ABSTRACT
Background: Despite improved survival a substantial number of Fontan patients eventually develop late failure. Fontan-associated liver disease (FALD) is the most frequent end-organ dysfunction. Although impaired hemodynamics and Fontan failure correlate with FALD severity, no association between hepatic functional metabolic impairment and Fontan hemodynamics has been established. Hypothesis: Metabolic liver function measured by liver maximum function capacity test (LiMAx®) correlates with Fontan hemodynamics and Fontan failure. Methods: From 2020 to 2022, 58 adult Fontan patients [median age: 29.3 years, IQR (12.7), median follow-up time after Fontan operation: 23.2 years, IQR (8.7)] were analyzed in a cross-sectional study. Hemodynamic assessment included echocardiography, cardiopulmonary exercise testing and invasive hemodynamic evaluation. Fontan failure was defined based on commonly applied clinical criteria and our recently composed multimodal Fontan failure score. Results: LiMAx® test revealed normal maximum liver function capacity in 40 patients (>315 µg/h*kg). In 18 patients a mild to moderate impairment was detected (140-314 µg/h*kg), no patient suffered from severe hepatic deterioration (≤ 139 µg/kg*h). Fontan failure was present in 15 patients. Metabolic liver function was significantly reduced in patients with increased pulmonary artery pressure (p = 0.041. r = -0.269) and ventricular end-diastolic pressure (p = 0.033, r = -0.325), respectively. In addition, maximum liver function capacity was significantly impaired in patients with late Fontan failure (289.0 ± 99.6 µg/kg*h vs. 384.5 ± 128.6 µg/kg*h, p = 0.007). Conclusion: Maximum liver function capacity as determined by LiMAx® was significantly reduced in patients with late Fontan failure. In addition, elevated pulmonary artery pressure and end-diastolic ventricular pressure were associated with hepatic functional metabolic impairment.
ABSTRACT
Objectives: Fontan-associated liver disease (FALD) is the most common end-organ dysfunction affecting up to 70-80% of the Fontan population. The clinical significance of FALD is incompletely understood and no unambiguous correlation between hepatic function and FALD severity has been established. In this study, we sought to evaluate maximal liver function capacity with liver maximum function capacity test (LiMAx®) in adult Fontan patients. Methods: Thirty-nine adult Fontan patients (median age: 29.4 years [IQR 23.4; 37.4], median follow-up after Fontan operation: 23.9 years [IQR 17.8;26.4]) were analyzed in a cross-sectional observational study using LiMAx® test (Humedics GmbH, Berlin, Germany), laboratory testing, transient elastography (TE) and hepatic ultrasound. The LiMAx® test is based on the metabolism of 13C-methacetin, which is administered intravenously and cleaved by the hepatic cytochrome P4501A2 to paracetamol and 13CO2, which is measured in exhaled air and correlates with maximal liver function capacity. Results: Maximal liver function capacity assessed by LiMAx® test was normal in 28 patients (>315 µg/h*kg) and mildly to moderately impaired in 11 patients (140-314 µg/h*kg), while no patient displayed severe hepatic impairment (<139 µg/kg*h). No correlation was found between maximal liver function capacity and hepatic stiffness by TE (r 2 = -0.151; p = 0.388) or the presence of sonographic abnormalities associated with FALD (r 2 = -0.204, p = 0.24). There was, however, an association between maximal liver function capacity and the laboratory parameters bilirubin (r 2 = -0.333, p = 0.009) and γ-glutamyl transferase (r 2 = -0.367; p = 0.021). No correlation was detected between maximal liver function capacity and the severity of FALD (r 2 = -0.235; p = 0.152). Conclusion: To the best of our knowledge, this is the first study to evaluate maximal liver function capacity using LiMAx® test in Fontan patients, which is a useful complementary diagnostic instrument to assess chronic hepatic injury. Maximal liver function capacity was preserved in most of our adult Fontan patients despite morphologic evidence of FALD. Moreover, maximal liver function capacity does not correlate with the extent of FALD severity evaluated by sonography or laboratory analysis. Thus, the development and progression of FALD in Fontan patients is not a uniform process and diagnostics of chronic hepatic injury during follow-up should encompass various modalities.
