Dear Editor,
We read with great interest the article by Rabbat et al. [
1], recently published in
Clinical and Molecular Hepatology. This multicenter investigation, which included 12,950 patients, offers a systematic analysis of the clinical relevance of discordant results between the Fibrosis-4 index (FIB-4) and vibration-controlled transient elastography (VCTE) derived liver stiffness measurement (LSM) in metabolic dysfunction-associated steatotic liver disease (MASLD). The authors’ work provides substantive evidence that advances the field, and we commend their contribution.
The study timely addresses a common dilemma in clinical practice regarding inconsistent results from non-invasive assessment tools. Its key findings indicate that approximately 30% of MASLD patients in tertiary care centers exhibit discordance between FIB-4 and LSM. Moreover, in cases of discordance, LSM demonstrates superior performance over FIB-4 in predicting histological severity (e.g., 30.6% had F3–F4 fibrosis in the low-FIB-4–high-LSM group) and long-term liver-related events (LREs). This finding provides crucial empirical support for the currently recommended two-step pathway of ‘FIB-4 first, then LSM for indeterminate cases’ outlined in international guidelines [
2-
4]. Particularly noteworthy is the observation that even among patients with discordant results, the absolute incidence of LREs remains relatively low (e.g., 2.58 per 1,000 person-years in the low-FIB-4–high-LSM group). This helps alleviate excessive clinical anxiety about missing patients with progressive liver disease and, overall, affirms the robustness of the current pathway in terms of risk control and cost-effectiveness.
However, the findings also raise several questions warranting in-depth discussion to further optimize clinical management. First, the discordance itself exhibits significant population heterogeneity. The study found that obesity (body mass index [BMI]≥30 kg/m
2) may attenuate the predictive ability of LSM in discordant cases, suggesting potentially complex underlying mechanisms [
1]. Beyond the known potential impact of obesity on VCTE accuracy [
5], these may include the influence of acute or chronic inflammation on aminotransferase levels, non-hepatic causes of thrombocytopenia, and metabolic phenotypic differences across populations, such as between European/United States and Asian centers [
1]. Future research integrating additional biomarkers and imaging features would help elucidate the biological basis of this discordance, enabling more precise subgroup risk stratification.
Second, the generalizability of the study results and their applicability in primary care settings require careful consideration. The study cohort was derived from tertiary centers, where the patient disease spectrum is more severe compared to primary care or community populations [
1]. Consequently, the reported rate of discordance and the corresponding risk of LREs might be higher than those observed in the general community-based MASLD population. A recent prospective validation study conducted in a primary care cohort of patients with type 2 diabetes revealed a discrepancy between the proportion of patients identified for referral based on guideline pathways and the proportion with confirmed significant fibrosis [
6]. This strongly suggests that management strategies derived from tertiary center data require rigorous external validation and potential risk calibration before being extrapolated to primary care. For individuals identified as low-FIB-4–high-LSM through community screening, the optimal management strategy, whether immediate referral, short-term reassessment, or intensified metabolic management alone, may need to be redefined based on actual local epidemiological data.
Furthermore, from a dynamic risk assessment perspective, the study’s median follow-up of 47.4 months provides valuable intermediate-term prognostic information [
1]. However, MASLD is a chronic progressive disease. Existing evidence indicates that repeated FIB-4 measurements can more effectively identify the risk of disease progression [
7]. Therefore, for patients with discordant results, especially those with low-FIB-4-high–LSM, management should not be relaxed based solely on a single-test low-risk label. A more reasonable strategy would be to incorporate them into a dynamic monitoring pathway, involving regular reassessment of both FIB-4 and LSM to observe trends. This approach likely holds greater clinical management value than focusing solely on a single discordant result.
Looking ahead, we recommend that subsequent research prioritize the validation of these findings in large, community‑based or primary‑care cohorts and explore the development of setting‑adjusted LSM thresholds or integrated risk scores appropriate for lower‑prevalence environments [
8]. Furthermore, to resolve clinical uncertainty in discordant cases, the cost‑effectiveness of incorporating a third‑line non‑invasive tool, such as magnetic resonance elastography or a serum‑based biomarker panel (e.g., the enhanced liver fibrosis test or steatosis-associated fibrosis estimator score), warrants evaluation [
9]. Ultimately, the integration of serial clinical data and artificial intelligence‑enhanced imaging analytics into dynamic risk‑prediction models will be pivotal in shifting from a static, cutoff‑dependent framework toward truly personalized, risk‑continuum-based management.
In summary, the study by Rabbat et al.1 represents a landmark contribution that solidifies the central role of LSM in the non‑invasive assessment of MASLD and provides a robust evidence base for navigating discordant test results. It reframes discordance not as a mere diagnostic quandary but as a nuanced clinical scenario demanding tailored interpretation and proactive management. The path forward lies in translating these specialist‑derived insights into adaptable, efficient, and personalized risk‑management strategies that are effective across diverse healthcare settings, thereby improving care for the global MASLD population.
FOOTNOTES
-
Authors’ contribution
Deliang Huang and Jun Chen drafted the manuscript; all authors reviewed and approved the final version.
-
Conflicts of Interest
The authors declare no competing interests.
Abbreviations
liver stiffness measurement
metabolic dysfunction-associated steatotic liver disease
vibration-controlled transient elastography
REFERENCES
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Citations
Citations to this article as recorded by
- Correspondence to letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”
Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(3): e419. CrossRef
