blacks and incorporate cultural competency training (Kansas City infoZine, 1/5). An abstract of the study is available online.
Hepatitis C: Blacks with hepatitis C are about 50% less likely than whites to have hepatic steatosis, or fat in the liver, a condition that indicates a more-advanced stage of the disease, according to a study published in the January issue of Hepatology, HealthDay News/Forbes reports. The study, lead by Hari Conjeevaram of the Division of Gastroenterology at the University of Michigan, examined the racial differences in steatosis in people with hepatitis C, genotype I and found that of 194 black participants and 205 white participants with hepatitis C, 61% of blacks had hepatic steatosis, compared with 65% of whites. The findings were then adjusted to consider other risk factors such as body-mass index and insulin resistance (HealthDay News/Forbes, 1/7). An abstract of the study is available online.
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Harm Reduction Center Screens for HIV, Hepatitis
http://www.newsreview.info
The board of directors of the Douglas County AIDS Council/HIV Resource Center has changed the organization’s name to Harm Reduction Center of Southern Oregon.
The primary goal of the Harm Reduction Center is to make the community safer by making HIV and hepatitis screening routine for high-risk individuals. The center offers presentations, introducing HIV and Hepatitis C prevention to teens at area public, private, charter and alternative schools; youth shelters; and youth treatment and juvenile detention programs in Douglas, Josephine, Coos and Curry counties. The center also brings harm reduction presentations to every treatment program, shelter and county jail in the 9,900-square-mile area and to the state prison in North Bend.
In Douglas and Josephine counties, the center offers clean syringes as a primary vehicle for reaching out-of-treatment injection drug users. The center also offers a 20-minute HIV Ora-quick test, nutritional supplements, wound care products, information and referrals.
Information: 440-2761.
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January 9h, 2007
Caregiving: Lawford Says Get Tested – 4
http://www.upi.com
By ALEX CUKAN
UPI Health Correspondent
ALBANY, N.Y., Jan. 9 (UPI) -- Hepatitis C, or HCV, is the most common chronic, blood-borne viral infection in the United States and is four times more prevalent than HIV, yet 70 percent don't know that they have the infection.
HCV is often referred to as the "silent epidemic" because most patients never develop symptoms -- nearly half of all infected people don't have any.
The most common symptom of HCV is fatigue, but there can also be flu-like symptoms as well as stiffness and aching of the joints. Patients with advanced liver disease may have a loss of appetite, nausea, weight loss and jaundice.
"It's asymptomatic for many, so it has to be picked up with a HCV blood test. It won't show up in regular blood work -- and the trouble is the longer you wait, the less effective the treatment," actor and author Chris Lawford told UPI's Caregiving. Lawford, the author of Symptoms of Withdrawal: A Memoir of Snapshots and Redemption, is sharing his experience with HCV to help increase the diagnosis and treatment of the disease.
Lawford says he tested positive for HCV in 2001, and although he had no symptoms, HCV had already begun to damage his liver. Four years after treatment with pegylated interferon and ribaviron there is no detectable trace of the virus in Lawford's blood.
"The treatment is difficult -- interferon once of week and than ribaviron. You feel like you have the flu for 24 hours to 36 hours, but it gets easier and easier," Lawford told UPI's Caregiving. "I was on a six- to eight-month protocol, but I maintained an active lifestyle -- it was absolutely manageable."
Treatments available today have been shown in clinical trials to reduce the virus to undetectable levels in more than half of patients, according to the Web site www.HepCSTAT.com.
"My doctor said, 'You have a life-threatening illness and there is a cure -- it worked for me and I feel very, very lucky," Lawford said. "A patient may have to adjust to the medication. It does get tiring. The most difficult is the mental part -- you can't wait for it to be over."
There are six different strains or "genotypes" of the virus, although only three of these are commonly seen in the United States.
The most widely used test is designed to detect antibodies to one or more HCV proteins. However, in most instances of patient testing, the clinical question is not whether the person has been exposed to HCV but whether the individual is currently infected, which requires testing of another sort: HCV RNA, according to Dr. D. Robert Dufour, chief of pathology and laboratory medicine at the Veterans Affairs Medical Center in Washington.
There are two major types of HCV RNA testing: one qualitative -- which simply tells whether the virus is present or not -- and one quantitative -- which tells how much of the virus is present.
But because antibody and HCV RNA tests do not indicate which strain of HCV an individual is infected with, tests to determine the genotype have been developed. Most rely on detecting sequences in the RNA that correspond to those of the six known strains of HCV.
There are three potential treatments for individuals positive for HCV RNA: interferon monotherapy, standard interferon plus ribaviron and pegylated interferon plus ribaviron. Combination treatments are more effective than interferon monotherapy, but some patients cannot take ribaviron, said Dufour.
The goal of treatment is to eradicate HCV RNA from the body, which correlates with the absence of HCV RNA in the blood after treatment has been stopped for six months.
Current studies suggest that HCV will probably never return in patients with a sustained virologic response unless they are once again exposed to this virus. No vaccine currently exists to prevent infection in an individual exposed to HCV, according to HepCSTAT.com.
HCV is a chronic liver disease, and 20 percent to 30 percent of patients with HCV can develop cirrhosis up to 20 to 30 years after infection. Some 5 percent of all HCV patients will develop liver cancer or liver failure and require a liver transplant.
"The point of this outreach is to get people tested. We have better treatment -- if people are at risk they can get the test done in a doctor's office or at home," Lawford said. "Many people don't know there is a treatment. If only one person from this outreach gets tested, that's a win."
-- Next: HCV and alcohol
Alex Cukan is an award-winning journalist, but she always has considered caregiving her real work. UPI welcomes comments and questions about this column. E-mail: consumerhealth@upi.com
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InterMune Achieves Manufacturing Milestone in HCV Collaboration with Roche
http://www.therapeuticsdaily.com
PR Newswire Europe
BRISBANE, Calif., Jan. 9 /PRNewswire-FirstCall/ -- InterMune, Inc. announced today that it successfully completed large-scale synthesis and delivery to its partner Roche of active pharmaceutical ingredient for hepatitis C virus (HCV) drug candidate ITMN-191, currently in a Phase 1a clinical trial. The milestone triggered a $10 million payment to InterMune from Roche as part of the companies' collaboration to develop and commercialize novel protease inhibitors for the treatment of HCV.
"InterMune has successfully executed key steps in the manufacture of a very sophisticated protease inhibitor molecule and transferred the materials to Roche for future studies," said Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune. "We're pleased to have completed these crucial manufacturing-related activities and that our HCV clinical development program that is partnered with Roche is off to an excellent start."
About HCV and ITMN-191
According to the Centers for Disease Control and Prevention (CDC), an estimated 3.9 million Americans (1.8%) have been infected with HCV, of whom 2.7 million are chronically infected. According to the World Health Organization (WHO), it is estimated that there are 170 million people worldwide afflicted with this disease. Currently available therapies are insufficient, creating a need for the development of novel therapeutic approaches. ITMN-191, the lead HCV NS3/4A protease inhibitor compound from the InterMune discovery program, has demonstrated in preclinical studies its potential to be an important drug candidate because of its favorable cross resistance and potency profiles, as well as pharmacokinetic results that support the exploration of twice-daily oral dosing in HCV patients.
About InterMune
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes two Phase III programs evaluating possible therapeutic candidates for treatment of patients with IPF. The INSPIRE trial is evaluating Actimmune(R) (interferon gamma-1b) and the CAPACITY program is evaluating pirfenidone. The hepatology portfolio includes the HCV protease inhibitor compound ITMN-191 in Phase 1a, a second-generation HCV protease inhibitor program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit http://www.intermune.com/.
Except for the historical information contained herein, this press release contains certain forward-looking statements that involve risks and uncertainties, including without limitation the statements related to the progress, future patient enrollment in and timing of InterMune's clinical trials and announcements of results thereof. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune's actual results could differ materially from those described in InterMune's forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading 'Risk Factors' in InterMune's annual report on Form 10-K filed with the SEC on March 13, 2006 (the "Form 10-K") and updates included in the most recent Form 10-Q filed with the SEC on November 7, 2006 (the "Form 10-Q"), and other periodic reports filed with the SEC, including the following: (i) risks related to the development of our product and product candidates; (ii) risks related to timely patient enrollment and retention in clinical trials, including the use of third parties to conduct such clinical trials; (iii) risks related to achieving positive clinical trial results; (iv) risks related to the uncertain, lengthy and expensive clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues; (v) risks related to our collaboration agreement with Roche; and (vi) risks related to our intellectual property rights. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the Form 10-K and InterMune's other periodic reports filed with the SEC.
InterMune, Inc.
