Kurtz Joshua D, Chowdhury Shahryar M, Black Allison K, Lambert Andrea N, Neal Ashley E, Kluthe Theresa, Sparks Joshua D
Division of Pediatric Cardiology, Department of Pediatrics, University of Louisville, 571 S. Floyd St. Ste 113, Louisville, KY, 40202, USA.
Norton Children's Hospital Heart Institute, Louisville, KY, USA.
Pediatr Cardiol. 2024 Sep 5. doi: 10.1007/s00246-024-03637-z.
The Fontan procedure is used to palliate complex forms of congenital heart disease. This results in adverse hepatic sequelae now known as Fontan-associated liver disease (FALD). Conventional laboratory measures of liver disease do not correlate well with FALD severity. Cytokeratin-18 (CK-18) is a measure of cell death and is sensitive in detecting other causes of liver disease. Our aim was to assess the use of a novel measure of liver disease, CK-18, in Fontan patients. This is a single-center, prospective, cross-sectional study of Fontan patients aged 8-21 years old. We performed ultrasound elastography, echocardiography, magnetic resonance imaging, and serum laboratory testing. Novel laboratory test CK-18 levels in Fontan subjects were compared to healthy age-matched controls. Thirteen Fontan patients were evaluated with a median age 15 years (10, 14), 4 Hypoplastic left heart syndrome, 11 were male, and 5 were symptomatic. Fontan patients had normal AST/ALT, but a significantly elevated liver stiffness by elastography (median 13.4 kPa). Hepatic stiffness by elastography was associated with diastolic-indexed (rho = 0.58, p = 0.04) ventricular volumes. Compared to 10 aged-matched controls, CK-18 was higher in the Fontan group-cleaved CK-18 protein (p < 0.01) and full CK-18 protein, (p = 0.02). CK-18 was positively associated with AST and ALT. Elevated CK-18 levels were found in Fontan patients compared to controls suggesting hepatic cell death even in these relatively healthy Fontan patients. CK-18 was elevated prior to changes in traditional testing. CK-18 may be a useful sensitive marker of liver disease in FALD.
Fontan手术用于缓解复杂形式的先天性心脏病。这会导致不良的肝脏后遗症，即现在所知的Fontan相关肝病（FALD）。传统的肝病实验室检测指标与FALD严重程度的相关性不佳。细胞角蛋白-18（CK-18）是细胞死亡的一个指标，在检测其他肝病病因方面很敏感。我们的目的是评估一种新型肝病指标CK-18在Fontan患者中的应用。这是一项针对8至21岁Fontan患者的单中心、前瞻性横断面研究。我们进行了超声弹性成像、超声心动图、磁共振成像和血清实验室检测。将Fontan受试者的新型实验室检测指标CK-18水平与年龄匹配的健康对照进行比较。对13例Fontan患者进行了评估，中位年龄为15岁（10, 14），4例为左心发育不全综合征，11例为男性，5例有症状。Fontan患者的AST/ALT正常，但弹性成像显示肝脏硬度显著升高（中位值13.4 kPa）。弹性成像测得的肝脏硬度与舒张期指数化（rho = 0.58，p = 0.04）心室容积相关。与10名年龄匹配的对照相比，Fontan组的CK-18更高——裂解的CK-18蛋白（p < 0.01）和完整的CK-18蛋白（p = 0.02）。CK-18与AST和ALT呈正相关。与对照组相比，Fontan患者的CK-18水平升高，提示即使在这些相对健康的Fontan患者中也存在肝细胞死亡。在传统检测指标发生变化之前，CK-18就已升高。CK-18可能是FALD中一种有用的肝病敏感标志物。
