Researchers Develop Blood Test to Predict Liver Cancer Risk

An estimated one-quarter of adults in the U.S. have nonalcoholic fatty liver disease (NAFLD), an excess of fat in liver cells that can cause chronic inflammation and liver damage, increasing the risk of liver cancer. Now, UT Southwestern researchers have developed a simple blood test to predict which NAFLD patients are most likely to develop liver cancer.

“This test lets us noninvasively identify who should be followed most closely with regular ultrasounds to screen for liver cancer,” said Yujin Hoshida, M.D. Ph.D., Associate Professor of Internal Medicine in the Division of Digestive and Liver Diseases at UTSW, a member of the Harold C. Simmons Comprehensive Cancer Center, and senior author of the paper published in Science Translational Medicine.

NAFLD is rapidly emerging as a major cause of chronic liver disease in the United States. With rising rates of obesity and diabetes, its incidence is expected to keep growing. Studies have found that people with NAFLD have up to a seventeenfold increased risk of liver cancer. For NAFLD patients believed to be most at risk of cancer, doctors recommend a demanding screening program involving a liver ultrasound every six months. But pinpointing which patients are in this group is challenging and has typically involved invasive biopsies.

Naoto Fujiwara, M.D., Ph.D., Research Scientist in the Hoshida lab, and his colleagues wondered whether blood samples from NAFLD patients could reveal those at highest risk of hepatocellular carcinoma (HCC), the most common form of liver cancer. In the new study, they analyzed samples from 409 NAFLD patients to reveal a set of 133 genes that were expressed at levels higher or lower than average in the livers of patients who developed HCC over a 15-year follow-up period. The patients were then stratified into high- and low-risk groups based on how much these genes were expressed. Over 15 years after the samples were taken, 22.7% of those in the high-risk group were diagnosed with HCC while no patients in the low-risk group were diagnosed.

“This test was especially good at telling us who was in that low-risk group,” said Dr. Hoshida, who directs UTSW’s Liver Tumor Translational Research Program. “We can much more confidently say now that those patients don’t need to be followed very closely.”

The researchers also converted the liver gene panel into four proteins whose levels could be measured in blood samples for easier risk assessment. When patients were stratified into high- and low-risk groups based on these proteins, 37.6% of patients in the high-risk group were diagnosed with HCC during the 15-year follow-up period while no patients in the low-risk group were diagnosed.

Most of the genes and proteins found to be predictive of HCC risk were immune and inflammatory molecules, which points toward the importance of inflammation in HCC development. Moreover, the researchers showed that levels of the molecules changed in conjunction with therapies known to decrease liver inflammation and HCC risk, including bariatric surgery, cholesterol drugs, and an immunotherapy.

“This means we could actually use these panels of molecules to track how well patients are doing over time or to inform potential effectiveness of medical interventions to reduce liver cancer risk,” said Dr. Hoshida. For instance, the protein blood test, dubbed PLSec-NAFLD, is already being used to monitor the effectiveness of a cholesterol drug in reducing liver cancer risk in an ongoing clinical trial.

Dr. Hoshida’s team is planning to continue assessing the utility of PLSec-NAFLD in larger groups of patients around the world. They also say that in the future, blood tests could be developed to measure cancer risk in other major liver diseases such as hepatitis B and alcoholic liver disease.

Source: UT Southwestern

New Blood Test Can Help Doctors Diagnose Tuberculosis and Monitor Treatment

Lance Sumler wrote . . . . . . . . .

Researchers at Tulane University School of Medicine have developed a new highly sensitive blood test for tuberculosis (TB) that screens for DNA fragments of the Mycobacterium tuberculosis bacteria that causes the deadly disease.

The test could give doctors a new tool to both quickly identify TB and then gauge whether drug treatments are effective by monitoring levels of DNA from the pathogen circulating through the bloodstream, according to a new study published in the journal The Lancet Microbe.

Tuberculosis is now the second most deadly infectious disease in the world, behind only COVID-19. In 2020, an estimated 10 million people contracted TB and 1.5 million people died from it, according to the World Health Organization.

Most TB tests rely on screening sputum, a thick type of mucus from the lungs. But collecting sputum from patients suspected of having TB can be difficult, especially for children. TB can also be harder to diagnose in immunocompromised HIV patients and others where the infection migrates outside of the lungs into other areas of the body. In these extrapulmonary cases, patients can have little bacteria in the sputum, which leads to false negatives using current testing methods, said lead study author Tony Hu, PhD, Weatherhead Presidential Chair in Biotechnology Innovation at Tulane University.

