• Chun Zhou, Yanjun Zhang, Ziliang Ye, Panpan He, Yuanyuan Zhang, Xiaoqin Gan, Sisi Yang, Mengyi Liu, Qimeng Wu, and Xianhui Qin.
• Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.
• Nutrition. 2024 Mar 1; 119: 112320112320.

ObjectivesThe prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association.MethodsThe study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death.ResultsDuring a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216).ConclusionsLower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.Copyright © 2023 Elsevier Inc. All rights reserved.

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