Consider Hepatitis C Infection in Some Arthritis Patients

CHICAGO – Sept 29

Data from two new trials, one in press and the other ongoing, suggest that two established tumor necrosis factor inhibitors may be the safest drugs for treatment of rheumatoid arthritis in a patient with active hepatitis C virus infection.

The recent pilot study (Journal of Hepatology, in press) of 50 patients with coexisting rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection clearly demonstrated that adding etanercept to traditional antiviral therapy was associated with clearing HCV and normalizing liver enzymes, Dr. Leonard H. Calabrese said at the Midwest Rheumatology Summit.

"This was kind of an opening salvo to us, saying, this is our drug. We should be looking at this ... to see if it’s an option to use to treat autoinflammatory disease and, in particular, rheumatoid arthritis," said Dr. Calabrese.

The ongoing Partner Trial is designed to answer the question of whether a tumor necrosis factor (TNF) inhibitor enhances antiviral responses to traditional therapy, specifically the efficacy of infliximab as an adjunct to peginterferon alfa-2b and ribavirin in the treatment of HCV genotype 1.

"One thing that is not a good idea is to use hepatotoxic drugs (like) methotrexate," said Dr. Calabrese.

Treatment is not the only challenge in caring for the patient with overlapping RA and HCV; just making the HCV diagnosis can be difficult.

"The most undiagnosed infection in our country is hepatitis C. There are probably about 3 million people walking around who are infected, who don't know it," said Dr. Calabrese, professor of medicine at the Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University. Most patients with undiagnosed hepatitis C have chronic infection, which is relatively asymptomatic, he said. "That’s why screening programs are essential."

He described a 49-year-old woman with a history of polyarthritis who presented for evaluation after a 7-month history of migratory arthritis involving feet, hands, wrists, and knees. The patient had a "fairly normal" hemogram and normal alanine transaminase (ALT) and was positive for the anti–cyclic citrullinated peptide (CCP) antibody.

"The most undiagnosed infection in our country is hepatitis C."

"So she clearly has rheumatoid arthritis ... and is an excellent candidate for methotrexate," he said. Lab results showed the woman to be positive for the HCV antibody, and negative for hepatitis B surface antigen and hepatitis B core antibody.

"So the question is, does this patient have active hepatitis C infection?" said Dr. Calabrese. And if so, how would that influence treatment decisions?

Nearly half of patients with chronic HCV have ALTs within the normal range, so the test has no negative predictive value. "The gold standard of diagnosis in HCV is the presence of fibrosis on liver biopsy," said Dr. Calabrese. "The reality is that if you have people with persistently normal ALT levels, upon biopsy, 75% have some evidence of damage, and about a third of them have advanced fibrosis."

This patient was found to have a normal ALT-38 u/mL, to have 1.2 million copies/mL of HCV-RNA, and to have genotype 1. Her liver appeared normal on ultrasound.

This patient has normal ALT but clearly has HCV, he said. "Normal liver enzymes do nothing at this juncture to tell us that this patient does not have a significant problem." While a biopsy is invasive, it has a very acceptable rate of complications, he said.

The alternative to biopsy is the transient elastography test, widely used in Europe. It is noninvasive and accurate, but not yet approved in the United States.

And the 49-year-old woman? "Patients such as this I would treat with a TNF-inhibitor monotherapy, and if that patient needs treatment, or my hepatologist says ‘I want to start this patient on therapy for hepatitis C next month’? Let’s do it – and keep them right on their TNF-inhibitor. We have enough data now to know that it’s probably a safe thing," he said.

Dr. Calabrese disclosed consultant and/or speaking income from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genentech, Pfizer, and Roche. The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB.

Source

Liver Health and Wellness

The outstanding performance of the new drugs to treat hepatitis c can overshadow the importance of liver health; also an important weapon in your arsenal to fight liver disease. While on HCV therapy a healthy diet, staying hydrated and getting the proper rest are all of great importance. Liver health should remain a priority, even if you are not on treatment, or have just finished. Hopefully the topics on the blog today will inspire the reader to consider healthy lifestyle changes.

The Bad News

Fatty liver disease, alcohol, certain medications and diet can accelerate the progression of liver disease.

The Warnings

Alcohol

Alcohol can damage or destroy liver cells. Liver damage can lead to the build up of fat in your liver (fatty liver), inflammation or swelling of your liver (alcoholic hepatitis), and/or scarring of your liver (cirrhosis).
For people with liver disease, even a small amount of alcohol can make the disease worse

Medicines
Different types of medicines are taken every day including over-the-counter and prescription medicines, vitamins, dietary supplements, and alternative medicines. Medicines can help you feel better. However, when medicines are taken incorrectly — by taking too much or the wrong type or by mixing — your liver can be harmed.

• Learn about your medicines and how they can affect your liver
• Follow dosing instructions
• Talk to your doctor or pharmacist often about all the medicines you are taking

Alcohol and Medicines
Mixing alcohol and medicines can be harmful even if they are not taken at the same time.

Avoid medications that may cause liver damage. Review your medications with your doctor, including the over-the-counter medications, in particular acetaminophen.

Acetaminophen
Acetaminophen is found in the following medications
Tylenol· Excedrin· Midol· NyQuil· Sudafed· Vicodin

Fatty Liver And HCV

There are two different forms of steatosis (Fatty Liver) that may be found in people with HCV: Metabolic steatosis and HCV-induced steatosis

Metabolic steatosis can result from obesity, raised blood fat levels (hyperlipidemia), insulin resistance and type II diabetes and is similar to the type of fatty infiltration caused by excessive alcohol consumption and that is also found in Non-Alcoholic Fatty Liver (NASH).

Metabolic steatosis is not triggered by the hepatitis C virus; however the combination of this form of steatosis and the presence of HCV can lead to a more rapid progression of scarring or fibrosis.

HCV-induced steatosis is fatty infiltration that is directly caused by the presence of the virus. It is possible for people with HCV to have both forms of steatosis simultaneously.

Genotypes and Fatty Liver Disease:
Although it seems that all genotypes can trigger steatosis, the risk of developing steatosis is significantly higher for people with genotype 3. There is a complex reaction between the genotype 3 virus and liver cells that is not seen in other genotypes that makes this group at much higher risk of developing the condition. Around 40% of people with hepatitis C have steatosis, compared to about 14% to 31% of the general population. However, 60% - 80% of people with genotype 3 have moderate or severe steatosis.

Liver Cancer And Fatty Liver

This week in a study led by Dr. Neeraj Bhala from the University of Oxford in the UK, researches reported that the incidence of liver cancer is lower in patients with nonalcoholic fatty liver disease, than in hepatitis C.

Liver cancer incidence lower in patients with nonalcoholic fatty liver disease than hepatitis C
"Our study reports on the long-term morbidity and mortality of NAFLD patients with advanced fibrosis or cirrhosis by prospectively following up cases from four international collaborating hepatology centers," explains lead author Dr. Neeraj Bhala from the University of Oxford in the UK. "Understanding the long term prognosis of NAFLD patients compared with patients affected by other liver diseases such as chronic HCV was an important aspect of our study." Medical evidence suggests that while HCV is currently the leading indication for liver transplantation, affecting more than 5 million individuals in the U.S, HCV incidence has plateaued, while that for NAFLD is on the rise.

In the largest prospective study of participants with advanced fibrosis or cirrhosis to date, the team recruited 247 patients with NAFLD and 264 patients with HCV infection who were not previously treated or were unresponsive to therapy from centers in Australia, Italy, the UK and the USA. Patients in both groups were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at the onset of the study. Follow-up in the NAFLD and HCV groups was a mean of 86 and 75 months, respectively.Of those patients in the NAFLD group, 19% had liver-related complications and 13% died (or received transplants). Liver-related complications and deaths (or transplants) in the HCV cohort were lower at 17% and 9%, respectively. However, after adjusting for age and gender, the incidence of liver-related complications, including liver cancer, was lower in the NAFLD group compared to the HCV cohort. Researchers found that cardiovascular complications and overall mortality were comparable between the groups, although moderate differences cannot be excluded, highlighting the need for even larger collaborative prospective studies.

