Editor's note: With the rapid development of modern medical technology, non-invasive assessment methods have attracted more and more attention. In the field of metabolically associated fatty liver disease (MAFLD), liver hardness measurement (LSM) has become an important indicator for non-invasive assessment of liver-related events. At the annual meeting of the European Association for the Study of the Liver (EASL) this year, Dr.Terry Yip of the Chinese University of Hong Kong presented an exciting research result, which explored the prognostic significance of liver hardness measurement in patients with MAFLD through a large-scale international collaborative study. The study provides a new perspective for clinicians and patients, revealing the great potential of non-invasive assessment in the management of liver disease.IH: At this year’s EASL annual conference, you presented a clinical research on MASLD orally. Could you please introduce the main background and purpose of this research?
Dr Yip: Thank you. We presented the results of our study this year in the General Session. Actually, I presented on behalf of the whole group of collaborators from the VCTE (vibration-controlled transient elastography) prognosis study group. This is an international collaboration and we gather information from around 18000 patients with MASLD (metabolic dysfunction-associated steatotic liver disease). They had carried out at least one VCTE examination. From this cohort, we further selected around 10000 patients who had repeated measurements of VCTE. The research aim was to study the change in the liver stiffness measurement by VCTE, and its implications on prognosis in patients with MASLD in terms of hepatic decompensation, liver cancer, liver transplantation and also liver-related death.
IH: In this study, you used vibration-controlled transient elastography (VCTE) to measure liver stiffness. What are the advantages of this method compared to other traditional assessment methods?
Dr Yip: Thank you. Traditionally, we still use liver biopsy as the gold standard to stage liver fibrosis or to diagnose MASH (metabolic dysfunction-associated steatohepatitis) in patients with MASLD. That is what is being used in current clinical trials to assess treatment endpoints, i.e., whether there is improvement in liver fibrosis and also resolution in MASH. But there is emerging data showing that the use of non-invasive tests, including VCTE, are also very good prognostic biomarkers in terms of detecting whether a patient will develop adverse liver outcomes in the future, and more and more data in support of VCTE being used as a monitoring biomarker in future clinical trials. The good thing about using VCTE is that it is non-invasive, unlike liver biopsy, and it is also not subject to sampling errors seen with liver biopsy, because liver biopsy only targets a very small region of the liver, and is also dependent on the pathologist’s interpretation of the liver biopsy slide. VCTE is more readily available in general in different liver clinic settings, and clinicians and even nurses are able to use the device to test the liver stiffness of our patients. So it is easily accessible, and non-invasive. In the future, it will have a role in monitoring our patients beyond the clinical trials.
IH: Based on your study results, what prognostic significance does the change in liver stiffness have in predicting disease progression in MASLD patients? Could you elaborate on this finding?
Dr Yip: Sure. Our major finding from this study is that the change in liver stiffness measurement is prognostic for the future development of liver-related complications. We studied this using two methods. The first method was the change in LSM (liver stiffness measurement) risk category across time. At the first VCTE examination, we classified patients as low risk, intermediate risk or high risk based on an LSM level of <10, 10-15 and >15 kPa. We observed whether the patient remained in the same risk category after the last VCTE. We noticed that 95% of the patients in the low risk category (LSM <10) remained low risk at the last VCTE, but for the intermediate risk patients, the category was pretty dynamic with only 31% remaining in the intermediate risk category. The rest of them either progressed or improved in their liver stiffness category. For the high risk group, about half of the patients remained high risk at the last VCTE, while the other half improved their liver stiffness category. We found this change in the risk category can predict future liver-related outcomes. The second method we used to look at the relative change of LSM was as a continuous variable, rather than a categorical variable. We actually noticed that the change in liver stiffness measurement and the risk of developing liver-related outcomes is non-linear. We identified an area of interest of -30% of change to +30% of change, because we think that the relationship between liver stiffness management change and outcomes is more linear within this area, so it is easier to identify patients as high risk, low risk or intermediate risk. Comparing patients with stable liver stiffness measurements, for those with >30% decrease in liver stiffness measurement, they would have a better outcome – so a low risk for liver-related events. Vice versa for patients with >30% change increase in liver stiffness measurement – they would have a high risk for liver-related outcomes.
IH: How do you think this study specifically impacts or guides the treatment and management of MASLD patients? Has it changed our previous understanding of the disease progression in MASLD?
Dr Yip: Thank you very much for the question. I think for the future, our study can imply that for a patient with MASLD, we can monitor them using serial liver stiffness measurement and observe the change in the liver stiffness measurement over time, and see if they have high risk, for example. If patients start with a lower LSM level, but at follow-up showing a 30% increase in the liver stiffness measurement, we need to be thinking that they are moving toward the high risk end, and that the patient will have a high risk of liver-related complications in the future. In the future, when a treatment is available and accessible, we will have to identify and prioritize the patient to receive treatment. Currently, the first-line treatment is still lifestyle modification. If we can see a trend moving towards higher risk, we can recommend intervention to our patients.
IH: In the future, do you plan to further expand or deepen this study? For example, by considering other potential assessment tools or treatment methods, as well as longer-term follow-up studies?
Dr Yip: Thank you very much. We are now doing an extended follow-up on this cohort, because we know that for MASLD patients, the absolute risk of liver-related outcomes is less frequent than what we see in chronic viral hepatitis or alcohol-related liver disease, so usually we need a longer follow-up to see the development of liver outcomes. We are now actively extending the follow-up hopefully to capture more outcomes to better understand the fate of patients who move from low to high risk. Besides our LSM measurements, we are also studying other biomarkers dependent on LSM, for example, the Agile 3+ and Agile 4 scores. These scores depend on LSM and other commonly used clinical parameters, and with these clinical parameters added to LSM, they can show a slight improvement in predictive power for the future of liver outcomes. In the future, we may also look into the changes in Agile 3+ and Agile 4 to see if the prognostic implications of these changes are also important.
