Showing posts with label Other Health News. Show all posts
Showing posts with label Other Health News. Show all posts

Wednesday, May 21, 2014

Pancreatic and Liver Disease Deaths Rise Due to Advancements in Other Cancer Care


Pancreatic and Liver Disease Deaths Rise Due to Advancements in Other Cancer Care

Liver cancer can be curable when caught early so get screened, advises Loyola hepatologist
 5/21/2014 
 
Newswise — Money changes everything. To date, lung, breast, prostate and colorectal cancers have accounted for the largest number of cancer deaths. In response, these cancers currently receive the most research funding from the National Cancer Institute and are highlighted through public health campaigns, special event fundraising and celebrity spokespeople.

And the extra money and attention is working to end those cancers and move other cancers up in frequency of cause of death.

Cancer Research reports that “by 2030 more people will be diagnosed with breast, prostate and lung cancers than with pancreatic cancers, but more pancreatic cancer and liver cancer patients will die of their disease.”

What should people do? Get screened if you are at risk.

“Primary liver cancer, hepatocellular carcinoma, is curable when caught early, so if you have high risk factors such as cirrhosis, particularly cirrhosis from hepatitis C virus, you should get screened,” says Steve Scaglione, MD, board certified hepatologist at Loyola University Health System. Hepatologists are specialists in treating liver disease. “Unlike a colonoscopy, liver cancer screening is non-invasive; just an ultrasound, every six months.” If liver cancer is diagnosed, curative treatment options are available and include surgery and liver transplantation.

There are more than 100 kinds of liver disease including cirrhosis, alcoholic induced, fatty and hepatitis. Hepatitis C is the leading cause of liver cancer in America. More than 5 million people are living with hepatitis, called a silent epidemic because it often is not detected until it has spread to the liver.

Screening measures for hepatitis C are not only recommended by public health organizations such as the Centers for Disease Control but are now mandated by lawmakers. In Colorado, a bill was signed into law on May 20, 2014 funding hepatitis screening. Specifically, hepatitis C testing is recommended for Baby Boomers (those born between 1945 and 1965) because they are estimated to be five times more likely to contract the disease.

The Loyola hepatology team offers treatment at 11 Loyola locations located in Illinois and also conducts research and research trials to improve prevention and treatment. “As new resources are devoted to these less common, but more deadly forms of cancer there is a higher likelihood of research advances to improve patient outcomes,” says Susan Uprichard, PhD, associate professor and director of hepatology research at Loyola University Stritch School of Medicine. “Patients who seek treatment from an academic medical center such as Loyola have the advantage of not only receiving the most progressive care but they also have the potential to participate in life saving research trials.”

Thursday, April 24, 2014

Vitamin D – should you take it?

Egg yolks contain a small amount of vitamin D istockphoto.comVitamin D – should you take it? 
By Lindsay Kobayashi
Posted: April 24, 2014

Egg yolks contain a small amount of vitamin D
iStockphoto.com

My hunch is that it depends. Vitamin D is a nutrient that helps our bodies regulate the metabolism of calcium and phosphate (1). Most vitamin D comes from sunlight, while it is also found in certain foods including fatty fish, mushrooms, egg yolks, vitamin-D fortified foods. For example, milk in many countries is always fortified with vitamin D, and some brands of breakfast cereals and orange juice are fortified as well (2).  Vitamin D can also be obtained through taking vitamin D supplements found at your local grocery or health food store. The classic health consequences of inadequate vitamin D are rickets in children, and low bone mineral density and osteoporosis in older adults (3). Low vitamin D has also been associated with increased risk for many other health conditions including breast, prostate, and colorectal cancer, multiple sclerosis, and cardiovascular disease (4-6). However, the quality of scientific evidence for these relationships varies because it is actually quite challenging methodologically to study the cause-effect relationship of vitamin D on health.

Because definitive high-quality evidence is lacking, the actual beneficial effect of vitamin D on health has been heavily debated in recent years. Like many other dietary or lifestyle factors that have been linked to health outcomes with scientific uncertainty (examples: coffee, alcohol, vitamin C, herbal supplements), the available information about whether to take vitamin D supplements can be very confusing. Here is where we stand right now:

In 2011, the American Institute of Medicine released an expert report on the dietary reference intakes for vitamin D (3). They stated that, for people aged 1 to 70 years old including pregnant and lactating women, the recommended dietary allowance (RDA) is 600 IU per day of vitamin D. For adults aged over 70 years the RDA is 800 IU per day. Intake should not exceed 4000 IU per day for people aged 9 years and over. The full RDA guidelines can be found here. Interestingly, their expert panel concluded that current scientific evidence is insufficient to conclude that vitamin D plays a causal role in non-bone-related health conditions (3). Now, this statement may or may not mean that vitamin D has no effect on health aside from bone conditions, simply that our current knowledge is insufficient.

Supplements can be a good source of vitamin D
iStockphoto.com
Supplements can be a good source of vitamin D istockphoto.comFast forward to today, and it doesn’t seem like our evidence base has evolved much. An ‘umbrella’ review of evidence on the link between blood plasma concentrations of vitamin D and 137 unique health outcomes was published in the British Medical Journal earlier this month (7). The review was the largest synthesis of knowledge to date, and the authors unfortunately had to conclude that:
“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable”
The authors concluded that vitamin D supplementation is probably linked to decreased dental caries (cavities) in children, reduced parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis, and to an increase in maternal vitamin D concentrations at term, and an increase in birth weight (7). These are very specific conditions that apply only to children, pregnant mothers, and chronic kidney disease patients. The authors also concluded that the evidence is ‘suggestive’ for a correlation between higher blood vitamin D concentrations and a lower risk of several conditions including colorectal cancer, non-vertebral fractures, cardiovascular diseases, depression, high body mass index, and type 2 diabetes (7). However, a major point to note is that these are correlations, which means that although vitamin D has been associated with these health conditions, it may not cause them. Because of the limitations of current research, including the difficulty in measuring the actual vitamin D intake of people, and how much of this actually gets absorbed and has a biological effect, the timing between vitamin D intake and disease onset, and determining the actual dose of vitamin D that may protect against disease, we don’t have definitive answers right now.

So, what should we do about our own health? It is clearly too soon to make any strong recommendations about population-level vitamin D supplementation. Following the current RDA for vitamin D is good, and achieving this level for yourself may include supplementation if you don’t eat many foods containing vitamin D. Always talk to your family physician if you have any concerns about your own health or vitamin D intake. And finally, as always, keep yourself informed with high quality information to make decisions for your own health.

References
1)      National Health Service. Vitamins and minerals – vitamin D. http://www.nhs.uk/Conditions/vitamins-minerals/Pages/Vitamin-D.aspx (accessed 21 April 2014).
2)      National Institutes of Health. Vitamin D: Fact sheet for consumers. http://ods.od.nih.gov/factsheets/VitaminD-QuickFacts/#h3 (accessed 21 April 2014).
3)      Committee to Review Dietary References Intakes for Vitamin D and Calcium, Institute of Medicine: Dietary Reference Intakes for Calcium and Vitamin D. Edited by Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Washington, DC: The National Academies Press; 2011.
4)      Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
5)      Munger KL, Zhang SM, O’Reilly E, Hernán MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62(1):60-5.
6)      Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-11.
7)      Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ2014;348:g2035

Source PLOS Blogs

Tuesday, April 8, 2014

Blood Test Could Detect Common Cancers

NPR - Simple Blood Test To Spot Early Lung Cancer Getting Closer 
by Richard Harris
April 06, 2014 1:22 PM ET
Listen Here 

Researchers at Stanford University have discovered a simple blood test has the potential to identify many different cancers.



Blood Test Could Detect Common Cancers

Early-stage lung and prostate cancers as well as their recurrence can be detected with a simple blood test, according to a study presented at the ANESTHESIOLOGY™ 2013 annual meeting. Serum-free fatty acids and their metabolites may be used as screening biomarkers to help diagnose early stages of cancer, as well as identify the probability of recovery and recurrence after tumor removal, researchers found.

"While cancer is the second-leading cause of death worldwide, diagnosis at the early stages of cancer remains challenging," said Jinbo Liu, M.D., M.S., researcher at Cleveland Clinic, and lead study author. "In this study, we identified compounds that appear to be new screening biomarkers in cancer diagnosis and prognosis."

The study looked at blood samples from 55 patients with lung cancer and 40 patients with prostate cancer and compared them to blood samples of people without cancer. In a second phase of the study, blood was examined preoperatively from 24 patients scheduled for curative lung cancer surgery and again at six and 24 hours after the surgery.

The cancer patients had one- to six-times greater concentrations of serum-free fatty acids and their metabolites (the biomarker) in their blood than patients without cancer. In the second phase, the serum-free fatty acid concentrations decreased by three to 10 times within 24 hours after tumor removal surgery.

Lung cancer is the most common cancer worldwide as well as the leading cancer killer in both men and women in the United States. It causes more deaths than the next three most common cancers combined (colon, breast and prostate), according to the American Lung Association.

Prostate cancer is the most common cancer in American men, other than skin cancer, according to the American Cancer Society. While there is a blood test for prostate cancer, the prostate-specific antigen test, or PSA, has a high false-positive rate that results in many unnecessary biopsies and complications, according to Dr. Liu. The test developed in this study could be a helpful additional blood test for prostate cancer.

"This is an exciting first step to having an uncomplicated way to detect early stages of lung, prostate and perhaps other cancers," said Daniel I. Sessler, M.D., chair of the Outcomes Research Department at Cleveland Clinic. "It could also be used to measure the success of tumor resection surgery, immediately after surgery and long-term for recurrence screening."

Story Source:
The above story is based on materials provided by American Society of Anesthesiologists (ASA). Note: Materials may be edited for content and length.

Video Source - NewsyScience

Tuesday, March 4, 2014

Your Liver Delivers - Protect It From Harm

Your Liver Delivers - Protect It From Harm

Your liver works hard to protect your health. It’s a rugged, strong organ. But certain things—like alcohol, drugs, viruses, and excess weight—can damage it. You may not even realize when your liver is struggling, because liver disease usually has no symptoms until the problem becomes severe. Help your liver to guard your health by avoiding the things that might cause it harm.

The liver is the largest organ inside your body. It’s about the size of a football, and rests just under your ribs against the right side of your stomach.

“The liver performs an amazing set of functions that keep you healthy,” says Dr. Jake Liang, a liver specialist and researcher at NIH.

Your liver helps fight infections. It cleans your blood by getting rid of your body’s natural waste products and other harmful substances, including alcohol and drugs. “The liver also transforms the foods you eat into energy and nutrients your body can use, and it regulates how nutrients flow to different parts of the body when needed,” Liang says.

Your liver can keep working even if part of it is damaged or removed. But if it starts to shut down completely—a condition known as liver failure—you can survive for only a day or 2 unless you get emergency treatment.

Many things can affect liver function. Some liver problems are inherited from your parents, some are caused by viruses (certain kinds of hepatitis), and some are related to your behavior. Certain liver diseases go away on their own. Others can last a lifetime and cause serious illness.

Although liver disease often has no symptoms, warning signs can include a swollen abdomen, nausea, itching, or jaundice (having a yellow tint to the skin and the whites of the eyes).

NIH supports large research networks across the country to learn more about liver disease. For instance, teams of scientists nationwide have joined forces to study rare and often-deadly liver disorders that strike newborns and older children.

“Research networks are important because no single medical center has enough patients with rare diseases to do a rigorous study or test new treatments,” says Dr. Edward Doo, a liver disease expert at NIH. “With this large pediatric network, we can combine the efforts and expertise of many clinical centers that specialize in rare childhood liver diseases.”

Other NIH studies are focusing on an increasingly common type of liver disorder—known as fatty liver disease—that affects both children and adults. A healthy liver contains just a little fat or none at all. But too much fat buildup in liver cells can cause swelling and damage. Over time, the excess fat can lead to cirrhosis, liver cancer, and even liver failure.

“Estimates vary, but 2 different studies in the past decade suggest that about 30% to 45% of Americans have excess fat in the liver,” says Dr. Yaron Rotman, an NIH specialist in fatty liver disease. “It’s also becoming a huge problem for children and teens.”

Drinking too much alcohol can cause fatty liver. But a growing number of people who drink little or no alcohol are also being diagnosed with fatty liver. “The rise seems to be tied to the nation’s obesity epidemic,” says Doo.

Studies suggest that fatty liver disease now also affects about 1 in 10 children nationwide. As with adults, most children with fatty liver disease are overweight and resistant to insulin, a critical hormone that regulates energy.

In its early stages, fatty liver disease usually has no symptoms. It’s often first detected by blood tests for liver function. But these tests can’t tell the difference between mild fatty buildup and more serious damage. And some people with fatty liver disease can have normal blood tests. The only sure way to diagnose the severity of fatty liver disease is by getting a liver biopsy. For this test, a doctor inserts a thin needle through the skin and into the liver to remove a small piece of tissue for analysis.

NIH-funded scientists have been searching for simpler ways to measure the severity of fatty liver disease. They’re also conducting clinical studies to assess possible treatments. There are currently no approved medications for fatty liver or its more severe form called NASH, or non-alcoholic steato-hepatitis.

“To treat fatty liver disease, we recommend lifestyle changes: Weight loss for people who are overweight, and exercise and a healthy diet to help reduce fat,” Rotman says. “In many patients, just a 5-8% reduction in body weight will translate into a large improvement to liver damage.” For people with alcohol-related fatty liver, stopping alcohol use can reverse or prevent further liver injury.

Another common type of liver disease—known as viral hepatitis—can be caused by at least 5 different viruses, named hepatitis A, B, C, D, and E. These infections can injure your liver and keep it from working properly.

“Collectively, about 20% of people worldwide may be affected by a hepatitis virus infection,” Liang says. “It’s a major public health problem.” The most common types in the United States are hepatitis A, B, and C.

Each hepatitis virus causes a different form of liver disease. All the viruses can trigger acute, or short-term, hepatitis. Hepatitis B, C, and D can also cause chronic hepatitis, in which the infection lasts a long time, sometimes for your whole life.

People are often exposed to hepatitis A and E viruses through contaminated food or water. “The other hepatitis viruses often pass through some type of break in the skin barrier, sometimes by injections or by close contact with blood or other body fluids,” Liang adds. Hepatitis B, C, and D can spread through sexual contact.

Because many infected people have few symptoms, they may not realize they have viral hepatitis. They can spread the infection to others without even knowing it.

Viral hepatitis is often treated with antiviral medications. Hepatitis A, B, and D infections can be prevented by vaccines. Practicing good hygiene—such as washing your hands and avoiding contact with infected blood—can also help block the spread of viral hepatitis.

Another potentially dangerous type of liver disease can be caused by taking certain drugs or supplements. “It’s important to be aware that a lot of drugs can cause liver injury,” Liang says. “This especially can be a problem for people who are taking several different medications.”

Taking too much acetaminophen (Tylenol) is the most common cause of sudden liver failure. “It’s particularly dangerous if you mix alcohol with acetaminophen or certain other drugs,” Liang adds. Talk with your doctor or pharmacist about all the medications you take and how they might affect your liver.

Maintain a healthy weight, stay physically active, and limit your alcohol use. Keep your liver healthy, and it will protect you for a lifetime.

Check out the March issue of NIH News in Health, the monthly newsletter bringing you practical health news and tips based on the latest NIH research

Wednesday, January 22, 2014

Synthetic Marijuana 'Spice' Linked to Stroke

Medscape Medical News > Psychiatry

Synthetic Marijuana 'Spice' Linked to Stroke
Dan Rankin
January 21, 2014

Ischemic stroke may be added to the list of health risks already associated with the recreational street drug spice, a team of neurologists from the University of South Florida (USF), in Tampa, suggests.

In a new report, the authors discuss the cases of 2 young and previously healthy siblings aged 26 and 19 years who experienced acute ischemic stroke shortly after smoking the Schedule I synthetic marijuana known as spice. Imaging results suggested the strokes may have been embolic.

The lead author of the article, Melissa J. Freeman, MD, said that all the tests they ran on the siblings to determine whether they were genetically predisposed to developing blood clots came back negative.

"We're proposing that perhaps it's a cardioembolic etiology, because smoking the synthetic marijuana spice has been associated in the medical literature with myocardial infarction and seizures," Dr. Freeman, a USF vascular neurology fellow, told Medscape Medical News. "If people are having heart attacks from it, perhaps there is a cardiac reason for the strokes."

The study was published in the December 10 issue of Neurology.

Spice-Associated Effects

The authors cite tachycardia, vomiting, agitation, confusion, and hallucinations as common side effects of smoking spice, adding that national news media outlets have also reported on spice-associated deaths within the past several months.