Suggested Reading; Jan 2011 Hepatitis C and Fatty Liver: Still unhappy bedfellows?

The Good News

Studies have revealed that diet, coffee, foods or spices such as artichokes, blueberries, curcumin and turmeric could have a protective effect on the liver.

Coffee

Researchers suggest that coffee consumption may improve response to standard HCV therapy and have an effect on liver cancer and fibrosis.

A Warning

Acetaminophen And Caffeine
According to consumer affairs , a 2007 study from the University of Washington in Seattle, scientists reported a potentially harmful interaction while taking acetaminophen in combination with caffeine.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake -- including energy drinks and strong coffee -- while taking acetaminophen.

Researchers from the University of Washington in Seattle tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs.Toxic byproductsThey found that caffeine triples the amount of a toxic by product, N-acetyl-p-benzoquinone imine (NAPQI) that the enzyme produces while breaking down acetaminophen.

This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.“People should be informed about this potentially harmful interaction,” chemist Sid Nelson says. “The bottom line is that you don’t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol.”MegadosesNelson points out that the bacteria used in the study were exposed to ‘megadoses’ of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis.

Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John’s Wort, a popular herbal supplement

The Research

Coffee and the response to HCV Therapy

ScienceDaily (June 8, 2011) — Advanced hepatitis C patients with chronic liver disease may benefit from drinking coffee during treatment, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. Patients who received peginterferon plus ribavirin treatment and who drank three or more cups of coffee per day were two times more likely to respond to treatment than non-drinkers.

"Coffee intake has been associated with a lower level of liver enzymes, reduced progression of chronic liver disease and reduced incidence of liver cancer," said Neal Freedman, PhD, MPH, of the National Cancer Institute and lead author of this study. "Although we observed an independent association between coffee intake and virologic response to treatment, this association needs replication in other studies."

Among non-drinkers, 46 percent had an early virologic response; 26 percent had no detectable serum hepatitis C virus (HCV) ribonucleic acid at week 20; 22 percent had no detectable serum at week 48; and 11 percent had a sustained virologic response. In contrast, the corresponding proportions for those who drank three or more cups of coffee per day were 73 percent, 52 percent, 49 percent and 26 percent, respectively.

Approximately 70 to 80 percent of individuals exposed to HCV become chronically infected. Worldwide, these individuals are estimated to number between 130 and 170 million. Higher coffee consumption has been associated with slower progression of pre-existing liver disease and lower risk of liver cancer. However, the relationship with response to anti-HCV treatment had not been previously evaluated. Treatment with peginterferon and ribavirin resolves chronic hepatitis C in about half of patients. It is unknown whether coffee will improve response with the addition of new drugs that were recently approved for use in the U.S.

Because patients in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial also had previously failed interferon therapy, it is not clear whether the results can be generalized to other patient populations. Future studies among patients with less advanced disease, those who are treatment-naïve to prior therapy, or who are being treated with newer antiviral agents are needed.

The Study;
2011 June edition of American Gastroenterology , a study published online in March 2011 found;
High-level consumption of coffee (more than 3 cups per day) is an independent predictor of improved virologic response to peginterferon plus ribavirin in patients with hepatitis C.

In November 2010 at the AASLD meeting in Boston, a presentation evaluated the relationship between drinking coffee and the response to HCV anti-viral treatment .

From NATAP: Coffee is associated with virologic response in chronic Hepatitis C: Findings from the Hepatitis C Long - Term Treatment against Cirrhosis Trial (HALT - C)
The Conclusion: Pre-treatment coffee intake was independently associated with improved virologic response during peginterferon alfa-2a and ribavirin in the HALT-C trial. "daily coffee consumption of 3 or more cups was associated with 25.8% SVR vs 20.7% for 1- less then 3 cups and 12.7% for less then 1 cup and these are all statistically significant. Coffee increased EVR & week20 responses too"Check out full data.

Liver Cancer

In August of 2010 data from a case-control study showed that: moderate coffee consumption significantly reduced the risk of HCC by almost half in chronic HBV.

Liver Fibrosis

A study from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), published in the January 2010 issue of Hepatology; has shown that in people with chronic hepatitis C virus who drink about two and a quarter cups of coffee (with caffeine) daily had milder liver fibrosis. However, researchers found that other beverages containing caffeine did not have the same effects.
Full Text

Foods And Spices

Artichokes
Artichokes, have been shown to improve various digestive health disorders. They significantly lower blood cholesterol levels, prevent heart disease and atherosclerosis, enhance detoxification reactions, as well as protect the liver from damage. Artichokes are very concentrated in cyanarin, which may also help in regeneration of liver tissue.

Published in Biological Trace Element Research in June 2010 researchers investigated the effect of artichoke leaf extract on the liver in mice. In the study they found that artichoke leaf extract decreased fat and cholesterol levels in the liver.

In a study in "Journal of Functional Foods" in 2009, Vincenzo Lattanzioa and colleagues describe the properties of artichoke leaf extract as antibacterial, anti-carcinogenic, diuretic, bile-expelling and hepatoprotective, which means it protects the liver from toxin overload.

Blueberries
Consuming blueberries, a food source that contains high levels of antioxidants, may help prevent the development of liver disease.

Published in the 2010 issue of World J Gastroenterol (full text available) researhers Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang, presented some data from their research on the effectiveness of blueberries on liver fibrosis induced in laboratory animals.

Innovations and breakthroughs
The present study showed that blueberries have therapeutic effects on CCl4-induced hepatic fibrosis in rats, through inhibition of liver inflammation and lipid peroxidation. This protective effect may not be related to the activation of NF-E2-related factor 2 in rat livers.

Applications
Increasing consumption of blueberries is a reasonable strategy to increase antioxidant intake, and may lead to a reduced risk of hepatic disease.

Research frontiers
Reactive oxygen species and oxidative stress have an important role in the development of hepatic fibrosis. Blueberries have high cellular antioxidant activity. Recent reports have suggested that proanthocyanidin isolated from blueberry leaves can be used against hepatitis C virus by inhibiting viral replication.

Another study in 2009 lead by Hiroaki Kataoka and colleagues at the University of Miyazaki (U-M) in Japan researchers screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US). They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine).

While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold, said a U-M statement.
Similar chemicals are found in many edible plants, suggesting it should be safe as a dietary supplement. Researchers now hope to explore the detailed mechanisms of how this chemical stops HCV replication.

Curcumin

In a 2010 study from the Saint Louis University suggested that Curcumin held promise in preventing or treating liver damage in fatty liver disease.

"High levels of leptin activate hepatic stellate cells, which are the cells that cause overproduction of the collagen protein, a major feature of liver fibrosis. The researchers found that among other activities, curcumin eliminated the effects of leptin on activating hepatic stellate cells, which short-circuited the development of liver damage."

Turmeric

In the 2010 issue of GUT researchers suggested that a major component of the Indian spice turmeric was found to decrease inflammation and fibrosis in vitro and in an animal model of chronic cholangiopathy. Chronic cholangiopathies, which are usually genetic or autoimmune in origin, cause inflammation and fibrosis and can lead to the need for liver transplantation. Primary biliary cirrhosis is one example of a chronic cholangiopathy.

From NHS
"Researchers in this animal study investigated how an extract of the spice protected mice that had been bred to have inflammation in their bile ducts from liver damage.
The results suggest that liver damage, jaundice and scarring were all reduced by the curcumin and that the underlying cellular pathways affected might, in time, become promising targets for new drug development. However, there is no suggestion from this study that eating turmeric will have the same effect or be a useful treatment for humans"

Conclusion
This well-conducted animal and laboratory study has identified cellular targets for new drug development. The theories are at an early stage and it is too soon to say that any new treatments might be developed from the spice. However, researchers will welcome these findings as they give a clear direction for new study into treatments for these severe and hard-to-treat conditions.
A variation of curcumin may be one of the drugs tested further; however, it is also possible that other related chemicals may have more effect. At this stage, it is not possible to say if the spice turmeric will be useful for treating liver disease in humans.

Diet

Dietary history and physical activity influence the risk of advanced liver disease in HCV, reports this month's issue of the Digestive Diseases & Sciences.

