Duration of type 2 diabetes and liver-related events in nonalcoholic fatty liver disease: A landmark analysis

• Published in: Hepatology (Baltimore, Md.) Vol. 78; no. 6; pp. 1816 - 1827
• Main Authors: Zhang, Xinrong, Yip, Terry Cheuk-Fung, Tse, Yee-Kit, Hui, Vicki Wing-Ki, Li, Guanlin, Lin, Huapeng, Liang, Lilian Yan, Lai, Jimmy Che-To, Chan, Henry Lik-Yuen, Chan, Stephen Lam, Kong, Alice Pik-Shan, Wong, Grace Lai-Hung, Wong, Vincent Wai-Sun
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.12.2023
• Subjects: Adult; Carcinoma, Hepatocellular - complications; Cohort Studies; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Humans; Liver Neoplasms - complications; Middle Aged; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - epidemiology; Risk Factors
• ISSN: 0270-9139; 1527-3350; 1527-3350
• DOI: 10.1097/HEP.0000000000000432

In a landmark analysis of 30,360 patients with NAFLD, we showed that the risk of liver-related events (cirrhotic complications, HCC or liver-related death) and all-cause mortality increased with the duration of type 2 diabetes at each landmark age of interest. Because of the small number of events in young patients, the HRs represent unadjusted univariate analysis at the age of 40 and 50 years. Background and Aims: We aimed to determine the impact of the duration of type 2 diabetes (T2D) on the risk of liver-related events and all-cause mortality in patients with NAFLD. Approach and Results: We conducted a territory-wide cohort study of adult patients with NAFLD diagnosed between January 1, 2000, and July 31, 2021, in Hong Kong. T2D was defined by the use of any antidiabetic agents, laboratory tests, and/or diagnosis codes. The primary endpoint was liver-related events, defined as a composite endpoint of HCC and cirrhotic complications. To conduct a more granular assessment of the duration of T2D, we employed landmark analysis in four different ages of interest (biological age of 40, 50, 60, and 70 years). By multivariable analysis with adjustment of non-liver-related deaths, compared with patients without diabetes at age 60 (incidence rate of liver-related events: 0.70 per 1,000 person-years), the adjusted subdistribution HR (SHR) of liver-related events was 2.51 (95% CI: 1.32-4.77; incidence rate: 2.26 per 1,000 person-years) in patients with T2D duration < 5 years, 3.16 (95% CI: 1.59-6.31; incidence rate: 2.54 per 1,000 person-years) in those with T2D duration of 6-10 years, and 6.20 (95% CI: 2.62-14.65; incidence rate: 4.17 per 1000 person-years) in those with T2D duration more than 10 years. A similar association between the duration of T2D and all-cause mortality was also observed. Conclusions: Longer duration of T2D is significantly associated with a higher risk of liver-related events and all-cause mortality in patients with NAFLD.