Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease

Chun Zhou; Yanjun Zhang; Ziliang Ye; Panpan He; Yuanyuan Zhang; Xiaoqin Gan; Sisi Yang; Mengyi Liu; Qimeng Wu; Xianhui Qin

doi:10.1016/j.nut.2023.112320

Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease

Nutrition. 2024 Mar:119:112320. doi: 10.1016/j.nut.2023.112320. Epub 2023 Dec 1.

Authors

Affiliations

¹ 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.
² 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. Electronic address: pharmaqin@126.com.

PMID: 38185094
DOI: 10.1016/j.nut.2023.112320

Abstract

Objectives: The 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.

Methods: The 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.

Results: During 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; P_interaction < 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 (P_interaction = 0.216).

Conclusions: Lower 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.

Keywords: Fibrosis stages; Genetic susceptibility; Serum 25-hydroxyvitamin D; Severe liver disease.

MeSH terms

Calcifediol
Carcinoma, Hepatocellular* / complications
Carcinoma, Hepatocellular* / genetics
Genetic Predisposition to Disease
Humans
Liver Cirrhosis / genetics
Liver Failure* / complications
Liver Neoplasms* / complications
Liver Neoplasms* / genetics
Vitamin D / analogs & derivatives*
Vitamin D Deficiency*

Substances

25-hydroxyvitamin D
Vitamin D
Calcifediol