IN CHILDREN WITH FONTAN PHYSIOLOGY, LIVER STIFFNESS IS CORRELATED WITH AGE, TIME SINCE FONTAN COMPLETION AND BIOCHEMICAL MARKERS OF LIVER DISEASE

Abstract

Liver disease is of growing concern in children and young adults with Fontan physiology. The natural history of liver disease is this patient population is not presently well defined, largely because a definitive diagnosis is reliant on invasive liver biopsy. Non-invasive investigations to detect liver pathology in Fontan patients have not yet been validated. Transient elastography (TE), to assess liver stiffness, is a validated measurement of liver fibrosis in patients a number of chronic liver diseases. This modality may represent a non-invasive method to assess liver fibrosis in pediatric Fontan patients. We hypothesized that TE values would be associated with age and biochemical markers of liver disease in children with Fontan physiology. We prospectively enrolled 60 patients with Fontan physiology at British Columbia Children’s Hospital. All patients underwent comprehensive liver evaluation including liver enzymes (ALT, AST, GGT, ALP), albumin, bilirubin, INR, CBC, abdominal ultrasound, and TE measurement. The AST to platelet ratio index (APRI) was calculated from the laboratory results. Trained personnel obtained TE measurements of liver stiffness using age-specific probes. A total of 86 TE measurements were performed on 60 unique patients with a median age of 11.3 years (interquartile range 7.7-14.7 years, 55% male). There was a significant correlation between liver stiffness and both the time since Fontan completion (rho=0.45, p < 0.001) and age at the time of TE measurement (rho=0.48, p < 0.001). In addition, there was a significant correlation between liver stiffness and laboratory measures of liver health including APRI (rho=0.39, p=0.01), AST (rho=-0.50, p < 0.01), and INR (rho=0.3128, p=0.05). Findings on ultrasound imaging of the liver and spleen did not correlate with liver stiffness. This represents the largest reported cohort of pediatric Fontan patients to undergo TE as part of a comprehensive liver assessment. While liver stiffness is elevated in the early post Fontan period, we found that TE measurements of liver stiffness increased with both age and time from Fontan completion. Furthermore, the rise in liver stiffness over time was also associated with worsening biochemical markers of liver disease. Our results support the notion that liver disease begins in childhood in this population, and that TE measurement of liver stiffness may be a non-invasive method to identify and monitor the progress of liver disease in pediatric Fontan patients.