Dear Editor,
We read with great interest the article by Yoon et al. [
1], which presents a rigorous and well-structured economic evaluation addressing the clinically and public health-relevant question of the minimum efficacy thresholds at which novel hypothetical therapies for metabolic dysfunction-associated steatotic liver disease (MASLD) may be regarded as cost-effective.
Beyond cardiovascular disease (CVD), the multifaceted health implications of MASLD are increasingly recognized across the life course [
2,
3]. In particular, emerging evidence highlights a strong association between MASLD and kidney damage (KD) [
2] since childhood, particularly in the context of obesity [
3,
4].
Given that KD may progress to chronic kidney disease (CKD) [
5], its coexistence with MASLD may further amplify cardiometabolic risk [
2,
6], leading to increased morbidity and mortality [
2,
5], as well as substantial additional healthcare costs related to CKD management [
5,
7,
8]. This issue is particularly relevant in light of the close interrelationship between CKD, CVD, and metabolic complications, such diabetes [
2,
6], which often coexist and synergistically exacerbate both clinical outcomes and economic burden [
5,
7,
8]. Notably, MASLD represents a substantial yet underprioritized contributor to the global burden of noncommunicable diseases [
9], underscoring the need to consider its systemic complications and long-term implications for healthcare systems [
7-
9].
Given the rising prevalence of MASLD, the broad spectrum of its systemic complications [
2,
9], and the currently limited pharmacological options [
10], the identification of cost-effective therapeutic strategies is increasingly urgent [
11].
While the modeling framework proposed by the authors is commendable, its robustness and real-world applicability could be further strengthened by considering a broader spectrum of MASLD-related comorbidities. In particular, KD warrants careful consideration, as its rising prevalence [
5]-even among pediatric populations [
3,
4]- underscores the importance of integrating kidney involvement into evaluations of long-term outcomes and cost-effectiveness. Accounting for renal comorbidity would more accurately reflect the complex metabolic network in which MASLD is embedded [
6] and improve projections relevant to clinical practice and healthcare planning.
As acknowledged by the authors, the proposed model represents a simplified analytical framework, capturing only selected risks of MASLD and CVD, with the exclusion of multiple metabolic comorbidities intended to avoid compromising statistical robustness [
1].
However, we believe that CKD represents a critical exception to this principle. CKD is intrinsically intertwined with the pathophysiological progression and economic burden of MASLD [
2,
5], and its omission risks systematically underestimating both clinical outcomes and long-term disease-related healthcare costs. From a real-world evidence perspective, CKD should be regarded not as a marginal comorbidity, but as a key determinant of disease trajectory and resource utilization [
5,
6].
From a health economic perspective, integrating CKD-related outcomes into the modeling framework would likely lower the minimum hepatic efficacy required for a MASLD therapy to be considered cost-effective. By capturing potential renal benefits, such as reduced CKD incidence or slower progression, the therapy would yield additional quality-adjusted life-year gains and long-term cost savings associated with renal care, improving the incremental cost-effectiveness ratio compared with estimates in the original model.
Moreover, pediatric evidence underscores the cumulative and lifelong trajectory of KD associated with metabolic dysfunction, with onset early in life and significant implications for long-term healthcare utilization and costs [
5,
11]. This life-course perspective highlights how renal complications may progressively amplify disease burden over time [
5,
11] and emphasizes the importance of incorporating long-term systemic outcomes into cost-effectiveness evaluations of MASLD therapies.
Therefore, while we fully agree with the need to avoid unnecessary model complexity, we contend that the inclusion of CKD is essential to preserve clinical relevance and economic validity, thereby substantially enhancing the accuracy and real-world applicability of cost-effectiveness analyses intended to inform healthcare decision-making. Indeed, omission of CKD-related outcomes may lead to conservative estimates of the minimum efficacy thresholds, particularly for therapies with broader cardiometabolic and renal benefits such as those targeting MASLD [
10]. Furthermore, excluding these outcomes from adult-focused models may underestimate the true lifetime clinical and economic impact of MASLD and associated comorbidities [
11].
Finally, the authors are commended for their valuable contribution to this evolving field. The study provides an important framework for interpreting therapeutic effects in MASLD, effectively bridging statistical significance, clinical relevance, and economic value.
Further large-scale studies that systematically account for the major systemic complications of MASLD are urgently needed to maximize the translational value of such economic models for clinicians, researchers, and policymakers shaping the development and implementation of MASLD therapies.
FOOTNOTES
-
Authors’ Contribution
Anna Di Sessa contributed to the writing, editing, and reviewing of the letter. Gianmario Forcina contributed to the writing of the letter. Emanuele Miraglia del Giudice contributed to the editing and reviewing of the letter. All authors contributed to the approval of the final manuscript before submission.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
metabolic dysfunction-associated steatotic liver disease
REFERENCES
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Citations
Citations to this article as recorded by
- Incorporating chronic kidney disease into the cost-effectiveness of MASLD treatment: Correspondence to letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disea
Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(3): e415. CrossRef - Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live
Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice
Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef
