Tseng Yuan-Tsung, Wang Chun-Hsiang, Wang Jung-Der, Chen Kow-Tong, Li Chung-Yi
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
Department of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan City, Taiwan.
Therap Adv Gastroenterol. 2025 May 8;18:17562848251338669. doi: 10.1177/17562848251338669. eCollection 2025.
Vitamin D deficiency is prevalent and linked to chronic diseases; its association with advanced liver disease progression requires clarification.
To investigate the association between vitamin D levels and risks of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality, and assess risk changes after achieving sufficiency post-supplementation.
This was a retrospective cohort study.
Utilized TriNetX US data (3,905,594 patients, 2000-2024). Adults with vitamin D deficiency (20.00-30.00 ng/mL) were compared with those with sufficient levels (30.01-80.00 ng/mL). Follow-up was initiated from the first vitamin D test or start of supplementation to minimize immortal time bias. Propensity score matching (1:1) balanced >20 baseline confounders.
After matching, 1,204,760 patients with vitamin D deficiency and 1,204,760 with sufficient vitamin D levels were included. Vitamin D deficiency was associated with an increased risk of liver cirrhosis (hazard ratio (HR), 1.30; 95% confidence interval (CI), 1.25-1.36), HCC (HR, 1.22; 95% CI, 1.08-1.37), and all-cause mortality (HR, 1.14; 95% CI, 1.13-1.16). Achieving sufficient vitamin D levels reduced the risk of all-cause mortality (HR, 0.93; 95% CI, 0.88-0.99) and aligned HCC outcomes (HR, 1.16; 95% CI, 0.68-2.00). However, it did not significantly reduce the risk of liver cirrhosis (HR, 2.05; 95% CI, 1.69-2.50). Dose-response analysis showed a U-shaped relationship for liver cirrhosis and HCC, with the lowest risks at 40-60 ng/mL.
Serum vitamin D levels showed a nonlinear association with liver cirrhosis and HCC risk; deficiency independently increased the risks for cirrhosis, HCC, and mortality. Supplementation achieving sufficiency reduced mortality and normalized HCC risk but not cirrhosis risk, potentially reflecting limitations in reversing established disease. The lowest liver disease risk was associated with vitamin D levels of 40-60 ng/mL in this cohort, although causality and the clinical benefit of targeting this specific range require confirmation.
维生素D缺乏症普遍存在且与慢性疾病相关；其与晚期肝病进展的关联尚需阐明。
研究维生素D水平与肝硬化、肝细胞癌（HCC）风险及死亡率之间的关联，并评估补充维生素D达到充足水平后风险的变化。
这是一项回顾性队列研究。
利用TriNetX美国数据库（3905594例患者，2000 - 2024年）。将维生素D缺乏（20.00 - 30.00 ng/mL）的成年人与维生素D水平充足（30.01 - 80.00 ng/mL）的成年人进行比较。随访从首次维生素D检测或开始补充维生素D时开始，以尽量减少不朽时间偏倚。倾向评分匹配（1:1）平衡了20多个基线混杂因素。
匹配后，纳入了1204760例维生素D缺乏患者和1204760例维生素D水平充足的患者。维生素D缺乏与肝硬化风险增加相关（风险比（HR），1.30；95%置信区间（CI），1.25 - 1.36）、HCC（HR，1.22；95% CI，1.08 - 1.37）以及全因死亡率（HR，1.14；95% CI，1.13 - 1.16）。维生素D水平达到充足可降低全因死亡率（HR，0.93；95% CI，0.88 - 0.99）并使HCC结局趋于一致（HR，1.16；95% CI，0.68 - 2.00）。然而，它并未显著降低肝硬化风险（HR，2.05；95% CI，1.69 - 2.50）。剂量反应分析显示肝硬化和HCC呈U形关系，在40 - 60 ng/mL时风险最低。
血清维生素D水平与肝硬化和HCC风险呈非线性关联；缺乏独立增加了肝硬化、HCC和死亡风险。补充维生素D达到充足水平可降低死亡率并使HCC风险正常化，但不能降低肝硬化风险，这可能反映了逆转已确诊疾病的局限性。在该队列中，最低的肝病风险与维生素D水平40 - 60 ng/mL相关，尽管因果关系以及针对这一特定范围的临床益处尚需证实。
