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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Risks of liver cirrhosis, hepatocellular carcinoma, hepatic-related complications, and mortality in patients with type 2 diabetes in Taiwan
Hua-Fen Chen, Yung-Yueh Chang, Peter Chen, Xiao-Han Shen, Chin-Huan Chang, Wan-Lun Hsu
Hua-Fen Chen, Yung-Yueh Chang, Xiao-Han Shen, Chin-Huan Chang, Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
Hua-Fen Chen, School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
Hua-Fen Chen, Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
Yung-Yueh Chang, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City 100, Taiwan
Peter Chen, Department of Gastroenterology, Choninn Hospital, Choninn Medical Group, New Taipei City 220, Taiwan
Xiao-Han Shen, Wan-Lun Hsu, Master Program of Big Data in Medical Healthcare Industry, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
Xiao-Han Shen, Wan-Lun Hsu, Data Science Center, Fu Jen Catholic University, New Taipei City 242, Taiwan
Co-corresponding authors: Hua-Fen Chen and Wan-Lun Hsu.
Author contributions: Chen HF and Chen P were involved in the study conception, design, and conduct; Chang YY and Shen XH analyzed the data, and Hsu WL interpreted the results; Chen HF, Chen P and Chang CH wrote the first draft of the manuscript; All authors edited, reviewed, and approved the final version of the manuscript. Chen HF and Hsu WL contributed equally to this article and they are co-corresponding authors. Hsu WL is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Supported by The Far Eastern Memorial Hospital, No. FEMH-2022-C-015, No. FEMH-2022-C-017 and No. FEMH-2023-C-082.
Institutional review board statement: This study was approved by the Institutional Review Board of Fu-Jen Catholic University (No. C110216).
Informed consent statement: The Institutional Review Board of Fu-Jen Catholic University waived the need for informed consent.
Conflict-of-interest statement: The authors declare that there is no duality of interest associated with this manuscript.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The datasets analyzed during the current study are not publicly available because the raw data contain potentially identifying patient information. The restrictions were imposed by the Health and Welfare Data Science Center, the Census and Statistics Department, Ministry of Health and Welfare, Republic of China (Taiwan). Data are available upon request
via Data Science Center, Fu Jen Catholic University (contact
via Wan-Lun Hsu, E-mail:
156521@mail.fju.edu.tw) to researchers who meet the criteria for access to these confidential data.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hua-Fen Chen, MD, Assistant Professor, Chief, Department of Endocrinology, Far Eastern Memorial Hospital, No. 21 Section 2, Nanya S Road, Banqiao District, New Taipei City 220, Taiwan.
hfchen@mail.femh.org.tw
Received: December 25, 2024
Revised: February 25, 2025
Accepted: March 21, 2025
Published online: May 15, 2025
Processing time: 121 Days and 16.1 Hours
BACKGROUND
Hepatitis B and C and alcoholic liver disease are the principal causes of hepatic-related morbidity and mortality. However, evidence of the associations between diabetes without the above risk factors and hepatic-related study endpoints is not well understood. In addition, the effects of associated metabolic dysfunction and exercise on hepatic outcomes are still not clear.
AIM
To investigate the incidence and relative hazards of cirrhosis of the liver, hepatocellular carcinoma (HCC), hepatic-related complications and mortality in patients with type 2 diabetes (T2D) who were nonalcoholic and serologically negative for hepatitis B and C in Taiwan.
METHODS
A total of 33184 T2D patients and 648746 nondiabetic subjects selected from Taiwan’s adult preventive health care service were linked to various National Health Insurance databases, cancer registry, and death registry to identify cirrhosis of the liver, HCC, hepatic-related complications, and mortality. The Poisson assumption and Cox proportional hazard regression model were used to estimate the incidences and relative hazards of all hepatic-related study endpoints, respectively. We also compared the risk of hepatic outcomes stratified by age, sex, associated metabolic dysfunctions, and regular exercise between T2D patients and nondiabetic subjects.
RESULTS
Compared with nondiabetic subjects, T2D patients had a significantly greater incidence (6.32 vs 17.20 per 10000 person-years) and greater risk of cirrhosis of the liver [adjusted hazard ratio (aHR) 1.45; 95%CI: 1.30-1.62]. The aHRs for HCC, hepatic complications, and mortality were 1.81, 1.87, and 2.08, respectively. An older age, male sex, obesity, hypertension, and dyslipidemia further increased the risks of all hepatic-related study endpoints, and regular exercise decreased the risk, irrespective of diabetes status.
CONCLUSION
Patients with T2D are at increased risk of cirrhosis of the liver, HCC, hepatic-related complications, and mortality, and associated metabolic dysfunctions provide additional hazard. Coordinated interprofessional care for high-risk T2D patients and diabetes education, with an emphasis on the importance of physical activity, are crucial for minimizing hepatic outcomes.
Core Tip: Nonalcoholic, hepatitis B and C serologically negative patients with type 2 diabetes, one of the cardiometabolic risk factors for metabolic dysfunction-associated steatotic liver disease, exhibited independently increased risks of cirrhosis of the liver, hepatocellular carcinoma, hepatic-related complications, and mortality, irrespective of age or sex. Coexisting obesity, hypertension, and dyslipidemia worsened this risk, but regular exercise could ameliorate hepatic outcomes even after adjustment for confounders.
