August 11, 2010

Appetite Hormone Could Inhibit HCV-Related Fibrosis

August 11, 2010

Ghrelin is mostly known as a naturally occurring hormone that stimulates the appetite. However, new research demonstrates that this hormone might have therapeutic value to those with Hepatitis C.

by Nicole Cutler, L.Ac.

A hormone normally found in the stomach is proving to be of great interest to the Hepatitis C community. Known as an appetite-stimulating hormone, ghrelin is regarded with disdain by dieters and overweight individuals. Interestingly, ghrelin has demonstrated the ability to minimize one of the greatest hazards of the Hepatitis C virus - liver fibrosis.

About Ghrelin

Made in the stomach, ghrelin levels rise when people are hungry and they wane after a meal. People who get injections of this hormone gorge themselves, and those suffering from a rare disease that keeps ghrelin levels unusually high tend to be obese overeaters. Not surprisingly, researchers seeking to help people shed excessive weight have been actively trying to block ghrelin since its recognition in the late '90s. Of course, blocking an essential hormone carries unknown risks to our health. For people with chronic liver disease, researchers from Spain have uncovered a valid reason to treasure ghrelin - and be weary of blocking this curious hormone.

Fibrosis

One of the few organs that can regenerate, the liver has the remarkable ability to recover from minor injuries by healing itself. Unfortunately, this regenerative capacity can't keep up with diseases that cause significant liver damage. For those individuals living with chronic Hepatitis C (or any other kind of chronic liver disease), progressive scarring of liver tissue is a major concern.

Otherwise known as fibrosis, continual liver scarring can lead to cirrhosis - which ultimately renders the liver unable to function. Over 27,000 Americans die from cirrhosis annually, making it the country's third leading cause of death for people between the ages of 25 and 59, and the seventh leading cause of death overall. Needless to say, strategies to prevent fibrosis from worsening to cirrhosis are in high demand. Despite this need, there are currently no approved anti-fibrotic therapies on the market.

Ghrelin Fights Fibrosis

Published in the March 2010 edition of Hepatology, researchers from Spain's Hospital Clinic of Barcelona discovered that ghrelin has the potential of being a novel, anti-fibrotic therapy. According to Dr. Ramón Bataller, part of the team involved in the Barcelona study, "Our aim was to determine if recombinant ghrelin could regulate the formation of fibrous tissue associated with chronic liver damage."

The research team found the following:

· In animal models, ghrelin reduced the amount of fibrogenic cells by 25 percent.

· Participants with chronic Hepatitis C and alcoholic hepatitis had significantly lower ghrelin levels than did healthy individuals.

The researchers concluded that ghrelin inhibits the development of liver fibrosis in both animals and humans.

Insulin Resistance

The link connecting this appetite-stimulating hormone to its protection against liver fibrosis remains unclear. However, research from 2003 may be on the right track. According to an Italian study published in the Journal of Clinical Endocrinology & Metabolism, insulin resistance may be the bridge between ghrelin levels and liver damage. In individuals with NAFLD (non-alcoholic fatty liver disease), insulin resistance is believed to be relatively independent of obesity. After evaluating subjects with NAFLD, the Italian researchers found that insulin resistance plays a primary role in controlling ghrelin levels.

Insulin resistance is a decreased ability to respond to the effects of insulin, a hormone that helps transport glucose into the body's cells for making energy. Since cells need glucose to survive, the body compensates for insulin resistance by producing additional amounts of this hormone. Although not a disease or specific diagnosis, insulin resistance has a ripple effect on the body and is associated with heart disease, polycystic ovarian syndrome, Type 2 diabetes, obesity and NAFLD.

Thanks to Bataller's team, the connection between ghrelin and fibrosis could help prevent liver scarring in people who are most prone. Future studies are likely going to take insulin resistance into consideration while determining the safety and efficacy of ghrelin in people with chronic liver disease. If this hormone continues to prove its value to the liver, efforts to block ghrelin for weight loss purposes will likely lose steam. On the other hand, those with Hepatitis C could benefit by finally having a therapeutic option to prevent the progression of liver scarring.