Dietary history and physical activity influence the risk of advanced liver disease in HCV, reports in the june issue of the Digestive Diseases & Sciences.

The role of customary diet and physical activity in development of advanced HCV-related liver disease is not well-established. Dr Donna White and colleagues conducted a retrospective association study in 91 male veterans with PCR-confirmed chronic HCV and biopsy-determined hepatic pathology.

Respondents completed the Block Food Frequency and the International Physical Activity questionnaires. The research team conducted 3 independent assessments based on hepatic pathology, including fibrosis, inflammation, and steatosis. Each assessment compared estimated dietary intake and physical activity in veterans with advanced disease to that in analogous veterans with mild disease.

Multivariate models adjusted for total calories, age, race/ethnicity, biopsy-to-survey lag-time, BMI, pack-years smoking, and current alcohol use.

Average veteran age was 52, with 48% African-American. The researchers found that advanced fibrosis was more prevalent than advanced inflammation or steatosis. The strongest multivariate association was the suggestive 14-fold significantly decreased advanced fibrosis risk with lowest dietary copper intake. The team observed that other suggestive associations included the 7-fold significantly increased advanced inflammation risk with lower vitamin E intake, and 6-fold significantly increased advanced steatosis risk with lower riboflavin intake.

The only physical activity associated with degree of hepatic pathology was a 2-fold greater weekly MET-minutes walking in veterans with mild compared to advanced steatosis. Dr White's team concluded, "Several dietary factors and walking may be associated with risk of advanced HCV-related liver disease in male veterans."

"However, given our modest sample size, our findings must be considered as provisional pending verification in larger prospective studies."
Dig Dis & Sci 2011: 56(6): 1835-47 21 June 2011

Vitamins, Diet and Nutrition
For most people, including those with hepatitis C, the best diet is one that is balanced, and contains the right amount of essential nutrients and calories.

In overweight patients with a fatty liver who subsequently lose weight, liver- related abnormalities improve. Therefore, patients with chronic hepatitis C are advised to maintain a normal weight. For persons who are overweight, it is crucial to start a prudent exercise routine and a low fat, well balanced, weight reducing diet. In diabetic patients, a sugar- restricted diet should be adhered to. A low cholesterol diet should be followed in those with hypertriglyceridemia. In individuals with NASH who are of normal weight, a low fat diet may be advantageous. It is essential that patients consult with their physician prior to the commencement of any dietary or exercise program.

Vitamins
The best way to get vitamins and minerals is through food. Food provides the greatest range of nutrients. However, a multivitamin/mineral supplement can be helpful, especially if you lose your appetite or can't eat a healthy diet. Folate is particularly important vitamin and is not obtained easily from food but is found in multivitamins.

Before taking any supplement, talk to a doctor or dietitian. If you take supplements, don't exceed the recommended doses. Some supplements in high amounts can be dangerous, particularly fat-soluble vitamins, such as A, D, E, and K.

Iron and Vitamin C
Some people with hepatitis C, particularly those with cirrhosis, have above-average levels of iron in their body. Too much iron can damage organs. If these people take multivitamin/mineral pills, they should take the ones without iron. These pills usually are marketed as formulas for men or adults over 50. These people also should avoid taking large doses of vitamin C because vitamin C helps the body absorb iron.
You do not want to take iron supplements if you have hepatitis C, unless you are specifically told to take iron by your provider.

Vitamin A
Vitamin A, if taken in doses larger than the recommended 10,000 IU, can harm the liver. Vitamin A is even more toxic in someone who drinks alcohol.
You won't get too much vitamin A from food, but be careful taking routine dietary supplements with high doses. There's a non-toxic form of vitamin A, present in many fruits and vegetables, called beta-carotene. If you take vitamin A supplements, look for those with beta-carotene.

Vitamin D
Vitamin D is important for health in normal amounts (such as diets with plenty of milk). The body also can make vitamin D when exposed to sunlight. Taking supplements of 800 IU of vitamin D daily may help people with poor diets or long winter seasons, or those who are housebound.

Vitamin E
Vitamin E supplements do not have benefits, though it used to be believed that Vitamin E prevented heart disease. High doses (greater than 400 IU/day) can have be dangerous.

Vitamin K
Vitamin K is involved in blood clotting. It is present in the diet mostly in green vegetables. It also is produced by bacteria in the intestines. Vitamin K supplements generally are not taken, nor are they recommended.
http://www.va.gov/

What foods can improve liver health?
Your liver is the organ responsible for an enormous number of metabolic activities, and you'll need a plentiful supply of virtually all nutrients for your liver to be optimally healthy. In general, fruits and vegetables would be at the top of our list in the support category, since they contain such a wide range of nutrients that participate in liver function. Additionally, if you are focused on liver health, it is important to consume foods that are organically grown; the liver is an organ that detoxifies chemicals and therefore with organically grown foods you'll reduce your exposure to agricultural chemicals. In this same toxic exposure category, moderate consumption of alcohol (or less) would also be important to the health of your liver, since this organ postpones other important functions when it is trying to metabolize excess alcohol.

Fried foods and other high-fat foods (like processed foods containing hydrogenated oils) would also be particularly hard on your liver. Just as with alcohol, there is a limit to the total amount of fat than your liver can process while maintaining all of its other metabolic activities.
There are a couple of food groups that would also be especially helpful in supporting your liver's ability to detoxify chemicals. First are foods rich in sulfur. Sulfur-containing compounds are one of the primary types of molecules used to help the liver detoxify a wide range of prescription medications, pesticides, and other types of environmental toxins. Foods in this category would include onions, garlic, and egg yolks. (We'd caution against over consumption of egg yolks, however, due to their higher concentration of cholesterol and saturated fat. Two-to-four eggs per week would be a very reasonable amount for most persons).

Some additional sulfur-containing foods are worth mentioning as a category of their own - namely, the cruciferous vegetables. There are some unique sulfur compounds in these foods that may be especially beneficial in liver detoxification processes. Foods in this group include broccoli, cabbage, cauliflower, collard greens, kale, and Brussels sprouts.
To support your liver's immune function, we also feel obligated to mention some culinary spices that have extensive research with respect to their role in liver support. Those spices include turmeric, cinnamon, and licorice.

According to the American Liver Foundation here are some additional ways to keep your liver healthy: Eat a well balanced, nutritionally adequate diet. If you enjoy foods from each of the four food groups, you will probably obtain the nutrients you need. Cut down on the amount of deep-fried and fatty foods you and your family consume. Doctors believe that the risk of gallbladder disorders (including gallstones, a liver-related disease) can be reduced by avoiding high-fat and cholesterol foods.

Minimize your consumption of smoked, cured and salted foods. Taste your food before adding salt! Or try alternative seasonings in your cooking such as lemon juice, onion, vinegar, garlic, pepper, mustard, cloves, sage or thyme.

Increase your intake of high-fiber foods such as fresh fruits and vegetables, whole grain breads, rice and cereals. A high-fiber diet is especially helpful in keeping the liver healthy. Rich desserts, snacks and drinks are high in calories because of the amount of sweetening (and often fat) they contain. Why not munch on some fruit instead? Keep your weight close to ideal. Medical researchers have established a direct correlation between obesity and the development of gallbladder disorders.

For more information on this topic,
see:
Broccoli [Brussels sprouts [Cabbage [Cauliflower [Cinnamon [Collard greens [Eggs, hen [Garlic [Kale [Onions [Turmeric, ground

Suggested Reading;

Preparing For Hepatitis C Treatment-Shaping Up, Before You Treat

Hepatitis C patients likely to falter in adherence to treatment regimen over time

Hepatitis C patients likely to falter in adherence to treatment regimen over time, Penn study shows

(PHILADELPHIA) – Patients being treated for chronic hepatitis C become less likely to take their medications over time, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Since the study also showed better response to the drugs when they're taken correctly, the researchers say the findings should prompt clinicians to assess patients for barriers to medication adherence throughout their treatment, and develop strategies to help them stay on track. The study is published online this month in Annals of Internal Medicine.

