Abstract
BACKGROUND: Evidence from cohort studies on the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and longitudinal changes in total bile acid (TBA) remains limited. This study aimed to investigate the association of TBA trajectories with new-onset MAFLD and liver fibrosis. METHODS: A total of 3259 participants who underwent at least three health examinations at a hospital in Zhejiang between 2019 and 2023 were included. MAFLD was diagnosed via abdominal ultrasound, and liver fibrosis was assessed using the NAFLD fibrosis score (NFS) and fibrosis-4 score (FIB-4). Logistic regression models were used to analyse the associations between TBA trajectories and the risk of MAFLD and liver fibrosis. RESULTS: During follow-up, 715 participants developed MAFLD. Among them, 15.10% had high NFS status, and 12.17% had high FIB-4 status. Compared with the low-stable TBA trajectory group, the high-stable trajectory group had a significantly higher risk of new-onset MAFLD (adjusted OR = 1.448, 95% CI 1.157-1.812). Subgroup analyses confirmed the robustness of these findings. Multinomial logistic regression revealed that the high-stable trajectory was associated with an increased risk of high NFS (adjusted OR = 2.435, 95% CI 1.568-3.781, P < 0.001) and high FIB-4 (adjusted OR = 3.194, 95% CI 2.006-5.087, P < 0.001). CONCLUSIONS: TBA trajectories are significantly associated with the risk of new-onset MAFLD and advanced liver fibrosis, as indicated by high NFS and FIB-4 scores. These findings highlight the potential role of TBA dynamics in MAFLD progression and fibrosis risk.