References:

http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RCN=31823, Body's own hormone may be liver disease's worst foe, Retrieved March 15, 2010, CORDIS Services, 2010.

http://jcem.endojournals.org/cgi/content/abstract/88/12/5674, Low Ghrelin Concentrations in Nonalcoholic Fatty Liver Disease Are Related to Insulin Resistance, G.Marchesini, et al, Retrieved March 19, 2010, Journal of Clinical Endocrinology & Metabolism, August 2003.

http://www.cbsnews.com/stories/2003/03/11/60II/main543614.shtml, The Hunger Hormone, Carol Kopp, Retrieved March 15, 2010, CBS Interactive Inc., 2010.

http://www.eurekalert.org/pub_releases/2010-03/w-gml022510.php, Ghrelin mitigates liver fibrosis in animal models; regulates human fibrosis, Retrieved March 15, 2010, EurekAlert, 2010.

http://www.healthsquare.com/fgpd/fg4ch20.htm, Dealing with Liver Disease, Retrieved March 19, 2010, The HealthCentral Network, Inc., 2010.

http://www.labtestsonline.org/understanding/conditions/insulin_resistance.html, Insulin Resistance, Retrieved March 19, 2010, American Association for Clinical Chemistry, 2010.

http://www.ncbi.nlm.nih.gov/pubmed/20077562, Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans, Moreno M, et al, Retrieved March 15, 2010, Hepatology, March 2010.

http://www.newscientist.com/article/dn13845-stomach-hormone-turns-hungry-people-into-junkies.html, Stomach hormone turns hungry people into junkies, Ewen Callaway, Retrieved March 18, 2010, Reed Business Information Ltd, 2010.

Source

Infergen Gives Hepatitis C Patients An Extra Chance

 

ALEXANDRIA, Va. (WUSA) -- Approximately 50 percent of chronic hepatitis C patients do not respond to their initial course of therapy, according to Bruce R. Bacon M.D. of Saint Louis University School of Medicine.

Dr. Bacon is the lead investigator of the registration trial for Infergen, a new treatment for Hepatitis C patients that recieved FDA approval last month.

Dr. Bacon says, "The FDA's recognition of the expanded label allows patients failing therapy a safe and efficacious retreatment strategy."

This is good news for 59 year-old Hubert "Shep" Sheppard. Shep is a physically active man who bikes 60 miles a week and used to jump out of airplanes as a paratrooper. Now he is a private detective.

However, the one challenge that could have cost Shep his vitality, even his life, was Hepatitis C.

Shep says, "I have no idea where I got it. I was totally shocked I had this disease."

He adds, "I probably had it for a while, and had no indications of it."

In Shep's case, the chronic infection was attacking his liver. His first round of treatment wasn't enough to clear it.

Shep says, "There's some difference in African-Americans in that we don't respond well to some treatment."

Dr. Jonathan McCone of Alexandria, Virginia says Hepatitis C can be a silent killer.

Dr. McCone says, "Its basically not a sexually transmitted disease. Its not transmitted by kissing or sneezing in somebody's face, or breathing the same air. It's a blood-to-blood disease."

He adds, "One can end up with advanced liver disease, cirrhosis, liver cancer, and the need for liver transplant."

Fortunately Shep was able to take advantage of Infergen, given daily with ribivirin pills, it delivers a one-two punch to the virus.

The down-side, the regimen that lasts for months also delivers a whallop of side effects from extreme fatigue to weight and hair loss, and anemia.

But Shep says he approached it with a military mind-set.

Shep says, "I just saw it as a personal combat between me and this disease, and I just thought that one of us is going to be carried out in a box and its not going to be me."

Shep tested clean of the virus last year, and is now considered cured.

There is no vaccine for Hepatitis C, like there is for A and B.

Source
11 August 2010
Ciência Viva - Agência Nacional para a Cultura Científica e Tecnológica

After a transplant – and to assure that the new organ is not rejected - patients are put on life-long therapy to suppress their immune system (IS), which, nevertheless, needs to be left intact enough to be able to defend the body against all kinds of disease. A tricky balance as the many rejected organs attest. But a discovery by Maria Monteiro and Luis Graça, two Portuguese scientists, could change all this, at least for the liver. Their work, just out in the Journal of Immunology (1), describes how they found a new type of white blood cell – baptised NKTreg (reg from regulatory) – that, once activated, migrate into the liver and suppress any immune response in its vicinity. What is most remarkable is that the immune system elsewhere is left intact. And the implications do not end in better liver transplants as, once these cells create an “immune tolerant organ”, we can graft any type of tissue or express any gene that the body might need into it, knowing that it would be safe from the IS. The potential of the discovery is such that a patent by Monteiro and Graça for the production and therapeutic use of NKTreg cells in humans has already been accepted.