"Our findings are particularly timely since many chronic hepatitis C patients are now being prescribed direct-acting antiviral drugs, which have a complex dosing regimen that may be even harder for patients to maintain than the two-drug standard therapy," said lead author Vincent Lo Re, MD, MSCE, an assistant professor of Infectious Disease and Epidemiology. "These data show us that we need to develop and test interventions to help patients be more successful at taking their medicine and have the best chance at being cured."

Literacy issues, financial hurdles, and socioeconomic problems such as unstable living situations can all hamper patients' abilities to properly maintain their drug regimen. The authors suggest that refilling patients' pill boxes for them, creating easy-to-follow dosing and refill schedules, and helping them set alarms to remind them to take their medicine may all help improve adherence.

The Penn researchers studied 5,706 chronic hepatitis C patients who had been prescribed the standard treatment for the virus -- pegylated interferon (given as a single weekly shot) and ribavirin (a twice-daily oral medicine) -- using pharmacy refill data and test results for virologic response during treatment. They found that patients who refilled their prescriptions on time had a higher likelihood of being cured of the infection. However, over the course of patients' treatment, adherence waned, and more often for ribavarin. That pattern, Lo Re notes, is similar to that among patients taking drugs for other chronic conditions, during which patients often develop so-called "pill fatigue."

The newer, more powerful direct-acting antiviral drugs, which must be taken every 8 hours, will add to the complexity, and cost, of chronic hepatitis C treatment. In addition, if the newer direct-acting antiviral drugs aren't taken properly, the hepatitis C virus may become resistant to treatment, compromising the chance of cure. Hepatitis C is a communicable disease spread via blood, from needle-sharing during IV drug use, tattooing or piercing, or even from more casual contact like sharing razors and toothbrushes. Worldwide, approximately 180 million people have the disease, about 4 million of them in the United States.

Monitoring for and treating drug-related side effects may also be a key factor in boosting adherence, Lo Re says. The study results showed that patients who received medication for thyroid dysfunction, anemia, or low white blood cell counts – common side effects associated with hepatitis C drugs – were more likely to remain adherent to their antiviral therapy. Although those drugs added more steps into their self care, Lo Re said the resulting relief for symptoms, including depression, fatigue and irritability, and more frequent visits to health care providers typically required with administration of these drugs, may play a role in patients' ability to maintain the regimen overall.

"We know that a major barrier to adherence is side effects of these drugs. People don't feel good when they're on them," he said. "If we can identify those problems and treat them when they occur, patients may be more motivated and feel well enough to continue with their prescribed regimen."

###

The study was funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Department of Veterans Affairs.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

http://www.eurekalert.org/pub_releases/2011-09/uops-hcp092911.php

Galectin-inhibiting therapeutics to treat fibrotic liver disease and cancer

Of Interest-
Tough Choices, Big Opportunities
Oct 3 2011
In an agonizingly slow process, funding found its way to this research, and some very interesting things were discovered about a particular type of carbohydrate that binds to and blocks a protein called galectin, which appears to cause cirrhosis....continue reading..

Sept. 29, 2011, 9:15 a.m. EDT
Galectin Therapeutics Posts New Corporate Presentation Video to its Website
Highlights Leadership Position Developing Galectin-Inhibiting Therapeutics to Treat Fibrosis & Cancer

NEWTON, Mass., Sep 29, 2011 (BUSINESS WIRE) -- Galectin Therapeutics Inc. today announced that it posted a new corporate presentation video to its website, http://www.galectintherapeutics.com/ (see below) , that highlights the Company's leadership position in developing galectin-inhibiting therapeutics to treat fibrosis and cancer. The video is narrated by Dr. Peter Traber, the Company's President, CEO and Chief Medical Officer.

"We continue to build the foundation for the development of our carbohydrate-based therapies for fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function," said Dr. Traber. "Our GM and GR series of compounds have demonstrated the ability to arrest and reverse liver fibrosis in pre-clinical studies and we are conducting additional studies to define the best compounds to take into clinical trials in 2012. There are currently no treatment options for liver fibrosis except liver transplantation.

"In our cancer chemotherapy program, we are awaiting review of the application for marketing approval in Colombia, South America for the use of GM-CT-01 in combination with 5-FU for metastatic colorectal cancer. We expect GM-CT-01 will be commercialized by our partner Pro-Caps in Colombia, pending regulatory approval in that country. We plan to make important progress in our cancer immunotherapy program as we expect The Ludwig Institute of Cancer Research in Brussels to initiate a Phase I/II clinical trial this year of our GM-CT-01 compound with their cancer vaccine in patients with metastatic melanoma. An IMPD (Investigational Medicinal Product Dossier) for this trial has been submitted to the EMA (European Medicines Agency). GM-CT-01 has demonstrated robust reactivation of tumor infiltrating T-cells in pre-clinical trials, an exciting new area of cancer immunotherapy."

Galectin Therapeutics Portfolio Overview
Galectin Therapeutics is focusing its galectin inhibitor development efforts in two key disease areas: fibrosis and cancer.

-- Liver Fibrosis: The Company is developing galectin inhibitors to treat liver fibrosis and the later stage of cirrhosis. Galectin Therapeutics candidates have demonstrated the ability to arrest and reverse liver fibrosis in pre-clinical studies.

-- 45,000 deaths from cirrhosis occurred last year in the United States of which only 6,200 of the approximately 400,000 U. S. cirrhosis patients received life saving liver transplants. Liver fibrosis is a disease with no current treatment options except liver transplantation.
Galectin Therapeutics' efforts in cancer encompass two distinct programs, cancer immunotherapy and chemotherapy.

-- Cancer Immunotherapy: Recent experiments by The Ludwig Institute of Cancer Research in Brussels, Belgium indicated that GM-CT-01 reactivates T-cell-dependent tumor cell killing that had been turned off by galectins secreted by cancer cells. The Ludwig Institute is planning a Phase 1/2 trial of GM-CT-01 for patients with advanced metastatic melanoma. Patients will receive a tumor-specific peptide vaccination combined with multiple systemic and intra-tumor doses of GM-CT-01 following the second month and subsequent month's vaccine administration.
-- Cancer Chemotherapy: The Company is currently awaiting review of its application for marketing approval in Colombia, South America for the use of GM-CT-01 in combination with 5-FU for metastatic colorectal cancer. GM-CT-01 will be commercialized by Galectin Therapeutics' partner in Colombia, Pro-Caps, pending regulatory approval in Colombia.

About Galectin Therapeutics
Galectin Therapeutics /quotes/zigman/5431495 GALT -4.97% is developing promising carbohydrate-based therapies for fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at http://www.galectintherapeutics.com/

Wednesday Hepatitis C News Ticker

Oil Painting "The Morning News" by Artist NORA KASTEN Naples, Florida

New On The Blog;

Telaprevir for Chronic Hepatitis C with Genotype 1: A Meta-Analysis
Liver cancer incidence lower in patients with nonalcoholic fatty liver disease than hepatitis C
Hepatitis C virus resistance to protease inhibitors
AASLD 2011 Updated Hepatitis C Practice Guidelines-Boceprevir-Victrelis, Telaprevir-Incivek,
Seeking Drugs to Fight and Prevent HCV Infection

HCV Daily News

I-Team: Doctors Believe Man at the Center of Hep C Outbreak Faking Illness

LAS VEGAS -- Late last week, state medical experts determined Dr. Depak Desai, the man at the center of the 2007 hepatitis C outbreak, was competent to stand trial.

Desai spent the last six months being evaluated by psychiatrists, psychologists and physicians at a state mental hospital, and those experts believe Desai is faking it....

Physician to stand trial for hepatitis outbreak

By: David LaHoda September 28th, 2011

The physician at a Las Vegas clinic associated a hepatitis outbreak is competent to stand trial. District Attorney David Roger confirmed that Nevada state medical experts have found Dr. Dipak Desai is competent to stand trial on criminal patient neglect charges for the hepatitis C outbreak at his Endoscopy Center of Southern Nevada in 2008, according to the Las Vegas Review-Journal, September 22. Last march, court-appointed medical experts from Las Vegas had found Desai incompetent to stand trial because of the effects of two strokes, reports the Journal. The charges in the case concern seven of Desai’s patients who allegedly were infected with the hepatitis C virus at Desai’s endoscopy clinics.

