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New On The Blog

Hepatitis C in Minority Populations

Trial Supports Addition of Telaprevir for HCV Genotype 2
Early TIPS for Ascites Study Seeks to Improve Survival

New On The Web Site
Study Suggests HCC Resection Superior to Transplant
Hepatitis C; Type II Cryoglobulinemia
Two New Videos; Posted in Multimedia

Todays News

From HIV and Hepatitis

What Factors Influence Adherence to Treatment for Hepatitis C?
Efficacy, or likelihood of achieving sustained virological response, was the most important factor influencing adherence among people considering treatment for chronic hepatitis C, according to a recent survey.
Increasing rates of non-adherence over time suggest that achieving SVR may not be the only important treatment factor taken into account by people with HCV. Skipping doses may indicate that patients are willing to reduce the likelihood of achieving sustained response in order to avoid treatment side effects.

September 2011 HCV Advocate Newsletter

In This Issue:
NYC: Sexual Transmission of HCV Among HIV Positive Men
Alan Franciscus, Editor-in-Chief
Important Updates at the HCV Advocate HealthWise: Back at Hepatitis C
Lucinda K. Porter, RN
Disability & Benefits: Medicare—Getting the Most Out of It
Jacques Chamber, CLU
HCV Snapshots
Lucinda K. Porter, RN
Clinical Trials
Alan Franciscus, Editor-in-Chief

Dendritic Cells in Liver Protect Against Acetaminophen Toxicity
Released: 9/1/2011 4:10 PM EDT
Source: New York University Langone Medical Center
Newswise —
NYU School of Medicine researchers have discovered that dendritic cells in the liver have a protective role against the toxicity of acetaminophen, the widely used over-the-counter pain reliever and fever reducer for adults and children. The study’s findings are published in the September issue of the journal Hepatology.

The liver is the organ that plays a central role in transforming and filtering chemicals from the body. High-doses of acetaminophen can cause hepatotoxicity, chemical driven liver damage. In fact, accidental and intentional acetaminophen overdose are the most frequent causes of acute liver failure (ALF) in the United States. Acetaminophen related liver failure by intentional or accidental overdose causes 56,000 emergency room visits, 2,600 hospital visits and 450 deaths annually. As a result, this year the FDA mandated drug manufacturers to start limiting the amount of acetaminophen in combination drug products and is currently exploring adding safer dosing instructions to children’s acetaminophen products.

In the new study, researchers found an abundance of dendritic cells in the liver can protect the organ from acetaminophen damage while low levels of dendritic cells in the liver are associated with exacerbated liver damage, liver cell and tissue death, known as centrilobular hepatic necrosis, and acute liver failure from acetaminophen.

“Our research results confirm a central role for dendritic cells and their powerful regulation of acetaminophen’s toxicity,” said George Miller, MD, senior author of study and assistant professor, Departments of Surgery and Cell Biology at NYU Langone Medical Center. “High levels of dendritic cells have a novel, critical and innate protective role in acetaminophen hepatotoxicity. We now have greater insight into the liver’s tolerance of acetaminophen toxicity and dendritic cell regulation of these toxins.”

In the study, researchers used acetaminophen-induced hepatic injured mice models to closely examine the protective role of dendritic cells. Dendritic cells are the main antigens in the liver that trigger an immune response and control the liver’s tolerance to high doses of invading toxins like acetaminophen. In the experiment all mice were injected with acetaminophen but some mice models were first depleted of dendritic liver cells using a diphtheria toxin while others had their dendritic cell levels bolstered with Flt3L, a protein in the blood previously shown to increase proliferation of dendritic cell levels.

Researchers discovered dendritic cell depletion exacerbates acetaminophen’s damage to the liver. The acetaminophen treated mice with depleted dendritic cells had more extensive liver cell and tissue death compared to other mice. Also, these mice died within 48 hours of acetaminophen challenge- whereas death was rare in other mice without dendritic cell depletion. In addition, the study shows dendritic cell expansion successfully diminished the hepatotoxic effects of acetaminophen protecting the liver from damage.

“Understanding the regulatory role of dendritic cells is an important step in the development of immune-therapy for acetaminophen induced liver injury,” said Dr. Miller, a member of the NYU Cancer Institute. “Advanced studies are warranted to investigate further the protective role of dendritic cells in humans and their use as a possible new therapeutic target for liver failure prevention in the future.”

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation’s premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world’s first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center’s tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research.
For more information, go to http://www.nyulmc.org/.

