« April 2005 | Main | June 2005 »
May 17, 2005
Vertex Update
This is an update on the earlier story about VX-950. I've put it up here because it gives a bit of a different perspective.
I love the part where Boger says, "We believe it will take weeks or months to defeat the virus..." and then he contrasts it to the current full year of treatment.
Also, be sure to note that they are claiming this drug has none of the negative side effects of current therapy. Hooray!
Vertex says drug quickly treats hepatitis C
17 May 2005 20:20:21 GMT
Source: Reuters
(Adds details on virus returning in 5 patients, share price)
By Ransdell Pierson
NEW YORK, May 17 (Reuters) - Vertex Pharmaceuticals Inc.
The tiny U.S. biotechnology company said the patients received a 750-milligram dose of its medicine, called VX-950, every eight hours during the two-week Phase 1 trial.
Results of the 34-patient study, which was conducted among patients with the hardest-to-treat genotype 1 strain of the virus, were presented at the annual Digestive Disease Week scientific meeting being held in Chicago.
"The big surprise is that half of patients in 14 days in this drug group went below levels of virus detection," Vertex Chief Executive Officer Joshua Boger told Reuters.
By contrast, he said current two-drug treatments typically must be taken for three months before half of patients reach undetectable levels of the virus. They must then be taken another nine months to make sure the virus does not re-emerge.
"Our drug by itself appears to be dropping the virus to undetectable levels dramatically quicker than standard combination treatments," Boger said, and without the flu-like side effects or other problems seen with existing medicines.
Another patient in the Vertex-sponsored trial also tested negative for the virus after receiving a different dose of VX-950.
The virus returned to detectable levels in five patients a month after the Vertex trial concluded, but virus levels remained more than 90 percent below original levels in two of them, the company said.
Boger said he is hopeful longer treatment in larger future trials will prevent the virus from re-emerging after it is knocked down.
Consequently, he said several Phase 2 trials that could begin late this year will last one to three months, testing the drug by itself and with at least one interferon used in current combo treatments, sold by Schering-Plough Corp.
"We believe it will take weeks or months to defeat the virus, and we'll conduct the studies to find out," said Boger, who noted that standard treatments last almost a full year.
Shares of Vertex closed up 22 cents, or 1.7 percent, at $13.20 on the Nasdaq.
Posted by Ralph at 01:19 PM --- Printer-friendly version | Comments (0)
May 16, 2005
Schering vs. Roche
What I find most significant about this report is that genotype 1 patients got somewhere between a 48% and 54% success rate. No wonder other drug companies are scrambling for an alternative treatment. It shouldn't be too hard to beat a 50-50 chance.
I also wonder what the results would have been if both drug therapies had been given in a weight based dosing manner. Perhaps Roche would have been the big winner. This helps demonstrate why variables are so important to look at when reading about clinical studies.
Schering-Plough hepatitis drug beats Roche's -study
16 May 2005 20:10:38 GMT
Source: Reuters
(Adds Roche criticism of trial)
By Ransdell Pierson
NEW YORK, May 16 (Reuters) - Schering-Plough Corp.'s
The study, which analyzed how patients treated for hepatitis C at the Cleveland Clinic fared between 2001 and 2004, was described at the annual Digestive Disease Week meeting being held in Chicago this week.
Clinic officials said a higher percentage of patients who received Schering-Plough's therapy, especially those who were obese, eliminated the virus after treatment than those taking Roche's therapy.
Complete data from the informal retrospective study was available on 28 obese patients and 58 non-obese patients, all of whom were Caucasian and had been infected with the hardest-to-treat genotype 1 strain of the virus. None of the patients had previously been treated.
Dr. Nizar Zein, a professor of medicine at the Cleveland Clinic, said he reviewed the patient records because no formal head-to-head trials of the two leading therapies has been completed.
Schering-Plough is conducting such a trial, but its results will not be known until 2007.
Schering-Plough's combination consists of an injectable interferon called Peg-Intron that is given along with an antiviral pill called ribavirin for 48 weeks. Roche's combo includes an interferon called Pegasys, which is also paired with ribavirin for the same duration.
But the dosage of Schering-Plough's interferon is based on a patient's body weight, whereas all patients receive the same standard dose of Roche's interferon -- regardless of whether thin or obese.
Zein said the virus was eliminated in 53 percent of obese patients getting the weight-based Schering-Plough interferon, similar to the 48 percent of non-obese patients receiving it.