Controlling an unwanted immune response, whether to stop organ rejection after a transplant or for the treatment of autoimmune diseases – in which an abnormal IS attacks the own body- can be tricky. At the moment there are two types of approaches: general immunosuppression or deletion of entire “arms” of the IS. Both methods require a difficult equilibrium between stopping the damaging immune response while allowing patients to remain immuno-competent, and both carry potentially serious side effects. Most recent therapies fall in the second approach and work by deleting a particular type of cell or protein (an “arm” of the IS) at the core of the immune response we want to stop. While these methods can be extraordinarily effective – thousand of patients had their lives changed by them – unfortunately, they do not seem to work for long, probably because the IS adapts and brings other cells and proteins to do the job of the lost “arm”. While this is not a problem for pharmaceutical companies that can go on developing new and even more expensive drugs, to patients it means a life of constant uncertainty and many potential problems– will the next new drug be effective, will it stop working, will then be yet another drug ready, what about side effects?

The truth is that these kinds of approaches are a far cry from a 21st century medicine with emphasis in personalised and very specific therapies, and it is crucial that new and better treatments are found.

It is in this context that a family of white blood cells called regulatory T cells has been hailed as “next big thing” - shown to suppress immune responses and part of the body’s mechanisms to stop undesired immune responses, these cells could be key to more specific treatments while are also less prone to be “overridden” by the body control mechanisms. And in fact, human trials for their use in transplantation are already under way although much work needs to be done. But meanwhile another family of white blood cells - called NKT cells - has also came to the attention of scientists when shown to protect mice from several autoimmune diseases, including diabetes and autoimmune encephalomyelitis (EAE) - the animal equivalent of multiple sclerosis

To try to understand better the potential of NKT cells Marta Monteiro, Luis Graça and colleagues at the Instituto de Medicina Molecular, University of Lisbon and the Instituto Gulbenkian de Ciência in Oeiras, Portugal looked at mice protected from EAE using NKT cells (like shown by others). In these mice they analysed the lymph nodes that drain the brain – the logic being that since EAE affects the brain, protective cells should be found in the lymph nodes directly linked to it. To their surprise they discover a total new population of NKT cells that expressed Foxp3 – a marker for regulatory T cell, linked to these cells immunosuppressive capabilities. When these new NKT cells were studied in laboratory they revealed several other similarities – not only they share many other receptors of regulatory T cells but, like them, both Foxp3 and their suppressive abilities are triggered by a protein called TGFbeta – leading Monteiro and Graça to name them NKTreg cells.

But how do these cells act when in the body? To answer this question, and after activating NKT cells to become NKTreg (so Foxp3 positive) and tag them with a fluorescent marker so they could be easily traced, Monteiro and Graça injected the (suppressive) cells back into mice. Remarkably these cells homed straight to the liver – in this they are very different from regulatory T cells that move into all lymphoid organs; spleen, lymph nodes, etc - suggesting that in normal conditions NKTreg cells could perform some immunosuppressive role in this organ.

The implications of this discovery are important and many. In liver transplants although success rate has increased substantially the odds that the organ will survive up to 15 years are still only around 58%, with as many as 10-15% of patients experiencing organ rejection before the end of the first year. Not only that, but current immunosuppression therapies are costly and affect patients’ life expectancy by putting them at higher risk of cancer and mortal infections. NKTreg cells – if proved to function in the same way in humans, and Monteiro has already shown that we at least have them - might be the answer to these problems.

As Luis Graça explains “the liver is already the transplanted organ with higher chances of success due to its unique characteristics, by using these new cells we might be able to achieve almost 100% organ acceptance and this without touching the remaining IS, what is remarkable. Patients might be able to survive with only a minimum dose of other immunsuppressors”.

But there are other major implications to be able to create a “bubble of tolerance” within the body. Many diseases caused by the absence of a molecule or metabolic tissue are being treated with therapies that insert replacements into the body. The problem is that the IS soon or later detects these new “parts” and attacks them. The liver is already a place where the immune system seems to be less vigilant - probably so it is not over-activated all the time by the food and microbial molecules that come through the digestive system – add NKTreg cells to this organ and it can became the perfect place to hide anything from the IS.

And in fact, at the moment, some diabetic patients – that lack insulin to metabolise sugars – already have insulin-producing grafts on their liver, while some gene therapies, for example for the production of clothing factors in haemophilia (a disease where patients can not coagulate their blood) are already being expressed in the organ. NKTreg, if they work in the same way in humans as in mice, can radically improve the chances of success of these and other therapies. The potential of being able to create a contained area of immunosuppression within the body without touching the remaining immune responses elsewhere in the body, is immense. But first we need to see if and how NKTreg cells work in humans and that is what Monteiro and Graça plan to do next.