Stem Cells

From Nature

Q&A with the new head of the NIH stem cell center
In October 2005, Mahendra Rao shocked the scientific community when he quit his job as head of the US National Institute on Aging’s stem-cell section and announced plans to go into industry.

The $52-million, seven-year center was launched in early 2010 by the agency to develop new therapies using stem cell approaches. With a heightened focus at the NIH on translational medicine, Elie Dolgin spoke to Rao to find out how he plans to turn stem cell discoveries into cell-based therapies.

What sets the regenerative medicine center apart from other academic institutes dedicated to stem cell technologies?

Neither in size nor in scientific quality could one say that this center is any different from some of the other more established centers. However, there are two crucial differences. One, this is a government center, and the government’s mandate is different than that at any other center. So, that’s a really important distinction. The second thing is that the center doesn’t function in isolation. It’s what’s around it that makes it very useful, and what’s around it is a whole lot of infrastructure and investment that’s gone in to building up a way to take things from the bench to the bedside. There are two really important pieces to that in the NIH Chemical Genomics Center and the NIH Clinical Center. Both of them are widely recognized, state of the art, best in class type of centers Continue Reading

Diabetes

Abstract

Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):503-16.
Current understanding of insulin resistance in hepatitis C.
Kaddai V, Negro F.
Source
Department of Pathology and Immunology, Centre Médical Universitaire, Rue Michel-Servet 1, 1205 Geneva, Switzerland.

Abstract
Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences.

Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-?-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.

Related-Diabetes Updates On The Blog

HCV-Diabetes-insulin resistance and Diabetes

From ScienceDaily
Crippling Condition Associated With Diabetes Is Often Misdiagnosed and Misunderstood

ScienceDaily (Sep. 1, 2011) —
Robert Winkler says he limped around on his painful left foot for six months, suffering unnecessarily from a misdiagnosis by a physician who didn't know about the symptoms and treatments for Charcot foot, a form of localized osteoporosis linked to diabetes that causes the bones to soften and break, often resulting in amputation.

When his primary care physician finally agreed to Mr. Winkler's request for an x-ray, they discovered the metatarsal bones in Mr. Winkler's left foot were all broken -- a common symptom of this serious and potentially limb-threatening lower-extremity complication.
A new article in the September issue of the journal, Diabetes Care, describes Charcot foot and its treatment with a goal of educating medical professionals about this painful inflammation of the foot. The article is the product of an international task force of experts convened by the American Diabetes Association and the American Podiatric Medical Association in January to summarize available evidence on the pathophysiology, natural history, presentations and treatment recommendations for Charcot foot syndrome.

"Even though it was first described in 1883, the diagnosis and successful treatment of Charcot foot continue to be a challenge because this syndrome is not widely known or understood by the broader medical profession," said Lee C. Rogers, D.P.M., co-director of the Amputation Prevent Center at Valley Presbyterian Hospital in Van Nuys, CA, and lead author of the Diabetes Care article. "Charcot foot is now considered to be an inflammatory syndrome most often seen in patients with diabetes which can be successfully treated in its early stages."
The article describes Charcot foot as a condition affecting the bones, joints and soft tissues of the foot and ankle, which is characterized by inflammation in the earliest phase and is associated with diabetes and neuropathy. The report finds offloading, or removing weight from the foot, is the most important initial treatment recommendation. Surgery can be helpful in early stages involving acute fractures of the foot or ankle or in later stages when offloading is ineffective, according to the article.

In Mr. Winkler's case, he was first diagnosed with Charcot foot in 2004 and had already undergone one surgery that relieved the problem for several years. By 2010, though, he was facing the potential amputation of the foot because of complications associated with Charcot foot syndrome.

His podiatrist referred him to Dr. Rogers at Valley Presbyterian Hospital's Amputation Prevention Center, an integrated limb salvage center that is one of only a handful in the nation. Since its December 2009 opening, the Amputation Prevention Center's specialized multidisciplinary team of highly skilled professionals has treated patients from all over the country and around the world with leading-edge technology, achieving a limb salvage rate of 96 percent.

George Andros, M.D., the Center's Medical Director, performed vascular surgery to restore circulation to Mr. Winkler's left foot so that it would heal. Then, Dr. Rogers performed surgery to rebuild the bones in Mr. Winkler's foot. Dr. Rogers also implanted a bone stimulator that acts like a pacemaker for bones which encourages Mr. Winkler's body to rebuild and fuse the broken bones in his left foot. As a result, Mr. Winkler is expected to be able to recover the use of his left foot.

