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A Prospective Open-Label Dose–Response Study to Correct Vitamin D Deficiency in Cirrhosis

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Abstract

Background

Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown.

Objective

We aimed to establish the dose–response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis.

Design

An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose–response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE).

Results

Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01).

Conclusions

A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.

Graphical Abstract

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Abbreviations

25(OH)D:

25-Hydroxyvitamin D

IU:

International units

HCV:

Hepatitis C virus

HCC:

Hepatocellular carcinoma

ALT:

Alanine transaminase

AST:

Aspartate transaminase

INR:

International normalized ratio

MELD:

Model for End-stage Liver Disease

GEE:

Generalized estimating equations

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Acknowledgments

The authors thank the physicians, staff, and patients at the Adult Liver Transplant Program at Mount Sinai for their important contributions and they thank Erin Doyle, Alisse Hannaford, and Alyssa Trochtenberg for a careful reading of the manuscript.

Funding

Health Services Research Programme, R01DA031095, Chip A Bowman, R01DK090317, Chip A Bowman

Author information

Authors and Affiliations

  1. Division of Digestive and Liver Diseases, Department of Medicine, Columbia University New York Presbyterian, New York, NY, USA

    Chip A. Bowman

  2. Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1428 Madison Ave, New York, NY, 10029, USA

    Kian Bichoupan, Shai Posner, Emily Schonfeld, Alexis Pappas, Thomas Schiano & Andrea D. Branch

  3. The George Institute for Global Health, School of Public Health, Imperial College London, London, UK

    Mark Woodward

  4. The George Institute for Global Health, University of New South Wales, Sydney, Australia

    Mark Woodward

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  1. Chip A. Bowman
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Contributions

KB, ES, AP, TS, MW and AB designed research and the data analysis plan; SP, KB, JB, ES, AP, and DB consented patients and collected data; AB and TS provided essential materials; SP, KB, MW and AB performed statistical analyses and analyzed data; SP, KB, JB, MW, TS, CB, and AB wrote the paper; SP, KB, JB, TS and AB had primary responsibility for final content.

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Correspondence to Andrea D. Branch.

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Bowman, C.A., Bichoupan, K., Posner, S. et al. A Prospective Open-Label Dose–Response Study to Correct Vitamin D Deficiency in Cirrhosis. Dig Dis Sci 69, 1015–1024 (2024). https://doi.org/10.1007/s10620-023-08224-5

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