Editor’s Note: The 33rd Annual Meeting of the Asian Pacific Association for the Study of the Liver (APASL 2024) was held in Kyoto, Japan from March 27 to 31, 2024. Metabolic-associated fatty liver disease (MAFLD) was one of the hot topics in the congress. MAFLD has become a common chronic liver disease worldwide and is caused by metabolic dysfunction. MAFLD is the main reason for the surge in the incidence of liver cirrhosis, liver failure, and liver cancer. In recent years, the incidence of MAFLD has been rising due to changes in lifestyles with high calorie, energy-dense diets and lack of exercise. During the conference, Dr. Jacob George from Westmead Hospital, University of Sydney, Australia, and Dr. Xiaolong Qi, founder of CHESS and Zhongda Hospital, School of Medicine, Southeast University, China, had in-depth exchanges and discussions on the prevalence trends, diagnosis and treatment progress, and comprehensive management of MAFLD. Hepatology Digest hereby reports.

01 Current prevalence and future trends of MAFLD in the Asia-Pacific region

Dr. Xiaolong Qi: Hi, doctor Jacob George. I think that we are very happy to have an interview with you today. Thank you because MAFLD is a really hot topic, not only in the world, but also is one of the major topics of this APASL meeting. So, my first question about that in recent years, is that Metabolic-associated fatty liver disease has attracted more and more attention from a clinical, scientific and research perspective in the field of liver disease. Could you introduce the prevalence and development trends of MAFLD in the Asia-pacific region?

Dr. Jacob George: Thank you very much. Doctor Xiaolong Qi. As you know, the rising prevalence of MAFLD is related to two things – increasing trends all over the world in the prevalence of overweight and obesity. And it is very important to understand that the number or figure that we use to define overweight and obesity is completely different in Asia-Pacific and people compared to that of the western world. So, Asians develop fatty liver disease at a much lower body weight than someone from the western world, say from a European background. The other big epidemic that we have in the Asia-Pacific and the world over is that of type 2 diabetes.

The studies actually suggest that the Asia-Pacific will be the epicenter for fatty liver disease worldwide. The biggest burden of fatty liver disease or MAFLD is going to be in mainland China. The other big country that is going to have a high prevalence is India. There was a paper published suggesting that the prevalence of fatty liver disease in adults is about one in three people. But the study published last week from India suggests that one in two people already have MAFLD in India. I suspect that with each passing year, if you do more surveys, up to 50% of people will have fatty liver disease. We know that the incidence of type 2 diabetes is increasing and because overweight and obesity are also increasing, we are going to have a large disease burden, I suspect. In 10 years, all our clinics will be full of patients with fatty liver disease.

02 Core measures for preventing and controlling MAFLD in the Asia-Pacific region

Dr. Xiaolong Qi: Thank you. And you mentioned high prevalence of MAFLD and some high risk patients like those with T2DM. So based on the existing management methods of MAFLD and practice experience in your country or by your team, what do you think about the core measures for preventing and controlling methods in various countries, in the Asia-Pacific region?

Dr. Jacob George: We’ve known about diabetes and its association with weight. Since the 1940s, and despite 80 years of development in the west, they haven’t been able to control it. And the problem is that in Asia-Pacific, the prevalence of overweight and T2DM is rising. How can we control it? Theoretically, it’s very easy: do exercise, sleep well, eat a healthy diet and maintain a healthy weight. But unfortunately, fewer and fewer people are actually doing physical work. We are all sitting the whole day, not doing any exercise. We are eating fast food. We don’t have playgrounds. Because of all this and the energy dense foods we eat, our weight is slowly creeping up and diabetes is slowly creeping up.

I think if you really want to tackle it, it needs government policy initiatives. And that involves everything from planning cities to planning for playgrounds, making sure that schools have physical activity as one of the things you do at school. I think at the higher grades, you need to teach people about nutrition. I believe that in every university and school, you need to talk about nutrition. What does it mean to be eating healthy? So, it needs policy level action. We can all give lectures and talks, but it needs to become a way of life for our patients

Dr. Xiaolong Qi: So, lifestyle control sounds easiest way, but actually it’s a very, very difficult.

Dr. Jacob George: Absolutely. Changing people’s lifestyle requires a lot of motivation to start. But then you have to persist with it. And you have to try and keep doing it till it becomes part of your life. And that’s difficult. That’s where policy can really help.

