Clinical laboratories and anatomic pathology groups should prepare for a marked increase in orders for liver disease testing
New research from Virginia Commonwealth University’s Institute for Liver Disease and Metabolic Health in Richmond shows that four out of every 10 Americans has fatty liver disease of some type, according to a news release. Forty percent of Americans is an astonishing number! The study’s findings will almost certainly lead to clinical laboratories performing more testing in support of diagnosis, treatment decision making, and patient monitoring for liver disease than currently ordered by physicians.
Hepatologist Juan Pablo Arab, MD, director of alcohol sciences at Virginia Commonwealth University (VCU), led the team that conducted the research. He noted that the driving force behind the numbers is obesity and type two diabetes.
“By 2018, federal data showed that 42% of adults had some form of fatty liver disease—higher than prior estimates,” Arab’s team told Newsmax, adding that “Hispanic adults were at especially high risk … with nearly half (47%) affected.”
“This study highlights a significant health issue that affects a large portion of the US population, and it shows that certain groups are at a higher risk. We hope these findings will guide more targeted health interventions to reduce the burden of liver disease, especially in high-risk communities,” said Juan Pablo Arab, MD (above), hepatologist with VCU’s Institute for Liver Disease and Metabolic Health, director of alcohol sciences, and lead researcher in the VCU study, in a VCU news release. These insights can be expected to lead to guidelines calling for more clinical laboratory testing associated with the diagnosis of fatty liver disease. (Photo copyright: Virginia Commonwealth University.)
“Groups at greater risk for MASLD include men, adults older than 40, individuals with health insurance, those with higher body mass index, and people with other health issues like diabetes, high blood pressure, high triglycerides, and low levels of good cholesterol. Interestingly, the study found that black individuals had the lowest risk of developing MASLD compared with other groups,” the VCU news release notes.
Fatty liver disease can also be caused by excessive alcohol consumption (called alcohol-associated liver disease or ALD) or a combination of both metabolic dysfunction and moderate-to-high alcohol intake, which is called MetALD, Newsmax reported.
“Although MASLD was the most common type of liver disease found in this study, the researchers also uncovered substantial rates of MetALD and alcohol-associated liver disease. For MetALD, the study showed that men and individuals with a higher BMI [body mass index] were at a greater risk, and Asians were at lower risk. Surprisingly, the only factor that appeared to lower the risk of ALD was having health insurance, though the reasons for this are not clear,” according to the VCU news release.
On its website, Mayo Clinic notes that NAFLD is often symptomless, and that doctors typically depend on routine clinical laboratory blood test results to reach a diagnosis. Additional testing helps determine whether higher than normal liver enzymes are actually from fatty liver disease or some other condition.
Medical laboratories play a key role in facilitating the final diagnoses. According to Mayo Clinic, blood tests to identify liver disease include:
Medical imaging could also be required to reach a diagnosis, beginning with an abdominal ultrasound, Mayo Clinic added. Additionally, more precise tests may be ordered to determine the stiffness of the liver and likelihood of scarring or fibrosis. Those modalities include:
Labs will often perform these tests on the same patient multiple times as the patient’s lifestyle changes. A liver biopsy may also be required to determine severity of damage, Mayo Clinic added.
abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid buildup and swelling of the legs (edema) and abdomen (ascites), and mental confusion,” the ALF added.
As more healthcare providers focus their attention on diagnosing and treating this potentially deadly disease, clinical laboratories and anatomical pathology groups will likely see an uptick in tests ordered by doctors moving from initial diagnoses to more detailed testing and eventually to treatment follow ups.
Though not biomarkers per se, these scores for certain genetic traits may someday be used by clinical laboratories to identify individuals’ risk for specific diseases
Can polygenic risk scores (a number that denotes a person’s genetic predisposition for certain traits) do a better job at predicting the likelihood of developing specific diseases, perhaps even before the onset of symptoms? Researchers at the Broad Institute of MIT and Harvard (Broad Institute) believe so, and their study could have implications for clinical laboratories nationwide.
In cooperation with medical centers across the US, the scientists “optimized 10 polygenic scores for use in clinical research as part of a study on how to implement genetic risk prediction for patients,” according to a Broad Institute news release.
The research team “selected, optimized, and validated the tests for 10 common diseases [selected from a total of 23 conditions], including heart disease, breast cancer, and type 2 diabetes. They also calibrated the tests for use in people with non-European ancestries,” the news release notes.
As these markers for genetic risk become better understood they may work their way into clinical practice. This could mean clinical laboratories will have a role in sequencing patients’ DNA to provide physicians with information about the probability of a patient’s elevated genetic risk for certain conditions.