Piece by:Catarina Amorim

http://www.jimmunol.org/cgi/content/abstract/jimmunol.1000359v1

Source

Highest Rates Of Hepatitis C Virus Transmission Found In Egypt

Article Date: 11 Aug 2010 - 1:00 PDT

The Arab Republic of Egypt has the highest rates of new hepatitis C virus (HCV) infection in the world, according to a new study published in the prestigious Proceedings of the National Academy of Sciences. The study also estimates more than 500,000 new HCV infections occur in Egypt every year, likely signaling an epidemic in a country of more than 77 million people. This high rate of HCV transmission may be due to the lack of sufficient standard safety precautions in medical and dental facilities, the authors suggest.
 
"Nearly 7 out of every 1,000 Egyptians acquire HCV infections every year, suggesting intense ongoing transmission. This is the highest level of HCV transmission ever recorded at a national level for a blood borne infectious disease transmitted parenterally, that is, by use of non-sterile medical instruments," said Dr. F. DeWolfe Miller, lead author of this study and professor of epidemiology at the Department of Tropical Medicine and Medical Microbiology and Pharmacology at the University of Hawaii.

Although the high prevalence of hepatitis C in Egypt has been well established for many years, and linked in part to limited safety measures during anti-bilharzia campaigns, published estimates of prevalence from different Egyptian communities failed to provide a nationwide picture of the magnitude of ongoing HCV infection transmission. To estimate the rate of new HCV cases of infection in Egypt, the authors of the study performed epidemiologic modeling of data from a range of studies, including a 2008 national HCV survey with a representative sample and well-documented study design.

"The study opened our eyes to a disease burden similar in scale and challenge to the HIV problem in sub-Saharan Africa: Millions of cases of an infection for which there is no vaccine, no effective treatment, and where case management is so expensive that it is beyond the reach of most patients," said Dr. Laith J. Abu-Raddad, co-author of the study and assistant professor of public health at the Infectious Disease Epidemiology Group at the Weill Cornell Medical College-Qatar.

The study necessitates not only further analysis of HCV transmission in Egypt but also justifies the immediate increase of resources to strengthen public health measures aimed at reducing the transmission of HCV in clinical and non-clinical settings, according to the authors. Failure to address this problem will result in a massive disease burden in the nation in terms of HCV infection complications, including active liver disease, liver failure, or liver cancer.

"There is only one way to deal with the HCV challenge in this country: HCV prevention," warned Dr. Miller. "Effective and stronger HCV prevention programs are urgently needed in Egypt. Failure to act could swamp the public health system over the coming decades with millions of cases of HCV disease complications with an economic and social cost that this nation does not have the means to confront."

Key scientific findings of the study

• Nearly 7 out of each 1,000 Egyptians acquire HCV infection every year for a total of 537,000 new HCV infections every year. This is by far the largest ever recorded rate of occurrence of HCV at a national level of all countries in the world.

• One in every 10 Egyptians is a carrier of the HCV infection, which means that there are at least 4,459,000 persons infected with HCV who are infectious to others. This is the largest reservoir of HCV infection in the world.

• Contrary to the widely-held perception that this rate of occurrence reflects merely the limited safety measures during anti-bilharzia campaigns, HCV incidence likely continues at alarming levels due to limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities.

F. DeWolfe Miller, PhD (Lead Author)
Department of Tropical Medicine and Medical Microbiology and Pharmacology
University of Hawaii
Honolulu, HI, USA

Laith Abu-Raddad, PhD (Co-Author)
Director of Epidemiology, Biostatistics and Biomathematics Research Core
Assistant Professor in Public Health
Weill Cornell Medical College - Qatar
Doha, Qatar

Source:
Weill Cornell

Source

Transplant Patients Can Benefit From Loved Ones' Care

August 10, 2010, 16:00 EST

Caregiving by those with emotional connection lessens anxiety, depression after surgery, study found
 
TUESDAY, Aug. 10 (HealthDay News) -- Transplant patients who have a close emotional connection with family members or other caregivers experience less depression and anxiety after surgery, new research has found.

The study included 74 liver transplant patients and their primary caregivers who were surveyed before surgery and six months after transplantation. Caregivers were asked to rate how close they felt to the patient, and the sample was divided into a group whose caregivers reported the most closeness and a group whose caregivers reported the least.

Symptoms of depression and anxiety decreased among the patients after their liver transplant, but the improvements weren't as significant for those with an emotionally distant caregiver, according to the researchers from the Henry Ford Hospital in Detroit.