"I'm very pleased because I had gone to another doctor and he wanted to amputate my foot," Mr. Winkler said. "When I found Dr. Rogers and Valley Presbyterian Hospital's Amputation Prevention Center, it's like I found a blessing and an angel in disguise. I have tears running down my face as I describe to you how I will be able to get up out of my chair and walk because of the care I received at Valley Presbyterian Hospital. All the people there are superb. They treat me like a king."

Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Valley Presbyterian Hospital, via EurekAlert!, a service of AAAS.

Journal Reference:
L. C. Rogers, R. G. Frykberg, D. G. Armstrong, A. J. M. Boulton, M. Edmonds, G. H. Van, A. Hartemann, F. Game, W. Jeffcoate, A. Jirkovska, E. Jude, S. Morbach, W. B. Morrison, M. Pinzur, D. Pitocco, L. Sanders, D. K. Wukich, L. Uccioli. The Charcot Foot in Diabetes. Diabetes Care, 2011; 34 (9): 2123 DOI: 10.2337/dc11-0844

Sjogren's

Learn More From Medical News Today;
What Is Sjogren's Syndrome? What Causes Sjogren's Syndrome?
Primary Sjogren's syndrome - experts are not sure what the exact cause of Sjogren's syndrome is. Most believe it is likely to be a combination of environmental and genetic factors. Some people are probably born with certain genes that make them more susceptible to having an abnormal immune system. Sometime during their life, an environmental factor, such as hepatitis C viral infection, or an infection with the Epstein-Barr virus may have triggered the immune system not to work properly.

Challenges in understanding Sjögren's syndrome - improved insights into the pathogenesis generate hope for innovative therapies?
Published:19 August 2011
With this in mind, the authors of these reviews address central questions about the immunopathogenesis of Sjögren syndrome. Sipsas and colleagues [4] explore the potential role of retroviruses in initiating or maintaining disease. Vitali [5] examines the differences and similarities of sicca symptoms and risk of developing lymphoma between patients with HIV or hepatitis C virus infection and those with Sjögren syndrome

From Medpage

Sjogren's Sidelines Venus Williams
By Nancy Walsh, Staff Writer, MedPage Today
Published: September 01, 2011
When former No. 1 women's tennis star Venus Williams withdrew from the U.S. Open this week, she brought immediate attention to the little-known autoimmune disease Sjögren's syndrome, thought to afflict some 0.5% of adults.The disease is characterized by destruction of the exocrine glands, leading to excessive dryness of the mouth and eyes.But Sjögren's syndrome also is associated with symptoms such as debilitating fatigue and musculoskeletal problems that could seriously interfere with athletic performance.

"It's my suspicion that it may have been the systemic manifestations like fatigue and joint pain that have been troubling her and that could be difficult for a person trying to function at that very physically demanding level," Robert Spiera, MD, director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York City, told MedPage Today. Spiera has not been involved in Williams' treatment.

Earlier in the week Williams, 31, won a match in the tournament, held at the Billie Jean King National Tennis Center in Flushing, N.Y., but when she left the venue, after withdrawing on Wednesday, she said in a statement, "I enjoyed playing my first match here and wish I could continue, but right now I am unable to," according to the New York Times.

Steven Taylor, who heads the Sjögren's Syndrome Foundation, said in a statement, "On behalf of the four million Americans with Sjögren's, we applaud Venus for publicly stepping forward and shedding light on this serious autoimmune disease."

Diagnosing the disease can be challenging, and can involve salivary flow testing, salivary gland biopsy, and blood tests for autoantibodies such as rheumatoid factor, antinuclear antibodies, SSA and SSB antibodies.

Williams, who has been sidelined in recent months because of what was thought to be a viral illness, said she was "thankful to finally have a diagnosis." In fact, according to Taylor, the average time to diagnosis is 6.5 years after symptom onset.

The condition affects women far more than men, as is the case with most autoimmune diseases, and generally begins when patients are in their 40s.
"When patients present with complaints such as fatigue, clinicians need to be proactive and think beyond the common diagnoses like depression and thyroid disorders and ask about dry eyes and mouth," Spiera said.

Some similarities exist between Sjögren's syndrome and other autoimmune disorders such as rheumatoid arthritis and lupus, including articular, renal, and neurologic involvement.
For many patients, symptoms can be managed with products such as eye lubricants.
But for those with more severe manifestations, systemic medications such as anti-inflammatories, antimalarial drugs, and immunosuppressive agents may be needed.
Williams apparently is taking an oral medication that could take several months for its full effects to be seen, according to another report in the Times.