However, the effectiveness of polygenic risk scores has faced challenges among diverse populations, according to the news release, which also noted a need to appropriately guide clinicians in use of the scores.
“With this work, we’ve taken the first steps toward showing the potential strength and power of these scores across a diverse population,” said Niall Lennon, PhD (above), Chief Scientific Officer of Broad Clinical Labs. “We hope in the future this kind of information can be used in preventive medicine to help people take actions that lower their risk of disease.” Clinical laboratories may eventually be tasked with performing DNA sequencing to determine potential genetic risk for certain diseases. (Photo copyright: Broad Institute.)
Polygenic Scores Need to Reflect Diversity
“There have been a lot of ongoing conversations and debates about polygenic risk scores and their utility and applicability in the clinical setting,” said Niall Lennon, PhD, Chair and Chief Scientific Officer of Broad Clinical Labs and first author of the study, in the news release. However, he added, “It was important that we weren’t giving people results that they couldn’t do anything about.”
In the paper, Lennon and colleagues explained polygenic risk scores “aggregate the effects of many genetic risk variants” to identify a person’s genetic predisposition for a certain disease or phenotype.
“But their development and application to clinical care, particularly among ancestrally diverse individuals, present substantial challenges,” they noted. “Clinical use of polygenic risk scores may ultimately prevent disease or enable its detection at earlier, more treatable stages.”
The scientists set a research goal to “optimize polygenic risk scores for a diversity of people.”
While performing the polygenic risk score testing on participants, Broad Clinical Labs focused on 10 conditions—including cardiometabolic diseases and cancer—selected by the research team based on “polygenic risk score performance, medical actionability, and clinical utility,” the Nature Medicine paper explained.
For each condition, the researchers:
Identified “exact spots in the genome that they would analyze to calculate the risk score.”
Used information from the NIH’s All of Us Research Program to “create a model to calibrate a person’s polygenic risk score according to that individual’s genetic ancestry.”
The All of Us program, which aims to collect health information from one million US residents, has three times more people of non-European ancestry than other data sources developing genetic risk scores, HealthDay News reported.
20% of Study Participants Showed High Risk for Disease
To complete their studies, Broad Institute researchers processed a diverse group of eMERGE participants to determine their clinical polygenic risk scores for each of the 10 diseases between July 2022 and August 2023.
Listed below are all conditions studied, as well as the number of participants involved in each study and the number of people with scores indicating high risk of the disease, according to their published paper:
Over 500 people (about 20%) of the 2,500 participants, had high risk for at least one of the 10 targeted diseases, the study found.
Participants in the study self-reported their race/ancestry as follows, according to the paper:
White: 32.8%
Black: 32.8%
Hispanic: 25.4%
Asian: 5%
American Indian: 1.5%
Middle Eastern: 0.9%
No selection: 0.8%
“We can’t fix all biases in the risk scores, but we can make sure that if a person is in a high-risk group for a disease, they’ll get identified as high risk regardless of what their genetic ancestry is,” Lennon said.
Further Studies, Scoring Implications
With 10 tests in hand, Broad Clinical Labs plans to calculate risk scores for all 25,000 people in the eMERGE network. The researchers also aim to conduct follow-up studies to discover what role polygenic risk scores may play in patients’ overall healthcare.
“Ultimately, the network wants to know what it means for a person to receive information that says they’re at high risk for one of these diseases,” Lennon said.
The researchers’ findings about disease risk are likely also relevant to healthcare systems, which want care teams to make earlier, pre-symptomatic diagnosis to keep patients healthy.
Clinical laboratory leaders may want to follow Broad Clinical Labs’ studies as they perform the 10 genetic tests and capture information about what participants may be willing to do—based on risk scores—to lower their risk for deadly diseases.
Clinical laboratory scientists and microbiologists could play a role in helping doctors explain to patients the potential dangers of do-it-yourself medical treatments
Be careful what you wish for when you perform do-it-yourself (DIY) medical treatments. That’s the lesson learned by a woman who was seeking relief for irritable bowel syndrome (IBS). When college student Daniell Koepke did her own fecal transplant using poop from her brother and her boyfriend as donors her IBS symptoms improved, but she began to experience medical conditions that afflicted both fecal donors.
“It’s possible that the bacteria in the stool can influence inflammation in the recipient’s body, by affecting their metabolism and activating their immune response,” microbial ecologist Jack Gilbert, PhD, Professor and Associate Vice Chancellor at University of California San Diego (UC San Diego) told Business Insider. “This would cause shifts in their hormonal activity, which could promote the bacteria that can cause acne on the skin. We nearly all have this bacterium on skin, but it is often dormant,” he added.