CONTACT: InterMune, Inc. Investor Relations Dept, +1-415-466-2242, or ir@intermune.com; or media, Pam Lord of Porter Novelli Life Sciences, +1-619-849-6003, or plord@pnlifesciences.com, for InterMune, Inc.
Web site: http://www.intermune.com/
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January 10th, 2007
Axed Prison Tattoo Program Too Short to Prove Worth: Public Health Agency Head
http://ca.news.yahoo.com
TORONTO (CP) - The head of the Public Health Agency of Canada says the government's cancellation of a pilot project designed to limit the spread of infectious diseases by providing sanitary tattooing services had too little time to prove its worth.
Dr. David Butler-Jones says the single year given the pilot project is inadequate to establish whether such a program affects rates of HIV, hepatitis C and other infectious diseases.
His comments appear online in an article published by the Canadian Medical Association Journal.
Public Safety Minister Stockwell Day chopped the $600,000 program, calling it a waste of taxpayers' dollars that wasn't "demonstrably effective."
A national survey suggests 45 per cent of prisoners get tattoos and 17 per cent have body piercing, often using dirty needles. The program trained an inmate to provide sterile tattoos to fellow prisoners under staff supervision.
Butler-Jones, whose agency is charged with tracking and preventing illness while promoting good health practices, says he wasn't consulted before the Corrections Canada program was ditched.
"When you have multiple inputs and factors, it's very difficult to do that in one year," he said of the trial. "In general, the best you could probably hope to see would be some change in behaviours that serve as a surrogate to, you would anticipate, lower rates of infection."
"But you need to do the research in a rigorous enough way, for long enough, to determine whether that behaviour is sustained."
Butler-Jones said he believes harm-reduction measures like safe tattooing are a key component of reducing the spread of infectious diseases in prisons.
"This was one method that, from a public health perspective, makes sense as one of the initiatives of a broader strategy or program," he said. "And in this case, the government has decided that it is not something that they want to continue."
Although not conclusively proven, it's likely "you run the risk of increasing" infection, Butler-Jones added. "But in terms of (the government's) overall strategy, if you reduce the risk in other ways, you end up with a 'disease-neutral outcome.' "
"It's too soon to tell exactly what's going to happen."
The prevalence of infectious diseases in Canadian prisons has long been of concern to public health officials, along with the cost of treating sick inmates.
Corrections Canada told the CMAJ that more than 3,300 male and female inmates in Canada's 54 prisons had hepatitis C in 2004, for a prevalence rate of 25 per cent, and almost 2,500 were released into the community that year. As well, almost 200 prisoners were infected with HIV.
The annual cost of treatment is $29,000 per inmate for HIV and $26,000 each for hepatitis C.
Day declined to release an evaluation of the pilot project undertaken by Corrections Canada's audit branch, saying it's in the final stages of translation and unavailable. The pilot was launched in August 2005 with money from the $85-million federal AIDS Initiative, which is overseen by the Public Health Agency.
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January 11th, 2007
Court Permanently Halts Abbott's Sale of HCV Genotyping Products for Infringing Innogenetics' Patent
http://www.wisbusiness.com
GENT, Belgium and MADISON, Wisc., Jan. 11 /PRNewswire-FirstCall/ -- Innogenetics announced that yesterday the U.S. District Court for the Western District of Wisconsin entered a permanent injunction against Abbott Laboratories, enjoining Abbott from any further sales or use of products, including components, that infringe on Innogenetics' patented Hepatitis C Virus (HCV) genotyping technology. The court's injunction also prohibits Abbott from exporting components of the infringing products to foreign countries.
In September 2006 a jury unanimously found that Abbott had willfully infringed Innogenetics' U.S. patent No. 5,846,704 ("the '704 patent"), covering a method of genotyping HCV, and awarded Innogenetics $7 million in damages.
Yesterday's ruling came at the close of an evidentiary hearing to determine the potential public impact of a permanent injunction against Abbott. At the hearing, the court reiterated its finding last week that Innogenetics suffered irreparable harm from Abbott's infringement. The court further found that Innogenetics has the capacity to serve the needs of the Hepatitis C diagnostic market and that Innogenetics had taken all reasonable steps to comply with Good Manufacturing Procedures set out by the FDA.
"This case is a clear example of why patent protections exist. Small, forward-looking companies must be able to protect their innovations from misappropriation by larger more powerful competitors," said Frank Morich, CEO of Innogenetics. "I hope that Abbott has learned through this process that other people's intellectual property can not be ignored in the pursuit of profit."
