Dear Editor
Metabolic dysfunction-associated steatohepatitis (MASH) is a major challenge facing global health, and new treatment options are urgently needed to break through[1,2]. Research by Lin JY et al. demonstrated that dapagliflozin has shown significant effects on patients with MASH and liver fibrosis[3]. Although the results of the study show strong persuasiveness, it may still be limited in the interpretation and promotion of the results due to the neglect of some factors.
First, the selection of potential diagnostic methods for MASH. In large-scale clinical trials, it is worth investigating alternative methods to liver biopsy for the diagnosis of MASH. Although liver biopsy is the gold standard for diagnosing MASH, its invasive and high cost make it generally less acceptable in the population[4], which may lead to a greater selection bias in the recruitment of study subjects. For example, in this study, the 154 participants recruited based on their willingness to undergo liver biopsy came from six tertiary hospitals in China and tended to be younger, which means that participants not only have higher combined medical conditions and economic conditions, but also likely had better physical fitness and stronger health awareness, resulting in underrepresentation of the population in the results. However, MASLD can progress to MASH, and the prevalence of MASLD is not only the highest but also more harmful among low- and lower-middle-income populations[5]. Therefore, it is worth recommending that the Jun Yu team recently launched an identification model (referred to as N3-MASH) for MASH patients based on the three parameters of C-X-C motif chemokine ligand 10 (CXCL10), cytokeratin 18 fragments M30 (CK-18) and BMI, which shows high accuracy[6]. If N3-MASH is applied in future experimental studies, it may recruit a more comprehensive research subjects to compensate for the underrepresentation of the research population caused by the limitations of liver biopsy in trial studies.
Secondly, the impact of a healthy lifestyle on MASH needs to be considered comprehensively. Although the researchers analyzed the differences in diet and physical activity between the dapagliflozin intervention group and the placebo group, they ignored the two important lifestyle factors: nicotine exposure and sleep. At present, numerous studies have confirmed that nicotine exposure and sleep status are also important influencing factors for the improvement or deterioration of MASH[7, 8]. If there are significant differences in lifestyle between the two groups in these two aspects, this may have a greater impact on the role of intervention drugs (dapagliflozin) in controlling the progress of MASH patients.
Third, the regional nature of multi-center research is worth pondering. The author claims that this study is a multi-center randomized controlled trial. However, from the article, we have not learned any detailed information about “multi-center”. Therefore, we inferred the origin of the participants based on contributing authors’ institutional affiliations. Almost all the participants in the study came from coastal regions of China with higher levels of economic development (Guangdong and Fujian Province). Study have shown that MASLD has a greater impact on populations in low-income regions[5]. Therefore, the level of economic development in the regions where the research subjects are located should also be included as an important considerations for careful interpretation of the research results.
Correspondence: Jianzhong Yin（yinjianzhong2005@sina.com）
Author Contributions: Jianzhong Yin, Xinqiang Chen and Ying Qian contributed equally to this work as first authors.
References
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