Click here for the archive of OSHA healthcare Advisor posts on the Las Vegas hepatitis C outbreak.

MVA-B Spanish HIV vaccine shows 90 percent immune response in humans
Phase I clinical trials developed by Spanish Superior Scientific Research Council (CSIC) together with Gregorio Marañón Hospital in Madrid and Clínic Hospital in Barcelona, reveals MVA-B preventive vaccine's immune efficiency against Human's immunodeficiency virus (HIV). 90% of the volunteers who went through the tests developed an immunological response against the virus and 85% has kept this response for at least one year. Safety and efficiency of this treatment have been described in articles for Vaccine and Journal of Virology science magazines.
The success of this vaccine, CSIC's patent, is based on the capability of human's immune system to learn how to react over time against virus particles and infected cells. "MVA-B vaccine has proven to be as powerful as any other vaccine currently being studied, or even more", says Mariano Esteban, head researcher from CSIC's National Biotech Centre.
In 2008, MVA-B already showed very high efficiency in mice as well as macaque monkeys against Simian's immunodeficiency virus (SIV). Due to it's high immunological response in humans, Phase I clinic trials will be conducted with HIV infected volunteers, to test its efficiency as a therapeutic vaccine.

Weapon's origins
Back in 1999, Esteban's research team began to work in the development and preclinical studies of MVA-B, which name comes from its composition, based in Modified Ankara Vaccinia virus. MVA-B is an attenuated virus, which has already been used in the past to eradicate smallpox, and also as a model in the research of many other vaccines. The "B" stands for the HIV subtype it is meant to work against, the most common in Europe.

Development of MVA-B is based in the insertion of four HIV genes (Gag, Pol, Nef & Env) in Vaccina's genetic sequence. A healthy immunitary system is able to react against MVA.
On the other hand, the inserted HIV genes in its DNA are not able to self-replicate, which guarantees the safety of the clinical trial.
30 healthy volunteers participated in this clinical trial. 24 of them were treated with MVA-B, while the other 6 were treated with a placebo, following a double-blind testing method. 3 doses of the vaccine were given via intramuscular route in weeks 0, 4 and 16. The effects were studied in peripheral blood until the trial ended on week 48.

Combat battalion
Inoculating the vaccine in a healthy volunteer is intended to train it's immune system to detect and learn how to combat those virus components. According to Esteban " it is like showing a picture of the HIV so that it is able to recognise it if it sees it again in the future".
Lymphocytes T and B are the main cells in this experiment, the soldiers in charge of detecting the foreign substances in the body and sending the right coordinates to destroy them.
"Our body is full of lymphocytes, each of them programmed to fight against a different pathogen" says Esteban. For that reason "Training is needed when it involves a pathogen, like the HIV one, which cannot be naturally defeated".

Lymphocytes B are responsible for the humoral immune response, producing antibodies which attack the HIV particles before they penetrate and infect the cell, anchoring themselves to the external structure and blocking it. 48th week blood tests reveal 72,7% of the treated volunteers hold specific antibodies against HIV.

On the other side, lymphocytes T control cell's immune response, in charge of detecting and destroying HIV infected cells. In order to verify their defence response to the vaccine, production of interferon gamma immunitary protein was measured.
Tests performed on the 48th week, 32 weeks after the last inoculation of the vaccine, show the production of lymphocytes T CD4+ and CD8+ of the vaccinated group is 38,5% and 69,2%, respectively, while it stays at 0% in the control group.

Action in several fronts
Besides interferon gamma, other immune proteins (cytokines and chemokines) are produced by the body when the presence of a pathogen is detected. Each of these proteins tends to attack a different enemy front. When T lymphocytes' defence action is able to generate several of these proteins it is called a polyfunctional action. CSIC's researcher adds "The importance of polyfunctionality has to do with the capability of pathogens to develop resistance to the immune systems attacks. The higher the polyfunctionality, the lower the resistance".
The defence spectrum of T lymphocytes in vaccinated subjects was measured based on the production of 3 other immunitary proteins. Tests indicate the vaccine generates up to 15 types of lymphocyte T CD4+ and CD8+ populations. 25% of CD4+ type and 45% of CD8+ type are able to produce two or more different proteins, proving their polyfunctionality.

War veterans
For a vaccine to become really effective, besides its immune system's defence capability, generating a long lasting response against future attacks is the key. For this purpose, the body needs to be able to keep a basic level of memory T lymphocytes. These lymphocytes, generated after a first pathogen attack, are veteran soldiers, which can circulate the body for years, prepared to respond to a new enemy's incursion.
48th week blood tests ran on vaccinated subjects show over 50% of CD4+ and CD8+ lymphocytes were memory T lymphocytes in the 85% of the patients who kept an immune response at this point of the trials.

In Esteban's opinión "MVA-B immune profile meets, initially, the requirements for a promising HIV vaccine". MVA-B is not capable of removing the virus from the body as once a cell is infected, virus' genetic data is integrated and replicated with the cell. However, the immune response induced by the vaccine could keep the virus under control, "if the virus enters the body and tries to develop in a cell, the immune system is ready to inactivate the virus and destroy the infected cell".

According to CSIC's researcher: "If this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays". Virus would not cause a disease anymore and would become a minor chronic infection, which would only show its effects in a low defence scenario, with a much lower contagious profile.

From Aids Beacon
Alcohol Abuse And Sexual Orientation Affect The Use Of Substance Abuse Treatment In People With HIV
Results of a recent study indicate that individuals with HIV who have alcohol dependence problems or who identify themselves as bisexual, gay, or lesbian are less likely to seek treatment for substance abuse problems.
However, individuals co-infected with hepatitis C and individuals who reported past physical or sexual abuse were more likely to seek substance abuse treatment....

From Natap
ICAAC: Responder-relapser (RR) patients might obtain benefit in liver fibrosis, after anti-HCV chemotherapy, in comparison to non-responders (NR) or non-treated (control) HIV- HCV coinfected patients
This study was aimed to investigate the possible benefit of unsuccessful anti-HCV therapy on LF estimated by non-invasive procedures, TE and BLFI (APRI, Fib-4 and Forns indexes) and by changes in liver stiffness staging (LSS) in 3 years of follow-up.

ICAAC: Longitudinal assessment of liver fibrosis (LF) by non-invasive methods in HIV- HCV coinfected patients, after HCV chemotherapy
Anti-HCV treatment may modify liver fibrosis (LF) progression in HCV/HIV-coinfected patients, which can be measured noninvasively by elastometry (TE) and biochemical indices (BLFI).

IL-17 in liver injury: an inflammatory issue?
Full story: Immunology and Cell Biology
Correspondence: Ian N Crispe, Seattle Biomedical Research Institute, 307 North Westlake Avenue, Seattle, WA 98109, USA.

Transplant

Living donor liver transplantation improves survival over deceased donor transplants
Patients with liver cancer and low MELD scores may not find similar benefit
New research shows liver transplantation candidates without hepatocellular carcinoma (HCC) derive a greater survival benefit from a living donor liver transplant (LDLT) than waiting for a deceased donor liver transplant (DDLT). The study now available in the October issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, reports that survival benefit from LDLT remains significant across the range of model for end-stage liver disease (MELD) scores, but this benefit was not apparent for low MELD candidates with HCC.

Liver diseases such as hepatitis B and C, nonalcoholic fatty liver disease, and HCC can range in severity from mild to life-threatening liver failure. In end-stage liver disease, when patient life is at risk, transplantation is the recommended option. According to the Organ Procurement and Transplant Network (OPTN), as of September 2011 more than 16,000 Americans are on the waiting list to receive a liver. Between January and June 2011 OPTN reported 3108 liver transplants were performed in the U.S., with roughly 96% being DDLTs and 4% LDLTs.
Previous studies found receipt of LDLT to be associated with improved survival compared with waiting for DDLT, however it remains unclear whether this advantage persists in candidates with low MELD scores (less than 15). "In order to better inform liver transplant candidates of survival outcomes, our study investigated the mortality risk of undergoing transplantation using livers from living donors versus waiting to receive a deceased donor organ," explains lead author Carl Berg, M.D., with the University of Virginia Health System.

