Hi Manuel! You’re on your way to the European Parliament today to contribute to a panel about the GripOnMash project and the importance of liver screening. Tell us a little bit about what GripOnMash is doing?
GripOnMash is an IHI project that aims to improve liver screening by 1) developing AI-based tools to better identify those at high risk of MASH; and 2) developing new imaging, biomarkers and organ-on-chip technologies for diagnosing MASH in the early stages. [Not sure what MASH and MASLD are? Check out our definitions box at the end of the page].
GripOnMash is currently running screening programmes for liver disease across ten countries. What does that screening look like?
We’ve identified high risk populations, for instance people with diabetes and obesity, where the prevalence of MASH and MASLD is the highest. We still don’t know what exactly the prevalences of MASH and MASLD are in the real-world in Europe. Those data are lacking, there’s a lot of data on US and Asian populations but the European data are unknown.
The screening programme is focused on identifying these high-risk people, followed by a non-invasive test, which is a blood-based test, followed by an imaging test. The imaging test is like an ultrasound and determines the fat content in the liver as well as the inflammation and scarring of the liver. Thanks to those technologies we end up with quite a nice picture of how healthy the liver is. That helps us to identify the very high risk people who are more likely to have MASLD or MASH and based on that information we can proceed with further, more sophisticated and invasive tests to establish the diagnosis. All of that together will provide more information on the prevalence, the severity and hopefully in the future better treatments for patients.
Not everyone who has MASLD will develop MASH. Will the screening also be able to determine that?
Yes, the most important risk factor for developing MASH is MASLD or the presence of excess fat in the liver . Determining the level of scarring of the liver will help to identify people at risk of MASH and eventually more advanced liver disease. Having excess fat in the liver is a very prevalent condition worldwide, 30% of the world’s population have it. So although the risk of developing MASH is not very high, the total numbers of people with excess liver fat are huge, so eventually we will have a problem. The most recent calculations are that at least 30% of the world population has excess liver fat. If only 1% of those develop MASH, the total number of patients with this serious condition will be impossible to handle.
The liver is a very flexible organ so if you have excess fat in the liver, it’s not so difficult to improve your liver condition. The liver can recover, but people have to be aware and change their lifestyle. Raising awareness in the population is very important and policymakers can help us to do that. Also new drugs are becoming available that specifically reduce liver fat and liver scarring, thereby improving liver health.
When you do the screening, do you also have an age profile you screen for?
We are screening the population between 18 and 70 years, but we know that fatty liver in children is also becoming a big problem. Children are becoming overweight and obese and that stimulates the accumulation of fat in the liver. In the US there are already children being diagnosed with MASH.
How many people will you screen overall?
Each country will include 1000 patients. It’s huge, it represents a lot of work, a lot of organisation, incredible amounts of money. We have an important partner within the screening study in our consortium, EchoSens, that makes a FibroScan device (an ultrasound-based imaging test) that measures the excess fat in the liver and the scarring of the liver (known as fibrosis of the liver). Excess fat in the liver leads to scarring which is scary because that increases your risk for cirrhosis, liver failure and liver cancer. In addition, increased liver fat also raises your risk for cardiovascular problems like heart attack, heart failure and stroke.
Having excess fat in the liver is not that bad in the short term, because it is also reversible, but when it progresses to inflammation and scarring you have a problem. The good thing is that the early phases of that process are reversible, so you can improve your liver condition.
Do you encounter any particular challenges when encouraging people to get screened?
When we speak to patients and ask them to participate in this study, we explain to them the importance and what they may gain. They are usually very interested and most of my patients are very happy to participate. People want to know about their health and how they can change things. If they have excess fat in the liver and we tell them how to change their lifestyle, then within a short period of time the liver condition improves. It’s wonderful that we can see that and communicate it to our patients.
As a patient, this is empowering. You have your health situation in your own hands, and you can really change things, because lifestyle remains the basis of liver improvement.
How is GripOnMash progressing overall?
It’s progressing well. We will screen until the beginning of 2027 and we have 4000 people already enrolled in the programme. Everyone is working very hard, all the logistics are in place. It’s a nice consortium with very nice people so it’s great fun working with them.
Why is it important for projects to come to the European Parliament and engage with policy makers?
We believe that the policy makers can help us to spread awareness about the need for liver screening among patients, among clinicians and among healthcare professionals. MASH and MASLD are very prevalent conditions related to many disorders and causing a lot of harm to patients and there is just not enough awareness. It’s very important to invest in more research and better understand this disorder.
When you’re talking to policymakers, are you trying to promote the widespread roll-out of screening programmes?
My dream would be to increase awareness but also to include MASLD screening in regular care – for example, in cardiovascular risk assessment. We know that excess fat in the liver is a risk factor for cardiovascular disease which is not included and overseen in guidelines.
Clinicians look at hypertension, cholesterol, obesity, glucose but they don’t look at the liver and excess fat in the liver doubles your cardiovascular risk. If you have diabetes, you have a very high risk of developing a heart attack, but if you have diabetes and excess fat in the liver your risk is four times higher.
Are there any lessons learned from your interactions with policymakers so far that would help somebody else who is doing this research in the future?
We haven’t had that much contact yet, this is the beginning! We have spoken to insurance companies, to boards of directors of hospitals who are very much involved in this study and are aware of the problem. We have talked to GPs and included primary care practitioners in our programme. We are very happy that ELPA and the European Parliament organised this day and that we were able to speak to the policymakers.
Definitions box
MASLD and MASH
Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD) affects more than 30% of people worldwide, and that number is rising. It is estimated to cost healthcare systems worldwide over €35 billion per year in direct costs, and further societal costs of €200 billion.
In one out of ten cases of MASLD, the liver cells become increasingly damaged and inflamed. Fibrosis and scarring can start to happen. At this point, the diagnosis shifts to MASH (metabolic dysfunction-associated steatohepatitis). People with MASH may start to experience symptoms like fatigue or a mild ache in the area of the liver. But because these symptoms may not appear, or may be caused by something else that is happening in the body, it is still quite difficult to diagnose MASH.
In a person with MASH, as the amount of scarring in the liver increases, the liver becomes cirrhotic and there is an increased risk of liver failure or liver cancer. Once the liver starts to fail, people may experience abdominal swelling and bruising easily, yellow discolouration in the skin and eyes (jaundice) or confusion (hepatic encephalopathy) This is the stage of advanced damage and loss of liver function, and, often the only treatment option is a liver transplant.
However, having MASLD does not necessarily mean that it will develop to MASH. If MASLD is detected early enough, lifestyle changes can be implemented which slow or halt the progression to MASH.