Prevalence of subclinical vitamin k deficiency in cholestatic liver disease

Jennifer Strople*, Glenda Lovell, James Heubi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background and Objective: Prothrombin time (PT), a surrogate marker of vitamin K deficiency, may underestimate the prevalence ofvitamin Kdeficiencyincholestatic 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. JPGN 49:78-84, 2009.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalJournal of pediatric gastroenterology and nutrition
Issue number1
StatePublished - Jul 2009
Externally publishedYes


  • Cholestasis
  • II
  • Pivka
  • Vitamin K

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology


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