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

doi:10.4239/wjd.v16.i5.104576

Risks of liver cirrhosis, hepatocellular carcinoma, hepatic-related complications, and mortality in patients with type 2 diabetes in Taiwan

World J Diabetes. 2025 May 15;16(5):104576. doi: 10.4239/wjd.v16.i5.104576.

Authors

Hua-Fen Chen^{1

2

3}, Yung-Yueh Chang^{1

4}, Peter Chen⁵, Xiao-Han Shen^{1

6

7}, Chin-Huan Chang¹, Wan-Lun Hsu^{6

7}

Affiliations

¹ Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan.
² School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
³ Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan. hfchen@mail.femh.org.tw.
⁴ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City 100, Taiwan.
⁵ Department of Gastroenterology, Choninn Hospital, Choninn Medical Group, New Taipei City 220, Taiwan.
⁶ Master Program of Big Data in Medical Healthcare Industry, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
⁷ Data Science Center, Fu Jen Catholic University, New Taipei City 242, Taiwan.

Abstract

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.

Keywords: Hepatic-related complications; Hepatocellular carcinoma; Liver cirrhosis; Metabolic dysfunction-associated steatohepatitis; Metabolic dysfunction-associated steatotic liver disease; Mortality; Type 2 diabetes mellitus.