Letter: Filling the Gaps—Enhancing MASLD Prognosis With Imaging, Diverse Populations and Extended Follow-Up. Authors' Reply

Abstract

In this study, we investigated whether the number of cardiometabolic criteria was associated with cardiovascular event risk and liver-related event risk [1]. We found that while the risk of cardiovascular events increased with the number of cardiometabolic criteria, no association was observed between the number of cardiometabolic criteria and liver-related event risk. Since the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) requires the presence of at least one cardiometabolic criterion, our findings indicate the need for further examination of the MASLD diagnostic criteria.

As noted by Shen et al., a limitation of the Japan Medical Data Center (JMDC) database is the lack of imaging data [2]. In this study, the diagnosis of steatotic liver relied on International Classification of Diseases (ICD)-10 codes and non-invasive steatosis markers. Although magnetic resonance elastography and proton density fat fraction provide accurate assessments of liver fibrosis and hepatic steatosis content, their application in large populations presents significant challenges [3, 4]. While steatotic liver is often diagnosed via ultrasound in large populations, ultrasound has low sensitivity for detecting mild steatosis [5, 6]. Furthermore, the phenomenon of ‘burned-out’, where hepatic steatosis decreases as fibrosis progresses, is well documented [7]. Consequently, ultrasound-based diagnosis of steatotic liver may introduce additional biases. Nonetheless, the use of ICD-10 codes and non-invasive steatosis markers for diagnosing steatotic liver in large cohorts remains meaningful.

We acknowledge that the JMDC cohort predominantly consists of relatively young males, which introduces a bias. As a result, the incidence rates of cardiovascular and liver-related events in this cohort are likely lower compared to higher-risk populations, such as the elderly. Therefore, while it is essential to evaluate the relevance of cardiometabolic criteria in high-risk populations, our findings raise important questions regarding the current MASLD diagnostic criteria.

Regarding the follow-up period, there may be some misunderstanding. In the follow-up analysis, we examined the association between the average number of cardiometabolic criteria and event risk from the first year of observation through the tenth year, with an average follow-up period of 5.2 years. Thus, our results reflect the association between long-term changes in clinical status and event risk.

In this study, we found that cardiometabolic criteria were not strongly associated with liver-related event risk. Although the impact of antidiabetic drugs and glycaemic control was beyond the scope of this investigation [8], we plan to explore this aspect in future research.

The authors' declarations of personal and financial interests are unchanged from those in the original article [Ref. 1].

Nobuharu Tamaki: conceptualization, writing – original draft, writing – review and editing, funding acquisition. Takefumi Kimura: conceptualization, writing – original draft, writing – review and editing. Shun-Ichi Wakabayashi: conceptualization, writing – original draft, writing – review and editing. Takeji Umemura: writing – review and editing, funding acquisition, supervision. Namiki Izumi: writing – review and editing, supervision. Rohit Loomba: writing – review and editing, supervision, funding acquisition. Masayuki Kurosaki: conceptualization, funding acquisition, writing – original draft, writing – review and editing, supervision.

Rohit Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. RL has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Co-founder of LipoNexus Inc. The other authors have no conflicts of interest to declare.

This article is linked to Tamaki et al papers. To view these articles, visit https://doi.org/10.1111/apt.18205 and https://doi.org/10.1111/apt.18338.