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Deficient vitamin D levels increase risk for NASH in NAFLD

Evidence of vitamin D deficiency increased the risk for nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease, according to study results published in American Journal of Gastroenterology.

“Recent studies of [vitamin D deficiency] in humans and animal models indicate that [vitamin D deficiency] also contributes to increased oxidative stress, systemic inflammation, decreased adiponectin levels, toll-like receptor activation, and nonalcoholic fatty liver disease … we have found that [vitamin D deficiency] in our NAFLD subjects was associated with a definitive diagnosis of NASH, increased lobular inflammation, more ballooning and the presence of fibrosis,” Kris V. Kowdley, MD, FACP, FACG, AGAF, FAASLD, director of Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, and colleagues wrote.

Kris V. Kowdley

Researchers quantified serum 25-hydroxyvitamin D (25(OH)D) using chromatography-tandem mass spectrometry in 190 adults with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network cohort.

They divided the patients based on 25(OH)D level:  19% of patients had sufficient levels (> 30 ng/mL), 26% had insufficient levels (≥ 20 and ≤ 30 ng/mL) and 55% had deficient levels (< 20 ng/mL).

Patients with vitamin D deficiency were more likely to be diagnosed with “definitive NASH” (67%) compared with patients with insufficient levels of vitamin D (47%) or sufficient levels (53%).

Analyses showed that vitamin D deficiency was independently associated with definitive NASH (OR = 3.15; 95% CI, 1.62–6.15), increased lobular inflammation (OR = 1.98; 95% CI, 1.08–3.61), increased ballooning (OR = 2.38; 95% CI, 1.32–4.30) and the presence of fibrosis (OR = 2.32; 95% CI, 1.13–4.77).

To determine if vitamin D deficiency is associated with changes in hepatic gene expression in NAFLD, researchers compared hepatic transcriptomic profiling data taken via RNA sequencing. For this analysis, they compared 31 vitamin D deficient patients with 38 patients with vitamin D 25(OH)D levels greater than 20 ng/mL. There was an inverse relationship observed between lower levels of serum resistin and increased vitamin D level category (P = .013). The following genes were expressed differently between the two groups of patients: KRT10, SEMA3B, SNORD3C, ARSD, and IGKV4-1 (false discovery rate < 0.05).

“[The] gene ontology and pathway analysis suggest activation of the mitogen-activated protein kinase and nuclear factor-κB pathways in [vitamin D deficiency] NAFLD subjects,” the researchers wrote.

The researchers concluded: “Novel associations in proinflammatory pathways were identified, which suggest the mechanism for [vitamin D deficiency] in the pathogenesis of NASH and support dietary and/or lifestyle modifications to increase vitamin D levels in these patients.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.