Crawford Darrell H G, Murphy Therese L, Ramm Louise E, Fletcher Linda M, Clouston Andrew D, Anderson Gregory J, Subramaniam V Nathan, Powell Lawrie W, Ramm Grant A
School of Medicine, The University of Queensland, Greenslopes Private Hospital, Brisbane, Australia.
Hepatology. 2009 Feb;49(2):418-25. doi: 10.1002/hep.22650.
Diagnosing the presence of cirrhosis is crucial for the management of patients with C282Y hereditary hemochromatosis (HH). HH patients with serum ferritin >1,000 microg/L are at risk of cirrhosis; however, the majority of these patients do not have cirrhosis. Noninvasive markers of hepatic fibrosis may assist in determining which patients with a serum ferritin >1,000 microg/L have cirrhosis and require liver biopsy. This study evaluated the utility of current diagnostic algorithms for detecting cirrhosis, including serum ferritin concentration, platelet counts, and aspartate aminotransferase (AST) levels, in combination with serum markers of fibrosis, hyaluronic acid and collagen type IV (CLIV), in predicting cirrhosis in HH patients. Stage of fibrosis, serum hyaluronic acid and CLIV levels, were measured in 56 patients with HH. No patient with a serum ferritin <1,000 microg/L had cirrhosis, but only 40% of patients with serum ferritin >1,000 microg/L were cirrhotic. A combination of platelet count (<200 x 10(9)/L), elevated AST, and serum ferritin >1,000 microg/L did not detect 30% of cirrhotic subjects. Serum hyaluronic acid was increased in HH compared with controls (42.0 +/- 9.8 ng/mL versus 19.3 +/- 1.8 ng/mL; P = 0.02). A hyaluronic acid concentration >46.5 ng/mL was 100% sensitive and 100% specific in identifying patients with cirrhosis. In patients with serum ferritin >1,000 microg/L, hyaluronic acid levels were significantly elevated in patients with cirrhosis versus those without cirrhosis (137 +/- 34.4 ng/mL versus 18.6 +/- 1.5 ng/mL, respectively; P = 0.006). CLIV >113 ng/mL was 100% sensitive but only 56% specific for cirrhosis (area under the curve = 0.78; P = 0.01).
In HH, the measurement of hyaluronic acid in patients with serum ferritin >1,000 microg/L is a noninvasive, accurate, and cost-effective method for the diagnosis of cirrhosis. (HEPATOLOGY 2009;49:418-425.).
诊断肝硬化的存在对于C282Y遗传性血色素沉着症（HH）患者的管理至关重要。血清铁蛋白>1000μg/L的HH患者有肝硬化风险；然而，这些患者中的大多数并没有肝硬化。肝纤维化的非侵入性标志物可能有助于确定哪些血清铁蛋白>1000μg/L的患者患有肝硬化并需要进行肝活检。本研究评估了当前用于检测肝硬化的诊断算法的效用，包括血清铁蛋白浓度、血小板计数和天冬氨酸转氨酶（AST）水平，结合纤维化的血清标志物透明质酸和IV型胶原（CLIV），以预测HH患者的肝硬化情况。对56例HH患者测量了纤维化阶段、血清透明质酸和CLIV水平。血清铁蛋白<1000μg/L的患者中没有肝硬化患者，但血清铁蛋白>1000μg/L的患者中只有40%患有肝硬化。血小板计数（<200×10⁹/L）、AST升高和血清铁蛋白>1000μg/L的组合未能检测出30%的肝硬化患者。与对照组相比，HH患者的血清透明质酸升高（42.0±9.8ng/mL对19.3±1.8ng/mL；P = 0.02）。透明质酸浓度>46.5ng/mL在识别肝硬化患者方面敏感性为100%，特异性为100%。在血清铁蛋白>1000μg/L的患者中，肝硬化患者的透明质酸水平显著高于无肝硬化患者（分别为137±34.4ng/mL对18.6±1.5ng/mL；P = 0.006）。CLIV>113ng/mL对肝硬化的敏感性为100%，但特异性仅为56%（曲线下面积 = 0.78；P = 0.01）。
在HH中，对血清铁蛋白>1000μg/L的患者测量透明质酸是一种非侵入性、准确且经济有效的肝硬化诊断方法。（《肝脏病学》2009年；49:418 - 425。）
