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Prevalence of subclinical vitamin K deficiency in cholestatic liver disease
Jennifer Strople1, Glenda Lovell, James Heubi
1Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, IL 60614, USA. jstrople@childrensmemorial.org
Insights
Vitamin K deficiency is common in cholestatic liver disease, even with supplementation, as indicated by elevated PIVKA-II levels. New strategies for vitamin K therapy are needed for these patients.
Area of Science:
- Hepatology
- Nutritional Biochemistry
- Pediatric Gastroenterology
Background:
- Prothrombin time (PT) may underestimate vitamin K deficiency in cholestatic liver disease.
- Cholestatic liver disease impairs vitamin K absorption and metabolism.
- Vitamin K deficiency can lead to coagulopathy and affect bone health.
Purpose of the Study:
- To determine the frequency of vitamin K deficiency in pediatric and adult cholestatic liver disease patients using PIVKA-II.
- To assess the correlation between PIVKA-II levels and cholestasis markers, PT, INR, and other vitamin levels.
- To evaluate the effectiveness of current vitamin K supplementation protocols.
Main Methods:
- Blood samples collected from 31 patients with cholestatic liver disease.
- Assessed liver biochemistries, PT, INR, bile acids, vitamins A, E, D, ucOC, and PIVKA-II.
- PIVKA-II measured to detect vitamin K deficiency.
Main Results:
- Elevated PIVKA-II (indicating vitamin K deficiency) found in 68% of patients, despite vitamin K supplementation in many.
- PIVKA-II levels correlated positively with cholestasis markers (bilirubin, bile acids, liver enzymes) and INR.
- High prevalence of vitamin D (71%), vitamin A (29%), and vitamin E (6%) deficiencies observed.
Conclusions:
- Elevated PIVKA-II is common in cholestatic liver disease, suggesting inadequate vitamin K status despite supplementation.
- Current vitamin K supplementation strategies may be insufficient.
- Improved guidelines for vitamin K dosing and monitoring are necessary for patients with 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 mug/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
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.
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