A Fecal Microbiota Transplant (FMT) is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition.
Our guts are home to trillions of microorganisms (aka, microbes), known as the gut microbiota, that serve many important functions in the body. The microbiome is a delicate ecosystem which can be pushed out of balance when advantageous microbes are outnumbered by unfavorable ones. An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes.
“With fecal microbiome transplants there is really compelling evidence, but the science is still developing. We’re still working on if it actually has benefits for wider populations and if the benefit is long-lasting,” said Gilbert in a Netflix documentary titled, “Hack Your Health: The Secrets of Your Gut.”
“The microbial community inside our gut can have surprising influences on different parts of our body,” microbial ecologist Jack Gilbert, PhD (above), of the Gilbert Lab at University of California San Diego told Business Insider. “Stools are screened before clinical FMTs, and anything that could cause major problems, such as certain pathogens, would be detected. When you do this at home, you don’t get that kind of screening.” Doctors and clinical laboratories screening patients for IBS understand the dangers of DIY medical treatments. (Photo copyright: University of California San Diego.)
Changing Poop Donors
When Koepke began experiencing symptoms of IBS including indigestion, stabbing pains from trapped gas and severe constipation, she initially turned to physicians for help.
In the Netflix documentary, Koepke stated that she was being prescribed antibiotics “like candy.” Over the course of five years, she completed six rounds of antibiotics per year, but to no avail.
She also changed her diet, removing foods that were making her symptoms worse. This caused her to lose weight and she eventually reached a point where she could only eat 10 to 15 foods.
“It’s really hard for me to remember what it was like to eat food before it became associated with anxiety and pain and discomfort,” she said.
In an attempt to relieve her IBS symptoms, Koepke made her own homemade fecal transplant pills using donated stool from her brother. After taking them her IBS symptoms subsided and she slowly gained weight. But she developed hormonal acne just like her brother.
Koepke then changed donors, using her boyfriend’s poop to make new fecal transplant pills. After she took the new pills, her acne dissipated but she developed depression, just like her boyfriend.
“Over time, I realized my depression was worse than it’s ever been in my life,” Koepke stated in the documentary.
She believes the microbes that were contributing to her boyfriend’s depression were also transplanted into her via the fecal transplant pills. When she reverted to using her brother’s poop, her depression abated within a week.
Gilbert told Business Insider his research illustrates that people who suffer from depression are lacking certain bacteria in their gut microbiome.
“She may have had the ‘anti-depressant’ bacteria in her gut, but when she swapped her microbiome with his, her anti-depressant bacteria got wiped out,” he said.
FDA Approves FMT Therapy for Certain Conditions
Typically, the fecal material for an FMT procedure performed by a doctor comes from fecal donors who have been rigorously screened for infections and diseases. The donations are mixed with a sterile saline solution and filtered which produces a liquid solution. That solution is then administered to a recipient or frozen for later use.
On November 30, 2022, the US Food and Drug Administration (FDA) approved the first FMT therapy, called Rebyota, for the prevention of Clostridioides difficile (C. diff.) in adults whose symptoms do not respond to antibiotic therapies. Rebyota is a single-dose treatment that is administered rectally into the gut microbiome at a doctor’s office.
Then, in April of 2023, the FDA approved the use of a medicine called Vowst, which is the first oral FMT approved by the FDA.
According to the Cleveland Clinic, scientists are exploring the possibility that fecal transplants may be used as a possible treatment for many health conditions, including:
Doctors and clinical laboratories know that do-it-yourself medicine is typically not a good idea for obvious reasons. Patients seldom appreciate all the implications of the symptoms of an illness, nor do they fully understand the potentially dangerous consequences of self-treatment. Scientists are still researching the benefits of fecal microbiota transplants and hope to discover more uses for this treatment.
Newly-defined Cardiovascular-Kidney-Metabolic Syndrome (CKM) means physicians will be in close collaboration with clinical laboratories to make accurate diagnoses
In a presidential advisory, the AHA defines a newly described systemic health disorder called Cardiovascular-Kidney-Metabolic Syndrome (CKM). The syndrome “is a systemic disorder characterized by pathophysiological interactions among metabolic risk factors, CKD (chronic kidney disease), and the cardiovascular system leading to multi-organ failure and a high rate of adverse cardiovascular outcomes.”
