Abstract
Background: Chronic liver disease (CLD) can cause vitamin D deficiency by several mechanisms including intestinal malabsorption related to cholestasis, decreased vitamin D binding protein, impaired 25-hydroxylation, and increased catabolism of 25-OH vitamin D (25-OH D) (1). Clinical Case: A 56-year-old woman was evaluated for severe vitamin D deficiency. She had a history of uterine sarcoma at age 14 treated with resection and radiation, complicated by radiation damage requiring multiple bowel resections and permanent ileostomy. She also had a history of hepatitis C treated with interferon-ribavirin at age 52, with clearance of virus. Annual CT scans for oncologic surveillance showed evidence of portal hypertension and cirrhosis as of age 50, but she was not clinically symptomatic. Initial tests showed 25-OH D of 8 ng/dL (ref 30-80 ng/dL, measured by HPLC). Treatment with ergocalciferol (D2) 50,000 IU daily for 14 days raised the level to 25 ng/dL, but it rapidly fell again to 14 ng/dL. Vitamin D replacement was then attempted with a combination of D2 and D3 supplements (the latter up to 3000 IU daily), but D3 levels were undetectable on this, so the D3 was stopped. Maintenance D2 dosing was then progressively increased to 500,000 IU per week, which achieved a level of 42 ng/dL. Despite continuing this same dose, the level gradually fell over the following 6 months back to 20 ng/dL. D2 was then escalated up to 150,000 IU daily, with 25-OH D levels ranging 17-27 ng/dL on this dose over the next 18 months. The high vitamin D requirements were attributed to intestinal malabsorption related to her bowel resections although the escalating nature of her requirements remained unexplained. PTH checked when 25-OH D had been ≤20 ng/dL for a full year showed no evidence of secondary hyperparathyroidism; in fact, PTH was low normal (range 16-20 pg/mL, ref 14-72 pg/mL). Bone specific alkaline phosphatase (BSAP) was also normal (16.9 μg/L, ref 7.0-22.4 μg/L). At age 61, she developed acute liver failure requiring transplant. 25-OH D just prior to transplant was 21 ng/dL on D2 150,000 IU daily. D2 was stopped post-transplant, and 25-OH D one month later was 40 ng/dL. Since her transplant, she has maintained 25-OH D levels of 34-46 ng/dL on D2 50,000 IU every 2 weeks, or 2% of her pre-transplant dose. In retrospect, her high vitamin D requirements were likely due to impaired 25-hydroxylation and/or low vitamin D binding protein (the latter would align with lack of elevation in PTH or BSAP, as free levels would have been normal) related to her CLD, as they resolved entirely post-transplant. Clinical Lesson(s): 1. CLD can cause vitamin D deficiency via several different mechanisms and may resolve with liver transplant. 2. CLD should be considered as a cause of recalcitrant vitamin D deficiency in the correct clinical context. Reference: (1) Stokes, C.S. et al. Vitamin D in Chronic Liver Disease. Liver International. 2013 March; 33(3): 338-52.