Patient A, a 26-year-old man, was brought to the emergency department with sudden-onset dysarthria, expressive aphasia, and weakness in his right face and arm.

He was found to have a clot in the left middle cerebral artery (MCA), which was confirmed by computed tomographic angiography, and was treated with tissue plasminogen–activator (tPA). He improved clinically and did not return for his follow-up visit, they write.

Patient B, a 19-year-old woman, was recognized by staff members as the sibling who had visited her brother on his previous admission. Magnetic resonance imaging showed a large MCA distribution infarction, with punctate infarcts in the right cerebral hemisphere, "suggestive of a proximal embolic event," the authors note. "She did not arrive within the window for tPA."

She stabilized neurologically, but at the last office visit, she still had right hemiparesis and expressive aphasia, they note.

Although both patients tested positive for regular cannabis and had in the past smoked conventional marijuana, each reported that they had smoked spice shortly prior to onset of the stroke and that they had obtained the drug from the same supplier.

The active ingredient in the spice smoked by the siblings in this report was JWH-018, a chemical compound first developed in the mid-1990s. But different compounds are constantly being developed by spice manufacturers, Dr. Freeman said. That makes them harder to regulate and more dangerous for users, she said.

"The chemicals might be slightly different on a molecular level and therefore wouldn't be part of the group that is considered illegal," said Dr. Freeman. "There is so much that is unknown, which is part of the problem. If it were one specific compound, it would be a lot easier to research."

Limitations to the findings listed by the authors in the article include possible unidentified contaminants in the product the siblings consumed and the fact that an unknown genetic mechanism could have caused the stroke, given the relationship of the patients.

Anything Pot Can Do…

In an editorial accompanying the publication, John C. M. Brust, MD, from the New York Neurological Institute and Columbia University College of Physicians and Surgeon, New York City, points out that many synthetic cannabinoids have several times the potency or efficacy of tetrahydrocannabinol (THC), the active ingredient in natural marijuana.

Citing 59 reported cases of marijuana-related strokes in the medical literature, Dr. Brust concluded by saying, "If marijuana can cause ischemic stroke, and if anything pot can do spice can do better, neurologists will likely encounter increasing numbers of spice-associated strokes in the years ahead."

In the meantime, Dr. Freeman encouraged doctors who see stroke patients who are not within the age range of people normally considered at risk for stroke to ask whether they have smoked spice recently.

"I think it should be reported, because we won't be able to figure anything more out unless we have more information," she said. "I think it's very important that they screen high school– and college-aged students. The prevalence of younger people smoking the substance is so much higher than I thought it would be."

Neurology. Published online November 8, 2013. Abstract, Editorial

Tuesday, January 14, 2014

New-Flu Forecasting Website Posts First Predictions

Flu Forecasting Website Posts First Predictions
January 13, 2014 

Posted in: Infectious Diseases, Public Health
Infectious disease experts at Columbia’s Mailman School of Public Health have launched a website that reports weekly predictions for rates of season influenza in 94 cities in the United States, based on a scientifically validated system.

http://cpid.iri.columbia.edu/


Reporting the latest data from the week of December 29, 2013, through January 4, 2014, the website—Columbia Prediction of Infectious Diseases: Influenza Forecasts, or CPID—shows that:

  • Flu cases are forecast to peak in January in most of the country, including San Francisco (Jan. 5-11), Chicago (Jan. 12–18), Atlanta (Jan. 12–18), Washington, D.C. (Jan. 12–18), Los Angeles (Jan. 12–18), New York City (Jan. 19–25), and Boston (Jan. 26–Feb. 1).
  • Flu cases are predicted to continue to rise into February for several cities, peaking in Miami during the week of Feb. 2–8 and Providence, RI, during Feb. 16–22.
  • Areas of the country hardest hit by seasonal flu—including Louisiana, Nevada, Tennessee, and  Texas—have already seen the worst of the outbreak.
  • Overall, the 2013–2014 flu season is currently predicted to peak later, with fewer cases, than the 2012–2013 season but to be considerably more severe than the 2011–2012 season.
New predictions are posted every Friday afternoon during the flu season.

“For the first time, people can see the outlook for seasonal flu in their area by going online,” says Jeffrey Shaman, PhD, assistant professor of environmental health sciences at the Mailman School, who led development of the site and forecasting system. “We hope the site will help foster greater awareness of influenza activity and risk around the country and that it will motivate individuals to take measures, such as vaccination, to protect themselves against the virus.” Dr. Shaman is also affiliated with the International Research Institute for Climate and Society at Columbia’s Earth Institute, which is hosting the website.

Website Features
  • Interactive map of the United States displays the incidence and relative severity of seasonal flu for cities across the country.
  • Influenza incidence predictions by city for the coming weeks.
  • Map showing the proportion of flu cases by region.
  • Charts that compare the timing and severity of the four most-recent flu seasons.
  • Exportable data for each week of the flu season (beginning in Sept. 29 for the 2013–2014 season).
The flu forecasting system adapts techniques used in modern weather prediction to turn real-time, Web-based estimates of influenza infection into local forecasts of future influenza incidence by locality.

For the public, the flu forecast may promote greater vaccination, the exercise of care around people sneezing and coughing, and better awareness of personal health.  For health officials, it could inform decisions on how the stockpiling and distribution of vaccines and antiviral drugs, and in the case of a virulent outbreak, whether other measures, such as closing of schools, are necessary.
“Flu forecasting is a powerful example of how public health research is leveraging technology to prevent the spread of infections and safeguard our health,” says Linda P. Fried, MD, MPH, dean of the Mailman School.

The Centers for Disease Control estimates that in the U.S. between 3,000 and 49,000 people die from the flu each year.

Funding for the project is provided by the National Institutes of Health (GM100467, 1U54GM088558, and ES009089), the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services, and the Department of Homeland Security.
This article originally appeared on the Mailman School of Public Health website.

Behind The Headlines -Could cannabis compound soothe arthritis pain?

Could cannabis compound soothe arthritis pain?

“Synthetic cannabis-like molecule developed in lab could help osteoarthritis sufferers,” reports The Daily Telegraph.

Anecdotal reports of cannabis’s ability to soothe chronic pain conditions such as osteoarthritis have been available for many years.

Aside from the obvious legal issues (cannabis is a Class B illegal drug), cannabis also carries the risk of side effects and complications such as psychosis and depression

So a compound containing the drug’s painkilling ability without its psychoactive effects could lead to useful new treatments. 

One candidate is “JWH133” a chemical that binds to and activates the cannabinoid 2 (CB2) receptor. Receptors are proteins found on the surfaces of cells. When activated receptors cause a response inside cells. The CB2 receptor is also activated by tetrahydrocannabinol (THC), the principle psychoactive constituent in cannabis. Activating the CB2 receptor is thought to relieve pain and inflammation. 

The new research found evidence that JWH133 relieves pain in a rat model of arthritis. Importantly, the JWH133 compound is selective for CB2 receptors and does not activate cannabinoid 1 (CB1) receptors. CB1 receptors are found in the brain and are believed to be responsible for the psychological effects of cannabis.

So this suggests JWH133 may be a useful candidate for an osteoarthritis treatment. However, this is very early stage research only involving rats.

As Professor Alan Silman, medical director of Arthritis UK, says in the press coverage, this research does not support recreational cannabis use.

Where did the story come from?
The study was carried out by researchers from the University of Nottingham in the UK in collaboration with researchers from the University of Pittsburgh and Virginia Commonwealth University in the US. It was funded by Arthritis Research UK and the National Institutes of Health. 

The study was published in the peer-reviewed journal PLOS One. PLOS One is an open-access journal, meaning that all the research it publishes can be accessed for free.

This study was reported on by the Daily Express and The Telegraph. The Telegraph made no mention of the fact that the current research was in rats. This was also unclear from the over-optimistic headline in the Express. However, the report in the Express was of a higher standard, as it explained that the research was in animals and that it would take a considerable amount of time before any pill could be available for patients.

What kind of research was this?
This was a laboratory experiment on animals.

The researchers wanted to test the hypothesis that activation of cannabinoid 2 (CB2) receptors would reduce osteoarthritis pain responses in an animal model of osteoarthritis.

What did the research involve?
To create the animal model of osteoarthritis, rats had an injection of a chemical (monosodium acetate) into one of their knees (on the left rear limb). This triggered the same kind of inflammation and functional damage to the limb that occurs in humans with osteoarthritis.