“This assay may be a game-changer for TB diagnoses that not only provides accurate diagnosis results but also has the potential to predict disease progression and monitor treatment,” Hu said. “This will help doctors rapidly intervene in treatment and reduce the risk of death, especially for children living with HIV.”

The study evaluated a CRISPR-based assay that screened for cell-free DNA from live Mycobacterium tuberculosis bacilli. The screening target is released into the bloodstream and cleared quite rapidly, providing a real-time snapshot of active infection.

Researchers tested preserved blood samples from 73 adults and children with presumptive TB and their asymptomatic household contacts in Eswatini, Africa.

The test identified adult TB with 96.4% sensitivity and 94.1% specificity and pediatric TB with 83.3% sensitivity and 95.5% specificity. (Sensitivity refers to how well a test can diagnose a positive case, while specificity is a measure of a test’s accurately determining a negative case.)

Researchers also tested 153 blood samples from a cohort of hospitalized children in Kenya. These were HIV-positive patients who were at high risk for TB and presented with at least one symptom of the disease. The new test picked up all 13 confirmed TB cases and almost 85% of unconfirmed cases, which were cases that were diagnosed due to clinical symptoms and not existing gold standard testing methods.

The CRISPR-based test uses a small blood sample and can deliver results within two hours.

“We are particularly excited that the level of Mycobacterium tuberculosis cell-free DNA in HIV-infected children began to decline within a month of treatment, and most of the children’s blood was cleared of the bacteria DNA fragments after treatment, which means that CRISPR-TB has the potential to monitor treatment and will give physicians the ability to better treat worldwide TB infections,” Hu said.

The researchers have since adapted the assay to a rapid test platform that can deliver results in 30 minutes without any special equipment. Results would be viewable on a paper strip like a rapid COVID-19 test.

“A highly accurate, rapid blood test that could be used anywhere would benefit millions of people living in resource-limited areas with a high TB burden,” Hu said.

Source: Tulane University

Epidemiologists Develop State-of-the-Art Tool for Measuring Pace of Aging

Researchers at Columbia University Mailman School of Public Health have developed a blood test to measure the pace of biological aging. Based on an analysis of chemical tags on the DNA contained in white blood cells called DNA methylation marks, the new test is named DunedinPACE, after the Dunedin Birth Cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome) is a new addition to a fast-growing list of DNA methylation tests designed to measure aging and contributes value-added over and above the current state of the art. The findings are published online in the journal e-Life.

“What makes DunedinPACE unique is that, whereas other tests aim to measure how old or young a person is, DunedinPACE measures whether you are aging quickly or slowly,” said Daniel Belsky, PhD, assistant professor of epidemiology at Columbia Mailman School and a researcher at the Columbia Aging Center. This design could make DunedinPACE a more sensitive tool to detect the effects of interventions that aim to slow aging or of exposures that accelerate aging processes.

“Whereas other measures of aging are designed to capture all aging-related change accumulated across the life course, our measure is focused on changes occurring over the recent past,” explained Belsky. “What is striking is that, even with this more restricted focus, DunedinPACE is equally precise as the best of the currently available tests in predicting disease, disability, and mortality in the future, and it adds value to risk assessments over and above these measures.”

Developed by Belsky and colleagues at Duke University and the University of Otago, DunedinPACE tracks changes in 19 biomarkers of organ-system integrity in the 1000-member Dunedin Study birth cohort, who were first enrolled in the study at birth in 1972-1973 and have been followed up ever since, most recently at the time of their 45th birthday. This study used data collected from the participants when they were all aged 26, 32, 38, and 45 years.

The use of a single-year birth cohort to develop the measure ensures DunedinPACE is not contaminated by biases that may affect studies that compare older to younger people, including survival bias and historical differences in exposure. The analysis of changes that occurred within study members’ bodies as they aged over the 20-year follow-up also ensured that DunedinPACE measures aging-related changes occurring during adult life.

In addition to the Dunedin Study, the researchers also used data from the Understanding Society Study, the Normative Aging Study, the Framingham Heart Study, and the Environmental Risk (E- Risk) Longitudinal Twin Study.

In the current analysis, midlife and older adults with faster DunedinPACE were at increased risk for incident chronic disease, disability, and mortality; across the lifespan, DunedinPACE was correlated with measures of biological age derived from blood chemistry and DNA methylation data, and with research participants’ subjective perceptions of their own health. It also indicated a faster Pace of Aging (how fast a person’s body is declining) in young adults with histories of exposure to poverty and victimization.