A CKM diagnosis, which is meant to identify patients who are at high risk of dying from heart disease, is based on a combination of risk factors, including:
weight problems,
issues with blood pressure, cholesterol, and/or blood sugar,
reduced kidney function.
CKM is a new term and doctors will be ordering medical laboratory tests associated with diagnosing patients with multiple symptoms to see if they match this diagnosis. Thus, clinical laboratory managers and pathologists will want to follow the adoption/implementation of this new recommendation.
“The advisory addresses the connections among these conditions with a particular focus on identifying people at early stages of CKM syndrome,” said Chiadi Ndumele, MD, PhD (above), Associate Professor of Medicine at Johns Hopkins University and one of the authors of the AHA paper, in a news release. “Screening for kidney and metabolic disease will help us start protective therapies earlier to most effectively prevent heart disease and best manage existing heart disease.” Clinical laboratories will play a key role in those screenings and in diagnosis of the new syndrome. (Photo copyright: Johns Hopkins University.)
Stages of CKM Syndrome
In its presidential advisory, the AHA wrote, “Cardiovascular-Kidney-Metabolic (CKM) syndrome is defined as a health disorder attributable to connections among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD), including heart failure, atrial fibrillation, coronary heart disease, stroke, and peripheral artery disease. CKM syndrome includes those at risk for CVD and those with existing CVD.”
The five stages of CKM syndrome, which the AHA provided to give a framework for patients to work towards regression of the syndrome, are:
Stage 0: No CKM risk factors. Individuals should be screened every three to five years for blood pressure, cholesterol, and blood sugar levels, and for maintaining a healthy body weight.
Stage 1: Excess body fat and/or an unhealthy distribution of body fat, such as abdominal obesity, and/or impaired glucose tolerance or prediabetes. Patients have risk factors such as weight problems or prediabetes and are encouraged to make healthy lifestyle changes and try to lose at least 5% of their body weight.
Stage 2: Metabolic risk factors and kidney disease. Includes people who already have Type 2 diabetes, high blood pressure, high triglyceride levels, and/or kidney disease. Medications that target kidney function, lower blood sugar, and which help with weight loss should be considered at this stage to prevent diseases of the heart and blood vessels or kidney failure.
Stage 3: Early cardiovascular disease without symptoms in people with metabolic risk factors or kidney disease or those at high predicted risk for cardiovascular disease. People show signs of disease in their arteries, or have heart function issues, or may have already had a stroke or heart attack or have kidney or heart failure. Medication may also be needed at this stage.
Stage 4: Symptomatic cardiovascular disease in people with excess body fat, metabolic risk factors or kidney disease. In this stage, people are categorized as with or without having kidney failure. May also have already had a heart attack, stroke or heart failure, or cardiovascular conditions such as peripheral artery disease or atrial fibrillation.
“We now have several therapies that prevent both worsening kidney disease and heart disease,” said Chiadi Ndumele, MD, PhD, Associate Professor of Medicine at Johns Hopkins University and one of the authors of the Circulation paper, in a news release. “The advisory provides guidance for healthcare professionals about how and when to use those therapies, and for the medical community and general public about the best ways to prevent and manage CKM syndrome.”
According to an AHA 2023 Statistical Update, one in three adults in the US have three or more risk factors that contribute to cardiovascular disease, metabolic disorders, or kidney disease. While CKM affects nearly every major organ in the body, it has the biggest impact on the cardiovascular system where it can affect the blood vessels, heart muscle function, the rate of fatty buildup in the arteries, electrical impulses in the heart and more.
“There is a need for fundamental changes in how we educate healthcare professionals and the public, how we organize care and how we reimburse care related to CKM syndrome,” Ndumele noted. “Key partnerships among stakeholders are needed to improve access to therapies, to support new care models, and to make it easier for people from diverse communities and circumstances to live healthier lifestyles and to achieve ideal cardiovascular health.”
New AHA Risk Calculator
In November, the AHA announced PREVENT (Predicting risk of cardiovascular disease EVENTs), a tool that doctors can use to assess a person’s risk for heart attack, stroke, and heart failure. The new risk calculator, which incorporates CKM, allows physicians to evaluate younger people as well, and examine their long-term risks for cardiovascular issues.
Doctors can use PREVENT to assess people ages 30 to 79 and predict risk for heart attack, stroke, or heart failure over 10 to 30 years.
“Longer-term estimates are important because short-term or 10-year risk in most young adults is still going to be low. We wanted to think more broadly and apply a life-course perspective,” Khan said. “Providing information on 30-year risk may reveal earlier opportunities for intervention and prevention efforts in younger people.”