The rats were then either given a drug called JWH133 or a placebo (“dummy”) injection. JWH133 binds with and activates the CB2 receptor of cells, causing them to respond. Eight rats were injected with JWH133 and eight were injected with placebo.

Pain behaviour was determined by measuring the change in weight distribution between the limbs and by testing the rats' sensitivity to pinch and touch.

Further experiments were performed on the animal model of osteoarthritis and normal rats that had been given an injection of saline (salty water) into their knee to see how JWH133 could reduce pain.

What were the basic results?
Once the rats had the injection of monosodium acetate into the knee of their left rear limb to model osteoarthritis, they placed less weight on that limb and their paw was more sensitive to pinch and touch.

Repeated injections with JWH133 significantly reduced the development of pain behaviour in the osteoarthritis model rats compared to the placebo injection.

The researchers went on to perform a series of further experiments. They found that:

treatment with JWH133 reduced the changes in inflammation-controlling chemicals which are released by osteoarthritis model rats

treatment with JWH133 reduced the firing of nerve cells in the spine in response to pain in osteoarthritis model rats, but not normal rats

osteoarthritis model rats have higher levels of the CB2 receptor “message” (mRNA) and protein in nerve cells in the spine 

The researchers then looked at the levels of CB2 receptor “message” in human spines of people who had died who had had knee osteoarthritis. They found that the more severe the disease, the lower the level of CB2 receptor “message”. The researchers say that this might reflect “events associated with later stages of joint pathology [disease]”.

How did the researchers interpret the results?
The researchers conclude that “activation of CB2 receptors attenuated [reduced] the development and maintenance of osteoarthritis-induced pain behaviour”. They go on to state that their “clinical and pre-clinical data support the further investigation of the potential of CB2 receptor agonists [chemicals that bind to the receptor and activate it] for the treatment of pain associated with osteoarthritis, in particular at earlier stages of the disease”.

Conclusion
This study found that a chemical called JWH133, which binds to and activates the cannabinoid 2 (CB2) receptor, could reduce osteoarthritis-induced pain behaviour in rats injected with a chemical to mimic the effects of osteoarthritis.

This early stage research supports the further investigation of the potential of chemicals which bind to activate the CB2 receptor as treatments for osteoarthritis-induced pain. However, so far the treatment has only been tested in a small number of rats injected with a chemical to mimic symptoms of osteoarthritis. This study does not show what positive or negative effect chemicals that activate the CB2 receptor may have in humans suffering from osteoarthritis.

Until further trials involving humans, such as a phase I trial are carried out, it is impossible to predict whether JWH133 will be effective, and probably more importantly, safe in humans.

If you are having problems coping with your arthritis symptoms, the NHS offers specialist services for people with chronic pain conditions. 

Read more about NHS Services for people with chronic pain.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines
Synthetic cannabis created for osteoarthritis. The Daily Telegraph, January 7 2014
‘Synthetic cannabis’ pill could end arthritis pain for millions. Daily Express, January 7 2014
Links to the science
Burston JJ, Sagar DR, Shao P, Bai M, King E, et al. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint. PLoS ONE. Published online November 25 2013

What is Behind the Headlines?
We give you the facts without the fiction. Professor Sir Muir Gray, founder of Behind the Headlines, explains more...

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Thursday, January 9, 2014

Vitals Predicts the Top 5 Health Care Consumer Trends for 2014


Vitals Predicts the Top 5 Health Care Consumer Trends for 2014

Wait times will go up, while doctor-patient relationships improve

LYNDHURST, NJ – January 07, 2014 – The health care industry has never made fast changes. But with the implementation of the Affordable Care Act, and the advent of the empowered online health care consumer, there are a number of ways that the system is poised for transformation in 2014.

Vitals CEO Mitch Rothschild outlines five key changes he predicts health care consumers will see in the coming year.

1. Wait Times Will Go Up. Over a million new people enrolled in the health care system in 2013, and many millions more are estimated to begin participating in 2014. Yet, medical resources are already stretched to capacity in this country. While Baby Boomers age and place greater demands on the health care system, medical schools have continued to graduate only a finite number of doctors each year. In fact, in the last half-century only one new medical school has opened in this country. Add to that a physician population that is aging rapidly. The American Medical Association found that by 2009, 45 percent of physicians were aged 55 and older.

The demand for even more primary care services will inevitably cause a major disruption to the system. For the unchanging supply of doctors, it will mean less time to spend with patients in examination rooms and with follow-up care. For patients, it will mean appointments will become harder to schedule and wait times longer.

Consider this: When Massachusetts implemented their health care reform, the average wait to get an appointment with a primary care doctor jumped from 39 days to 48 days. The Vitals Index, which tracks wait time data, also saw the average time a patient waits in the office creep up from 19 minutes, 48 seconds in 2010 to 20 minutes, 15 seconds in 2013.

2. Patients Will Continue to Love Their Doctors. While it may seem counterintuitive that patients will continue to love their physicians even as they make them wait longer, health care consumers are becoming more savvy about choosing a doctor with whom they can build a lasting relationship.

Today, more people go online first to research doctors to find that physician who is a better fit for them. In a recent Vitals Index survey, 56 percent of respondents said that they spend several days researching the right physician. And their work is paying off. Forty-five percent described their doctor as “the one.” That’s double the number of people who chose the same response in a similar survey last year.

“More people than ever realize that online resources can help them find a better match when it comes to finding the right doctor,” said Rothschild. “Sites like Vitals can help consumers identify the doctors with the characteristics they are looking for, whether it be a good bedside manner or specific hospital affiliations.”

3. Urgent Care and Alternate Care Center Use Will Continue To Grow. In 2014, consumers have more options to choose from than just their primary care physician when they want or need to receive care.

Urgent care centers are able to provide quick, walk in medical care for everything from skin irritations to the flu. Currently more than 9,000 urgent care facilities are operating today, with another 700 to 800 slated to open this coming year. At the same time, retailers like CVS and Walgreens have been opening more of their own clinics for access to low-cost care.

According to the Vitals Index, 41 percent of respondents indicated they have used urgent care centers for their health needs. Expect these figures to grow as consumers bear more of the brunt of medical costs and look for lower cost options.

“Alternative care centers are growing because they are convenient and provide easy, more affordable access to medical care and services,” said Rothschild. “Health care reform will fuel this further as patients become more aware that they can save up to 80 percent by avoiding an emergency room.”

A major driver for this sector of the medical care market is young adults. In a recent Vitals Index report, those between the ages of 18-29 were twice as likely to use alternative medical care facilities compared to adults over 50. Yet, they’re also less likely to have a primary care physician. Only 1 in 3 said they have a primary care doctor to rely on in the case of an emergency.

4. More Online Appointments. In 2005, only 6 percent of family doctors offered online appointment scheduling. Fast forward to 2013 and about 20 percent of practices allow online appointment requests either through patient portals or online scheduling services like Vitals. Our Vitals Index report indicates that today, 80 percent of health care consumers still prefer to make appointments “the old fashioned way” – over the phone. Changing demographics and the availability of technology to enable online scheduling will be key in changing consumer behavior.

“Just as the travel industry made a shift towards online reservations, doctor practices will follow suit,” said Rothschild. “It’s not only a less manual process for the office staff, it also allows patients to schedule office visits when convenient and without waiting on hold.”

5. Increase in the Power of Online Patient Reviews. Before we eat out or even choose a movie, many of us take to the web to read reviews and gain a level of confidence in our choice. And in 2014, more will turn to online reviews for comparing doctors, just like we do for other purchase decisions, as well.

Doctor reviews are finally coming into their own in 2014, thanks to a critical mass that has been building. When it comes to online reviews, most people believe that 5-6 reviews provide an accurate indicator of quality, according to a recent Vitals Index report. Vitals has more than 3 million reviews in its doctor database – one of the largest online collections.

And the reviews are having an impact. Almost 47 percent of the people who looked up a physician online felt differently about that doctor after viewing their profile. About 40 percent said they felt reassured or more comfortable with their choice after reading the review, while 7 percent said they felt the need to find a different doctor.

In fact, as an indicator of quality, patient reviews were considered just as important as a doctor’s years of experience when it came to determining a doctor’s qualifications – both were selected by 76 percent of all respondents.

“Over the past decade, the internet has transferred power from the buyer to the seller in several different consumer sectors,” said Rothschild. “We’re helping shape that transition in health care. Other patients’ feedback on doctors has become a critical part of the process of selecting a doctor.”

