BACKGROUND: - Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, leading to substantial disease burden globally. Whether sleep duration is associated with the risk of MASLD, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality remains underexplored. METHODS: - A total of 489,261 middle-aged and older adults from the UK Biobank without prior liver diseases were included. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, HCC, and liver-related mortality ascertained through linked hospital records and death registries. Sleep duration was self-reported at baseline survey and categorized into ≤ 5, 6, 7, 8 and ≥ 9 hours. RESULTS: - During a median (IQR) follow-up of 13.8 (1.5) years, 7,133 MASLD, 5,527 cirrhosis, 1,126 HCC, and 1,125 liver-related mortality cases were identified. After adjusting for potential confounders, the HRs [95% CIs] of MASLD were 1.44 [1.32
1.57], 1.17 [1.09
1.24], 1.00 (reference), 1.05 [0.99
1.11] and 1.35 [1.24
1.46] for ≤ 5, 6, 7, 8 and ≥ 9 hours of sleep duration, respectively. Similar trends were also observed for cirrhosis, HCC, and liver-related mortality. In addition, the U-shaped association between sleep duration and MASLD was more pronounced among participants without abnormal body mass index (overweight and obese), hypertension or insomnia (P for interaction <
0.05). CONCLUSIONS: - Both short and long sleep duration are associated with an increased risk of MASLD, cirrhosis, HCC, and liver-related mortality. Maintaining a moderate sleep duration of 7 to 8 hours per day could be crucial to prevent against this escalating public health concern.