Cao Jacob Y, Wales Kathyrn M, d'Udekem Yves, Celermajer David S, Cordina Rachael, Majumdar Avik
Department of Cardiology, St. Vincent's Hospital, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
Department of Cardiology, Liverpool Hospital, Sydney, Australia.
JACC Adv. 2025 Mar 25;4(5):101694. doi: 10.1016/j.jacadv.2025.101694.
Patients with Fontan circulation are at risk of progressive liver disease, but the prevalence and risk factors for Fontan-associated liver disease (FALD) remain unclear.
The aim of the study was to review unbiased data on FALD prevalence, diagnostic methods, risk factors, and prognostic significance, and to undertake exploratory meta-analysis on available data.
This systematic review included studies with unselected FALD screening. Outcomes were imaging or biopsy-proven cirrhosis, advanced fibrosis, portal hypertension, and hepatocellular carcinoma. Exploratory meta-analysis was performed, as well as subgroup analyses and meta-regression to explore contributors towards outcome heterogeneity.
Thirty-seven studies comprising 5,701 patients were included, with a median of 17 years of follow-up post-Fontan completion. All estimates of FALD were highly heterogeneous, reflecting variable patient factors and institutional practices. Cirrhosis was diagnosed in 21% of patients, but ranged from 0% to 76%. Advanced fibrosis without cirrhosis was noted in 30%, portal hypertension in 17%, and hepatocellular carcinoma in 2%, also with significant heterogeneity. Subgroup analysis and meta-regression highlighted several factors that contributed to such heterogeneity. It was found that cirrhosis was less commonly diagnosed by biopsy than by imaging (10% vs 26%). Other risk factors for cirrhosis included years post-Fontan completion, atriopulmonary Fontan, moderate or greater ventricular dysfunction, and higher pulmonary capillary wedge pressure. Qualitative synthesis noted FALD to be associated with elevated risk of cardiovascular and all-cause mortality.
Liver disease is common post-Fontan completion, though prevalence varies widely. Several risk factors should guide patient screening. A universal, prognostically meaningful FALD definition is needed to advance research and clinical care.
接受Fontan循环手术的患者有发生进行性肝病的风险，但Fontan相关肝病（FALD）的患病率和危险因素仍不清楚。
本研究旨在回顾关于FALD患病率、诊断方法、危险因素和预后意义的无偏倚数据，并对现有数据进行探索性荟萃分析。
本系统评价纳入了对FALD进行非选择性筛查的研究。结局指标为影像学或活检证实的肝硬化、重度纤维化、门静脉高压和肝细胞癌。进行了探索性荟萃分析，以及亚组分析和Meta回归，以探讨导致结局异质性的因素。
纳入了37项研究，共5701例患者，Fontan手术完成后的中位随访时间为17年。所有FALD的估计值均高度异质性，反映了患者因素和机构实践的差异。21%的患者被诊断为肝硬化，但范围从0%到76%。30%的患者有无肝硬化的重度纤维化，17%有门静脉高压，2%有肝细胞癌，同样存在显著异质性。亚组分析和Meta回归突出了导致这种异质性的几个因素。发现活检诊断肝硬化的比例低于影像学诊断（10%对26%）。肝硬化的其他危险因素包括Fontan手术完成后的年限、心房肺分流Fontan、中度或更严重的心室功能障碍以及较高的肺毛细血管楔压。定性综合分析指出，FALD与心血管和全因死亡率升高相关。
Fontan手术完成后肝病很常见，尽管患病率差异很大。几个危险因素应指导患者筛查。需要一个通用的、具有预后意义的FALD定义来推进研究和临床护理。
