Scientists develop new test to help identify people at risk for developing liver cancer

Scientists have developed a new test that can help identify people who are likely to develop hepatocellular carcinoma (HCC), the most common form of liver cancer. The approach uses a simple blood test to check for the patient's previous exposure to certain viruses.

A study of the new approach was led by researchers at the National Cancer Institute (NCI), part of theNational Institutes of Health. The study also involved researchers from the National Institute of Diabetes and Digestive and Kidney Diseases and several academic centers. The findings were published June 10 in Cell.

Together with existing screening tests, the new test could play an important role in screening people who are at risk for developing HCC. It could help doctors find and treat HCC early. The method is relatively simple and inexpensive, and it only requires a small blood sample.

Xin Wei Wang, Ph.D., study's leader, co-leader of the NCI Center for Cancer Research (CCR) Liver Cancer Program

Certain factors increase a person's chances of developing HCC, such as infection with hepatitis B or hepatitis C virus or cirrhosis of the liver. People who have risk factors are recommended to get screened for HCC every six months with an ultrasound with or without a blood test for alpha-fetoprotein.

But not everyone with risk factors for HCC will develop the disease. Although screening can lead to earlier detection, most patients are diagnosed when the cancer is advanced and often incurable. However, HCC that is caught early has a much better chance of being cured.

"We need a better way to identify people who have the highest risk for HCC and who should get screened more frequently," said Dr. Wang, who is also part of NCI's Translational Liver Cancer Consortium. Better early detection and surveillance approaches are particularly important because rates of HCC are rising in the United States.

"A main focus of the NCI CCR Liver Cancer Program is to develop new methods for early detection, diagnosis, and treatment, with the goal of improving outcomes for patients with HCC," said Tim Greten, M.D., co-leader of the Liver Cancer Program and a collaborator of the study.

Many screening tests detect features of cancer cells. But those features can change over time, and not all cancer cells in a tumor have the same characteristics. The NCI team took a different approach: detecting features of the cancer's environment rather than cancer cells themselves.

More research is providing evidence that cancer development is influenced by interactions between viruses and the immune system. The team reasoned that certain interactions between viruses and the immune system may raise the risk of developing HCC.

To explore that possibility, the scientists scanned people's blood for "footprints" left behind by past viral infections. Because these footprints are left in antibodies, proteins made by the immune system, they also reflect how the immune system reacted to the infection. The mixture of footprints each person has creates a unique pattern, which the researchers called a viral exposure signature.

The team checked for the footprints of more than 1,000 different viruses in blood samples from around 900 people, including 150 who had HCC. They identified a specific viral exposure signature that could accurately distinguish people with HCC from people with chronic liver disease and healthy volunteers. This signature contained footprints from 61 different viruses.

The researchers then tested the signature on blood samples from 173 people with chronic liver disease who were part of a 20-year study. During that time, 44 of the participants developed HCC. Using blood samples taken when the cancer was diagnosed, the signature correctly identified those who developed HCC (area under the curve, AUC=0.98). Importantly, the signature also worked when the researchers used blood samples taken at the beginning of the study, up to 10 years before diagnosis (AUC=0.91).

The signature appeared to be far more accurate than an alpha-fetoprotein test (AUC=0.91 vs. 0.62). An AUC of 0.5 indicates that a test is no better than chance in identifying disease, whereas an AUC of 1.0 represents a test with perfect accuracy.

The scientists are continuing to study their approach and plan to test it in clinical trials. They are collaborating with Katherine McGlynn, Ph.D., of NCI's Division of Cancer Epidemiology and Genetics to test the approach in a prospective surveillance study of people with risk factors for HCC.

It's possible that viral infections--even ones that don't cause cancer--may change the immune system in ways that influence the development of other cancers. For example, certain infections may lessen the immune system's ability to keep cancer cells in check. NCI scientists are testing the viral exposure signature in a study of prostate cancer, and others are considering applying the approach to a screening study for ovarian, esophageal, liver, and breast cancer in Africa.

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How does diet influencediabetes risk?

The kind of food one eats and even the order in which it is consumed can affect the risk of developing type 2 diabetes. 

In a study of 2,717 young adults in the U.S. with long-term follow-up, people who increased the amount of fruits, vegetables, whole grains, nuts and vegetable oils in their diet over 20 years had a 60% lower risk of type 2 diabetes compared to those with a small decrease in plant foods. The findings suggested that long-term shifts towards a more plant-centered diet could help prevent diabetes.

Other findings suggested that people with higher intake of vitamins B 2 and B 6 from food or supplements have a lower risk for type 2 diabetes. The study, which included more than 200,000 people, also revealed that consuming higher levels of vitamin B 12 from foods was associated with a higher type 2 diabetes risk, which may be due to the consumption of animal products.

According to another study changing the order in which food is eaten could reduce post-meal blood sugar spikes.

The researchers found that eating rice first and then a vegetable and meat caused significantly higher blood sugar levels after eating compared to other sequences.

The results point to a simple but effective way to lower blood sugar levels after eating, which could prevent the transition from pre-diabetes to diabetes.

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MRI brain scans can predict MRI dementia risk before symptoms appear

MRI brain scans can help predict whether a person will develop dementia in the next three years, before the symptoms of the disorder appear, scientists have found. In a study, researchers  used magnetic resonance imaging (MRI) brain scans to predict dementia with 89 per cent accuracy.
 
The findings suggest that doctors may one day be able to use widely available tests to tell people their risk of developing dementia before symptoms arise.

"Right now it's hard to say whether an older person with normal cognition or mild cognitive impairment is likely to develop dementia," said  an assistant professor.

"We showed that a single MRI scan can predict dementia on average 2.6 years before memory loss is clinically detectable, which could help doctors advise and care for their patients," said the Prof.

Although there are no drugs available yet to prevent or delay the onset of Alzheimer's disease, identifying those at high risk of developing dementia within the next few years could still be beneficial, the researchers said. People could make decisions on their financial and living arrangements while they are still in full control of their faculties.

Researchers analysed MRI scans for physical signs of impending cognitive decline. They used a technique called diffusion tensor imaging to assess the health of the brain's white matter, which encompasses the cables that enable different parts of the brain to talk to one another.

"Diffusion tensor imaging is a way of measuring the movement of water molecules along white matter tracts," the Prof. said.

"If water molecules are not moving normally it suggests underlying damage to white tracts that can underlie problems with cognition," he said.

Using information from the Alzheimer's Disease Neuroimaging Initiative -- a multisite collaboration that pools data, funding and expertise to improve clinical trials for Alzheimer's disease -- researchers identified 10 people whose cognitive skills declined over a two-year period and matched them by age and sex with 10 people whose thinking skills held steady.

The average age of people in both groups was 73. Then, the researchers analysed diffusion tensor MRI scans taken just before the two-year period for all 20 people. The researchers found that people who went on to experience cognitive decline had significantly more signs of damage to their white matter.

The researchers repeated their analysis in a separate sample of 61 people, using a more refined measure of white matter integrity. With this new analysis, they were able to predict cognitive decline with 89 per cent accuracy when looking at the whole brain. When the researchers focused on specific parts of the brain most likely to show damage, the accuracy rose to 95 per cent.

"We could tell that the individuals who went on to develop dementia have these differences on diffusion MRI, compared with scans of cognitively normal people whose memory and thinking skills remained intact,"the Prof. said. 

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