Severe Vitamin D Deficiency Associated with Higher Liver-Related Events and Malignancies in Subjects with Primary Sclerosing Cholangitis

by | Mar 20, 2023 | 2023, Liver Health, Vitamin D - Recommended Levels

Written by Taylor Woosley, Staff Writer. Serum levels of ALT (p < 0.001), bilirubin (p < 0.001), IgG (p = 0.008), and INR (p = 0.005) were significantly higher in patients with PSC and a severe vitamin D deficiency when compared to their counterparts. 

liver scanVitamin D is known as an immunomodulatory hormone that exerts immunologic activities on multiple components of the innate and adaptive immune system1. There is consensus that severe vitamin D deficiency (serum25-hydroxyvitamin D (25(OH)D) concentrations <30 nmol/L) should be corrected, whereas most guidelines recommend serum 25(OH)D concentrations of >50 nmol/L for optimal health in older adults2. Evidence from observational studies indicates that low vitamin D status is associated with higher mortality from life threatening conditions and chronic diseases3.

Primary Sclerosing Cholangitis (PSC) is a chronic autoimmune cholestatic liver disease in which inflammation and fibrosis lead to multifocal biliary strictures and progression to end-stage liver disease4. The pathogenesis of PSC is not fully defined but may stem from genetic, immunological, and environmental factors5. It is widely believed that an imbalance of proinflammatory and anti-inflammatory immune responses within the liver play a large role in disease development6.

Ebadi et al. conducted a retrospective study to identify the prevalence of severe vitamin D deficiency in subjects with PSC and to investigate its association with cirrhosis progression, hepatobiliary malignances, liver-related mortality, and the need for liver transplantation. Subjects (n=354) were assessed and evaluated by the Autoimmune Liver Disease Clinic at the University of Alberta, Edmonton, Canada from 1972-2019. Vitamin D (25-hydroxyvitamin D) levels were evaluated at diagnosis and liver function tests including alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and international normalized ratio (INR) were evaluated at each clinical visit. Cirrhosis at diagnosis or cirrhosis development was identified based on the presence of histological findings in liver biopsies, elevated FibroScan score (>14 kPa), and through ultrasound (US), computerized tomography (CT) or magnetic resonance imaging (MRI) findings.

Vitamin D predictive association was analyzed as a continuous variable followed by comparing subjects with and without a severe deficiency. Univariate and multivariate Cox proportional hazards regression models were utilized to investigate an association between vitamin D and outcomes. Of the 354 subjects with PSC included in the study, 118 (33%) were female, with a mean age at diagnosis of 35 ± 1 years, and the mean body mass index (BMI) was 25 ± 0.3 kg/m2. Cirrhosis at the time of diagnosis was identified in 38 (11%) patients. The mean vitamin D level was 59 ± 2 nmol/L and 63 (18%) participants had a severe vitamin D deficiency. Significant findings of the study are as follows:

  • Serum levels of ALT (166 ± 29 vs. 83 ± 5, p < 0.001), bilirubin (116 ± 15 vs. 36 ± 3, p < 0.001), IgG (1.3 ± 0.4 vs. 0.6 ± 0.1, p = 0.008), INR (1.3 ± 0.04 vs. 1.2 ± 0.02, p = 0.005), and Mayo Score (1.40 ± 0.2 vs. 0.53 ± 0.1, p < 0.001) were significantly higher in patients with PSC and a severe vitamin D deficiency when compared to their counterparts.
  • There was a statistical trend regarding hepatobiliary malignancies occurring more commonly in patients with a severe vitamin D deficiency than in patients without a severe deficiency (11% vs. 5%, p = 0.07). Patients with a severe vitamin D deficiency were 2.5 times more likely to experience hepatobiliary malignancies over the duration of the follow-up (HR 2.55, 95% CI, 1.02–6.40, p = 0.046).
  • At a follow-up period of 153 months (95% CI, 130-177), 24 deaths were related to liver-related disease, and 137 patients underwent a liver transplantation. In patients with a liver transplantation, the mean level of serum vitamin D was lower (54 ± 3 vs. 63 ± 2 nmol/L, p = 0.01).

Results of the study show that severe vitamin D deficiency was associated with a higher frequency of liver-related events and hepatobiliary malignancies. Further research should continue to explore the potential therapeutic application of vitamin D on a variety of chronic diseases and conditions. Study limitations include the single-center nature of the study with a limited number of subjects, lack of evaluating dietary vitamin D, and needing further consideration of genetic variability which was not addressed.

Source: Ebadi, Maryam, Elora Rider, Catherine Tsai, Sarah Wang, Ellina Lytvyak, Andrew Mason, and Aldo J. Montano-Loza. “Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis.” Nutrients 15, no. 3 (2023): 576.

© 2023 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Posted March 20, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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