Clinical complications of liver disease in adults after the Fontan operation

Background: The natural history and complications of Fontan-associated liver disease (FALD) are not well-characterized. We aim to describe the incidence and prevalence of and risk factors for adverse liver-related complications in FALD. Methods: This is a single-center, retrospective cohort study of adult Fontan patients followed in an adult congenital heart disease center from 2006 to 2019. The primary outcome was clinical complications of liver disease (CCLD) defined as portal hypertension (pHTN)-related ascites, pHTN-related gastrointestinal bleeding, hepatic encephalopathy, or hepatocellular carcinoma. We also explored the composite outcome of CCLD, transplantation, or death. Results: Among 182 adult Fontan patients (46% female), median time from Fontan to first liver evaluation was 25.5 years (interquartile range [IQR] 22.3–30.4) with median subsequent follow-up of 4.1 years (IQR 2.5–7.6). There were 14 CCLD, 6 heart-liver and 1 heart transplant, and 16 deaths. The cumulative incidence of CCLD and the composite outcome were 2.6 per 1000-person years and 6.2 per 1000 person-years, respectively. Median time from Fontan to CCLD was 26.8 years (IQR 23.1–31.2), and to the composite outcome 26.6 years (IQR 23.1–30.5). Prior diuretic use was associated with the development of CCLD (hazard ratio [HR] 10.03, 95% confidence interval [CI] 1.25–80.22, P 0.030). Diuretic use (HR 16.47, 95% CI 3.90–69.57, P < 0.001), thrombocytopenia (HR 2.30, 95% CI 1.05–5.01, P 0.036), and cyanosis (HR 5.68, 95% CI 2.47–13.08, P < 0.001) were associated with the composite outcome. Conclusion: We identified clinical factors associated with adverse outcomes in FALD that may help guide early recognition of complications and clinical management.