By contrast, 18 percent of obese patients receiving the fixed-dose Roche interferon cleared the virus from their bloodstreams. That was lower by a statistically significant magnitude than the 28 percent of non-obese patients taking the same therapy who eliminated the virus.
"It was extremely surprising that patient responses were so much better with (Peg-Intron's) weight-based dosing, especially in obese patients," Zein told Reuters. He said he received no funding from Schering-Plough but has received past funding from Roche.
Roche questioned the validity of the study, saying its findings were "totally inconsistent" with large formal clinical trials of Pegasys in which far higher percentages of hepatitis C patients emerged free of the virus.
"This misleading research, which is based on a small number of patients outside the controlled setting of a clinical trial, is not valid from a scientific perspective and does a disservice to hepatitis C patients and their physicians," said Juan Carlos Lopez-Talavera, Roche's medical director.
But Cleveland Clinic's Zein said drugs sometimes fare less well in "real-world" medical practice than in the carefully controlled settings of clinical trials.
An estimated 4 million Americans are believed to be infected with the hepatitis C virus. The damage it does to the liver, typically for 10 to 20 years before symptoms develop, is the biggest reason for undergoing liver transplants.
Posted by Ralph at 01:10 PM --- Printer-friendly version | Comments (0)
Steatosis and Fibrosis
Reading selectively in this article gives us this tidbit: "Age, ADD, diabetes and increase of ALT seem to be the only independent factors associated with liver fibrosis progression.”
Among other things, this demonstrates the importance of keeping ALT levels as reduced as possible.
No Correlation Found Between Steatosis and Liver Fibrosis in HCV Genotype 1 Infection
Liver steatosis is generally regarded as a risk factor for chronic liver disease. Moreover, steatosis is considered in HCV-related chronic active hepatitis (CAH) as an adjunctive factor of progression and evolution of liver disease. In particular, steatosis is thought to be specifically related to the course of the disease in genotype 3a patients with CAH.
The aim of this study was to test the role of steatosis in liver damage (fibrosis) in a consecutive case-study of genotype 1b patients who have undergone liver biopsy because of an increase of serum ALT.
180 patients ( sex: M98/F82; median age: 51 range 17 - 68) underwent ultrasound examination and liver biopsy. Based on liver histology patients were divided according to steatosis into four classes: 1 (no steatosis), 2 (steatosis < 30%), 3 (steatosis 30 – 50 %), 4 (steatosis > 50 %).
Results:
·Histological Activity Index (HAI) was evaluated according to ISHAK’ s score.
·Median fibrosis value was S 2 (ranging 0 – 6; 23 patients showed liver cirrhosis) in all the 4 classes and no statistical significance was found between groups.
·Virological and epidemiologic characteristics, biochemical data, BMI, Apparent Duration of Disease (ADD) of all patients were recorded and statistical correlation checked.
·A univariate and multivariate analysis vs fibrosis were performed in all the patients and tested statistically significant only for age, ADD, diabetes and ALT (p< 0.00), but not for steatosis.
Conclusion
The authors conclude, “Steatosis does not seem to be an independent adjunctive risk factor of liver disease progression in CAH/genotype 1b HCV-infected patients….Age, ADD, diabetes and increase of ALT seem to be the only independent factors associated with liver fibrosis progression.”
05/02/05
Reference
M Persico and others. NO CORRELATION BETWEEN FAT LIVER ACCUMULATION AND LIVER FIBROSIS IN GENOTYPE 1B HCV RELATED CHRONIC LIVER DISEASE. Abstract 593. 40th EASL. April 13-17, 2005. Paris, France.
Posted by Ralph at 08:58 AM --- Printer-friendly version | Comments (0)
May 13, 2005
Small Molecule Drugs Are Coming for HCV
The following appeared in "Pharmaceutical Business Review Online". While this is just a short blurb, it is quite informative. The prediction for two more effective drugs to be launced in the next six or seven years is very, very encouraging.
Hepatitis C: small molecules, big business
13 May 2005, 16:44 GMT - Although interferons and ribavirin currently dominate the hepatitis C treatments market and soon-to-be-launched products will predominantly be improvements to these types of drugs, small molecule antivirals are expected to gain a much greater footing in the long-term. Indeed, the launches of the first two hepatitis C virus (HCV)-specific small molecule antiviral drugs, expected in 2011 and 2012, are predicted to be instrumental in helping to grow the value of the HCV pharmaceutical market in the next decade.
