Goldberg David J, Surrey Lea F, Glatz Andrew C, Dodds Kathryn, O'Byrne Michael L, Lin Henry C, Fogel Mark, Rome Jonathan J, Rand Elizabeth B, Russo Pierre, Rychik Jack
Division of Cardiology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
J Am Heart Assoc. 2017 Apr 26;6(5):e004809. doi: 10.1161/JAHA.116.004809.
Congestive hepatopathy is a recognized complication of Fontan physiology. Data regarding the incidence of hepatopathy and risk factors are lacking.
Liver biopsies and cardiac catherizations were performed as part of an evaluation offered to all patients ≥10 years after Fontan. Quantitative determination of hepatic fibrosis was performed using Sirius red staining with automated calculation of collagen deposition per slide (%CD). Biopsies from included subjects were compared to stained specimens from controls without known fibrotic liver disease. Patient characteristics, echocardiographic findings, and hemodynamic measures were evaluated as potential risk factors. The cohort consisted of 67 patients (31 female) at mean age of 17.3±4.5 years and mean time from Fontan of 14.9±4.5 years. Right ventricular morphology was present in 37 subjects. Median %CD by Sirius red staining was 21.6% (range 8.7% to 49.4%) compared to 2.6% (range 2.2% to 3.0%) in controls. There was a significant correlation between time from Fontan and degree of Sirius red staining (=0.33, <0.01). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava pressure was 13 mm Hg (range 6-24 mm Hg) and did not correlate with %CD. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency.
In this cohort of predominantly asymptomatic children and adolescents electively evaluated after a Fontan operation, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from Fontan was the only factor significantly associated with collagen deposition. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.
充血性肝病是Fontan循环生理的一种公认并发症。目前缺乏关于肝病发病率及危险因素的数据。
对所有接受Fontan手术10年及以上的患者进行评估时，同时进行肝活检和心导管检查。使用天狼星红染色法对肝纤维化进行定量测定，并自动计算每张切片的胶原沉积百分比（%CD）。将纳入研究对象的活检标本与无已知肝纤维化疾病的对照者的染色标本进行比较。评估患者特征、超声心动图检查结果和血流动力学指标作为潜在危险因素。该队列由67例患者（31例女性）组成，平均年龄为17.3±4.5岁，距Fontan手术的平均时间为14.9±4.5年。37例患者存在右心室形态异常。天狼星红染色法测得的%CD中位数为21.6%（范围8.7%至49.4%），而对照组为2.6%（范围2.2%至3.0%）。距Fontan手术的时间与天狼星红染色程度之间存在显著相关性（=0.33，<0.01）。血清肝酶和血小板计数与%CD无相关性。下腔静脉压力中位数为13 mmHg（范围6 - 24 mmHg），与%CD无相关性。基于心室形态或房室瓣关闭不全的严重程度，%CD无差异。
在这组主要为无症状儿童和青少年、接受Fontan手术后进行选择性评估的队列中，所有患者均表现出肝脏胶原沉积所测量的肝纤维化证据。距Fontan手术的时间是与胶原沉积显著相关的唯一因素。这些发现表明，肝纤维化是Fontan循环生理的一个固有特征，且纤维化程度随时间增加。
