Fontan-Associated Liver Disease: Trends Over Time and Relationship With Outcomes

Fontan associated liver disease is a poorly understood complication of long-term single ventricle palliation. This study sought to describe serial liver function changes in patients with a Fontan circulation from 2014 to 2020 and determine if these findings can be used to predict adverse clinical outcomes.

We conducted a retrospective chart review of Fontan patients age≥18 who were followed by a specialist clinic between 2014 and 2020. Annual bloodwork, including liver enzymes and AFP (alpha-fetoprotein), and liver imaging were analyzed. Common liver function scores were calculated. Trends over time and their correlation to clinical events were assessed. Events were defined as congestive heart failure, cardiac hospitalization, thrombosis, protein losing enteropathy, and death. The study assessed possible associations with the composite event of adverse outcomes.

One hundred twelve Fontan patients were included with a mean age of 24.9±8.1 years. Age-adjusted AFP and creatinine increased over the study period, whereas alkaline phosphatase decreased. There was no significant change in other liver biomarkers over the study period. The proportion of patients with higher liver imaging scores increased over the study period. Over a follow-up time of 6.1 years (95% control limit, 5.5-6.9 years), 44 (39.3%) patients experienced at least 1 event, most commonly cardiac hospitalization. In multivariable analysis, age was associated with a greater risk of events (hazard ratio, 1.035 [95% CI, 1.008-1.063]; P=0.010); no other biomarkers or scores were significant.

Routine liver biomarkers do not increase over time despite increasing proportion of patients with higher liver imaging scores over the same time. Although our sample size was limited, current modalities to assess progression of liver dysfunction on bloodwork and imaging were not related to clinical outcomes.