B cells are thought to play a crucial part in the development of Sjögren's syndrome, accumulating and becoming hyperactive in the exocrine glands and heightening immune antigenic responses.
For reasons that are not yet clear but which may involve B-cell proliferation and mutagenicity, in some patients the immune hyperactivity can evolve into a lymphoproliferative malignancy.
"Patients with Sjögren's have a risk of lymphoma that is as much as 40-fold higher than the general population," Spiera said.

Certain features of the disease seem to be associated with the development of lymphoma, such as bulky lymph or parotid gland enlargement, skin vasculitis, and low blood levels of complement.
"But the vast majority of patients with Sjögren's syndrome never develop lymphoma," Spiera said.
"Most patients with the disorder live very productive lives. Sjögren's does affect their quality of life, but there are strategies to help deal with their problems," he added.

Pharmaceuticals

From Reuters
FDA may get two more months to review new drugs
(Reuters) - U.S. regulators and the drug industry want to extend by two months the deadline for the Food and Drug Administration to approve or reject new drugs.

The extended timeline was tucked into the proposed deal the FDA forged with the prescription drug industry on the fees companies pay for drug reviews. The FDA posted the proposal on its website on Thursday.

The FDA said it would need an extra 60-day "filing date" before the clock starts ticking on its 10-month deadline to review new drugs, or six months for a priority review.
The new five-year agreement, which will be put out for public comment, comes as the FDA faces increased criticism from congressional Republicans and the industry for being too slow in approving new products, which they say stifles innovation and job creation.
"People are kind of scratching their heads" over the longer review time, said an industry source familiar with the negotiations on the user fees.

"But the idea is that FDA will use those two months to really prepare for the review so the hope is that it gives us more predictability and makes everything shorter in the long-run."
The Prescription Drug User Fee Act (PDUFA), first enacted in 1992, gives the FDA millions of dollars annually to review new products for the U.S. market in exchange for quicker approvals and other promises.

Congress must reauthorize the current PDUFA legislation before it expires in September 2012. The FDA's new fee agreement with industry, which would kick in at the beginning of 2013, would be part of the reauthorization legislation .

MORE FEE FLEXIBILITY
The fees system is controversial, with some critics contending they influence the FDA, which is supposed to protect the health and safety of consumers.
Currently, about a third of the agency's funding comes from makers of drugs and medical devices -- and that could grow if the FDA reaches a final agreement with generic drugmakers.
In 2010, the FDA collected $922 million in user fees out of a total budget of about $3.28 billion. The agreement with the prescription drug industry would increase user fees 6 percent over levels in 2012 for an estimated total of about $713 million in 2013, FDA Commissioner Margaret Hamburg said in Congressional testimony in late July.

The FDA also wants more flexibility on how it spends the money. Some of the fees will go toward drug safety, rare diseases and for training FDA staff in new technologies and science -- part of a broader push to improve the agency's scientific expertise.

"If you look at the original PDUFA, all of that went directly to just review processes," said Ryan Hohman, the director for communications and policy at Friends of Cancer Research, a think-tank and advocacy group.
"But the FDA and industry stepped back and recognized that in the economic environment, they need to have the increase in science or else they won't be able to approve these drugs at a speedy time for patients."

The FDA must still agree on the specifics of its user-fee program with the medical device industry, which started paying fees in 2002. It is also planning a new fee program with makers of generic drugs and 'biosimilars' -- copycat versions of brand-name biotech drugs.
(Editing by Karey Wutkowski and Andre Grenon)

From Pharmalot

Pfizer’s Lipitor Webpage Is Slammed By FDA

By Ed Silverman
September 2nd, 2011
Once again, a web page is deemed problematic by the FDA. In a letter sent by the agency earlier this week, Pfizer was chastised because its Lipitor web page made misleading representations and suggestions about several other drugs. The issue came to light, by the way, thanks to the FDA ‘Bad Ad’ program, which encourages people to file complaints about troublesome promotions (see this). Continue Reading..

Cancer Research

Jennerex press release
Jennerex cheered by early efficacy data for cancer-killing virus
A small, mid-stage study of Jennerex's genetically engineered virus offered some important preliminary proof-of-concept data on its ability to zero in on cancer cells with just a single infusion. Reporting in Nature, investigators said biopsies confirmed the virus was replicating inside the tumors of 7 of the 8 people with metastatic cancers who were given the engineered dose, leaving healthy tissue untouched. Researchers noted several weeks after treatment the tumors in half of the group had stopped growing, indicating their cancers may have stabilized, and that in one case tumors appeared to shrink.