Source: Datamonitor Researchwire
Posted by Ralph at 01:01 PM --- Printer-friendly version | Comments (0)
May 12, 2005
Breakthrough HCV Therapy?
Vertex has been getting press on VX-950 for some time. Early tests were good which led to this Phase 1b study.
If all remains well with this drug it could be a major step forward in the process of treating Hepatitis c.
Stay tuned...
Experimental HCV Protease Inhibitor VX-950 Demonstrates Potent Anti-HCV Activity
Interim results of a Phase Ib study indicate that the experimental hepatitis C virus protease inhibitor VX-950 has potent anti-HCV activity and is well tolerated, according to an announcement from drug maker Vertex Pharmaceuticals. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.
As an oral drug that shows potency and no serious adverse side effects, VX-950 has the potential to become a breakthrough therapy for chronic hepatitis C.
The study enrolled 34 patients with chronic genotype 1 HCV infection who were treated for 14 days with placebo or one of three dose regimens of VX-950. HCV genotype1 infection is the most difficult strain of HCV to treat and the most prevalent strain in the United States, Western Europe and Japan.
Every patient receiving VX-950 achieved greater than a 2 log10 reduction in HCV-RNA within the first three days of treatment, according to Vertex.
Complete results from the study will be presented on May 17 at DDW 2005 in Chicago. In accordance with the DDW embargo policy of the meeting, the specific data from the trial beyond what is described in today’s announcement from Vertex will not be disclosed until the DDW presentation.
Study Design
The Phase Ib clinical trial was a double-blind, randomized placebo-controlled study designed to evaluate the tolerability, pharmacokinetics and effect on viral kinetics of three doses of VX-950 -- 450 mg every 8 hours, 1250 mg every 12 hours, or 750 mg every 8 hours -- over a period of 14 days, with additional post-treatment follow-up.
A key goal of the study was to assess different dosing levels and frequencies for VX-950 to provide insight into dose selection for future monotherapy and combination therapy studies. Thirty-four patients with chronic genotype 1 hepatitis C virus infection were enrolled in the study; six patients received placebo and 28 patients received VX-950. The study was conducted at three centers in Europe. The trial included treatment-experienced and treatment-naive HCV-infected patients.
Results
Principal results of the Phase Ib clinical trial are as follows:
· VX-950 was well-tolerated across all three dose groups with no serious adverse events reported, and no treatment discontinuations.
· Treatment with VX-950 also resulted in significant reductions in plasma HCV-RNA. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.
· In the dose group receiving 750 mg of VX-950 every 8 hours, there was a further reduction in viral levels between days 3 and 14 of treatment, with mean and median HCV-RNA reductions of greater than 4 log10 at day 14.
· Trough plasma concentrations of VX-950 were highest in the 750 mg every 8 hour dose group. In the 450 mg q8h and 1250 mg q12h dose groups, maximal effects were seen between days 3 and 7 of treatment.
· Subsequently, there was an increase of approximately 1 log10 in median HCV-RNA between days 7 and 14 evident in both groups.
Full analysis of the study, including a detailed pharmacokinetic and viral sequencing evaluation, is underway.
"Vertex is committed to developing innovative compounds for the treatment of chronic HCV infection. VX-950, one of the most advanced agents in a promising new class of direct antivirals, underscores that commitment," said Joshua Boger, Ph.D., Chairman and Chief Executive Officer of Vertex. "The demonstration of antiviral activity in this early clinical study is highly encouraging, and we look forward to sharing these data in greater detail at DDW next week."
Based on the results of the Phase Ib clinical study, the Company plans to explore the development of VX-950 as monotherapy and in combination with other HCV treatments. Vertex plans to consult with the US FDA and European regulatory authorities on the Company's development plans.
Vertex expects to file an investigational new drug (IND) application in the second half of 2005
to support Phase II clinical development of VX-950 in the United States. In collaboration with Vertex, Mitsubishi Pharma Corporation is developing VX-950 in Japan and certain Far East countries.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor fosamprenavir (Lexiva) with GlaxoSmithKline.
Sources
PR Newswire-FirstCall.
http://www.vrtx.com
Posted by Ralph at 12:42 PM --- Printer-friendly version | Comments (0)
May 11, 2005
Phase 1 Trial of Tarvacin
Another experimental anti HCV drug in the pipeline! The more companies working on a solution, the greater the odds of a practical treatment for HCV genotype 1.
