Clin Mol Hepatol > Volume 30(3); 2024 > Article
Clinical and Molecular Hepatology 2024;30(3): 487-499.
doi: https://doi.org/10.3350/cmh.2024.0145
Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study
Seogsong Jeong1,2, Yun Hwan Oh3, Joseph C Ahn4, Seulggie Choi5, Sun Jae Park2, Hye Jun Kim2, Gyeongsil Lee6, Joung Sik Son7, Heejoon Jang8, Dong Hyeon Lee8, Meng Sha9, Lei Chen10,11, Won Kim8,12 , Sang Min Park2,6
1Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea
2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
3Department of Family Medicine, College of Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea
4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
5Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
6Department of Family Medicine, Life Clinic, Seoul, Korea
7Department of Internal Medicine, Hanyang University Hospital, Seoul, Korea
8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
9Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
10The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
11National Center for Liver Cancer, Shanghai, China
12Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Correspondence :  Won Kim ,
Tel: +82-2-870-2233, Fax: +82-2-831-2826, Email: drwon1@snu.ac.kr
Sang Min Park ,
Tel: +82-2-2072-3331, Fax: +82-2-766-3276, Email: smpark.snuh@gmail.com
Received: February 4, 2024  Revised: April 22, 2024   Accepted: May 7, 2024
ABSTRACT
Background/Aims
To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort.
Methods
Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression.
Results
Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68–3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63–2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18–1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD.
Conclusions
The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.
KeyWords: Liver neoplasms; Fatty liver; Epidemiology; Cohort studies

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