Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging as a critical global health challenge due to its increasing prevalence and associated clinical burden [
1]. Despite its high prevalence, only a subset of patients progress to advanced complications such as cirrhosis and hepatocellular carcinoma (HCC), underscoring the importance of effective risk stratification to identify at-risk individuals early while minimizing strain on healthcare systems [
2].
A recent study by Lee and colleagues provided compelling evidence supporting a two-step risk stratification approach using the Fibrosis-4 (FIB-4) index followed by liver stiffness measurement (LSM) [
3]. Their findings, derived from a large MASLD cohort with a median follow-up of 4 years, demonstrate that this sequential strategy is both practical and effective in determining which MASLD patients warrant referral to tertiary care.
There are four key insights from this study. Firstly, this study reaffirms that the risk of LREs correlates strongly with fibrosis severity, even when assessed using non-invasive tools such as Agile 3+, Agile 4+, FAST, or LSM [
4]. Notably, FAST exhibited the lowest predictive accuracy, consistent with prior research [
5,
6]. Furthermore, replacing LSM with Agile scores does not significantly enhance LRE prediction, highlighting the robustness of the Korean Association for the Study of the Liver (KASL) pathway when applying LSM after FIB-4.
Secondly, among patients diagnosed via non-invasive test (NIT), the overall risk of LRE was low (~1.1%), aligning with prior studies using NIT [
4,
5,
7]. This contrasts with higher LRE rates observed in biopsy-derived MASLD cohorts, likely reflecting preferential selection of MASLD patients with more advanced disease. Such nuances are critical for interpreting absolute LRE risk in MASLD populations [
3,
8].
Thirdly, since age is a component of FIB-4, older patients often present with higher scores, potentially overestimating their risk of LRE. The KASL pathway addresses this by incorporating age-adjusted thresholds (>2.0 in those over 56 years). A recent study suggests the use of high FIB-4 (>2.67) alone may overestimate the risk of LRE in older patients [
9]. Further clarification on the risk of LRE among elderly patients with FIB-4>2.67 would provide insights into whether a 2nd step NIT needs to be considered before considering them as high-risk [
9].
The question of how to best monitor low-risk MASLD patients in primary care settings remained unclear. Patients initially classified as low-risk but transitioned to an intermediate or high-risk category within three years demonstrated a significantly elevated HCC risk (low risk: 0.05 per 1,000 person-year; intermediate risk: 0.21 per 1,000 person-year; high-risk: 0.76 per 1,000 person-year) [
10]. Additionally, changes in FIB-4 correlated with LSM trends [
11], suggesting that FIB-4 could serve as a practical monitoring tool in primary care settings where LSM may not be readily available. In settings where LSM is available, serial LSMs may help to refine the LRE risk in MASLD patients [
12,
13].
To conclude, the current work by Lee and colleagues provides validation of 2-step risk stratification for MASLD patients. It is expected that the KASL algorithm can reduce unnecessary referrals [
3,
14,
15]. Future studies evaluating the cost-effectiveness and healthcare utilization of this approach will further encourage the hepatology community to adopt as part of our routine clinical practice.
FOOTNOTES
-
Authors’ contribution
Study conception: YJW; Manuscript draft: YJW; Critical review of the manuscript and final review: All authors.
-
Acknowledgements
WYJ received funding support from SingHealth Duke-NUS Academic Medical Center (03/FY2020/P2/14-A87) and Changi General Hospital, Singapore (RIG202409-016PI).
-
Conflicts of Interest
WYJ received funding support from SingHealth Duke-NUS Academic Medical Center (03/FY2020/P2/14-A87) and Changi General Hospital, Singapore (RIG202409-016PI), VLC was supported in part by NIH/NIDDK K08 DK132312.
Abbreviations
Korean Association for the Study of the Liver
liver stiffness measurement
metabolic dysfunction-associated steatotic liver disease
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Citations
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- Correspondence to letter to the editor on “Risk Stratification of Metabolic Dysfunction-Associated Steatotic Liver Disease: The KASL Pathway
Hye Won Lee, Seung Up Kim
Clinical and Molecular Hepatology.2025;[Epub] CrossRef