TUSTIN, Calif., May 5 /PRNewswire-FirstCall/ --
Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) announced today that it has submitted an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) to initiate a phase 1 clinical trial using Tarvacin(TM) to treat patients with chronic Hepatitis C virus infection.
The objectives of the phase 1 clinical protocol submitted in the IND are to evaluate safety, pharmacokinetics and viral load in patients chronically infected with Hepatitis C virus who have failed standard treatment.
There are estimated to be 2.7 million people in the U.S. and 170 million people worldwide with chronic Hepatitis C infection. "This IND filing is an important next step in expanding the potential of Tarvacin(TM)," said Steven King, president and CEO of Peregrine Pharmaceuticals. "We anticipate this anti-viral IND will be the first in a series of steps to explore the anti-viral potential of Tarvacin(TM)."
The new application is the second IND filing for Tarvacin(TM). The first IND allows enrollment of patients with any solid cancer and has been cleared by the FDA to begin patient enrollment. Peregrine Pharmaceuticals will work closely with the FDA to address any questions that may arise during review of the anti-viral IND submission.
Patient enrollment can begin once the clinical protocol has been accepted by the FDA and initiation of clinical sites has been completed. In the meantime, the company expects to treat patients in the phase I solid cancer clinical trial within the next few weeks.
Pre-clinical studies using Tarvacin(TM) for the treatment of viral diseases have yielded promising results in Lassa fever, influenza, and cytomegalovirus, which are included in a viral category called enveloped viruses. Based on Tarvacin's(TM) anti-viral mechanism, the drug has potential for the treatment of enveloped viruses including Hepatitis B and C, Human Immunodeficiency Virus (HIV), herpes, influenza including SARS and Avian flu and potential bioterrorism threats such as Marburg virus and Lassa fever.
About Anti-Phospholipid Therapy in the Treatment of Viral Diseases
Tarvacin(TM) is Peregrine's first product under its anti-phospholipid therapy technology platform. Anti-phospholipid therapy is a novel approach to treating cancer, viral infections and certain ocular diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed on the outside of the cellular membrane in response to certain disease states such as virally infected cells and cancer. A large number of viruses significant to global health and security possess an "envelope" derived from their host cell membrane. Since viruses lack the means to maintain structural organization of the envelope, amino-phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) become exposed on the surface of these viruses, making them a potential therapeutic target. Peregrine Pharmaceuticals, together with its collaborators, has developed a series of monoclonal antibodies, including Tarvacin(TM), directed against aminophospholipids to take advantage of this property.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a broad portfolio of products under development directed towards the treatment of cancer, viruses and other diseases. The company is in the process of initiating patient enrollment in a Tarvacin(TM) clinical trial for the treatment of all solid cancers and in a Cotara(R) clinical trial for the treatment of brain cancer. In addition, the company has submitted an IND application to initiate a Tarvacin(TM) clinical trial for the treatment of Hepatitis C virus infection. Peregrine Pharmaceuticals is also developing Vascular Targeting Agents, Anti-Angiogenesis, and Vasopermeation Enhancement Agents (VEAs) for the treatment of cancer and other diseases. Peregrine Pharmaceuticals also has in-house expertise to develop and manufacture antibodies and recombinant proteins through its wholly-owned subsidiary, Avid Bioservices, Inc., (http://www.avidbio.com). Avid is engaged in providing contract manufacturing services and development of biologics for biopharmaceutical and biotechnology companies, including Peregrine. Copies of Peregrine Pharmaceuticals press releases, SEC filings, current price quotes and other valuable information for investors may be found at http://www.peregrineinc.com
Posted by Ralph at 12:04 PM --- Printer-friendly version | Comments (0)
May 10, 2005
Milk Thistle Doses Studied Are Too Low
This study of previous studies showed inconclusive results for milk thistle preventing death from liver disease.
However, the researchers conclude that higher doses should be studied because milk thistle is non-toxic and has been seen to protect liver cells in many in vitro studies.
Incidentally, the 140mg studied in the past is clearly sub-standard. Maximum Milk Thistle, taken as recommended, provides 720mg of silybin phytosome which delivers many times more protection to your liver with no negative side effects. Go to http://www.maximummilkthistle.com for more information on protecting your liver with this powerful natural remedy.