In September 2005, Innogenetics sued Abbott Laboratories alleging that Abbott was infringing the company's '704 patent, which covers a method of genotyping the Hepatitis C Virus. The court found the patent was infringed as a matter of law. On September 1, 2006, a jury returned a unanimous verdict for Innogenetics that the '704 patent was valid in all respects. On September 8, 2006, the same jury unanimously found that Abbott's actions had been willful, and directed Abbott to pay Innogenetics $7 million in damages related to the infringement up to the time of the trial. On January 4, 2007, the judge in this case dismissed Abbott's requests for a new trial, affirmed the jury's finding that Abbott infringed the patent, that the patent was valid in all respects and approved the award of $7 million in damages. The judge overturned the jury's unanimous finding that Abbott's infringement had been willful. Today's evidentiary hearing was to determine whether or not Abbott should be permanently enjoined from selling products that infringe Innogenetics' patent.
Innogenetics is currently evaluating the total case and its legal options including an appeal on willfulness.
About Innogenetics
Innogenetics is an international biopharmaceutical company building parallel businesses in the areas of specialty diagnostics and therapeutic vaccines.
In 2005, total revenues (product sales, royalties, and license fees) reached euro 48.6 million, with a profitable Specialty Diagnostics Division. Its Diagnostics Division develops a large number of specialty products covering three areas: infectious diseases (hepatitis C, hepatitis B, and HIV), genetic testing (HLA tissue typing and cystic fibrosis), and neurodegeneration (Alzheimer's disease). In its Therapeutics Division, Innogenetics focuses on the development of therapeutic vaccines to address unmet medical needs in the field of infectious diseases, with two compounds now in clinical trials (hepatitis C in phase IIb and hepatitis B in phase I).
Founded in 1985, Innogenetics is listed on Euronext Brussels [Ticker: INNX]. Innogenetics' headquarters are in Gent, Belgium, with sales subsidiaries in France, Germany, Italy, Spain, Brazil, and the United States. Innogenetics employs 525 people worldwide and has a market capitalization of approximately euro 295 million.
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Findings in Hepatitis C Virus Reported from Spain, India and France
http://www.therapeuticsdaily.com
Hepatitis Weekly - Jan. 15, 2007
2007 JAN 15 - (NewsRx.com) -- New findings reported from Spain, India and France describe advances in hepatitis C virus.
Study 1: According to a study from Spain, the -670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C virus (HCV) infection.
"Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of HCV infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas."
"Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, -1377G > A and -670A > G," wrote J. Aguilar-Reina and colleagues, University of Virgen Rocio Hospital.
"We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C."
The researchers explained, "A cohort of 197 patients with chronic hepatitis C and 100 controls were analyzed for both polymorphisms by fluorescence resonance energy transfer using specific probes and the Lightcycler system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system."
"We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection."
"However," Aguilar-Reina and coinvestigators wrote, "we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the -670A > G variant among those patients with higher Knodell scores (p=.049) and necroinflammatory activity (p=.036). The -670A allele was associated with higher levels of periportal necrosis (p=.012)."
"Our findings suggest an association between the -670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C," concluded the authors.
Aguilar-Reina and colleagues published the results of their research in the Journal of Viral Hepatitis (The -670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C. J Viral Hepat, 2005;12(6):568-573).
For additional information, contact J. Aguilar-Reina, University of Virgen Rocio Hospital, Hepatology Section, Service Aparato Digestivo, Avda Manuel Siurot S-N, Seville 41013, Spain.
Study 2: Recent research from India has documented the detection of hepatitis C virus (HCV) TAQ1 polymorphism in the 3'untranslated region of IL-12P40 gene in HCV patients infected predominantly with genotype 3.
"Host immunity plays an important role in viral persistence and progression of liver disease in HCV infected patients. IL-12 induces production of IFN-gamma, a potent antiviral agent," wrote P.V. Suneetha and colleagues, GB Pant Hospital.
They continued, "IL-12 comprises two subunits; IL-p35 and IL-12p40, which are encoded by two different genes located on chromosome 3 and 5, respectively. Single nucleotide polymorphism at A1188C in the 3'UTR of IL-12p40 gene is associated with immune mediated diseases. Association of IL-12p40 A1188C polymorphism with the outcome of HCV infection was investigated in this study."
