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.
*Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, IL, USA
†General Clinical Research Center, Cincinnati Children's Hospital Medical Center, USA
‡Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Received 27 June, 2008
Accepted 18 December, 2008
Address correspondence and reprint requests to Jennifer Strople, MD, Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, 2300 Children's Plaza, Box #65, Chicago, IL 60614, USA (e-mail: firstname.lastname@example.org).
This study was supported by National Institutes of Health grants NCRR M01 08084 and NIDDK T32 07727. The authors report no conflicts of interest with respect to this article.
The authors report no conflicts of interest.