Long-Term Glycemic Control and the Risk of Liver Stiffness Progression and Liver-Related Events in MASLD

Background & aims: The long-term impact of type 2 diabetes (T2D) status and long-term glycemic control on disease progression and clinical outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. The study sought to assess the association of diabetes status and long-term glycemic control with liver stiffness progression or regression, and liver-related events (LREs) in MASLD. Methods: We analyzed patients with MASLD from the VCTE-Prognosis cohort who underwent serial vibration-controlled transient elastography (VCTE) assessments and hemoglobin A1c (HbA1c) measurements. Long-term glycemic control was evaluated using the time-weighted average (TWA) HbA1c, which reflects both the magnitude and duration of glycemia. Patients were categorized as non-T2D, well-controlled T2D (TWA HbA1c<7%), or poorly controlled T2D (TWA HbA1c ≥7%). Liver stiffness progression, regression, and LREs were examined using Kaplan-Meier analyses and Cox proportional hazards models. Results: Of 7543 patients with MASLD, 4090 had T2D (2045 well controlled, 2045 poorly controlled) and 3453 did not have T2D. Over a median follow-up of 4.1 years, patients with T2D had a higher risk of liver stiffness progression (hazard ratio [HR], 1.501, 95% confidence interval [CI]. 1.148-1.962; P = .003) and LREs (HR, 2.030; 95% CI, 1.241-3.320; P = .005), but not liver stiffness regression, compared with non-T2D patients. Among patients with T2D, poor glycemic control was associated with a higher risk of liver stiffness progression compared with good glycemic control (HR, 1.524; 95% CI, 1.182-1.965; P = .001). No differences were observed for liver stiffness regression (P = .957) or LREs (P = .625) with glycemic control. Findings were consistent across sensitivity analyses. Conclusions: T2D was independently associated with a higher risk of liver stiffness progression and LREs in MASLD. Good glycemic control was associated with slower liver stiffness progression, but not regression or LREs.