STUDIES OF HIGHER DOSES OF MILK THISTLE URGED BY RESEARCHERS
Milk thistle, a widely used alternative medicine, is not proven effective in lowering mortality in alcoholic or hepatitis B or C liver disease, according to a systematic review of current evidence.
While some studies found that liver-related mortality may be significantly reduced in patients treated with milk thistle, these findings were not duplicated in the higher quality clinical trials.
However, milk thistle was found safe to us with no serious side effects and with participants perceiving improvement in symptoms — although no more than with placebo.
Dr. Andrea Rambaldi, visiting researcher at the of the Centre for Clinical Intervention Research at Copenhagen University Hospital, led a team that reviewed 13 randomized clinical trials involving 915 patients who were treated with milk thistle or its extracts.
Participants had acute or chronic alcoholic liver cirrhosis, liver fibrosis, hepatitis and/or steatosis, and viral-induced liver disease (hepatitis B and/or hepatitis C). Patients with rarer specific forms of liver disease were excluded.
All the trials compared the efficacy of milk thistle or any milk thistle constituent versus placebo or no intervention in patients with liver disease. “There is no evidence supporting or refuting milk thistle for alcoholic and/or hepatitis B or C virus liver diseases,” the authors found.
The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
According to the Centers for Disease Control and Prevention, 170 million people worldwide are infected with hepatitis C, and 2 billion are infected with hepatitis B. While a vaccine exists to prevent hepatitis B, there is no vaccine for hepatitis C.
Although the virus can be cleared in a handful of patients, many strains are resistant to treatment. Drug therapies that focus on long-term suppression of the virus are expensive, and many patients develop a resistance. The current gold standard treatment, which combines injections of interferon and ribavirin, has serious side effects and is hard for patients to tolerate.
With lack of effective treatment for liver disease, researchers have been looking for alternative therapies that curb symptoms with minimum adverse effects on patients.
Milk thistle and its extracts have been used since the time of ancient Greece for medicinal purposes, are currently widely used in Europe for liver disease, and are readily available in the United States at alternative medicine outlets and outdoor markets.
G. Thomas Strickland, M.D., Ph.D., professor at the University of Maryland School of Medicine, has been studying the role of silymarin, an extract of milk thistle, in preventing complications of chronic hepatitis virus infection. Strickland says that the exact mechanism of action of silymarin is unclear.
A problem with current trials, according to Dr. Strickland, is that the dose of silymarin administered, typically 140 mg three times daily, is too low. “I would certainly double it,” he says, “especially since at the current dose we’re not seeing any improvement in acute viral or chronic hepatitis, and we’ve shown that silymarin is totally safe.”
“The problem is, there is no cure for viral hepatitis except bed rest and diet, and treatments like silymarin are worth pursuing,” Strickland says, calling for more research funding.
“We should consider doing randomized clinical trials with higher doses of silymarin,” Dr. Rambaldi concurs.
According to the National Center for Complementary and Alternative Medicine , a part of the National Institutes of Health, studies in laboratory animals suggest that silymarin may benefit the liver by promoting the growth of certain types of liver cells, demonstrating a protective effect, fighting oxidation (a chemical process that damages cells) and inhibiting inflammation.
In their review, Dr. Rambaldi and colleagues conclude, “Milk thistle could potentially affect alcoholic and/or hepatitis B or C virus liver diseases. Therefore, large-scale randomized clinical trials on milk thistle for alcoholic and/or hepatitis B or C liver diseases versus placebo may be needed.”
Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. The Cochrane Database of Systematic Reviews 2005, Issue 2.
Posted by Ralph at 11:52 AM --- Printer-friendly version | Comments (0)
May 06, 2005
Specific Genes Predict HCV Treatment Success
Wow! Now this is a great discovery. Imagine being able to know in advance if you can be helped by interferon combination therapy. You would not need to go through any discomfort to discover whether or not it would be effective for you.
Toronto, Ontario, May 2 /PR Direct/ -
Identification of specific genes predicts which patients will respond to Hepatitis C treatment
Simple blood test in the near future possible
(Toronto, May 2, 2005) - For the first time, physicians at University Health Network and University of Toronto have identified a small subset of genes that can predict whether a patient with chronic Hepatitis C will be able to respond to current treatments.
These genes could also become the basis of a simple new test in the future to predict which patients will respond to therapy.
The study, published in the May issue of the American Gastroenterological Association's Gastroenterology, found that the difference between those patients who responded to treatment and those who did not was the level of expression - whether the genes were turned on or turned off - of 18 genes.