According to CDC data, about 695,000 people died of heart disease in the US in 2021. That equates to one in every five deaths. Clinical pathologists will need to understand the AHA recommendations and how doctors will be ordering clinical laboratory tests to determine if a patient has CKM. Then, labs will play a role in helping doctors monitor patients to optimize health and prevent acute episodes that put patients in the hospital.
Clinical laboratory leaders will want to pay close attention to a significant development in Maryland. The state’s All-Payer Medicare program—the nation’s only all-payer hospital rate regulation system—is broadening in scope to include outpatient services starting Jan. 1. The expanded program could impact independent medical laboratories, according to the Maryland Hospital Association (MHA), which told Dark Daily that those labs may see hospitals reaching out to them.
The Centers for Medicare and Medicaid Services (CMS) and the state of Maryland expect to save $1 billion by 2023 in expanding Maryland’s existing All-Payer Model—which focused only on inpatient services since 2014—to also include primary care physicians, skilled nursing facilities, independent clinical laboratories, and more non-hospital settings, according to a CMS statement.
Healthcare Finance notes that it represents “the first time, CMS is holding a state fully at risk for the total cost of care for Medicare beneficiaries.”
Value of Precision Medicine and Coordination of Care to Clinical Labs
“If a patient receives care at a [medical] laboratory outside of a hospital, Maryland hospitals would be looking at ways to coordinate the sharing of that freestanding laboratory information, so that the hospital can coordinate the care of that patient both within and outside the hospital setting,” Erin Cunningham, Communications Manager at MHA, told Dark Daily. Such a coordinating of efforts and sharing of clinical laboratory patient data should help promote precision medicine goals for patients engaged with physicians throughout Maryland’s healthcare networks.
The test of the new program—called the Total Cost of Care (TCOC) Model—also could be an indication that Medicare officials are intent on moving both inpatient and outpatient healthcare providers away from reimbursements based on fees-for-services.
CMS and the state of Maryland said TCOC gives diverse providers incentives to coordinate, center on patients, and save Medicare per capita costs of care each year.
“What they are really doing is tracking how effective we are at managing the quality and the costs of those particular patients that are managed by the physicians and the hospitals together,” Kevin Kelbly, VP and Chief Financial Officer at Carroll Hospital in Westminster, told the Carroll County Times. “They will have set up certain parameters. If we hit those parameters, there could be a shared savings opportunity between the hospitals and the providers,” he added. (Photo copyright: LifeBridge Health.)
The TCOC runs from 2019 through 2023, when it may be extended by officials for an additional five years.
How Does it Work?
The TCOC Model, like the earlier All-Payer Model, will limit Medicare’s costs in Maryland through a per capita, population-based payment, Healthcare Finance explained.
It includes three programs, including the:
Maryland Primary Care Program (MDPCP), designed to incentivize physician practices by giving additional per beneficiary, per month CMS payments, and incentives for physicians to reduce the number of patients hospitalize;
Care Redesign Program (CRP), which is a way for hospitals to make incentive payments to their partners in care. In essence, rewards may be given to providers that work efficiently with the hospital to improve quality of services; and,
Hospital Payment Program, a population-based payment model that reimburses Maryland hospitals annually for hospital services. CMS provides financial incentives to hospitals that succeed in value-based care and reducing unnecessary hospitalizations and readmissions.
CMS and Maryland officials also identified these six high-priority areas for population health improvement:
Substance-use disorder;
Diabetes;
Hypertension;
Obesity;
Smoking; and
Asthma.
“We are going to save about a billion dollars over the next five years, but we are also providing better quality healthcare. So it’s going to affect real people in Maryland, and it helps us keep the whole healthcare system from collapsing, quite frankly,” Maryland Gov. Larry Hogan, told the Carroll County Times.
OneCare in Vermont, Different Approach to One Payer
Maryland is not the only state to try an all-payer model. Vermont’s OneCare is a statewide accountable care organization (ACO) model involving the state’s largest payers: Medicare, Medicaid, and Blue Cross and Blue Shield of Vermont, Healthcare Dive pointed out. The program aims to increase the number of patients under risk-based contracting and, simultaneously, encourage providers to meet population health goals, a Commonwealth Fund report noted.
Both Maryland’s and Vermont’s efforts indicate that payment plans which include value-based incentives are no longer just theory. In some markets, fees-for-service payment models may be gone for good.
Clinical laboratory leaders may want to touch base with their colleagues in Maryland and Vermont to learn how labs in those states are engaging providers and performing under payment programs that, if successful, could replace existing Medicare payment models in other states.