About Vitals

Vitals aims to make better health possible. We are a leader in providing online tools that enable health care consumers to make informed decisions about both the quality and cost of their medical care. Through health plans, hospitals and our leading consumer websites, Vitals helps more than 150 million people each year access information for better, more affordable care. The Vitals Index is an ongoing report about the state of doctor-patient relationships based on proprietary data and surveys.

http://www.vitals.com/posts/press-center/press-releases/vitals-predicts-the-top-5-health-care-consumer-trends-for-2014#ixzz2pwYMWox0

Monday, January 6, 2014

Meditation for Anxiety and Depression?

Meditation for Anxiety and Depression?

Johns Hopkins research suggests meditation may reduce symptoms

Released: 1/3/2014 12:25 PM EST     
Source Newsroom: Johns Hopkins Medicine

Newswise — Some 30 minutes of meditation daily may improve symptoms of anxiety and depression, a new Johns Hopkins analysis of previously published research suggests.

“A lot of people use meditation, but it’s not a practice considered part of mainstream medical therapy for anything,” says Madhav Goyal, M.D., M.P.H., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine and leader of a study published online Jan. 6 in JAMA Internal Medicine. “But in our study, meditation appeared to provide as much relief from some anxiety and depression symptoms as what other studies have found from antidepressants.” These patients did not typically have full-blown anxiety or depression.

The researchers evaluated the degree to which those symptoms changed in people who had a variety of medical conditions, such as insomnia or fibromyalgia, although only a minority had been diagnosed with a mental illness.

Goyal and his colleagues found that so-called “mindfulness meditation” — a form of Buddhist self-awareness designed to focus precise, nonjudgmental attention to the moment at hand — also showed promise in alleviating some pain symptoms as well as stress. The findings held even as the researchers controlled for the possibility of the placebo effect, in which subjects in a study feel better even if they receive no active treatment because they perceive they are getting help for what ails them.

To conduct their review, the investigators focused on 47 clinical trials performed through June 2013 among 3,515 participants that involved meditation and various mental and physical health issues, including depression, anxiety, stress, insomnia, substance use, diabetes, heart disease, cancer and chronic pain. They found moderate evidence of improvement in symptoms of anxiety, depression and pain after participants underwent what was typically an eight-week training program in mindfulness meditation. They discovered low evidence of improvement in stress and quality of life. There was not enough information to determine whether other areas could be improved by meditation. In the studies that followed participants for six months, the improvements typically continued.

They also found no harm came from meditation.

Meditation, Goyal notes, has a long history in Eastern traditions, and it has been growing in popularity over the last 30 years in Western culture.

“A lot of people have this idea that meditation means sitting down and doing nothing,” Goyal says. “But that's not true. Meditation is an active training of the mind to increase awareness, and different meditation programs approach this in different ways.”

Mindfulness meditation, the type that showed the most promise, is typically practiced for 30 to 40 minutes a day. It emphasizes acceptance of feelings and thoughts without judgment and relaxation of body and mind.

He cautions that the literature reviewed in the study contained potential weaknesses. Further studies are needed to clarify which outcomes are most affected by these meditation programs, as well as whether more meditation practice would have greater effects.

“Meditation programs appear to have an effect above and beyond the placebo,” Goyal says.

The research was supported by a contract from the Agency for Healthcare Research and Quality (HHSA 290 2007 10061).

Other Johns Hopkins researchers involved in the study include Sonal Singh, M.D., M.P.H.; Erica M.S. Sibinga, M.D., M.H.S.; Neda F. Gould, Ph.D.; Anastasia Rowland-Seymour, M.D.; Ritu Sharma, B.Sc.; Zackary Berger, M.D., Ph.D.; Dana Sleicher, M.S., M.P.H.; David D. Maron, M.H.S.; Hasan M. Shihab, M.B.Ch.B., M.P.H.; Padmini D. Ranasinghe, M.D., M.P.H.; Shauna Linn, B.A.; Shonali Saha, M.D.; Eric B. Bass, M.D., M.P.H.; and Jennifer A. Haythornthwaite, Ph.D.

##

Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading academic health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's vision, “Together, we will deliver the promise of medicine,” is supported by its mission to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 35 Johns Hopkins Community Physicians sites. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation for 21 years in a row by U.S. News & World Report. For more information about Johns Hopkins Medicine, its research, education and clinical programs, and for the latest health, science and research news, visit www.hopkinsmedicine.org.

Saturday, January 4, 2014

How to use acetaminophen safely, from the January 2014 Harvard Men's Health Watch

How to use acetaminophen safely in people with HCV

Hepatitis C Review - Acetaminophen -Tylenol
The maximum recommended dose of acetaminophen (Tylenol®) for patients with hepatitis C is two grams (four 500mg tablets) per day....

Evaluation, Staging, and Monitoring of Chronic Hepatitis C
Based on available information and recognition that many patients with chronic hepatitis C have limited pain treatment options, most experts believe that low dosages of acetaminophen can safely be used in most patients with chronic hepatitis C infection. Specifically, patients without cirrhosis can take acetaminophen if they limit their intake to two grams per day; those with cirrhosis should limit their intake of acetaminophen to one gram per day....


How to use acetaminophen safely from the January 2014 Harvard Men's Health Watch

Acetaminophen Safely - The Average Healthy Adult

January 2014

Cold, cough, and flu season is a good time to revisit the risks of acetaminophen, a medication found in many cold, cough, and flu remedies. Although billions of doses of acetaminophen are consumed safely every year, some people taking the drug end up in the emergency room or need hospitalization, and some die from acetaminophen overdose or interaction. In the January 2014 issue of the Harvard Men's Health Watch, Dr. Melisa Lai Becker, an instructor in medicine at Harvard Medical School, suggests some ways to avoid getting into trouble when taking acetaminophen.

Acetaminophen is the chemical name for the widely used pain and fever reliever in Tylenol and other over-the-counter medications. High doses of acetaminophen can inflame and damage the liver. Because acetaminophen is in more than 600 different medications, it can be easy to get more than is healthy.

"People don't realize that these doses all add up, and before you know it you've exceeded the recommended dose of acetaminophen," says Dr. Lai Becker, director of the Division of Medical Toxicology at Harvard-affiliated Cambridge Health Alliance.

For the average healthy adult, the generally recommended maximum daily dose is no more than 4,000 milligrams (mg) from all sources. But in some people, doses close to the 4,000 mg daily limit could still harm the liver. It's safest to take only what you need, and not to exceed 3,000 mg a day whenever possible.

Dr. Lai Becker suggests these guidelines for taking acetaminophen safely:

Stick to recommended doses. When taking acetaminophen, don't be tempted to add a little extra to the recommended dose. A small-bodied person should stay on the low end of the recommended dose range (3,000 mg).

Cold and flu remedies count. When you reach for an over-the-counter cough, cold, or flu product, take a look at the label. Does it contain acetaminophen? If so, add the dose to your daily total.

Know your pills. Over-the-counter acetaminophen pills may contain 325, 500, or 650 mg of the drug. Be extra cautious when taking the 500 or 650 mg pills.

Go easy on alcohol. Drinking alcohol causes the liver to convert more of the acetaminophen you take into toxic byproducts. Men should have no more than two standard drinks per day when taking acetaminophen, women no more than one.

Beware of medication interactions. Ask your doctor or pharmacist if any of your prescription medications could interact badly with acetaminophen.

Acetaminophen: How much can you take safely? 
325 mg 500 mg 650 mg extended release
Take how many pills at a time? 1 or 2 1 or 2 1 or 2
Take how often? Every 4 to 6 hours Every 4 to 6 hours Every 8 hours
Safest maximum daily dose
for most adults
8 pills 6 pills 4 pills
Never take more than this in a 24-hour period 12 pills (3900 mg) 8 pills (4000 mg) 6 pills (3900 mg)

The maximum daily dose for a healthy adult who weighs at least 150 pounds is 4,000 milligrams (mg). However, in some people, taking the maximum daily dose for extended periods can seriously damage the liver. It's best to take the lowest dose necessary and stay closer to 3,000 mg per day as your maximum dose. If you need to take high doses of acetaminophen for chronic pain, check with your doctor first.