"Our results demonstrate that a relatively small number of genes can predict response to therapy. These genes may be important to the ability of the patient to eliminate the virus, so studying these genes in more detail will hopefully lead to novel antiviral treatments," said Dr. Ian McGilvray, the senior author of the study. Dr. McGilvray is a transplant surgeon at Toronto General Hospital, University Health Network and an Assistant Professor of Surgery at the University of Toronto. "By manipulating the products of these genes we might be able to improve treatment responses to this chronic disease."
"This information is helpful for patients because it's one more piece of evidence that we hope will encourage 'responder' patients to start and continue treatment for Hepatitis C, despite it's many side effects," said Dr. Jenny Heathcote, a hepatologist at Toronto Western Hospital, University Health Network and Professor of Medicine at University of Toronto, who contributed to the study and treats many of the patients in the study. "We want to be able to give patients as much information as we can, so that they can make the best decisions about their treatment options."
Tony Angelini, 42, was one of the patients in the study who responded to treatment. He is now clear of the virus. "Knowing that you are a responder gives you the courage and the fight to go on. It was devastating, but having the support of my friends and hospital staff really helped me through the treatment. And I wanted to participate in this study so that the research could help others in the future."
The study followed 31 patients with chronic Hepatitis C who were treated at Toronto Western Hospital from October 2001 until May 2004. Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). About 230,000 Canadians are infected with it, and about 170 million people worldwide. Over time the viral infection leads to liver damage, cirrhosis and/or liver cancer. It is currently the leading indication for liver transplants.
Liver biopsies were performed on the 31 chronic HCV patients before treatment, and were compared to 20 biopsies from healthy, uninfected livers. 16 patients did not respond to subsequent treatment, while 15 did; both groups were well matched with respect to age, HCV viral load (number of viral particles circulating in the blood), and liver disease activity.
In order to define which genes discriminate between those patients who respond to therapy to those who do not, microarray technology, based in a Banting and Best Department of Medical Research laboratory at University of Toronto, was used to analyze the pattern of genes in all participants. This technology allows scientists to compare levels of expression for tens of thousands of genes on a glass slide - these "gene chips" are the size of a postage stamp. The technology is able to quickly scan the expression of those genes and differentiate between genes which are "turned on" or "turned off". Comparing "genetic fingerprints" allows researchers to rapidly and effectively identify sensitive genetic changes associated with various stages of disease, and hopefully identify the most suitable candidates for specific therapies.
"We went into this experiment without any hypothesis about what to look for," said Aled Edwards, a Professor in the Banting and Best Department of Medical Research at University of Toronto with cross appointments in the Departments of Medical Biophysics and Medical Genetics and Microbiology. He is also a senior scientist at the Clinical Genomics Centre at the University Health Network and Director and CEO of the Structural Genomics Consortium. "We cast a very wide net, looking at 19,000 genes of each of the patients."
The researchers found that the difference between those patients who did not respond to therapy to those who did was a subset of 18 genes. In the non-responders to treatment, 16 genes were turned on and two were turned off. Many of the 16 genes which were turned on are stimulated by interferon, one of the key antiviral agents that the body produces in response to viral infection and a medication that patients currently receive as part of their therapy. "Paradoxically, in the non-responders, the liver is revved up and the genes are responding like mad, but there is something about the response that just does not work," said Dr. McGilvray.
In the near future, determining the levels of a small subset of genes in patients' liver biopsies, with perhaps a simple blood test, may be helpful in deciding who will respond to treatment of chronic Hepatitis C with the current combination therapy using the synthetic antiviral agent ribavirin and interferon. This treatment can currently get rid of the virus in only roughly 50% of persons infected with genotype 1, the most common genotype in North America and world-wide.
The study was supported by grants from the PSI Foundation and the Canadian Institute of Health Research.
University Health Network consists of Toronto General, Toronto Western and Princess Margaret Hospitals. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has one of the largest hospital-based research programs in Canada, with major research projects in transplantation, cardiology, neurosciences, oncology, surgical innovation, infectious diseases, and genomic medicine. University Health Network is a teaching hospital affiliated with the University of Toronto.
Posted by Ralph at 11:39 AM --- Printer-friendly version | Comments (0)
May 05, 2005
Primary Concerns of HCV Patients
As researchers learn more about what issues are of most importance to patients they will be able to provide more relevant information and support.