"Two hundred and fifty three histologically proven chronic hepatitis C patients (43±13 years, male:female: 185:68) and 380 matched controls were included. Genotyping was performed by RFLP and confirmed by direct sequencing.
"To assess correlation of immune gene polymorphism with severity of HCV-related liver disease, patients were divided into those with fibrosis score of less than or equal to2 (mild) or >2 (severe), and histological activity index (HAI) of=5 (mild) or >5 (severe). The distribution of A/A A/C or C/C alleles in the controls was comparable to the patients. The distribution of C/C allele was significantly more common in patients with mild as compared to severe fibrosis (23.7% vs. 6.25%, p=.004). No significant difference was observed for any of the genetic markers with HAI or with normal or raised Ala aminotransferase (ALT)," reported the authors.
The researchers concluded, "These results show that the C/C allele of IL-12p40 gene could render genetic protection against development of severe liver disease in patients infected with HCV."
Suneetha and colleagues published their study in the Journal of Medical Virology (Studies on TAQ1 polymorphism in the 3'untranslated region of IL-12P40 gene in HCV patients infected predominantly with genotype 3. J Med Virol, 2006;78(8):1055-1060).
Additional information can be obtained by contacting S.K. Sarin, GB Pant Hospital, Department of Gastroenterology, New Delhi 110002, India.
Study 3: Recent research from France has reported on the lack of association between microsomal triglyceride transfer protein gene polymorphism and liver steatosis in hepatitis C virus (HCV)-infected patients.
"It has been shown that the HCV-core protein reduces the activity of microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients," wrote J.M. Petit and colleagues, CHU Bocage.
They continued, "The aim of our study was to investigate the influence of a functional polymorphism in the promoter region of the NITP gene (493G/T) on the development of HCV-related steatosis."
"Eighty-six chronic hepatitis C patients were studied to assess: the effects of body mass index, age, HCV genotype, and 493G/T MTP polymorphism on steatosis. Steatosis was observed in 39 patients (45.3%)," the investigators reported.
They concluded, "The 493G/T MTP polymorphism were not related to the development of steatosis. The functional G/T MTP polymorphism do not seem to play any role in the development of steatosis in chronic hepatitis C."
Petit and colleagues published their study in Molecular Genetics and Metabolism (Lack of association between microsomal triglyceride transfer protein gene polymorphism and liver steatosis in HCV-infected patients. Mol Genet Metab, 2006;88(2):196-198).
For additional information, contact J.M. Petit, CHU Bocage, INSERM, Laboratory Unite 498, BP77908, F-21079 Dijon, France.
This article was prepared by Hepatitis Weekly editors from staff and other reports.
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Caregiving: Lawford Says Get Tested – 5
http://www.sciencedaily.com
By ALEX CUKAN
ALBANY, N.Y., Jan. 11 (UPI) -- Researchers say that alcohol promotes the progression of hepatitis C virus, or HCV, in human liver cells.
"Alcoholics can get liver disease from alcohol and they can also have HCV, which can progress the virus more quickly to cirrhosis," Dr. Donald Jensen, director of the section of hepatology at Rush University Medical Center in Chicago, told United Press International's Caregiving.
"Those with HCV can -- with as little as two drinks a day -- hasten the progression of the virus, as well as someone who drinks heavily," Jensen said.
Someone with HCV has a greater chance of liver disease, although about 40 percent never develop cirrhosis, according to Jensen.
Just testing positive for HCV does not automatically mean that those infected need treatment; it's recommended they consult a liver specialist to develop a strategy for treatment.
"Treatments are getting better, so those who suspect they may have a risk factor for HCV should get tested because there is an overall eradication rate of 55 percent and higher for some strains."
If drug therapy, such as interferon monotherapy, standard interferon plus ribavirin and pegylated interferon plus ribavirin, is given soon enough, liver damage can be averted. But if there is a delay, the patients may end up having to get a liver transplant.
Currently, more than 17,000 people in the United States are waiting for liver transplants, due to a shortage of donor organs. The vast majority of those with HCV are baby boomers, and so a liver donor transplant crisis is looming, Jensen said.
HCV is one of the leading known causes of liver disease in the United States, with approximately 4 million people infected. HCV is a major cause of cirrhosis and liver cancer, as well as the most common reason for liver transplantation.
