Correspondence to letter to the editor 2 on “Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study”

Article information

Clin Mol Hepatol. 2025;31(2):e210-e211

Publication date (electronic) : 2025 January 6

doi : https://doi.org/10.3350/cmh.2024.1175

Seogsong Jeong^1,2, Won Kim^,3,4, Sang Min Park^,5,6

¹Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea

²Biomedical Research Center, Korea University Guro Hospital, Seoul, Korea

³Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

⁴Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

⁵Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

⁶Departmenet of Family Medicine, Seoul National University Hospital, Seoul, Korea

Corresponding author : Sang Min Park Department of Family Medicine and Biomedical Sciences, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-3331, Fax: +82-2-766-3276, E-mail: smpark.snuh@gmail.com

Won Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2233, Fax: +82-2-831-2826, E-mail: drwon1@snu.ac.kr

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2024 December 26; Accepted 2025 January 2.

Dear Editor,

We appreciate the insightful comments by Wang et al. [1] regarding our study on the evolution of metabolic dysfunction-associated steatotic liver disease (MASLD) and its impact on hepatocellular carcinoma (HCC) risk [2]. Their analysis comparing MASLD and metabolic-associated fatty liver disease (MAFLD) outcomes provides valuable additional perspectives. Wang et al. [1] found that the MASLD-only group had a higher adjusted hazard ratio (aHR) for liver-related outcomes compared to the MAFLD-only group (3.22 vs. 2.65). This difference may stem from MAFLD criteria including overweight individuals with hepatic steatosis but no cardiometabolic risk factors, who do not meet MASLD criteria. Further investigation is needed to confirm this finding.

Our previous work showed MASLD, MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD) were each associated with increased risk of liver-related events in fully adjusted models. However, intrahepatic cholangiocarcinoma risk did not significantly differ among steatotic liver disease (SLD) subtypes [3]. Future research should incorporate a non-SLD cohort (individuals without hepatic steatosis) as a reference and compare MAFLD subtypes (overweight or obesity, type 2 diabetes mellitus, and two or more metabolic risk factors) against SLD subtypes (MASLD, MetALD, and ALD) to elucidate their prognostic implications on liver-related outcomes more effectively.

Regarding cardiovascular outcomes, Wang et al. [1] found no significant elevation in the MASLD-only group, possibly due to limited events. This aligns with our prior study showing no significant difference in cardiovascular disease (CVD) risk between groups with and without hepatic steatosis when only one metabolic dysfunction was present [4]. In another study, we noted that individuals who developed nonalcoholic fatty liver disease (NAFLD) had a 15% elevation in CVD risk compared to those with persisting non-NAFLD (aHR 1.15, 95% confidence interval 1.13–1.17) [5]. The principal difference between these two studies is that one stratified patients according to the number of metabolic dysfunctions, whereas the other did not stratify but adjusted for cardiometabolic risk factors. We did observe increased CVD risk with MASLD (aHR 1.20), MetALD (aHR 1.29), and ALD (aHR 1.31) compared to those without SLD in a recent analysis [6].

To clarify the prognostic effects of different SLD classifications, future research should use a non-SLD group (individuals without hepatic steatosis) as the reference, compare MAFLD subtypes (based on overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors) with SLD subtypes (MASLD, MetALD, and ALD), and examine both liver-related and extrahepatic outcomes. This approach may provide more comprehensive insights into the relative impacts of these disease classifications on patient prognosis.

Factors like racial/ethnic differences, potential confounders (e.g., chronic hepatitis B, antiviral treatments), and reference group selection can limit direct comparisons between studies [7,8]. Addressing these methodological considerations in future research will be crucial for accurately assessing the prognostic value of MASLD and MAFLD criteria.