"If you live with someone who loves you, the quality of care they provide may be much better, they may be more encouraging, you may want to please them and recuperate faster so you can spend quality time with them," lead author Anne Eshelman, of the Henry Ford Health System Behavioral Health Services, said in a hospital news release.

"Caregivers who are not close may provide the basic requirements, but don't help give someone a reason to live and look to the future," she added.

The study findings also indicated that emotional closeness was critical in male patients, but less so for women (although the researchers pointed out that interpretation of the results was difficult due to the small sample size).

"Men who had an adequate number of support people, but did not have close support, were still depressed and anxious at follow-up, compared to those who had closer support," Eshelman said. "Other literature shows that women have wider support, more friends and family they are connected to than men, and if the primary support person is not that close, they probably rely on the other people such as girlfriends."

The study was scheduled for presentation Aug. 6 at the International Congress of Behavioral Medicine in Washington, D.C.

More information
The American Society of Transplantation has more about health after transplantation.

-- Robert Preidt

SOURCE: Henry Ford Hospital, news release, Aug. 6, 2010

Source
August 10, 2010

Wearing gloves reduces the risk of injury by needles and sharp medical devices, or sharps injuries, by about 66 percent, according to a new study by Canadian and U.S. researchers. Double-gloving brought the risk down further, by about 80 percent.

The study involved 636 health care workers from 13 medical centers in the United States or Canada who presented to employee health clinics after a sharps injury. Of the workers, 195 were scrubbed in an operating room or procedure suite when injured, and 441 were non-scrubbed and injured elsewhere. The latter were more likely to be gloved when treating patients who were perceived to have a high risk of HIV, hepatitis B or hepatitis C.

In case-crossover analyses, gloves reduced injury risk (incidence rate ratio [IRR] 0.33 [95 percent CI, 0.22-0.50]. Among scrubbed individuals, "involvement in an orthopedic procedure was associated with double-gloving at injury (adjusted odds ratio, 13.7 [95 percent CI, 4.55-41.3]); this gloving practice was associated with decreased injury risk (IRR, 0.20 [95 percent CI, 0.10-0.42])."

"Gloving actually reduces the likelihood that a needle will go through your skin and inoculate you with blood," said senior study author Dr. David Fisman, an epidemiologist and researcher with the University of Toronto and Toronto's Hospital for Sick Children. In passing through the latex or vinyl membrane, some of the blood from the needle will be removed, reducing the inoculum or potentially infected blood, he explained.

Yet despite this, "There are kind of these weird beliefs about if you glove then you get clumsier and if you get clumsier, then you stick yourself," Fisman said.

The full report, "Use of Gloves and Reduction of Risk of Injury Caused by Needles or Sharp Medical Devices in Healthcare Workers: Results From a Case-Crossover Study," was published in Infection Control & Hospital Epidemiology (2010;31:908-917).

Source

For Lilly, it's a big one that got away

J.K. Wall August 11, 2010

Mark this one in Eli Lilly and Co.’s “Oops!” category.

An experimental medicine for hepatitis C that Lilly helped identify and develop is now on the cusp of market approval. According to an article in Xconomy.com, a biotech trade publication, some analysts are predicting as much as $2 billion in annual U.S. sales after the drug's expected market launch in 2011.

But in December 2002, Lilly sold back its rights to the drug, telaprevir, to its inventor, Massachusetts-based Vertex Pharmaceuticals Inc

Any revenue from telaprevir, which would have been split with Vertex, would have been awfully nice right now for Lilly. The Indianapolis-based drugmaker will watch patents expire on its cancer drug Gemzar in November and its antipsyhotic blockbuster Zyprexa a year later.

Cheaper generic copies will steal the lion’s share of those two drugs’ $6 billion in annual sales.

“It’s a decision that Lilly has to regret,” Xconomy.com reporter Ryan McBride wrote about telaprevir, which proved effective for three out of four patients with hepatitis C, a chronic liver disease, during a large Phase 3 clinical trial.

McBride cited a former Vertex executive who said telaprevir’s champions within Lilly were shuffled off the program, and it subsequently fell down Lilly’s priority list.

Vertex later signed co-development deals with New Jersey-based Johnson & Johnson and Japan-based Mitsubishi Tanabe, according to Xconomy.com.

“At Lilly, we regularly review our portfolio and sometimes re-prioritize assets based on resource availability,” Lilly spokesman Mark Taylor said in a statement. “Although we may decide to discontinue internal development of a molecule, we many times try to find ways to allow partner companies to continue the development. We believe this is in the best interest of the patients who may ultimately benefit if a new medicine makes it to the market."
 
Source