Prof Jacob George discusses the shifting trends in liver fibrosis etiology and the new innovations in fibrosis detection

Interview transcript:

What is the current liver disease landscape in APAC?

So firstly, we know that the largest burden of liver disease across the world is in the APAC or the Asia Pacific region. We know that traditionally the APAC region had a high proportion of patients with viral hepatitis, and while the numbers have decreased, they are still an enormous burden in APAC.

However, the etiology of liver diseases, the main four liver diseases have significantly changed. One of the consequences of our current modern western lifestyle with overnutrition and lack of physical activity, is that the incidence and the prevalence of fatty liver disease, which I like to call metabolic associated fatty liver disease or MAFLD, has increased. And even in patients with viral hepatitis, whether it be hepatitis B or C, the concomitant association of fatty liver disease in these patients has increased. And the last group of patients is with alcohol-related liver disease. And across our region, we are seeing an increasing burden of alcohol-related liver disease in combination with MAFLD or fatty liver disease. So the epidemiology has changed and probably the commonest liver disease in APAC now is MAFLD or fatty liver disease, followed by various combinations of alcohol, hepatitis C or hepatitis B with fatty liver disease occurring concomitantly.

We know that the major clinical manifestation of end stage liver disease occurs in patients with advanced liver fibrosis or cirrhosis. These are the patients that die from liver cancer or liver failure. But the very interesting thing about liver disease as opposed to for example myocardial infarction or heart attacks, is that when you get cardiac disease, you develop symptoms. Liver disease is very asymptomatic until you have the development of cirrhosis, liver failure or liver cancer. So we’ve got this silent disease in our community affecting about 1 in 3 individuals. And we really need to be able to identify these individuals because for many of these diseases we have got good effective treatments. We can cure hepatitis C, we can control hepatitis B virus replication, we can reduce the risk of liver cancer, and even for fatty liver disease, there are treatments on the horizon and lifestyle intervention and treating the target of cardiovascular risk factors can be very, very beneficial for these patients.

So case finding becomes very, very critical in this large group of asymptomatic patients. And we need now to focus on biomarkers and biomarker algorithms to case find and diagnose disease starting from primary care but also in specialist care. When I talk about specialist care, I’m talking about the non-liver community, endocrinologists, cardiovascular physicians, kidney physicians. And we need to identify those patients with advanced fibrosis using some of the biomarkers in algorithms so that the hepatologist or the gastroenterologist can give them appropriate care so that we can detect liver cancer early and we can either treat or prevent liver failure before it occurs.

What are the current gaps in the diagnosis of liver fibrosis? What are some up-and-coming innovations for liver fibrosis detection?

Diagnosing liver fibrosis, the fundamental problem is the patient is asymptomatic, so you need to be able to use some sort of test to be able to diagnose it. The traditional tests that we all use are liver function tests: an AST, an ALT, but they’re very, very insensitive and not even very specific. And indeed you can have cirrhosis or even require a liver transplant with a normal AST and ALT. So we need to be able to look for tests or algorithms that diagnose fibrosis in an asymptomatic individual.

And over the last 3 to 4 years, there’s been a consilience of opinion and there’ve been guidelines from across the world, including from APAC, talking about algorithms to diagnose these patients. And the most simple algorithm is the FIB-4 test, which basically uses elements of the AST, ALT, and platelet count in an individual to calculate a score that predicts and stratifies patients according to the risk of fibrosis. There is also imaging-based techniques such as FibroScan and various transient elastography techniques. And there are new emerging biomarkers and biomarker combinations, such as the ADAPT score which is based on PRO-C3, that we developed a few years ago that has the potential, in combination, when used appropriately by appropriately educated individuals, to stratify patients and refer patients appropriately for therapy in specialist care.

How might the adoption of new diagnostic tools into clinical practice across healthcare systems be accelerated?

So I think for some of the simple tools such as the FIB-4 or elastography techniques, we have quite a lot of data, but we really need to do several things.

At the patient level, we need to be able to talk to patients. We need to increase awareness of two simple facts: that we do have liver disease treatments and that liver disease is asymptomatic. So the message really is we’ve got good treatments, please get your liver health assessed. That’s what we need to do for patients.

For the care groups, including the medical profession and allied health groups, we need to be able to have appropriate use and cascading use of these tests, so that it’s in a cost-effective manner; we need to be able to identify these patients.

But the other aspect that needs to happen is we need to work at a policy level, at government level, again to emphasize the importance of being able to diagnose asymptomatic disease and risk stratify individuals so that we can take care of them earlier, link them to appropriate care. So we need policy decisions at the big picture level from government, and we also need to interact with hospital and pathology systems to implement some of these algorithm-based tests. What we need to do is we need to be talking to the pathologists that run the machines, but we also need at the backend to link it to the IT services, and then integrating all that information from a pathology test, to IT development, to putting it into the electronic health records.

So a lot of work from patient level, to health professional level, to pathology laboratories, to policy has to happen. But I think we’ve now got a very good set of tests that are available. What we need now is to actually begin to implement. So we need to implement to improve patient outcomes.

What recommendations do you have for other APAC clinicians who are looking to improve their fibrosis detection and diagnosis strategy?

I think the simple message that I would give is we should be talking about liver health and we should be encouraging this concept of assessing liver health in all our patients. 70% of the world’s population today dies of cardiometabolic diseases, non-communicable diseases and liver disease is one of them. So just as you manage diabetes, chronic kidney disease, cardiac disease, we should be screening and stratifying patients for their liver disease. And many of these are very simple tests that can be easily ordered and we can also easily stratify these patients. And based on the risk stratification, patients should be appropriately referred for care.

The views and opinions expressed by Prof. Jacob George are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.