Read the full-length article: "Acetaminophen safety: Be cautious but not afraid"

Tuesday, December 17, 2013

High-Fat Diet Linked to Fewer Gallstones

High-Fat Diet Linked to Fewer Gallstones

Published: Dec 17, 2013 | Updated: Dec 17, 2013

By Cole Petrochko, Staff Writer
MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Patients undergoing rapid weight loss who either received ursodeoxycholic acid (Ursodiol) or ate a high-fat diet had a reduced risk of gallstones, researchers found.

Action Points
In a meta-analysis of randomized controlled trials of participants undergoing weight loss, ursodeoxycholic acid use was associated with a reduced risk of gallstones.

Diets high in fat content also were associated with fewer gallstones, compared with those with low fat content

Compared with control treatments, risk for gallstones was significantly reduced among patients who received daily supplements of ursodeoxycholic acid (RR 0.33, 95% CI 0.18-0.60), according to Frank Lammert, MD, of Saarland University Hospital in Homburg, Germany, and colleagues.

There was also a significant reduction in gallstone formation in patients who consumed a high-fat diet versus a low-fat diet (RR 0.09, 95% CI 0.01-0.61), they wrote online in the journal Clinical Gastroenterology and Hepatology.

A study printed in the journal Hepatology in July 2013 showed a causal relationship between high body mass index (BMI) and gallstones, particularly among women.

Similar findings were reported in the Journal of Pediatric Gastroenterology and Nutrition in August 2012 among overweight or obese children and teens; those who were moderately obese had more than four-fold risks for gallbladder disease compared with normal-weight pediatric patients.

The authors noted that these risks were also present in patients who underwent rapid weight loss or who underwent weight cycling.

The authors reviewed randomized controlled trials of nonsurgical gallbladder stone preventive interventions in adult patients who underwent rapid weight loss through bariatric surgery or with diet alone, an analysis that included 13 studies and 1,837 obese participants combined.

Outcomes included in the analysis were formation of ultrasonically-verified gallstones, mortality, and adverse events. Secondary outcomes included quality of life, cholecystectomy, bile lithogenicity, and weight loss.

Control interventions included placebo treatment, no intervention, or pharmacological and nonpharmacological interventions.

Low- versus high-fat diets were examined in two studies, which included groups receiving 3 g versus 12.2 g of fat, and 2 g versus 30 g of fat, each in daily quantities. Participants in the remaining 11 studies received 300 to 1,200 mg daily of ursodeoxycholic acid at a median 750 mg per day.

Participants were treated from 6 weeks to 18 months and were followed up with for 6 weeks to 24 months.

In the studies of ursodeoxycholic acid, 5% of those in a treatment arm developed gallstones versus 23% of those in the control arm. No deaths occurred in either arms of the studies. Treatment with ursodeoxycholic acid was associated with a reduced risk of cholecystectomy (RR 0.20, 95% CI 0.07-0.53).

Weight loss was equal among groups in all of the ursodeoxycholic acid trials. Among those who received bariatric surgery as their weight-loss intervention, type of surgery did not affect ursodeoxycholic acid-related outcomes, nor did dosage of ursodeoxycholic acid. Quality of life was not assessed in these studies.

In studies comparing high- versus low-fat diets, no patients in the high-fat groups developed gallstones, compared with 45% of control patients. There was no significant difference in weight lost. Quality of life was not assessed. Bile lithogenicity did not differ significantly between the two studies.

There were no adverse events reported with the high- versus low-fat diet studies.

Few serious events were reported related to ursodeoxycholic acid consumption; gastrointestinal-related complaints were the most common adverse events.

The authors noted that the small number of identified trials and low sample sizes in each trial limited their study. In addition, high risk of attrition bias may have also limited outcomes. The research was limited by an inability to perform a meta-analysis of other interventions that reduce cholesterol precipitation in bile.

Primary source: Clinical Gastroenterology and Hepatology
Source reference: Lammert F, et al "Ursodeoxycholic acid and high-fat diets prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials" Clin Gastroenterol Hepatol 2013; DOI: 10.1016/j.cgh.2013.11.031.

http://www.medpagetoday.com/Gastroenterology/GeneralGastroenterology/43474

Liver physiology and liver diseases in the elderly

World J Gastroenterol 2013 December 14; 19(46): 8459-8467
 
Published online 2013 December 14. doi: 10.3748/wjg.v19.i46.8459.
Liver physiology and liver diseases in the elderly
 
Kazuto Tajiri and Yukihiro Shimizu.
Kazuto Tajiri, Third Department of Internal Medicine, Toyama University Hospital, Toyama 930-0194, Japan
Yukihiro Shimizu, Gastroenterology Unit, Nanto Municipal Hospital, Toyama 932-0211, Japan
Author contributions: Both authors contributed to this paper equally.
Correspondence to: Yukihiro Shimizu, MD, PhD, Gastroenterology Unit, Nanto Municipal Hospital, 938 Inami, Nanto City, Toyama 932-0211, Japan. rsf14240@nifty.com
Telephone: +81-763-821475 Fax: +81-763-821853
Received June 11, 2013; Revised August 12, 2013; Accepted September 13, 2013;
 
Liver physiology and liver diseases in the elderly 
 
Abstract

The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.

Keywords: Liver disease, Aging, Physiology, Immunology

Core tip:
The morphology and physiology of the liver changes with aging and an understanding of those changes is important for the management of liver diseases. We first summarized the various changes in the liver with aging. We then reviewed the reported characteristics of liver diseases found in the elderly. This kind of information could be increasingly important in the near future, because the proportion of the world’s population over 60 years old is increasing, especially in developed countries.
 
INTRODUCTION
The proportion of the world’s population over 60 years old is increasing, especially in developed countries. Morphology and functions of the liver as well as other organs change with aging. Understanding these changes is important for the management of liver diseases in the elderly. In addition, the pathogenesis of many liver diseases is immune-mediated, and immune systems also change with aging, affecting the clinical picture of liver diseases
 
CHANGES IN LIVER MORPHOLOGY AND FUNCTIONS WITH AGING
Morphology of the aged liver and microscopic or molecular characteristics of senescent hepatocytes
In general, liver volume is reduced by 20%-40% in the elderly, with these reductions more marked in women (up to 44% decline) than in men[1]. Microscopically, elderly subjects have elevated numbers of hepatocytes with increased ploidy. Hepatocytes show decreased numbers of mitochondria but increased volume of individual mitochondria, although functional impairment of mitochondria has not been demonstrated. Hepatocytes in elderly subjects contain denser body compartments, such as secondary lysosomes and lipofuscin, than do hepatocytes in younger subjects[2]. Lipofuscin accumulation has been associated with chronic oxidative stress and a failure to degrade damaged and denatured proteins[3]. Moreover, accumulating evidence suggests that lipofuscin interferes with cellular pathways due to its ability to trap metallic cations and facilitate further free radical formation[4].
 
Vacuolation of hepatocyte nuclei has been associated with diabetes mellitus and non-alcoholic fatty liver disease. However, vacuolated hepatocyte nuclei were recently shown to be more abundant in senescent hepatocytes expressing p21 or γH(2)AX[5], suggesting they are a marker of hepatocyte senescence. Moreover, increased size of hepatocyte nuclei in nonalcoholic fatty liver disease (NAFLD) has been associated with telomere shortening and p21 upregulation[6], suggesting that increased nuclear size is also a marker of hepatocyte senescence.
 
Cellular senescence is associated with aberrant activation of oncogenes, and senescent pre-malignant hepatocytes have been found to secrete cytokines and chemokines through interactions with their environment, resulting in immune-mediated clearance of these cells. Impairment of immune surveillance has been associated with the development of hepatocellular carcinoma (HCC)[7]. This scenario could account for the preferential development of HCC in aged patients with chronic liver diseases, irrespective of the etiology of these diseases[8].
 
Recently, resistin, an adipokine that inhibits phosphorylation of AMP-activated protein kinase and modulates insulin resistance, has been shown to induce senescence-associated β-galactosidase in mouse hepatocytes[9]. Resistin has been shown to act by inhibiting the function of sirtuin 1, one of the 7 members of the sirtuin family of histone deacetylases shown to act as crucial negative regulators during the aging process[9].
 
Molecular changes during hepatocyte senescence should be clarified in more detail in the near future. The identification of senescence-causing factors may be beneficial in preventing senescence-associated liver diseases.
 
Blood flow
Liver blood flow is estimated to be decreased by 35%-50% in the elderly, and may be responsible for age-related reductions in liver volume[10].
 
