Glycemic control target for liver and cardiovascular events risk in metabolic dysfunction-associated steatotic liver disease

Aims: Optimizing glycemic control may prevent liver-related events and major adverse cardiovascular events (MACE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal hemoglobin A1c (HbA1c) threshold associated with a lower risk of complications, particularly liver-related events as well as MACE is unknown. Methods: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications. Results: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and >= 9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE). Conclusion: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.