New software tool enables early detection of liver fibrosis

Steatotic liver disease often develops by stealth and worsens without obvious signs, potentially developing into fibrosis or cirrhosis. But now there is hope: a simple software tool that uses a standard blood test to predict liver fibrosis. Using common laboratory results, this tool can detect risks early so that action can be taken rapidly and reduce unnecessary examinations. This breakthrough could change steatotic liver disease treatment and make the screening process easier and more accessible to many people.

“Steatotic liver disease is a hidden health threat because it rarely causes symptoms before the damage is severe,” explains first author of the study Katrine Prier Lindvig, Postdoctoral Fellow, Clinical Research Assistant, Research Unit of Medical Gastroenterology, Department of Medical Gastrointestinal Diseases, Odense University Hospital, Denmark. “Many people are not aware that steatotic liver disease can develop without drinking alcohol, and it is often only discovered when there are life-threatening complications. Our tool can use simple blood tests to determine a person’s risk of liver fibrosis, thereby enabling us to intervene in time and perhaps avoid severe complications such as cirrhosis or liver failure – without resorting to expensive tests or specialists.”

LiverPRO is a new tool that detects liver fibrosis early by analysing standard blood tests along with the patient’s age. This will help general practitioners to identify people without symptoms who may have a higher risk of liver fibrosis or other complications.

“LiverPRO helps us to detect liver fibrosis early,” explains Aleksander Krag, Professor and Senior Physician in Hepatology at Odense University Hospital. “By combining standard blood tests with advanced calculations and models, LiverPRO can identify people who might otherwise be overlooked. This is an effective way to improve early diagnosis and ensure timely treatment.”

Finding the rust before it spreads

Steatotic liver disease often develops without obvious signs or symptoms. Over time, alcohol consumption, obesity and diabetes can damage the liver and ultimately result in fibrosis – scar tissue that can be dangerous if not detected in time.

“Detecting warning signs early is therefore crucial,” says Aleksander Krag.

Fibrosis is like rust that slowly destroys a ship. If detected early, before it spreads, people can be helped with advice on drinking less alcohol, eating healthier or seeking healthcare.

“All doctors can use LiverPRO – not just specialists. This makes detecting early signs of liver fibrosis easier with regular blood tests. The aim is to make screening easier and less expensive,” explains Aleksander Krag.

The problem is that many people do not even know that steatotic liver disease has other causes than alcohol. “This is particularly challenging for us,” says Katrine Prier Lindvig. “Many people think that steatotic liver disease is only caused by alcohol. But it can also result from overweight. We still have much to elucidate.”

Patients are often surprised when they find out that their steatotic liver disease is not necessarily caused by alcohol. “They say: ‘I don't drink.’ But you can get steatotic liver disease without having drunk a drop of alcohol,” explains Katrine Prier Lindvig. “Unfortunately, there is still a gap in understanding among both patients and healthcare personnel. Many doctors did not learn about this at medical school.”

The essence of LiverPRO

One problem is that steatotic liver disease rarely causes symptoms.

“In contrast to heart failure, in which people become short of breath, or lung diseases, in which breathing is difficult, people cannot feel steatotic liver disease. The liver has no nerves, so the damage is often discovered too late. There needs to be some sort of prompt for people to seek help,” says Katrine Prier Lindvig.

Discovering steatotic liver disease too late can have serious consequences. “Three fourths of the patients we diagnose with liver fibrosis or cirrhosis already have severe complications,” notes Katrine Prier Lindvig. “They have been living with steatotic liver disease for years, maybe decades, without knowing it. And they only come to us when it is life-threatening. As a hepatologist, it is frustrating to see people in this condition in which we can only try to limit the damage and help them in the short remaining life they often have.”

Tools that more easily detect liver fibrosis early are urgently needed since many current tests require advanced equipment or are too expensive for general practitioners to use.

“What we want is a test that is directly compatible with the blood tests general practitioners already order,” says Aleksander Krag. “Focusing on the tests doctors already use can make detection less expensive and easier. The aim is to ensure that fewer people fall through the system and that we start focusing on prevention rather than only reacting when the damage has occurred. This is the essence of LiverPRO.”

Who should be referred?

The researchers recruited people from various clinics and hospitals. All had high risk of developing alcoholic steatotic liver disease because of heavy alcohol consumption or metabolic dysfuction–associated steatotic liver disease because of conditions such as diabetes and obesity. The participants had a blood test and underwent elastography scanning, which measures liver stiffness (and thereby fibrosis) without being invasive.

“We used the data from standard blood tests to detect signs of fibrosis, which is scarring of the liver,” explains Katrine Prier Lindvig.

The project considered that clinics have access to different types of data. The researchers therefore created a method that could adapt and use available data.

“LiverPRO is a new tool that general practitioners can use to determine who should be referred for further tests at a hospital,” says Katrine Prier Lindvig.