Hepatic function
 
Liver function tests: Although interindividual differences have been observed, liver functions are relatively well preserved in elderly individuals. Hepatic enzymes and high-density lipoprotein cholesterol are well maintained, while bilirubin levels may decline with age due to reductions in muscle mass and hemoglobin concentrations[11]. Moreover, age was reported to be associated with modest decreases in albumin and γ-glutamyl transpeptidase concentrations, and increases in bilirubin concentration, after adjustments for sex, alcohol use, and components of the metabolic syndrome, suggesting that liver function may be decreased in these individuals[12].
 
Alanine aminotransferase (ALT) concentrations have been reported to decrease with age in both men and women, independent of components of the metabolic syndrome. These findings suggest the need to identify an optimal cut-off point for normal ALT in elderly patients[12].
 
Drug metabolism
Phase I hepatic metabolism (first-pass hepatic uptake) of drugs has been reported to be decreased in the elderly, possibly due to reduced liver volume and hepatic blood flow, leading to a decline in hepatic drug metabolism. Metabolism of drugs with low phase I hepatic metabolism is likely to be impaired mainly by liver volume reduction.
 
A previous report suggested that drug metabolism is reduced by up to 30% after 70 years of age, and that a reduction in liver cytochrome P450 may also contribute to decreased drug metabolism. Cytochrome P450 activity was shown to be 32% lower in subjects > 70 years than in subjects aged 20-29 years[13].
 
Liver regeneration
Liver regeneration capacity has been reported to decline with age[14,15]. The mechanisms underlying the reductions in regeneration capability are complex. One of these mechanisms involves a decrease in the concentrations of circulating epidermal growth factor (EGF), with the response of hepatocytes to EGF also reduced due to age-associated loss of EGF receptors or deficits in signaling after EGF binds to its receptor[16]. Another mechanism underlying reduced hepatocyte proliferation capacity may be the inhibition of cyclin-dependent kinases by interaction with the chromatin remodeling protein Bim, which is expressed in aged hepatocytes[17]. Along with reductions in regenerative capacity, telomere length has been reported reduced in aged livers, especially in patients with liver diseases[18].
 
Immune system
Many liver diseases are mediated by the host immune response. Therefore, changes in immune functions may affect the clinical picture of various liver diseases. Several changes in the immune system have been observed in elderly individuals.
 
Innate immunity:
Most of the immune cells involved in innate immunity, such as monocytes/macrophages and natural killer (NK) cells, show decreased function with aging[19]. Although the percentage and number of CD56bright NK cells gradually decline with age, the percentage and number of CD56dim NK cells progressively increase[20].
 
In addition, dendritic cells (DCs), which are the most potent antigen-presenting cells, show significant functional changes with aging. DCs play pivotal roles in the onset and regulation of adaptive immune responses and control the state of tolerance to self-antigens[21]. Immature DCs promote tolerance through induction of regulatory T cells (Treg), whereas mature DCs stimulate effector T cells. DCs in the elderly show inappropriate maturation induced by infections or tissue injury, which may lead to alterations in the balance between the tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases[22].
 
Adoptive immunity:
T cell number and diversity of repertoire are decreased and T cell expansion, differentiation, and signaling intensity are impaired with aging. The numbers of CD4+ T cells are decreased, while the numbers of CD8+ T cells are increased. The expression of the costimulatory molecule CD28 is decreased on T cells, impairing their ability to proliferate and secrete interleukin-2[23]. Treg function is decreased after age 50 years, which may be associated with the increases in autoimmunity[24].
The numbers of B cell precursors in the bone marrow (pre-B cells), as well as peripheral B cells, decrease with age[25]. In contrast, immunoglobulin concentrations may increase with age[26], but the quantities of specific antibodies and the diversity of the B cell repertoire decrease[27].
 
In summary, immune responses against foreign antigens and malignant cells seem to be impaired with age because of the reductions in number and functions of most immunocompetent cells. In contrast, the decrease in Tregs and the impairment of DC maturation may result in a predisposition to autoimmunity.
 
LIVER DISEASES IN THE ELDERLY
The prevalence of some liver diseases increases with aging, and advanced liver disease is observed more often in older than in younger patients. Moreover, various physiological changes associated with aging may affect the pathogenesis of liver diseases. In addition, the decreased reserve capacity of most organs in elderly individuals may impair their ability to manage liver diseases.
 
Viral hepatitis
 
Hepatitis A:
Acute hepatitis A virus (HAV) infection is usually self-limiting. However, elderly patients with acute HAV infection experience hepatocellular dysfunction with frequent jaundice and coagulopathy, as well as an increased incidence of complications, such as prolonged cholestasis, pancreatitis, and ascites[28]. Higher hospitalization and mortality rates have been reported in elderly patients with HAV. For example, during an outbreak of HAV infection in the United States, 42% of patients aged 70 years or older required hospitalization compared with 3%-20% of adults aged 40-49 years[29].

Age-related differences in outcomes were also reported, with death rates of 0.004% in individuals aged 5-14 years and 2.7% in those older than 49 years[30]. More recent data from the Centers for Disease Control and Prevention (CDC, 2009 Surveillance) also indicate that mortality due to HAV increases with age, with no fatalities reported in patients younger than 34 years of age. The mortality rates have been estimated to be 0.05 per 100000 patients aged 45-54 years, and 0.11 per 100000 patients older than 75 years. Vaccination for hepatitis A should, therefore, be considered for people, especially the elderly, who plan to travel to endemic areas[30].
 
Hepatitis B:
Acute hepatitis B virus (HBV) infection is uncommon in the elderly because the opportunities for HBV infection are estimated to be low in this population. However, hepatitis B and hepatitis C infections have been reported in aged residents of nursing homes[31,32]. Risk factors include sharing bath brushes, non-disposable syringes, and shaving blades, as well as sexual contact. Clinical manifestations of acute HBV infection are similar to those in younger adults. During an outbreak of acute HBV in elderly nursing home residents, most infected patients were asymptomatic, and no patient died or required hospitalization during the outbreak[31]. However, the rate of progression to chronic hepatitis B is higher in elderly than in younger patients. A report on an outbreak of acute HBV infection in a nursing home showed that 59% of patients older than 65 years of age developed chronic infection[31]. This may be due to a decreased immune response to the pathogens.
 
In chronic HBV infection, the prevalence rates of HBeAg and HBsAg are inversely related to patient age during the natural course of HBV infection. The prevalence rates of HBsAg in Taiwanese men and of HBeAg among HBsAg-positive men older than 60 years of age were reported to be 12.5% and 5.5%, respectively, while prevalence rates in patients aged 30-39 years were 23.8% and 23.3%, respectively[33]. Serum HBV DNA levels were found to vary by country and to be associated with HBeAg or HBV genotype[34]. Older age and male sex, in addition to serum HBV DNA levels, are regarded as risk factors not only for progression to cirrhosis[35], but the development of HCC[36].
 
Nucleos(t)ide analogs are effective in treating HBV infected patients, with similar efficacy in the elderly as in younger patients[37]. Although interferon-based therapy may also be effective for the treatment of chronic HBV infection, its therapeutic effects are inferior in elderly patients[38].
 
Hepatitis C:
The prevalence of hepatitis C virus (HCV) infection varies by age because HCV infection is transmitted by blood contact, such as blood transfusion (especially before 1992), military service, intravenous drug use, tattoos, hemodialysis, and health care work. In the United States, the prevalence of HCV infection is highest in patients aged 40-49 years (4.3%), whereas those aged 60-69 years and 70 years or older have lower prevalence rates of 0.9% and 1%, respectively[39,40]. A European study showed that the prevalence of genotype 1 HCV increases with age, being 57% in patients aged < 65 years, 72% in those aged 65-80 years, and 84% in patients older than 80 years of age[41]. Older age at the time of infection, but not duration of infection, has been associated with fibrotic progression[41] and hepatocarcinogenesis[42]. Normal ALT levels are more likely observed in elderly than in younger HCV-infected patients (46% vs 10.6%, respectively)[43]. However, older patients often show more fibrosis regardless of serum ALT levels[41]. Moreover, the incidence of hepatocellular carcinoma increases with aging both in hepatitis C[42] and hepatitis B[44] infected patients. Therefore, progression of fibrosis and development of hepatocellular carcinoma should be considered, especially in elderly patients with chronic viral hepatitis.
 