03 What is the progress of drug therapy for MAFLD?

Dr. Xiaolong Qi: Yes. And I am very glad we heard good news recently in the field of drug treatment, in addition to lifestyle. Resmetirom has been approved by the US FDA, all the Chinese social media was boosted by this news is it becomes the first MASH drug to be launched. So, could you talk about your opinion on this drug for its clinical and scientific impact?

Dr. Jacob George: The first point to actually note is that Resmetirom was approved by the FDA on march 14. When you read the label, it says in conjunction with diet and exercise. So don’t forget that the drug has to be used in combination with diet and exercise. What they have suggested is that it is useful for patients with quite advanced liver disease (stage 2 and 3 fibrosis). Because the idea is that you want to change the clinical outcome for these patients.

We normally stage the amount of liver damage by saying fibrosis level 0, 1, 2, 3, while 4 is end stage disease or cirrhosis. This drug is approved for F2 and F3 in conjunction with lifestyle and exercise. And what the studies have shown is that it does improve inflammation in the liver. When you get obese or when you have diabetes, you get metabolic inflammation. The inflammation causes scarring. And what this drug does is it reduces inflammation, and also reduces the scarring. So, it benefits the liver.

Resmetirom is an exciting new drug. But for me, even more exciting is that this drug is a proof of concept that you can develop drugs for the liver that works. We have several drugs in the pipeline that over the next 2 to 3 years will come online for the treatment of this condition.

04 What role do the leading academic institutions such as APASL play?

Dr. Xiaolong Qi: As you mentioned, the government is very important and lifestyle looks like still the basic instrument. In addition to the drug, we can get better outcomes. But definitely the government is very important as are leading academic institutions like yours and many good institutions in China. How do you think APASL or very high-level institutions can play a role in promoting the prevention and control of MAFLD and reducing the burden of this disease?

Dr. Jacob George: I think one of the differences with MAFLD compared to other liver diseases is that until the very late stage, people have no symptoms. This is completely different from, say, if you have lung disease, you can’t breathe, or you have heart disease, you get chest pain, and you go to your doctor. MAFLD is a completely silent disease. I think peak organizations like APASL for the Asia-Pacific, the Chinese society of hepatology, the Chinese society of gastroenterology, and other national societies, have a lot of work to do.

The big part is that we need to think about the continuum. There are patients, there are doctors, and then there are treatments. For patients, we need to be increase awareness that this disease is asymptomatic. We can check for the disease, so come and get tested for MAFLD, see how bad it is. Lifestyle intervention is important. Since there is some drug therapy on the horizon, increasing patient awareness becomes important.

The next thing we, as physicians have to do, is really emphasize the importance of lifestyle, diet and exercise. I think there’s been a lot of talk about reducing weight. Now, weight loss is actually very difficult to do but exercise, everyone can do. The main exercise I do is just walking. You don’t need to go and run and exhaust yourself. You just do brisk walking. The quality of the diet is also important. So increasing awareness of the disease getting tested for the disease, talking about lifestyle intervention, and finding a physician with an interest in MAFLD is important.

I think allied health also has a very important role to play. We are talking about physiotherapists, exercise, physiologist, dietitians. It has got to be a team approach to tackle this disease on all fronts

05 How is the application progress of non-invasive assessment methods?

Dr. Xiaolong Qi: We know there is a high prevalence of MAFLD and we have a potential drug. The next question is, who are the candidates for treatment? So we need non-invasive measurement to identify the patients. What’s your opinion about the non-invasive tests?

Dr. Jacob George: As I said before, in one of the earlier questions, at least one in three, maybe one in two people have fatty liver disease or MAFLD. In the clinical trials, everyone was required to have a liver biopsy.

The problem with liver biopsy is that you cannot do it on half the population. It’s not feasible to do it, and it’s got risks. It is also expensive. So, we need to be able to diagnose how bad the liver is based on non-invasive tests. If we had a perfect test that we could use everywhere, including in primary care, secondary care and tertiary care, it would be a blood test. We’ve got blood tests that are simple to do, but they do not pick up every single person with significant disease, and they’re not 100% accurate. However non-invasive tests such as the FIB-4 calculation does exist. And then we can measure the stiffness of the liver. So as the liver gets damaged and scarred, it becomes very, very stiff. We’ve got a simple machine in the west that is called a FibroScan that measures liver stiffness. I think in China, it’s called the iLivTouch that does the same thing.

So, between non-invasive tests that are currently available and liver stiffness measurements, we can identify a large number of people with significant disease. We talk about this as a two-step approach that will be able to diagnose how bad the MAFLD is and determine if you can be managed just with lifestyle intervention or should you be referred to tertiary care or a specialist with an interest in drug therapy for MAFLD.

06 Who needs to be focused on with MAFLD?

Dr. Xiaolong Qi: The last question, so actually, we mentioned a lot about the government’s role in the whole picture about MAFLD. In China, for example, the government put a lot of money and human resources to control type 2 diabetes in primary care, but MAFLD or any other liver disease, not yet. I’m not sure in your country or in other situations, what’s your opinion about the future? How to get government to play a role?

Dr. Jacob George: China is not unique. There was a study that I was involved in looking at MAFLD preparedness of about 194 countries. Basically, everyone scored poorly, so the awareness among government and policy makers, not only China, but everywhere is low about MAFLD.

We need advocates. You can think of various types of advocates. Patients can be advocates for themselves and talk to government or their local member or member of parliament and can say, I’ve got fatty liver disease. Why don’t you invest or develop some policy around MAFLD? Then senior academic clinicians who are well respected, become important. They can funnel their views through organizations like the Chinese society of hepatology, or Chinese gastroenterology society to government. The last group are public health physicians.

When you think about it in China, there’s very good monitoring, excellent monitoring for hepatitis B and hepatitis C and you’ve got very, very good statistics, showing your vaccination rates, your cure rates for hepatitis C and B etc. All those people are already aware of liver disease, and these people should be able to make the case to government on MAFLD: These are the numbers with fatty liver disease in China. If you do not something about it now, we are going to have the same burden of cirrhosis and liver cancer that we are seeing with hepatitis, B and C. So I think if all of these people individually, but also collectively advocate for MAFLD control, then you can succeed. It is not going to happen overnight. Advocacy can take a few years, but when governments decide to shift, it’s a big shift, and suddenly they will have a plan. When that happens, we all need to be prepared.

Dr. Xiaolong Qi: So, we can see more and more evidence about the co management of diabetes. I remember, like 1 month ago in the BMJ cohort from Korea, it showed people with MAFLD had high incidence of liver cancer and outcome was poor. In the CHESS group, what we do in the past 2 years, just as you mentioned, we try to talk with government and powerful persons. We should pay more attention to MAFLD because it’s a huge burden. They don’t have enough money and resources so that is difficult. So, what we do is to help to co-manage people who have diabetes, because before they only care about the other complications of diabetes.

But now we try to promote liver fat and liver stiffness in our patients in endocrinology, and in primary care. We try to make it the first step to make the government know this is a huge disease burden. And you can successfully manage a specific population like the diabetes population first. And then we will spread to other high- risk patients with MAFLD.

Dr. Jacob George: I think that is really the appropriate strategy, they are the patients that are at highest risk of adverse outcomes. Those are the ones you want to identify first and treat first. And there is lots of data to show that in the MAFLD group, the type 2 diabetics are the highest risk. Interestingly, the group after the type 2 diabetics that are at the highest risk is actually the lean MAFLD group: people who are thin, but have fatty liver disease and two metabolic risk factors.

So, there are several studies now that look at risk of outcomes in the various groups of MAFLD. Type 2 diabetes is the first one, and it’s fantastic that you actually have a planned approach to that group. The next risk group is the group with lean fatty liver disease with two metabolic risk factors. So, that would be another group that you need to manage in the second step. And then there is going to be the overweight and obese group that you have to tackle. So, the problem keeps getting bigger. But I think you have to start somewhere. And what you have done is the right place to start.

Dr. Xiaolong Qi: Thank you so much. I think it’s just a short interview:  Doctor Jacob George gave us a whole picture about the prevalence, about the non-invasive tests for diagnosis, and about treatment for MAFLD. The most important thing we need to do is to work together to treat and manage MAFLD. Thank you very much for this interview.

Dr. Jacob George: Thank you very much.