The available tools were not suitable for steatotic liver disease

Both Katrine Prier Lindvig and Aleksander Krag are co-founders of Evido Health, a company that works to translate health research into practical solutions for patients and the healthcare system. Katrine Prier Lindvig is currently Chief Scientific Officer, and Aleksander Krag is a member of the Board of Directors.

“The aim of the new study was to make the test as realistic as possible. It therefore included people with definite symptoms and people with only weak or no symptoms. We used standard results from blood tests such as liver enzymes and platelets to develop an algorithm. We focused on being able to use the tool everywhere, even if a clinic does not have special equipment,” explains Aleksander Krag.

“The validation of LiverPRO showed that the algorithm can reliably predict the risk of liver fibrosis,” says Katrine Prier Lindvig.

The algorithm of LiverPRO was developed to use the data present in general practice, since the current tools are often not suitable to detect the steatotic liver disease that is prevalent today.

Katrine Prier Lindvig adds: “In the 1980s and 1990s, we mostly focused on viral hepatitis. Although we have made great progress, especially in hepatitis C treatment, the current tools are not adequate to deal with steatotic liver disease caused by, for example, alcohol or obesity.”

Clear message with just a few clicks

The researchers developed software that can process incomplete data and still accurately assess the risk of fibrosis. They tested its accuracy by comparing its predictions with the results from elastography scanning.

“Our data showed patterns that could have detected disease earlier. The key to LiverPRO is improving the use of simple blood tests,” explains Katrine Prier Lindvig.

“The most challenging aspect has been making LiverPRO precise but still simple to use,” says Aleksander Krag. “A laboratory analyses the blood samples as usual, and the software automatically receives the results and calculates the risk of fibrosis. With a few clicks, the doctor gets a clear indication of whether the patient needs further examinations.”

The new study has now thoroughly tested LiverPRO to ensure that it is reliable and can be used with minimal effort. “The aim is to give doctors a tool that, with just a few clicks, gives them clear information about whether a patient should undergo more specialised examinations of the liver,” explains Aleksander Krag.

Identifying the people who need help early

LiverPRO was very accurate in diagnosing people with severe liver fibrosis. Among the 462 participants in the first test, LiverPRO detected with high confidence those with clinically significant liver fibrosis.

“In addition,” says Aleksander Krag, “people with high scores had a greater risk of severe liver fibrosis and could then get the necessary monitoring and help from specialists.”

Overall, LiverPRO avoids false positives while identifying those at high risk.

“Finding the right balance is important,” explains Aleksander Krag. “We aimed to create a tool that could reassure those who are not at high risk and find those who need extra follow-up. When we tested it on a larger group of 6,468 people, it was still very accurate.”

Smarter and more effective treatment

The researchers emphasise that LiverPRO can avoid many unnecessary examinations because it very accurately excludes people with low risk. Only a few people assessed as low risk developed serious problems later. This means that LiverPRO can help doctors to focus their attention on those who really need help.

“By following these patients over time, we found that LiverPRO really worked,” says Aleksander Krag. “Those with high scores more often developed serious liver fibrosis, and most of those with low scores remained healthy. This information helps doctors to decide who needs monitoring and who can avoid unnecessary examinations.”

Can LiverPRO work in areas with few resources and without specialised laboratories? Will it be as accurate for people with other risk factors such as heart disease or autoimmune disorders?

“Future studies can examine how LiverPRO works across age groups and ethnic backgrounds. We also see potential in adapting it to automated systems that can alert doctors immediately if the data shows worrying signs of liver damage,” says Katrine Prier Lindvig.

LiverPRO is now CE-certified, which means that it meets the European Union’s high requirements for safety, quality and function. This gives the green light for using LiverPRO widely in health systems in the European Union and beyond, enabling doctors in hospitals and general practitioners to use it and integrate it into their daily routines.

“This is reminiscent of care pathways for cancer and screening programmes for various diseases. The goal is to find the patients who need help before the acute symptoms appear,” explains Katrine Prier Lindvig.

Avoiding unnecessary examinations

The research must be transferred to general practice to enable early detection. LiverPRO is based on standard blood tests and uses advanced technology such as machine learning to identify patterns that can help diagnose early. Aleksander Krag emphasises that testing LiverPRO in controlled studies differs from making it work in daily practice.

“I think that it can be integrated into routine blood tests, but we must ensure that it really makes a difference for both patients and doctors,” he says.

The researchers think that LiverPRO could help change how doctors detect steatotic liver disease and treat the people who have it.

“Many patients already have blood samples taken, but we often diagnose them too late,” explains Katrine Prier Lindvig.

With LiverPRO, patients with low risk scores can avoid unnecessary examinations, and those with high scores can be rapidly referred to specialist treatment or receive lifestyle advice.

“Our goal is to make LiverPRO available in general practice in Denmark and possibly other European countries and thus reduce the number of people with advanced steatotic liver disease, deaths and hospitalisations,” concludes Katrine Prier Lindvig. “We are also striving to get it approved in the United States.”