Strople Jennifer, Lovell Glenda, Heubi James
Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, IL 60614, USA.
J Pediatr Gastroenterol Nutr. 2009 Jul;49(1):78-84. doi: 10.1097/MPG.0b013e31819a61ff.
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.
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.
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.
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.
凝血酶原时间（PT）作为维生素K缺乏的替代指标，可能低估胆汁淤积性肝病中维生素K缺乏的患病率。本研究通过测定维生素K缺乏诱导蛋白II（PIVKA-II）来调查儿童和成人胆汁淤积性肝病中维生素K缺乏的频率，并评估血浆PIVKA-II水平与胆汁淤积标志物、测定的PT、国际标准化比值（INR）、血清未羧化骨钙素（ucOC）、血清维生素A和E以及血清25-羟维生素D水平之间的关系。
采集胆汁淤积性肝病患者的血液，检测肝功能、PT、INR、胆汁酸、25-羟维生素D、维生素A、维生素E、ucOC和PIVKA-II。
共纳入31例患者（年龄范围0.5 - 54岁，中位年龄5.7岁，女性17例）。9例患者（29%）INR升高，而21例（68%）血浆PIVKA-II水平升高。所有INR升高的患者血浆PIVKA-II均升高。21例血浆PIVKA-II升高的患者中有15例正在接受维生素K补充治疗（剂量范围7.8 - 700μg/kg/天）。血浆PIVKA-II水平与血清结合胆红素、胆汁酸、天冬氨酸转氨酶、丙氨酸转氨酶、PT、INR和血清ucOC呈正相关（P≤0.02），与血清25-羟维生素D水平呈负相关（P = 0.01）。22例患者（71%）存在维生素D缺乏，9例患者（29%）存在维生素A缺乏，2例患者（6%）存在维生素E缺乏。
尽管补充了维生素K，但在胆汁淤积性肝病中，提示持续维生素K缺乏的血浆PIVKA-II升高仍很常见。需要更好的维生素K补充策略和给药指南。
