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. 2024 Nov 1;119(11):2241-2250.
doi: 10.14309/ajg.0000000000002778. Epub 2024 Mar 7.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes

Yi-Ting Chen  1 , Tzu-I Chen  1 , Tsai-Hsuan Yang  1 , Szu-Ching Yin  1 , Sheng-Nan Lu  2 , Xia-Rong Liu  1 , Yun-Zheng Gao  1 , Chih-Jo Lin  1 , Chia-Wei Huang  1   3 , Jee-Fu Huang  4   5   6 , Ming-Lun Yeh  4   5   6 , Chung-Feng Huang  4   5   6 , Chia-Yen Dai  4   5   6 , Wan-Long Chuang  4   5   6 , Hwai-I Yang  1   7   8 , Ming-Lung Yu  4   8   9   10 , Mei-Hsuan Lee  1   3   8   11
Affiliations

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes

Yi-Ting Chen et al. Am J Gastroenterol. .

Abstract

Introduction: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD).

Methods: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC.

Results: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference.

Discussion: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

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Conflict of interest statement

Guarantor of the article: Mei-Hsuan Lee, PhD.

Specific author contributions: M.-H.L.: study concept and design. M.-H.L.: acquisition of data. Y.-T.C. and M.-H.L.: analysis and interpretation of data. Y.-T.C. and M.-H.L.: drafting of the manuscript. Y.-T.C., T.-I.C., T.-H.Y., S.-C.Y., S.-N.L., X.-R.L., Y.-Z.G., C.-J.L., C.-W.H., J.-F.H., M.-L.Y., C.-F.H., C.-Y.D., W.-L.C., H.-I.Y., M.-L.Y., and M.-H.L.: critical revision of the manuscript for important intellectual content. M.-H.L.: acquisition of funding and study supervision.

Financial support: This study was supported by the National Science and Technology Council, Taipei, Taiwan (grant: 112-2628-B-A49-007), by NYCU-KMU Joint Research Project (NYCUKMU-112-I001), and by the National Health Research Institute, Chunan, Taiwan (grant: NHRI-EX112-11117PI); Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. None of the funding organizations contributed to the study design and delivery; data collection, management, analysis, and interpretation; data preparation and review; or manuscript approval.

Potential competing interests: None to report.

Data transparency statement: All or part of the data used in this research were authorized by and received from MJ Health Research Foundation (Authorization Code: MJHRF2022001A) and Health and Welfare Data Science Center Database, Ministry of Health and Welfare (NHIRD_MOHW: H111164). M.-H.L. applied for all data use. Other researchers may request the materials used through collaboration.

Figures

Figure 1.
Figure 1.
Flowchart of the study population and definition of SLD subtypes. ALD, alcohol-associated liver disease; CMRF, cardiometabolic risk factor; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, MASLD and increased alcohol intake; SLD, steatotic liver disease.
Figure 2.
Figure 2.
Cumulative risk of (a) cirrhosis and (b) HCC across SLD subtypes (n = 327,878). ALD, alcohol-associated liver disease; HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, MASLD and increased alcohol intake; SLD, steatotic liver disease.
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