“In sum, DunedinPACE represents a novel measure of aging that can complement existing DNA methylation measures of aging to help advance the frontiers of geroscience,” noted Belsky, who is also with the Robert N. Butler Columbia Aging Center, Columbia Mailman School.

The current analysis establishes DunedinPACE as a novel single-time-point measure that quantifies Pace of Aging with whole blood samples, that can be readily implemented in most DNA methylation datasets, making it immediately available for testing in a wide range of existing datasets as a complement to existing methylation measures of aging.

“There is growing interest in technologies to measure biological age, defined as how much older or younger a person is biologically than their birthdate would predict. Our study reveals that it is also possible to measure Pace of Aging, or how fast a person’s body is declining. Together, these measurements can help us understand the factors that drive accelerated aging in at-risk populations and identify interventions that can slow aging to build aging health equity.”

Source: University of Columbia

Scientists Develop Simple Blood Test for Early Detection of Alzheimer’s Disease

An international research team led by HKUST has developed a simple but robust blood test from Chinese patient data for early detection and screening of Alzheimer’s disease (AD) for the first time, with an accuracy level of over 96%.

Now, a team led by Prof. Nancy IP, Vice-President for Research and Development at HKUST, has identified 19 out of the 429 plasma proteins associated with AD to form a biomarker panel representative of an “AD signature” in the blood. Based on this panel, the team has developed a scoring system that distinguishes AD patients from healthy people with more than 96% accuracy. This system can also differentiate among the early, intermediate, and late stages of AD, and can be used to monitor the progression of the disease over time. These exciting findings have led to the development of a high-performance, blood-based test for AD, and may also pave the way to novel therapeutic treatments for the disease.

“With the advancement of ultrasensitive blood-based protein detection technology, we have developed a simple, noninvasive, and accurate diagnostic solution for AD, which will greatly facilitate population-scale screening and staging of the disease,” said Prof. Nancy Ip, Morningside Professor of Life Science and the Director of the State Key Laboratory of Molecular Neuroscience at HKUST.

The work was conducted in collaboration with researchers at University College London and clinicians in local hospitals including the Prince of Wales Hospital and Queen Elizabeth Hospital. The discovery was made using the proximity extension assay (PEA) – a cutting-edge ultrasensitive and high-throughput protein measurement technology, to examine the levels of over 1,000 proteins in the plasma of AD patients in Hong Kong.

As the most comprehensive study of blood proteins in AD patients to date, the work has recently been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, and has also been featured and actively discussed on different scholarly exchange platforms on AD research such as Alzforum.

AD, which affects over 50 million people worldwide, involves the dysfunction and loss of brain cells. Its symptoms include progressive memory loss as well as impaired movement, reasoning, and judgment. While patients often only seek medical attention and are diagnosed when they have memory problems, AD affects the brain at least 10-20 years before symptoms appear.

Source : The Hong Kong University of Science and Technology

New Blood Test Shows Great Promise in the Diagnosis of Alzheimer’s Disease

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer’s disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer’s Association International Conference.

For many years, the diagnosis of Alzheimer’s has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer’s research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles—corresponding to the diagnosis of Alzheimer’s—in living people.

“The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s,” said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. “While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting.”

Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute’s Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer’s disease (ADAD)-causing mutation carriers and non-carriers from the world’s largest ADAD cohort.

  • In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of “intermediate or high likelihood Alzheimer’s” (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of “high likelihood Alzheimer’s” with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.
  • In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer’s and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.
  • In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer’s disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer’s) and several other studied blood tests.

Other study leaders include Jeffrey Dage, PhD, from Eli Lilly and Company, who developed the p-tau217 assay, co-first authors Sebastian Palmqvist, MD, PhD, and Shorena Janelidz, PhD, from Lund University, and Eric Reiman, MD, Banner Alzheimer’s Institute, who organized the analysis of Arizona and Colombian cohort data.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer’s. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer’s. It has the potential to advance the disease’s research and care in other important ways.

“Blood tests like p-tau217 have the potential to revolutionize Alzheimer’s research, treatment and prevention trials, and clinical care,” said Eric Reiman, MD, Executive Director of Banner Alzheimer’s Institute in Phoenix and a senior author on the study. “While there’s more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years.”

Alzheimer’s is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

Source: Lund University