Cirrhosis is the result of chronic liver disease that causes scarring of the liver and liver dysfunction. This often has many complications, including accumulation of fluid in the abdomen, bleeding disorders, increased pressure in the blood vessels of the liver and confusion or change in a person's consciousness.
Habitual alcohol drinkers have higher blood levels of HCV compared to infrequent drinkers, even when both are infected with the virus. But a study at The Children's Hospital of Philadelphia investigated how alcohol affects HCV at the cellular level.
"Our study provides a biological mechanism to support clinical observations," said Dr. Wen-Zhe Ho, the director of retroviral research at the hospital.
The researchers found alcohol increases the activity of the protein nuclear factor kappa B and causes HCV to replicate. That protein is an important cellular regulator of gene products involved in inflammation. Furthermore, the researchers found that alcohol interferes with the anti-viral activity of interferon-alpha, a key therapy used for patients infected with HCV.
The researchers also found that naltrexone, a drug used to help patients with alcoholism avoid relapse, may also block the deleterious effects of alcohol in promoting HCV.
Some readers have asked: Since drugs -- illegal, prescription and over-the-counter can all affect the liver, does taking drugs affect HCV?
"There is less evidence about specific medications. Certainly a drug may have the protein. It's not straightforward, but alcohol is pretty clearly shown to hasten the progression of the illness," Jensen said.
Alex Cukan is an award-winning journalist, but she always has considered caregiving her real work. UPI welcomes comments and questions about this column. E-mail: consumerhealth@upi.com
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Valeant Hepatitis Drug Deal Goes Through
http://www.ocregister.com
By MARY ANN MILBOURN
THE ORANGE COUNTY REGISTER
Schering-Plough will get the rights for development and the sale of pradefovir.
Valeant Pharmaceuticals International got a boost to its bottom line with the announcement today that its hepatitis drug deal with Schering-Plough Corp. went through.
Costa Mesa-based Valeant has been working with Metabasis Therapeutics in San Diego on the use of pradefovir for the treatment of chronic Hepatitis B.
The Schering-Plough deal, which grants the company a license for the development and commercial rights to pradefovir, was awaiting federal anti-trust reviews by the U.S. Federal Trade Commission. The deal was completed following the early termination of the waiting period.
Under the agreement, Valeant will get $19.2 million upfront and approximately $65 million in additional fees pending the achievement of certain milestones. Metabasis will get $1.8 million upfront and $25 million in subsequent fees. The two companies will also get royalties once the drug is commercialized.
Contact the writer: 714-796-3646 or mmilbourn@ocrgister.com
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OraSure Sees Hep C Test Trials Done '07
http://biz.yahoo.com
OraSure Sees Trials of Oral Hepatitis C Test Ending This Year
NEW YORK (AP) -- OraSure Technologies Inc.'s chief executive Thursday said he expects clinical trials of a rapid oral test for the detection of hepatitis C to be completed by the end of this year.
Once the trials of the test -- being jointly developed by OraSure and Schering-Plough Corp. -- are completed, the company will apply for marketing approval in the United States and in Europe soon thereafter, CEO Douglas Michels said in an interview.
Last week, Schering-Plough and Beaverton, Ore.-based OraSure -- which already makes the only approved HIV rapid oral test -- inked a two-year deal to jointly develop and market the oral hepatitis C test in the United States, beginning the day the test is marketed.
Schering-Plough will provide the test -- which is expected to be similar to the HIV product and take 20 minutes to administer -- to physicians. OraSure will be responsible for sales and marketing of the product, and Michels said the company will utilize its experience in the HIV testing world, as many of those infected with the hepatitis C virus are also infected with HIV.
The CEO said OraSure was looking to expand the product globally through distribution agreements, and was also looking to acquire companies with complementary product profiles and with new technologies related to the treatment of infectious diseases.
"We have $90 million in cash right now and are looking to deploy it," Michels said. "We are actively evaluating potential acquisitions and technology-licensing agreements."
Michels said the development of novel treatments for hepatitis C that cut down on treatment time would be a boost to the market's acceptance of the company's test, which he said would be as accurate as current lab-based testing.
Vertex Pharmaceuticals Inc. is engaged in developing such a therapy, as is Schering-Plough, which makes the current standard treatment for hepatitis C, pegylated interferon, called Peg-Intron, which is often used with ribavirin.
The hepatitis C virus is the most common blood-borne infection in the United States, with around 4 million people suffering from it. It affects as many as 170 million people worldwide. It is the main reason for liver transplants in the United States.
Michels said as many as 2 million to 3 million Americans who may have the virus remain untested.
While new infection rates have declined in the United States, and blood is now screened for the virus, those who caught it through infected blood in the late 1970s and early 1980s are approaching treatment age, and many more in the population may have the virus but remain unchecked as symptoms can take up to 20 years to appear.
Shares of OraSure rose 3 cents to close Thursday at $8.63 on the Nasdaq Stock Market.
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January 12th, 2007
Relapse of HCV Common in HIV/HCV Coinfected Patients after Liver
www.aidsmap.com
Michael Carter
Every HIV/hepatitis C-coinfected patient who survived liver transplant at a hospital in Barcelona experienced a recurrence of hepatitis C, and only one patient had a virological response to the subsequent use of anti-hepatitis C therapy, according to a study published in Antiviral Therapy. The authors note, however, that all the surviving patients were engaged in their normal daily activities two years after liver transplantation and that anti-HIV therapy was safely and effectively reintroduced within weeks.
Liver disease has become a major cause of illness and death amongst HIV-positive individuals, with hepatitis C virus often being the cause. Progression to cirrhosis caused by hepatitis C is faster amongst patients with HIV, and they also have shorter survival once liver decompensation occurs. Several studies have shown that anti-hepatitis C therapy has only limited efficacy in HIV-positive patients, possibly due to toxic effects of some anti-HIV drugs on the liver, and interactions between anti-hepatitis C and antiretroviral drugs.
It is therefore anticipated that the number of HIV/hepatitis C virus-coinfected individuals requiring liver transplantation will increase. Although there is limited experience of liver transplantation in coinfected patients, the evidence to date suggests that survival, in the short-term at least, is just as good as that seen in hepatitis C monoinfected patients.
Many hepatitis C-infected patients experience a relapse of their infection after liver transplant. The optimal use of anti-hepatitis C therapy in transplant recipients experiencing a relapse of their hepatitis C is unknown. Investigators in Barcelona therefore reported their experiences of transplant outcome and treatment for hepatitis C recurrence in six patients between 2002 and 2004.
The patients had a median age of 42 years. Five were male and four had injecting drug use as their HIV/hepatitis C risk category. All were taking antiretroviral therapy with an undetectable viral load immediately before their liver transplant. Median CD4 cell count at this time was a little over 250 cells/mm3. Median hepatitis C serum RNA was almost 800,000 copies/ml in the patients prior to transplant. Two patients had taken unsuccessful anti-hepatitis C therapy. Hepatitis C genotype was 1a in three patients, 1b was present in one case, and 1a/1b in two patients.
One patient died of post-operative complications without a recurrence of hepatitis C virus 78 after liver transplantation. In the surviving five patients, anti-HIV therapy was reintroduced between four and 16 days after their operation, and in all individuals HIV viral load remained undetectable.
In all the surviving patients, hepatitis C virus had recurred within eleven weeks of transplant. Anti-hepatitis C therapy consisting of pegylated-interferon and ribavirin was initiated in all patients within two weeks of the recurrence being detected. Only one patient experienced a sustained virological response to this therapy. In the other patients, the median fall in hepatitis C RNA was 0.87 log10 at week twelve and 1.04 log10 at week 24.
Despite this poor rate of virological response, the investigators noted that all five patients were alive and had resumed their “normal active lives” two years after transplant. The patient who had achieved a sustained virological response still had an undetectable hepatitis C viral load at month 26. Of the other patients, two developed cirrhosis and two moderate chronic hepatitis.
In the light of these cases, the investigators make some recommendations for the management of HIV/hepatitis C-coinfected patients undergoing liver transplantation. First, they suggest that efforts should be made to diagnose a recurrence of hepatitis C as soon as possible. They believe that regular biopsies may be a useful tool. Second, the use of steroids and immunosuppressive therapy to prevent organ rejection should be tapered off slowly (over six months) and should not be stopped suddenly in the event of hepatitis C recurrence. Third, ribavirin should be used at the maximum possible dose. And, finally, longer-term anti-hepatitis C therapy, perhaps of indefinite duration, should be considered.
The investigators conclude, “newer strategies to prevent recurrence and increase response rates…are urgently needed.”
Reference
Castells L et al. Early antiviral treatment of hepatitis C virus recurrence after liver transplantation in HIV-infected patients. Antiviral Therapy 11: 1061 – 1070, 2006.
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