Association of serum 25-hydroxyvitamin D levels with severe necroinflammatory activity and inflammatory cytokine production in type I autoimmune hepatitis

Abstract

25-Hydroxyvitamin D [25(OH)D] has been reported to be associated with several chronic liver diseases. The relationship between 25(OH)D and autoimmune hepatitis (AIH) pathogenesis is incompletely understood. We investigated the association of serum total and free 25(OH)D levels with necroinflammatory activity and cytokine levels in 66 patients with AIH diagnosed in our hospital. The median age at AIH diagnosis was 57 years, and the male:female ratio was 7:59. The median serum total 25(OH)D level in therapy-naïve patients with AIH was 14.2 ng/mL (interquartile range [IQR], 11.4–17.9 ng/mL). Of the 66 patients with AIH, 36 had serum total 25(OH)D levels of < 15 ng/mL and were considered to have vitamin D deficiency, and 30 had serum total 25(OH)D levels of ≥ 15 ng/mL. Patients with acute-onset AIH had significantly lower serum total 25(OH)D levels than those with chronic-onset AIH. In particular, serum total 25(OH)D levels were significantly lower in patients with severe forms of AIH. Furthermore, the serum total 25(OH)D level was positively correlated with the serum albumin level and prothrombin time and negatively correlated with the serum total bilirubin level and necroinflammatory activity in AIH. Multivariate logistic regression analysis showed that the serum total 25(OH)D level was an independent factor for severe necroinflammatory activity. Interestingly, AIH patients with serum total 25(OH)D levels of < 15 ng/mL had higher levels of inflammatory cytokines such as interferon-γ and interleukin-33. Free 25(OH)D levels were correlated with total 25(OH)D levels, and the percentage of free 25(OH)D was significantly associated with necroinflammatory activity. In conclusion, 25(OH)D deficiency may play an important role in predicting AIH severity via inflammatory cytokine production.

Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease

“…A few studies have explored the relationship between AIH and vitamin D. Efe et al [ 92 ] found that mean vitamin D levels were significantly lower in 68 AIH patients than in controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p < 0.0001) [ 4 ]. This finding was confirmed in a more recent study by Abe et al [ 93 ], in which they also highlighted that serum total vitamin D levels were significantly lower in patients with acute AIH than in those with chronic AIH (13.2 ng/mL vs. 16.0 ng/mL, p = 0.029). [ 3 ] A study showed that serum total vitamin D levels were significantly lower in patients with severe necro-inflammatory activity (12.4 ng/mL vs. 16.8 ng/mL; p = 0.0017) [ 93 ]; by contrast, levels of pro-inflammatory cytokines (IFN-γ and IL-33) were significantly higher in AIH patients with serum total Vitamin D levels of <15 ng/mL (IFN-γ: 0.21 vs. 0 pg/mL, p = 0.0181; IL-33: 26.54 vs. 13.13 pg/mL, p = 0.0036).…”

“…Finally, three studies [ 92 , 93 , 94 ], found a correlation between low vitamin D levels and less probably response to therapy, with a higher number of patients needing a combination therapy (steroids + azathioprine) when Vitamin D levels were <15 ng/mL. These findings may correlate to vitamin D’s ability to promote the anti-inflammatory action of glucocorticoids [ 95 ].…”

Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets

“…Furthermore, five drugs (pioglitazone, medroxyprogesterone, dexamethasone, calcitriol, and rimonabant) have demonstrated therapeutic effects against liver diseases in clinical studies. Previous studies have also highlighted the therapeutic effects of dexamethasone and calcitriol on AIH ( Supplementary Table 6 ) [ 20 - 22 ].…”

Causal Association between Circulating Complement Components and Non-Viral Liver Diseases and Their Potential as Therapeutic Targets: An Integrated Analysis Based on Multi-omics Data

“…We identi ed calcitriol and dexamethasone as potential therapeutic agents for treating AIH. It is worth noting that vitamin D levels are signi cantly lower in patients with chronic-onset AIH (23). Moreover, corticosteroid regimens including dexamethasone are widely recognized as the standard treatment for AIH (24).…”