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. 2025 Jun 18:16:1585725.
doi: 10.3389/fendo.2025.1585725. eCollection 2025.

Association between metabolic-associated fatty liver disease and risk of cardiometabolic multimorbidity: a disease trajectory analysis in UK Biobank

Yaqian Gao  1 , Jianjun Yao  2 , Suyi Liu  3 , Song Yin  4 , Zhenyu Jia  5 , Yueqing Huang  1 , Chunhua Zhao  1 , Dingliu He  6
Affiliations

Association between metabolic-associated fatty liver disease and risk of cardiometabolic multimorbidity: a disease trajectory analysis in UK Biobank

Yaqian Gao et al. Front Endocrinol (Lausanne). .

Abstract

Objective: While metabolic-associated fatty liver disease (MAFLD) has been associated with individual cardiometabolic diseases (CMDs), its role in the dynamic progression to cardiometabolic multimorbidity (CMM) remains unclear. We investigated the association of MAFLD, its severity and subtypes with CMM in individuals with no or one CMD at baseline.

Methods: This prospective cohort study involved 386,651 individuals (344,415 without and 42,236 with a single CMD at baseline) from the UK Biobank. MAFLD was defined as the presence of hepatic steatosis plus overweight/obesity, type 2 diabetes (T2D), or metabolic abnormalities. CMM was defined as the coexistence of two or more CMDs in the same person, including T2D, coronary heart disease (CHD) and stroke. Cox proportional hazard models and multistate models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results: During a median follow-up of 13.85 years, 4,622 new-onset CMM cases emerged among participants free of CMD at baseline. MAFLD was significantly associated with an increased risk of incident CMM (adjusted HR: 2.78, 95% CI: 2.60-2.96). Multistate models showed that MAFLD adversely affected most transitions from baseline to single CMDs and then to CMM. Among the single-CMD participants, the adjusted HRs of incident CMM in the MAFLD group were 1.21 (95% CI: 1.13-1.31) for T2D patients, 1.90 (1.75-2.05) for CHD patients, and 1.65 (1.45-1.87) for stroke patients, respectively.

Conclusion: MAFLD independently elevated the risk of incident CMM, regardless of the baseline CMD status. These findings emphasize the necessity of targeted MAFLD interventions for CMM prevention.

Keywords: UK Biobank; cardiometabolic multimorbidity; disease trajectory; metabolic-associated fatty liver disease; multistate model.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of selecting study population. MAFLD, metabolic-associated fatty liver disease; T2D, type 2 diabetes; CHD, coronary heart disease; CMD, cardiometabolic disease; CMM, cardiometabolic multimorbidity.
Figure 2
Figure 2
Role of metabolic-associated fatty liver disease (MAFLD) in the development of cardiometabolic multimorbidity. HR, hazard ratio; CI, confidence interval. Models adjusted for age, sex, ethnicity, educational levels, family income, socioeconomic status, employed status, smoking status, alcohol drinking, physical activity, sleep duration, healthy diet score, family history of diabetes, hypertension, heart disease and stroke.
Figure 3
Figure 3
Hazard ratios and 95% confidence intervals for associations between severity of metabolic-associated fatty liver disease and the development of cardiometabolic multimorbidity HR, hazard ratio; CI, confidence intervals; MAFLD, metabolic-associated fatty liver disease; T2D, type 2 diabetes; CHD, coronary heart disease; CMM, cardiometabolic multimorbidity. Multi-state models were conducted to estimate the role of MAFLD in the development of cardiometabolic multimorbidity, and disease transitions were presented in Figure 2 . Model adjusted for age, sex, ethnicity, educational levels, family income, socioeconomic status, employed status, smoking status, alcohol drinking, physical activity, sleep duration, healthy diet score, family history of diabetes, hypertension, heart disease and stroke.
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