Letter: severe vitamin D deficiency is a prognostic biomarker in autoimmune hepatitis—offender or bystander? Authors’ reply

EDITORS, We thank Drs Chen and Wang for their comments regarding our recent publication and for highlighting some interesting issues regarding severe vitamin D deficiency in patients with autoimmune hepatitis (AIH). As Drs Chen and Wang indicate, vitamin D is hydroxylated by the liver to 25‐hydroxyvitamin D, and this intermediate form is hydroxylated further by the kidney to the active metabolite, 1, 25‐dihydroxyvitamin D. Vitamin D deficiency implies the lack of 1,25‐ dihydroxyvitamin D, and it may occur because of defective hepatic or renal hydroxylation. The main circulating form of vitamin D is 25‐hydroxyvitamin D which is a reflection of hepatic rather than renal hydroxylation, and this is the form that we measured to define vitamin D deficiency. We agree with Drs Chen and Wang that impaired renal function might contribute to severe vitamin D deficiency in patients with AIH. In our cohort, baseline serum creatinine levels were lower in patients with severe vitamin D deficiency compared to patients without severe deficiency (58.1 ± 15.1 vs 68.1 ± 15.2 μmol/L, P = 0.005; normal, 50‐120 μmol/L), and we could not implicate renal disease as a contributing factor. Low serum vitamin D levels have been associated with the histological grade of inflammatory activity in Turkish patients with AIH. In our study, we did not demonstrate significant differences in histopathological grading or staging between groups with different vitamin D status, and we have reported these findings in Table 1 of our article. As requested by Drs Chen and Wang, we have conducted further univariate and multivariate binary logistic regressions to identify factors associated with severe vitamin D deficiency, especially the status of liver fibrosis, inflammation and liver function. Age, gender, MELD score, albumin level, sodium concentration and cirrhosis at diagnosis were independent predictors of severe vitamin D deficiency in univariate analysis, and cirrhosis at diagnosis was independently associated with severe vitamin D deficiency (OR 12.29; 95% CI 2.31‐65.39, P = 0.003) after adjusting for confounding factors (Table 1). These findings suggest that vitamin D deficiency is associated with the stage of fibrosis. Drs Chen and Wang have raised an important concern regarding the value of oral vitamin D supplementation in our patients with severe vitamin D deficiency. Of the 42 patients with severe vitamin D deficiency at baseline, 36 patients (86%) were supplemented with vitamin D, and 27 patients (75% of those supplemented) continued to have severe deficiency at 6 months. In the 36 supplemented patients with severe deficiency at presentation, no significant difference was observed in the frequency of patients who did (49%) and did not (52%) respond to glucocorticoid treatment (P = 0.21). The small number of patients with severe deficiency at presentation who were treated with vitamin D (9 responders vs 27 nonresponders) precluded a meaningful assessment of vitamin D supplementation and long‐ term outcome. Future clinical trials must be designed to answer this question.