What Are the Primary Concerns and Priorities of Individuals with Chronic Hepatitis C?
Counseling of patients with chronic hepatitis C infection is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counseling strategies and content.
Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them.
- The most common volunteered concerns of newly diagnosed patients
in decreasing order were:
- disease progression (27%)
- premature death (19%)
- infecting family members (13%) and
- side-effects of treatment (11%)
In decreasing order, prioritized concerns included:
- infecting family members
- development of liver cancer
- infecting others
- development of cirrhosis
- social stigma of having liver disease
- need for liver transplant, and
- loss of employment
The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, and modes of viral acquisition, and in the case of follow-up patients, duration of follow-up.
The authors conclude, "These results indicate that health care providers who focus counseling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection."
Reference
G Y Minuk and others. Patient concerns regarding chronic hepatitis C infections. Journal of Viral Hepatitis 12(1): 51-57. January 2005.
Posted by Ralph at 12:30 PM --- Printer-friendly version | Comments (0)
May 02, 2005
Fibrotest vs. Biopsy
While primarily about Hyperlipidemia, this article verifies that FibroTest has been validated in chronic Hepatitis c. So, why are doctors still using biopsies???
Screening for Fibrosis with Non-invasive Biomarkers (Fibrotest) in Hyperlipidemic Patients
Insulin resistance is a cause of liver disease that can lead to cirrhosis. Hyperlipidemic patients (HP) have multiple insulin resistance factors and frequent abnormal liver function tests. HP should be screened for significant liver fibrosis (bridging fibrosis: early F2, advanced F3, cirrhosis F4) but biopsy is inappropriate because of the high number of patients at risk.
The aim of the current study was to use FibroTest, validated in chronic hepatitis C, B, alcoholic and non-alcoholic steatosis, to identify HP with F2F3F4.
A consecutive cohort of HP, HCV-HBVneg, <50g alcohol/day, followed in a lipid center was analyzed. Fibrotest was retrospectively performed on frozen fasting sera (–80 C); a control group of blood donors was prospectively included. Fibrotest was performed blinded with security algorithms to identify high-risk of false negative/positive.
Results
Among 1,542 subjects, 40 (2.59%) were excluded using security algorithms, and 1,502 included: 50.3% female, median age 49yrs, 957 HP and 545 controls.
Among HP, 83.4% had cholesterol >=200mg/dl, 93.6% LDL-C >=100mg/dl, 17.5% triglycerides >=200mg/dl, 35.9% BMI >=27, 33% arterial hypertension, 31.8% insulinemia >=10mUI/ml and 13.7% glucose >=6mmol/L.
GGT or ALT were elevated (>=50 IU/L) in 215 HP (22.5%).
F2F3F4 were identified by Fibrotest in 25/957 (2.6%) HP, including 13 F2, 8 F3 and 4 F4 but in none (0%) of the 545 controls (P<0.0001).
Among 25 HP with fibrosis, 19 had normal ALT, 14 normal GGT, 12 normal ALT and GGT, 4 elevated ALT and GGT and 9 elevated ALT or GGT.
Factors associated (p<0.01) with fibrosis were higher age, BMI, triglycerides, uricemia, and insulinemia. In multivariate logistic regression, including alcohol consumption, insulinemia (P=0.003) and triglycerides (P=0.008) were the most significant risk factors.
In HP with triglycerides >=200 mg/dl prevalence of fibrosis was 8.3% and 6.6% with insulinemia >=10mUI/ml.
Conclusions
Based on these results, the authors conclude, “Screening strategies for liver fibrosis are feasible with biomarkers in high-risk groups such as HP.”
“Without such non-invasive strategies a liver biopsy would have been indicated in up to 22.5% of HP with elevated GGT or ALT and would have probably missed half of HP with fibrosis, who had normal GGT and ALT.”
Biopredictive Department, Metabolism Unit, Biochemistry Department, Transfusion Unit, and Hepato-Gastroenterology Department,GHPS, Paris, France.
05/02/05
Reference
M Munteanu and others. SCREENING FOR SIGNIFICANT FIBROSIS USING NON-INVASIVE BIOMARKERS (FIBROTEST) IN HYPERLIPIDEMIC PATIENTS (HP). Abstract 689. 40th EASL. April 13-17, 2005. Paris, France.
Posted by Ralph at 08:44 AM --- Printer-friendly version | Comments (0)