Prevalence of subclinical vitamin K deficiency in cholestatic liver disease.
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.


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 <or= 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.
Strople
Jennifer
J
Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, IL 60614, USA. jstrople@childrensmemorial.org
Lovell
Glenda
G
Heubi
James
J
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D002779:Cholestasis / Q000097:blood / Q000150:complications*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D019934:International Normalized Ratio; D008107:Liver Diseases / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015995:Prevalence; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D014813:Vitamin K Deficiency / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D055815:Young Adult
D001647:Bile Acids and Salts; D015415:Biomarkers; D001798:Blood Proteins; D011498:Protein Precursors; D015675:Osteocalcin; C008208:acarboxyprothrombin; D011516:Prothrombin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin