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

Abstract

We read with great interest the recent article published in Alimentary Pharmacology & Therapeutic titled ‘Cardiometabolic criteria as predictors and treatment targets of liver-related events and cardiovascular events in metabolic dysfunction-associated steatotic liver disease (MASLD)’ [1]. This study utilised a nationwide claims database from the Japan Medical Data Center (JMDC) to highlight the role of cardiometabolic criteria in predicting major adverse cardiovascular events (MACE) and liver-related events in patients with metabolic dysfunction-associated MASLD.

The study provides significant insights into the value of cardiometabolic criteria for prognostic assessment in patients with MASLD [1]. However, several aspects of the study methodology and its implications for liver-related events may warrant a deeper discussion.

First, the JMDC database lacks detailed imaging data, which is a critical limitation given the importance of imaging in accurately diagnosing and staging MASLD. The lack of imaging data such as ultrasound, MRI, or elastography data, highlights the concerns about the potential for misclassification and underestimation of disease severity, especially in patients with early-stage fibrosis who may not experience liver-related events within a short follow-up period [2]. And Liver fibrosis is recognised as a key predictor of liver-related outcomes in MASLD [2, 3]. To strengthen future research, it is imperative to incorporate imaging studies to assess the risk stratification and progression to fibrosis and cirrhosis more accurately in MASLD.

Second, the JMDC database introduces potential selection bias. The database predominantly includes data from corporate-sponsored health insurance plans, which may skew the demographic representation toward younger, employed and healthier individuals. Elderly individuals, women and those of lower socioeconomic status are underrepresented, yet these groups are likely more prone to advanced MASLD and higher risks of cardiovascular and liver-related complications [3, 4]. Older and socioeconomically disadvantaged individuals are more likely to progress to advanced stages of MASLD and experience poorer health outcomes, including higher mortality from liver-related events [4, 5]. Therefore, incorporating data from national health insurance databases and other healthcare systems that include more diverse patient cohorts, particularly those at higher risk of severe complications, is crucial.

Third, the study's 1-year follow-up period significantly impacts the ability to assess long-term prognoses in MASLD patients, a chronic progressive disease where cardiovascular and liver-related complications typically manifest over a longer duration [6, 7]. Liver-related events, such as cirrhosis and hepatocellular carcinoma, often develop over several years to decades [5, 6]. Extending the follow-up period in future research to at least 5–10 years would more accurately reflect the long-term risks associated with cardiometabolic criteria.

Moreover, the role of diabetes medications in MASLD patients, particularly those with diabetes, could confound the results. Antidiabetic medications such as GLP-1 receptor agonists and SGLT2 inhibitors have been shown to beneficially impact glycemic control and steatosis, with some even reducing liver fibrosis and inflammation [8, 9]. But attributing these benefits solely to cardiometabolic criteria could be misleading. Future research should stratify patients based on the basis of the use of diabetes medications and assess their differential impacts on liver-related outcomes.

Qi-En Shen: writing – original draft, methodology, conceptualization. Chengfu Xu: writing – review and editing, writing – original draft, supervision.

The authors declare no conflicts of interest.

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.18356.