For the present study, data on liver transplant candidates and potential donors were supplied by transplant centers involved in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. A total of 868 adult liver transplant candidates were included in the study and were followed for a mean of 4.6 years. Living donors of the study candidates were evaluated between February 2002 and August 2009—the period following MELD-based liver allocation. DDLT recipients transplanted at study centers were obtained for comparison during the same time period.

Mortality for LDLT recipients was compared to mortality of candidates remaining on the waiting list or who received DDLT, with categories of MELD score lower or greater than 15, and HCC diagnosis. Researchers reported that of the potential LDLT recipients, 453 had MELD scores lower than 15 and 415 were greater than 15. Transplantation was performed on 712 candidates (406 LDLT; 306 DDLT), 83 died without transplant, and 73 remained without transplant at the final follow-up.

"We found that survival was significantly higher for candidates without HCC who underwent LDLT, rather than waiting for DDLT," concluded Dr. Berg. Results showed that LDLT recipients had a 56% lower mortality rate, and among candidates without HCC the mortality benefit was seen in both patients groups—those with MELD scores above and below 15. However, researchers did not observe a similar survival benefit for candidates with HCC who had MELD scores lower than 15.

"Dr. Berg and colleagues have provided very valuable new insights that will help answer the important question of optimal time to transplant. However, this study group was comprised of candidates who were deemed appropriate for LDLT and was not a randomized trial," said Julie Heimbach, M.D., an Associate Professor of Surgery with the Mayo Clinic College of Medicine in Minnesota, in her editorial also published in this month's issue of Hepatology. "Future studies validating quality of life outcomes following LDLT compared to prolonged wait listing or DDLT would assist physicians in advising patients and families in timing of and donor options for liver transplantation."
###

Diabetes

Blood sugar control beyond standard target doesn't improve cognitive decline for diabetics
Intensive treatment provides no benefit over standard when it comes to memory
WINSTON-SALEM, N.C. – Sept. 27, 2011 – Intensive control of blood sugar levels beyond standard targets provides no additional protection against cognitive decline in older people with diabetes than standard treatment, according to a national study coordinated by researchers at Wake Forest Baptist Medical Center.

The first results of the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study appear online today in The Lancet Neurology.
"We know that people with type 2 diabetes have a much higher risk of dementia and memory loss than people without diabetes," said Jeff D. Williamson, M.D., chief of the Department of Geriatrics and Gerontology and principal investigator of the study's coordinating center at Wake Forest Baptist. "What we didn't know was, if you intensively control blood sugar levels in people who have had a history of trouble controlling them, does the added cost and effort to control blood sugar result in a slowed rate of memory loss? After conducting this study, there remains no evidence that it does.

"We also learned, however, that the intensive blood sugar control does preserve brain volume," added Williamson, director of the Roena Kulynych Center for Memory and Cognition Research at Wake Forest Baptist. "What that means for the long term preservation of cognitive function of these patients, we're still trying to figure out."

The ACCORD-MIND trial is a national study sponsored by the National Heart Lung and Blood Institute – part of the National Institutes of Health – designed to examine the effects of different glucose-lowering strategies on the risk for cardiovascular disease.
Wake Forest Baptist was asked to lead the ACCORD-MIND study because of its international reputation in both gerontology and in the conduct of very large clinical trials in the elderly, Williamson explained. A growing area of research focus at the medical center lies in the relationship between chronic diseases, such as diabetes and obesity, and memory loss.
To determine whether intensive blood glucose control would improve cognitive outcomes, the research team recruited nearly 3,000 people with long-standing type 2 diabetes and a high risk for heart disease for the study. Each was assigned either to an "intensive" program to maintain their hemoglobin A1c lower than standard targets at below 6 percent, or to a "standard" program to maintain the levels between 7 and 7.9 percent. Hemoglobin A1c is a marker for control of blood glucose levels. The patients ranged in age from 55 to 80 years old.
All of the participants underwent cognitive testing and more than 600 people also received magnetic resonance imaging (MRI) scans to measure any change in brain volume during the study.

The initial study plan was to measure the participants' cognitive ability (through cognitive tests) and brain volume (through MRI) after 40 months, but an increased risk of dying in the intensive strategy group led the researchers to switch all the participants to the standard glucose-lowering strategy at a median treatment time of 39 months.
Cognitive test scores revealed no difference between the groups. People in the intensive treatment group had larger total brain volume. However, this result, when weighed against the lack of cognitive benefit, the increased risks of cardiovascular problems and increased mortality in the intensive treatment group, did not support use of the more intensive therapy, the researchers concluded.

"While these findings do not support the use of intensive therapy to reduce the possible effects of diabetes on the brains of older people, it remains important for older adults with type 2 diabetes to continue well-established regimens to keep their blood glucose levels under control," said lead author Lenore J. Launer, Ph.D., of the National Institute on Aging (NIA). "Cognitive health is of particular concern in type 2 diabetes. We will continue to investigate how managing blood sugar levels might be employed to protect people with diabetes from increased risk of cognitive decline as they age."

Wake Forest Baptist researcher Michael E. Miller, Ph.D., who served as the lead statistician for the trial, added that, while the study's findings do not support the use of intensive blood glucose control therapy beyond standard targets to preserve cognition, there are other things people with diabetes may be able to do to gain benefit.

"It is important to note that the average person in this study had type 2 diabetes for more than 8 years and had demonstrated difficulty in controlling their blood sugar," Williamson said. "Today, many people like this with diabetes spend lots of money, time and energy worrying about and trying to drive their blood sugar levels down lower than recommended goals, but we've already shown that using lots of medication to do this does not help prevent heart attacks. This result on memory gives added guidance to those people and some relief from that pressure to take more and more medication. Now, they will be able to focus their attention and money on other things to improve their overall health, such as diet, exercise and behavioral interventions that may work to preserve memory and reduce heart disease."
###
Co-authors on the study are: Jingzhong Ding, Ph.D., Laura C. Lovato, M.S., James Lovato, M.S., Laura Coker, Ph.D., and Joseph Maldjian, M.D., all of Wake Forest Baptist; Ron M. Lazar, Ph.D., of Columbia University College of Physicians and Surgeons; Ann M. Murray, M.D., of Hennepin County Medical Center and Chronic Disease Research Group; Karen R. Horowitz, M.D., of Case Western Reserve University School of Medicine; Santica Marcovina, Ph.D., of Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington; Hertzel C. Gerstein, M.D., of McMaster University and Hamilton Health Sciences; Mark Sullivan, M.D., of the University of Washington; Karen L. Margolis, M.D. and Patrick O'Connor, M.D., of the Health Partners Research Foundation; Edward W. Lipkin, M.D., of the University of Washington Medical Center; Joy Hirsh, M.D., of Columbia University; Jeffrey L. Sunshine, M.D., of Case Western Reserve University; Charles Truwit, M.D., of Hennepin County Medical Center and Hennepin Faculty Associates Facility; and Christos Davatzikos, Ph.D. and R. Nick Bryan, M.D., of the University of Pennsylvania Health System.
For a pre-embargo copy of the study, please contact The Lancet Neurology. ARTICLE: "Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (MIND): a randomised open-label substudy of the ACCORD trial," by Lenore J. Launer, et al., Lancet Neurology. Published online September 27, 2011.

Media Relations Contacts: Jessica Guenzel, jguenzel@wakehealth.edu, (336) 716-3487; or Bonnie Davis, bdavis@wakehealth.edu, (336) 716-4977.

Wake Forest Baptist Medical Center (http://www.wakehealth.edu/) is a fully integrated academic medical center located in Winston-Salem, N.C. Wake Forest School of Medicine directs the education and research components, with the medical school ranked among the nation's best and recognized as a leading research center in regenerative medicine, cancer, the neurosciences, aging, addiction and public health sciences. Piedmont Triad Research Park, a division of Wake Forest Baptist, fosters biotechnology innovation in an urban park community. Wake Forest Baptist Health, the clinical enterprise, includes a flagship tertiary care hospital for adults, Brenner Children's Hospital, a network of affiliated community-based hospitals, physician practices and outpatient services. The institution's clinical programs and the medical school are consistently recognized as among the best in the country by U.S.News & World Report.

China: Where a blood test determines everything
BEIJING—For at least 10 per cent of China’s population, the future can hinge on a blood test.
While China is home to an estimated one-third of the world’s hepatitis B carriers, it’s also a place where those with the virus are routinely rejected by employers and schools, spurned by friends and romantic partners. And while discrimination isn’t going away, the nation’s hepatitis sufferers have new means, some legal and some deceitful, to battle bias.
In recent years, a plethora of websites has emerged where China’s hepatitis carriers can hire “gunmen” to take blood tests on their behalf. Hired guns can be paid to take just about any test in China these days and blood screening is no exception. For between $125 to $300 U.S., gunmen with no viral infections show up at pre-employment health exams and, essentially, give job candidates with hepatitis equal footing...

Pharmaceutical

From Pharmalot

FDA Warns Website For Selling ‘Professional Cialis’

The barrage of prescription meds being peddled by websites is spurring the FDA to go after bogus operators who are apparently located in Ukraine, Panama, New York or who-knows-where. Of course, whether the warning letters issued last week to two such operators will ever be received is unclear - there is so much confusion about locations that the missives were addressed to e-mail addresses...

From Pharma Times
Fury over Australian "Coke and fries" prescription deal
Strong criticism has greeted a deal agreed by the Pharmacy Guild of Australia to promote dietary supplements with prescription drugs..

For Your Reading Pleasure

Grand Rounds

Grand Rounds is a weekly summary of the best health blog posts on the Internet. Each week a different blogger takes turns hosting Grand Rounds, and summarizing the best submissions for the week.

This Weeks Host Is ZDoggMD

In the midst of this galactic chaos, Starfleet Command has asked us to host the 8th anniversary edition of medical bloggers’ Grand Rounds. So the great medical bloggers from around the galaxy have kindly contributed their bits and bytes, included below with my own two cents thrown in. Thanks to longtime Borg plastic surgeon Dr. Ramona Bates for hosting the last Grand Rounds; the next will be hosted by those crazy Klingons over at The Healthcare Economist on October 11th, so make sure to boldly go where no…awwww, never mind.

And Now: Grand Rounds Vol. 8 No. 1

A few submissions from this weeks grand rounds below, to read more click here

Funny Medical Stuff:

And speaking of ER nurses, the AWESOME blog Madness: Tales of an Emergency Room nurse presents a case of “one in a million shot, doc. One in a million shot.” Scary stuff.

My evil counterpart in the emergency room, Dr. Rob Orman of ERCast, presents a great podcast wherein whiny docs rant about stuff that pisses them off. Gold, people.

Turns out the Happy Hospitalist is too sexy for his scrubs.

Unfunny Medical Stuff:

Colorado Health Insurance Insider actually sent me this article in response to my request for submissions with the theme “Funny Medical Stuff.” This is riotously hilarious…if you are a Colorado health insurance insider.

iReveal: Medical Lessons discusses Steve Jobs’ medical privacy.

Check out the amusing videos here @ZDoggMD

Worth A Look

What the Doc Didn't Tell Me
What didn't the doc tell me? Plenty! Due to cirrhosis caused by hepatitis C, I had a liver transplant and my world was forever changed. Doctors explained the risks and said it would be tough, but their warnings didn't begin to adequately prepare us for what laid ahead. This blog describes my experiences and what I've learned, including the things my docs didn't tell me. I created it to be a place for learning, complaining and celebrating while traveling our difficult journeys.

Telaprevir for Chronic Hepatitis C with Genotype 1: A Meta-Analysis

Telaprevir for Chronic Hepatitis C with Genotype 1: A Meta-Analysis

Dang SS, Wang WJ, Wang XF, Li YP, Li M, Jia XL, Wang Y, Liu E, Zhao S; Hepato-Gastroenterology 59 (114)
S-S Dang, et al.
http://www.hepato-gastroenterology.org/
DOI 10.5754/hge11312
2012; 59(114): Ahead of print.

Download PDF

Background/Aims:
The examination of HCV virological clearance through several randomized clinical trials of telaprevir in genotype 1 chronic hepatitis C.

Methodology:
We analyzed the effect of telaprevir on the end of treatment virological response and the sustained response, and investigated its harmful effect using meta-analysis of 5 randomized controlled trials.

Results:
Overall analysis revealed a significant effect of telaprevir in both naive patients (RR, 1.32; 95% CI, 1.08-1.60) and previously failed treated patients (p<0.0001). Monotherapy and double therapy seemed to show no effect in naive patients.
Triple therapy followed with PegIFN-2a plus ribavirin seemed to be effective in both naive patients and previously failed treated patients. Telaprevir was associated with a significantly higher incidence of serious adverse events (RR, 1.45; 95% CI, 1.00-2.10) and with discontinuation (RR, 2.23; 95% CI, 1.40-3.55) because of adverse events. In naive patients, relapsers and non-responders, the regimen of telaprevir/ PegIFN-2a/ribavirin for 12 weeks followed by PegIFN-2a/ribavirin for 12 weeks (T12PR24) was the optimal regimen regarding to efficiency and duration.

Conclusions:
Telaprevir combined with PegIFN-2a plus ribavirin may improve sustained response in genotype 1 chronic hepatitis C. Regimen T12PR24 may be the best regimen in this respect. New randomized controlled trials are required to confirm this meta-analysis.

ABBREVIATIONS: Sustained Response (SR); End Of Treatment Response (ETR); Interferon (IFN); Nonstructural3/4A (NS3/4A); Randomized Controlled Trial (RCT); Relative Risk (RR); Confidence Interval(CI); Telaprevir/Pegifn-2a/Ribavirin for 12 weeks, followed by Placebo/Pegifn-2a/Ribavirin for 12 weeks(T12PR24); Telaprevir/Pegifn-2a/Ribavirin for 24 weeks, followed by Pegifn-2a/Ribavirin for 24 weeks(T24PR48); Telaprevir/Pegifn-2a for 24 weeks (TP24); Placebo/Pegifn-2a/Ribavirin for 24 weeks, followedby Pegifn-2a/Ribavirin for 24 weeks (PR48); Telaprevir/Pegifn-2a/Ribavirin for 12 weeks, followed by Placebo/Pegifn-2a/Ribavirin for 36 weeks (T12PR48); Telaprevir/Pegifn-2a/Ribavirin for 12 weeks (T12PR12);Telaprevir/Pegifn-2a for 12 weeks (T12P12).

INTRODUCTION
Hepatitis C is an infectious disease of the liver caused by the hepatitis C virus (HCV)(1). HCV is a major public health problem and a leading cause of chronic liver disease.Currently, an estimated 180 million people are infected worldwide (2). About 50-80%of patients with primary HCV infection develop chronic infection; about 25% ofpatients with chronic infection develop cirrhosis within 10 to 30 years; and 5-10% of patients with cirrhosis develop hepatocellular carcinoma (HCC) (3).More than ten years ago, interferon (IFN) therapy provide a sustained virologicalresponse (SR) in 15-20% of patients with chronic hepatitis C. Combining ribavirinwith IFN improved the SR to 40% (4) and until recently has been the most effectivetherapy. Several factors influence the rate of SR. In naive HCV patients with genotype1, which is the predominant genotype in Europe and North America, the SR is about40-50%, whereas an SR is observed in 80% of patients with genotype 2 or 3. Patientswho do not have an SR to the combination therapy have a low likelihood of successwith retreatment, only 12-22% (5-8).

Therefore, the development of effective regimens is required, especially in patients who did not have an SR to previous therapy.Telaprevir, also known as VX-950, has been developed to treat hepatitis C. It is anorally bio available inhibitor of the non-structural 3/4A (NS3/4A) HCV serine protease,an enzyme required for viral replication (9,10). Recently, some controlled clinical trials have shown that telaprevir treatment appears to be promising. However, its effect varied depending on how it was combined with IFN, with or without ribavirin,and treatment duration. We were unable to identify any systematic reviews or meta-analysis addressing the effects of telaprevir for patients with chronic hepatitis C. In this systematic review, we sought to assess both the beneficial and harmful effect of telaprevir. For this purpose,we used an evidence-based approach consisting of meta-analysis of randomized controlled trials (RCT). We assessed its antiviral efficiency in untreated patients and in patients who did not have an SR to previous therapy in order to identify an optimal regimen for each type of patient.

DISCUSSION
After combining all sorts of telaprevir regimens, our meta-analysis found that telaprevir was associated with a higher rate of SR than in control, both in naive patients and previously failed treated patients. However, in naive patients, we did not find that telaprevir monotherapy or double therapy produced an improved rate of SR versus control. This may be due to small-sized samples in the monotherapy or double therapy groups. In fact, not all telaprevir/IFN/ribavirin regimens induced a higher rate of SR than the recommended IFN + ribavirin regimen. The regimen telaprevir/PegIFN-2a/ribavirin for 12 weeks without followed PegIFN-2a/ribavirin did not improve SR, although it improved ETR. However, longer duration of followed PR may not induce higher rates of SR, as 48 weeks and 24 weeks of followed PR did not show a significant difference in the rate of SR.

Regarding efficiency and duration, the T12PR24 regimen may be the best regimen for chronic hepatitis C in genotype 1 naive patients according to the recent RCTs. In previously failed treated patients, of which the majority were relapsers and non-responders, double therapy with telaprevir did not seem to improve SR.

Two regimens of triple therapy with telaprevir (T12PR24 and T24PR48) improved SR versus the recommended PR regimen. However, the T24PR48 regimen, which had alonger duration of telaprevir and IFN plus ribavirin treatment than the T12PR24 regimen, did not further improve SR, regardless of relapsers or non-responders.

Regarding efficiency and duration, the T12PR24 regimen may be the best regimen for chronic hepatitis C in genotype 1 relapsers or non-responders according to the recent RCTs. We found that telaprevir intervention was associated with a significant increase in serious adverse events and with discontinuation because of adverse events. Increased adverse events such as rash, pruritus, hemorrhoids and nausea were also likely due to telaprevir. From the available data in only one trial (14) it was difficult to estimate the effects of duration of intervention therapy on the incidence of adverse events.

In the analysis of these data, we found that adverse events and the discontinuation because10 of adverse events were more common in long-duration therapy, although they were not statistically significant. Therefore, the T12PR24 regimen appeared to provide a better risk-benefit profile than the T24PR48 regimen. However, there were several factors which limited the context of our results. Firstly,only 5 RCTs could be included in the review. Secondly, our compiled data lacked the long-term outcomes of intervention, such as liver histology, the incidence of endstage liver disease or requirement for liver transplantation and liver-related mortality.

However, no clinical trials assessing these outcomes have been carried out. Finally, 2RCTs (55,56) did not supply SR, one of the most important outcomes. However,because of their low numbers of patients, they were less weighted and results were less influenced. Although the total number of patients included in this review seems sufficient in underlining the effects telaprevir, more trials are required: to confirm its treatment effect; to identify any adverse events associated with it; and to assess the effect of telaprevir on subgroups of patients regarding factors influencing treatment effect (such as other genotype, ALT level, cirrhosis, etc.).
In summary, this meta-analysis of five RCTs indicates that telaprevir is an effective therapy in naive patients, relapsers, and non-responders with genotype 1 chronic hepatitis C with respect to virological sustained response, albeit with higher rates of discontinuation because of adverse events. The T12PR24 regimen may have been the optimal treatment regimen for HCV. It is advisable to carry out more randomized trials in order to draw a firmer analysis of the long-term effects of telaprevir.

Full Text Available Here

Liver cancer incidence lower in patients with nonalcoholic fatty liver disease than hepatitis C

Liver cancer incidence lower in patients with nonalcoholic fatty liver disease than hepatitis C

Study shows rates of mortality similar in NAFLD and HCV infection

Patients with non-alcoholic fatty liver disease (NAFLD) with advanced fibrosis or cirrhosis have a lower incidence of liver-related complications and hepatocellular carcinoma (HCC) than patients infected with hepatitis C virus (HCV), according to the prospective study published in the October issue of Hepatology, a journal of the American Association for the Study of Liver Diseases. Patients with both NAFLD and HCV had similar mortality rates.

NAFLD has become the most prevalent cause of chronic liver disease worldwide, with studies reporting up to 30% of the general population and 75% of obese individuals having the disease. A minority of cases develop fibrosis or cirrhosis of the liver, and NAFLD with advanced fibrosis or cirrhosis can lead to hepatic-related complications, HCC, liver failure or death. While the incidence of NAFLD has increased, studies of the natural history of the disease in conjunction with advanced fibrosis or cirrhosis and later outcomes have been limited.

"Our study reports on the long-term morbidity and mortality of NAFLD patients with advanced fibrosis or cirrhosis by prospectively following up cases from four international collaborating hepatology centers," explains lead author Dr. Neeraj Bhala from the University of Oxford in the UK. "Understanding the long term prognosis of NAFLD patients compared with patients affected by other liver diseases such as chronic HCV was an important aspect of our study." Medical evidence suggests that while HCV is currently the leading indication for liver transplantation, affecting more than 5 million individuals in the U.S, HCV incidence has plateaued, while that for NAFLD is on the rise.

In the largest prospective study of participants with advanced fibrosis or cirrhosis to date, the team recruited 247 patients with NAFLD and 264 patients with HCV infection who were not previously treated or were unresponsive to therapy from centers in Australia, Italy, the UK and the USA. Patients in both groups were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at the onset of the study. Follow-up in the NAFLD and HCV groups was a mean of 86 and 75 months, respectively.

Of those patients in the NAFLD group, 19% had liver-related complications and 13% died (or received transplants). Liver-related complications and deaths (or transplants) in the HCV cohort were lower at 17% and 9%, respectively. However, after adjusting for age and gender, the incidence of liver-related complications, including liver cancer, was lower in the NAFLD group compared to the HCV cohort. Researchers found that cardiovascular complications and overall mortality were comparable between the groups, although moderate differences cannot be excluded, highlighting the need for even larger collaborative prospective studies.

In a related editorial published this month in Hepatology, Dr. Mary Rinella with Northwestern University Medical School in Chicago, Illinois said, "The study by Bhala and colleagues expands our knowledge of the natural history of NAFLD and NASH. While HCC was not surprisingly higher in untreated patients with HCV compared to NAFLD, this study highlights the potential of HCC development in non-cirrhotic patients with HCV and NASH. If patients with NAFLD or HCV are likely to develop HCC before the development of cirrhosis, this has tremendous implications for how and when liver cancer screening should begin in patients with liver disease."
###
Full Citations: "The Natural History of Nonalcoholic Fatty Liver Disease with Advanced Fibrosis or Cirrhosis: An International Collaborative Study." Neeraj Bhala, Paul Angulo, David van der Poorten,Eric Lee, Jason M. Hui, Giorgio Saracco, Leon A. Adams, Punchai Charatcharoenwitthaya, Joanne H. Topping, Elisabetta Bugianesi, Christopher P. Day and Jacob George. Hepatology; Published Online: August 9, 2011 (DOI: 10.1002/hep.24491); Print Issue Date: October 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24491/abstract.
Editorial: "Will the Increased Prevalence of NASH in the Age of Better HCV Therapy Make NASH the Deadlier Disease?" Mary Rinella and Hildegard Büning. Hepatology; Published Online: August 30, 2011 (DOI: 10.1002/hep.24634); Print Issue Date: October 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24634/abstract.
These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.

About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Media Advisory

What: The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
Founded in 1950, AASLD is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD has grown into an international society responsible for all aspects of hepatology, and the annual meeting attracts 8,500 physicians, surgeons, researchers, and allied health professionals from around the world.
The Liver Meeting® is the premier meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies.

When: November 4-8, 2011
Where: Moscone West Convention Center San Francisco, California
Contact: Please contact Ann Haran at 703-299-9766 or aharan@aasld.org to obtain a press pass for this event.