Prevalence of Subclinical Vitamin K Deficiency in Cholestatic Liver Disease

Background and Objective: Prothrombin time (PT), a surrogate marker of vitamin K deficiency, may underestimate the prevalence of vitamin K deficiency in cholestatic liver disease. This study investigated the frequency of vitamin K deficiency in children and adults with cholestatic liver disease by determining plasma protein induced in vitamin K absence II (PIVKA‐II), and assessed the relation between plasma PIVKA‐II levels and markers of cholestasis, measured PT, international normalized ratio (INR), serum undercarboxylated osteocalcin (ucOC), serum vitamins A and E, and serum 25‐hydroxyvitamin D levels. Patients and Methods: Blood was collected from patients with cholestatic liver disease for liver biochemistries, PT, INR, bile acids, 25‐hydroxyvitamin D, vitamin A, vitamin E, ucOC, and PIVKA‐II. Results: Thirty‐one patients were enrolled (age range 0.5–54 years, median age 5.7 years, 17 females). Nine patients (29%) had increased INRs, whereas 21 (68%) had elevated plasma PIVKA‐II levels. All patients with increased INRs had increased plasma PIVKA‐II. Fifteen of 21 patients with increased plasma PIVKA‐II were receiving supplemental vitamin K therapy (range 7.8–700 μg/kg/day). Plasma PIVKA‐II levels were positively correlated with serum conjugated bilirubin, bile acids, aspartate aminotransferase, alanine aminotransferase, PT, INR, and serum ucOC ( P ≤ 0.02) and negatively correlated with serum 25‐hydroxyvitamin D levels ( P = 0.01). Twenty‐two patients (71%) had vitamin D deficiency, 9 patients (29%) had vitamin A deficiency, and 2 patients (6%) had vitamin E deficiency. Conclusions: Despite vitamin K supplementation, elevation of plasma PIVKA‐II suggesting ongoing vitamin K deficiency is common in cholestatic liver disease. Better strategies for vitamin K supplementation and dosing guidelines are needed.