# Disrupted Vitamin D Metabolism in Hepatocellular Carcinoma: Free and Bioavailable 25(OH)D as Novel Biomarkers of Hepatic Reserve and Clinical Risk

## TL;DR

This study shows that vitamin D metabolism is disrupted in liver cancer patients, with free and bioavailable vitamin D being better indicators of liver health than total vitamin D levels.

## Contribution

The study introduces free and bioavailable 25(OH)D as novel biomarkers for assessing vitamin D status and liver function in hepatocellular carcinoma.

## Key findings

- HCC patients had significantly lower VDBP and albumin levels compared to controls.
- Free and bioavailable 25(OH)D were negatively correlated with VDBP in HCC patients.
- Vitamin D fractions in HCC patients lacked seasonal variation, unlike healthy controls.

## Abstract

Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer.