An in-depth exploration of difference and similarity between NAFLD and MASLD

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver diseaseJournal of HepatologyVol. 80Issue 5PreviewRecently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. Full-Text PDF None. Writing manuscript: Yubo Liu, Liao Tan; formal analysis: Yubo Liu, Liao Tan; reviewing and editing: Yubo Liu, Liao Tan; conceptualization, project administration, and supervision: Yubo Liu, Liao Tan. We are writing to express my thoughts on the publication titled "Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease" by Younossi et al.1Younossi Z.M. Paik J.M. Stepanova M. et al.Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.J Hepatol. 2024; 27: S0168-S8278Google Scholar Younossi and his colleagues compared metabolic dysfunction-associated steatotic liver disease (MASLD) with non-alcoholic fatty liver disease (NAFLD) in terms of disease prevalence and performance of non-invasive tests (NITs) and their long-term outcomes using data from a tertiary care NAFLD Database and a U.S. population based national database (NHANES). The study's findings reveal a striking similarity between NAFLD and MASLD, suggesting their interchangeable use. This investigation marks the first attempt to assess the applicability of prior evidence based on NAFLD to the newly defined MASLD, a timely and significant contribution. While acknowledging the rigorous efforts and valuable contributions made by the authors, we would like to offer some constructive suggestions for further refinement. A primary concern revolves around the relevance of conclusions drawn from MASLD data collected three decades ago to the current population. The rapid economic development, evolving dietary habits, and lifestyle changes observed in recent decades have contributed to a notable increase in metabolic diseases. The NHANES III database, encompassing participants from 1988 to 1994, may not adequately represent the current prevalence and clinical characteristics of MASLD. Recent epidemiological findings from 2017 to 2020 indicate a substantial increase in MASLD prevalence among U.S. adults, reaching 32.45%,2Kalligeros Markos Vassilopoulos Athanasios Vassilopoulos Stephanos et al.Prevalence of steatotic liver disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020.Clin Gastroenterol Hepatol. 2023; 8: S1542-S3565Google Scholar compared to 18.01% reported in NHANES Ⅲ. Different baseline characteristics and comorbidities may impact the generalizability of the results to the present population. To enhance the accuracy and applicability of the conclusions, we propose either a comparative analysis of baseline data from both NHANES Ⅲ and NHANES 2017-2020 or the inclusion of more contemporary datasets. If the baseline data are broadly in line, the applicability of the conclusions may be extended to the present population; otherwise, the conclusions should be validated using updated cohort data. In addition, more comprehensive potential confounding factors should be included. The study has commendably adjusted for key covariates, including age, sex, race, smoking, income, education, marital status, healthy eating index, physical activity and cardiometabolic criteria. We noticed that cardiovascular disease, chronic kidney disease, and sarcopenia presented in the baseline data, but were not included as covariates in the Cox regression analysis. These comorbidities have been shown to be closely relevant to mortality in individuals with NAFLD.3Lee H.H. Lee H.A. Kim E.J. et al.Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease.Gut. 2023; 31 (gutjnl-2023-331003)Google Scholar, 4Bilson J. Mantovani A. Byrne C.D. et al.Steatotic liver disease, MASLD and risk of chronic kidney disease.Diabetes Metab. 2023; 50101506Crossref PubMed Scopus (1) Google Scholar, 5Kuchay M.S. Martínez-Montoro J.I. Kaur P. et al.Non-alcoholic fatty liver disease-related fibrosis and sarcopenia: an altered liver-muscle crosstalk leading to increased mortality risk.Ageing Res Rev. 2022; 80101696Crossref PubMed Scopus (15) Google Scholar Therefore, considering more comprehensive potential confounders, including these covariates, might further enhance the robustness of the findings after excluding multicollinearity. Finally, the Cox regression results indicate that MASLD's association with all-cause mortality and diabetes-specific mortality diminishes when considering cardiometabolic criteria. To further elucidate the relationship between MASLD and long-term outcomes, we suggest incorporating a mediating effects analysis.6Hu Z. Li Y. Yang Y. et al.Serum lipids mediate the relationship of multiple polyaromatic hydrocarbons on non-alcoholic fatty liver disease: a population-based study.The Sci total Environ. 2021; 780146563Crossref Scopus (25) Google Scholar This would provide insights into whether the effects of MASLD on long-term outcomes are mediated by specific cardiometabolic criteria and, if so, which criteria are most influential. In conclusion, the study by Younossi et al. is a noteworthy advancement in our comprehension of the similarities and differences between NAFLD and MASLD. The suggestions provided aim to refine an already outstanding piece of research, and I look forward to witnessing further insightful works from the authors in the future. The author declared that there is no conflict of interest. The following is/are the supplementary data to this article. Download .docx (.03 MB) Help with docx files