Powerful regimens have been established for the treatment of chronic HCV infection, including pegylated interferon and ribavirin, have been established. However, adverse effects are observed more often in older patients[45]. The sustained viral response rate has been shown lower in elderly than in younger patients (46% vs 69.7%, respectively), perhaps due to the high proportion of elderly patients who stop antiviral therapy due to side effects[46].
 
Hepatitis E:
The prevalence of hepatitis E virus (HEV) infection differs markedly in endemic and non-endemic areas. However, recent reports suggested that exposure to HEV occurs frequently in Western countries. In the United States, 16% of blood donors younger than 60 years of age were positive for anti-HEV IgG, compared with 25.5% of those older than 60 years[47]. Furthermore, 3% of patients with acute liver injury suspected of being drug-induced liver injury were seropositive for anti-HEV IgM. Most patients with serology consistent with acute HEV infection were older than 60 years of age[48].
 
Autoimmune liver disease
The prevalence rates of autoimmune liver diseases, including autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), are relatively high in older patients, whereas primary sclerosing cholangitis is more common in those in the third or fourth decade of life[49-51]. However, the results of laboratory tests associated with these autoimmune liver diseases are not associated with age, and treatment strategies are usually identical in older and younger patients.
 
AIH:
Almost 20% of patients develop AIH after 60 years of age, and the disease is frequently progressive and unexpected because ascites and cirrhosis are common manifestations at presentation with few other symptoms[49,52,53]. Most elderly patients respond well to corticosteroid therapy[52]. Rates of treatment failure are lower in older than in younger patients (5% vs 24%), and elderly patients have lower rates of fatality from liver failure or need for liver transplantation (5% vs 21%)[52,53]. Notably, elderly patients are at risk of treatment-related complications, especially osteopenia and compression fracture[54]. Furthermore, they may have other comorbidities and medication requirements that complicate their management.
 
PBC:
Advancing age has been associated with poor prognosis in patients with PBC, and elderly patients diagnosed with PBC at a young age are likely to show a poor prognosis[55]. In contrast, patients with PBC diagnosed after 65 years of age are less likely to have progressive or advanced disease[56]. Two types of phenotypic expression of PBC were recently reported: the classical asymptomatic onset in middle-late age with mild biochemical activity, and symptomatic onset at a younger age with high biochemical activity[57]. Administration of ursodeoxycholic acid, which is the only recommended therapy for PBC, appears to be safe and has few side effects. Osteoporosis should also be considered, especially in elderly patients.
 
Alcoholic liver disease:
Alcohol consumption is common in the elderly. In a study of individuals in the United Kingdom, 62% of subjects aged 60-92 years were drinkers, with 13% of men and 2% of women being heavy drinkers[58]. Elderly people presenting with alcoholic liver disease (ALD) had more advanced disease than younger patients[59]. Half of the elderly patients who develop cirrhosis die within 1 year of diagnosis[60]. In patients with HCV infection, alcohol drinking was associated with accelerated disease progression[61]. Adverse effects of benzodiazepines as treatment for withdrawal symptoms, such as drowsiness, fatigue, confusion, ataxia, falls and incontinence, are more common with increasing age[62].
 
NAFLD:
NAFLD is a disease predominantly seen in middle-aged to older people. A significant proportion of cryptogenic cirrhosis may be due to the end-stage of NAFLD, and age has been reported to be a risk factor for liver fibrosis and higher mortality rate in patients with NAFLD[63]. Older patients have significantly more risk factors for NAFLD, including hypertension, obesity, diabetes, and hyperlipidemia[64]. A study of 351 consecutive patients in the United Kingdom found that albumin, alanine aminotransferase (ALT), ALT/aspartate aminotransferase ratio, and platelet counts were significantly reduced with advancing age[64]. Thus, aged patients with NAFLD are considered to have advanced liver disease.
 
Recently, sirtuin 1, a negative regulator of aging, was reported to play key roles in the regulation of lipid and glucose homeostasis[65]. This finding suggested that aging was associated with the development of NAFLD, and that activating sirtuin 1 may be a novel therapeutic strategy for patients with NAFLD. Several molecular characteristics of hepatocyte senescence have been observed in patients with NAFLD, with hepatocyte senescence being closely associated with advanced fibrosis stage and poor clinical outcome[66]. Thus, the development and pathogenesis of NAFLD may be closely associated with the aging process.
 
Drug-induced liver injury:
Old age is a risk factor of drug-induced liver injury (DILI) because the elderly are more susceptible to adverse drug reactions[67]. Moreover, patients over 75 years old required significantly longer hospitalization for DILI[68]. In contrast, a recent report suggested that older age is associated with a cholestatic type of liver injury[69], and a study in Japan also showed rates of cholestatic liver injury was higher in patients > 65 than < 65 years of age (46% vs 31.6%).
 
Elderly patients may receive many types of drugs for treatment of comorbid conditions. For example, a Japanese study of patients with DILI showed that elderly patients > 75 years of age were taking significantly more concomitant drugs at the time of liver injury[68]. Other reports from Western countries also suggested greater drug usage among elderly patients. For example, a study of 466 patients in Germany > 70 years of age found that these patients were receiving an average of 3.7 prescribed medicines in addition to 1.4 over-the-counter medications daily[70]. In a prospective study in the Netherlands, 94.2% of elderly patients, mean age 82.3 years, were taking more than one drug, and 73.3% were prescribed four or more drugs[71]. Several pharmacokinetic and pharmacodynamic mechanisms that may predispose a patient on multiple medications to an increased risk of DILI have been proposed[72]. Adverse effects of both the individual drugs and their synergistic interactions must be taken into consideration in elderly patients.
 
Liver tumor:
HCC is more common in elderly patients with liver cirrhosis[73]. Elderly patients were reported to develop HCC even without fibrosis[74], suggesting that aging itself may be a predisposing factor for hepatocarcinogenesis. The impact of viral eradication on HCC prevention was found to be less significant in older than in younger patients chronically infected with HCV, especially in patients at an advanced stage of liver disease[75]. These observations indicate the need for long-term follow-up of elderly patients with chronic HCV infection, even after viral eradication and especially in male patients with liver cirrhosis.
 
Hepatic resection for HCC can be performed safely and effectively in elderly patients[76]. Regional therapies, such as radiofrequency ablation and transarterial chemoembolization, may also be considered for elderly patients with HCC, if liver function and tumor stage are acceptable[77].
 
Liver transplantation:
The proportion of adult liver transplantation recipients in the United States older than 60 years of age increased from 10% in 1990 to more than 20% by 1999[78]. Some problems remain to be addressed regarding liver transplantation in elderly patients. Increased age has been associated with a poorer survival rate[79,80], although other studies suggested that advanced age alone should not be a contraindication for liver transplantation[81,82]. Among 2141 patients who underwent retransplantation, more than 10% were over 60 years of age[82]. Being over 60 years of age was not independently associated with an increase in mortality when adjusted for factors that were found to influence survival[82]. Elderly patients may have multiple risk factors, including coronary artery disease or malignancy, and face age-associated quality of life impairments, such as instability, incontinence, immobility, dementia, and polypharmacy[83]. Moreover, aged recipients have a significantly lower quality of life, as assessed by physical functioning, bodily pain, general health, vitality, social functioning, role emotional, and physical component score[84]. Therefore, careful consideration is required in choosing liver transplantation for elderly patients.
 
CONCLUSION
Aged patients show various changes in the liver, which could affect the clinical characteristics of liver diseases in these patients (Table 1). Decreases in functioning of the liver and other organs as well as alterations in immune functions should be taken into consideration in the management of the liver diseases (Figure 1).
 
Table 1
Clinical characteristics of liver diseases in patients
Liver diseasesCharacteristics
Viral hepatitis
Hepatitis AHigher hospitalization and mortality rates
Hepatitis BMore likely to progress to chronic hepatitis or cirrhosis
Hepatitis CMore likely to progress fibrosis
Higher rates of hepatocellular carcinoma development
Decreased tolerability to treatment
Autoimmune diseases
Autoimmune hepatitisSometimes progressive
Primary biliary cirrhosisHigher rates of treatment-related complications
Sometimes progressive
More likely to have osteoporosis
Alcoholic liver diseaseProgressive
Nonalcoholic fatty liver diseaseHigher prevalence
Progressive
Hepatocellular carcinomaHigher rates of development

World J Gastroenterol.2013 December 14; 19(46): 8459-8467.
Published online 2013 December 14. doi: 10.3748/wjg.v19.i46.8459