Why cancer cells change their appearance?
Like snakes, tumor cells shed their skin. Cancer is not a static disease but during its development the disease accumulates changes to evade natural defenses adapting to new environmental circumstances, protecting against chemotherapy and radiotherapy and invading neighboring organs, eventually causing metastasis.
Fondo de Investigaciones Sanitarias (FIS), Josef Steiner Cancer Research Foundation, Lilly Foundation, European Research Council Advanced Grant, Health Department of the Catalan Government, Instituto de Salud Carlos III, ICREA

FYI

Comprehensive Management of Liver Disease ?at the Montefiore Einstein Center for Transplantation
Friday, September 02, 2011
“The Marion Bessin Liver Research Center is a highly respected and internationally renowned research facility that performs revolutionary work in the fields of liver transplantation and stem cell research,” says Milan Kinkhabwala, M.D., Surgical Director of the Montefiore Einstein Center for Transplantation, Chief of the Division of Transplantation, Montefiore Medical Center, and professor of surgery, Albert Einstein College of Medicine. “The program needed a clinical arm to help advance the treatment of liver disease and provide direct benefits to patients. We brought together a team of highly trained hepatologists, hepatobiliary surgeons and gastroenterologists, and integrated those clinicians with the existing team of research professionals to create a truly interdisciplinary center featuring both clinical and research expertise that is dedicated to providing innovative, novel treatments for liver disease.”
Physicians are also involved in clinical trials utilizing Telaprevir, a new medication for treatment of viral hepatitis C..

Healthy You

Diet and hep C
Staying as healthy as possible will help you cope better with hep C. To help improve your health, eating a wide variety of food in the right balance is important. The following advice about diet and food has been developed by dietitians who work with hep C. It aims to dispel myths and help you to stay as healthy as possible.
Avoid restrictive or cleansing diets as there is little clinical or biological basis to support them. The bottom line is that if you don’t have serious liver damage (e.g. cirrhosis) there are no particular foods that you should seek or avoid because of your hep C. If you do have serious liver damage, speak to your specialist or doctor for dietary adviceContinue Reading..

The Low-Fat Con?
By Simon Donovan
Published: September 2, 2011
Posted in: Editorial, Nutrition
Products such as mayonnaise, cottage cheese and other dairy products often come in low-fat or reduced fat varieties. But what are reduced or low-fat products? In order for a food or product to be classified as low-fat it must contain fewer than 30% of its total calories from fat, in simple terms the product must be constitute less than 30% fat. Whilst reduced fat products do not have to meet set criteria with regards to their fat content, they must just contain less fat than their natural products. For products such as cheese and mayonnaise to be less than 30% fat requires a significant proportion of the fat to be removed. Common sense tells us that if we take something out we must put something back in to replace it. So what is replacing this fat? Yes, you have guessed, it is sugar.Continue reading..

Osteoarthritis (OA)

Glucocorticoid treatment may prevent long-term damage to joints
Joint injury can result in irreversible damage of cartilage which, despite treatment and surgery, often eventually leads to osteoarthritis (OA) in later life. New research published in BioMed Central's open access journal Arthritis Research & Therapy demonstrates that short term treatment of damaged cartilage with glucocorticoids can reduce long term degenerative changes and may provide hope for prevention of OA after injury.

A normal joint is covered by a layer of cartilage containing proteoglycans such as aggrecan and lubricating fluid containing glycosaminoglycans (GAG) such as hyaluronic acid. In a double whammy, after injury proteoglycans and other molecules in cartilage begin to break down and the synthesis of these proteoglycans within cartilage is reduced. Additionally proinflammatory cytokines such as TNF?, IL-1?, and IL-6 are released into the synovial fluid after injury and further increase GAG loss from cartilage.

Using a 'worst-case scenario' system in which cartilage was subjected to mechanical injury and bombarded with immune system-stimulating bio-molecules (TNF? and IL-6) the glucocorticoid dexamethasone (DEX) was able to reduce GAG loss and restore proteoglycan synthesis levels to normal.

Prof Alan Grodzinsky from the MIT Center for Biomedical Engineering said, "Glucocorticoid injections are sometimes used to relieve the pain of established osteoarthritis, but there are concerns about long-term use. Our results suggest that short-term glucocorticoid treatment after joint injury may help restore components of cartilage to preinjury levels and consequently may prevent the long term changes which lead to osteoarthritis."

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