Clinical Characteristics Associated With Variability in Biopsy Grade Severity of Liver Fibrosis in Fontan Circulation

Liver fibrosis in Fontan circulation (FC) is universal with variable severity. We explore associations between patient-specific characteristics and fibrosis magnitude measured by liver biopsy.

The purpose of this study was to identify clinical and hemodynamic factors associated with fibrosis severity in FC, quantified by Sirius red staining of liver biopsy specimens, and to evaluate relationships with patient characteristics, Fontan hemodynamics, and noninvasive liver assessments.

Subjects with FC underwent a standardized evaluation including cardiac catheterization, percutaneous liver biopsy, liver elastography, and blood laboratories. Sirius red % staining was used to quantitatively assess collagen deposition per liver tissue to measure fibrotic severity and associations with clinical characteristics explored.

Among 173 subjects, median age at Fontan operation (FO) was 2.2 years (range: 0.5-15), and median age at biopsy was 17.5 years (range: 4.7-39.4). Sixty-seven percent had dominant right ventricular morphology. Median systemic venous pressure at catheterization was 13 mm Hg (IQR: 11.0,15.0). Median Sirius red % staining was 21.6% (IQR: 17.3,30.2). Sirius red % staining was not associated with ventricular morphology, catheter hemodynamics, or liver elastography. Sirius red % staining correlated with aspartate aminotransferase/platelet ratio (P = 0.026). Years of FC exposure correlated positively with Sirius red % staining, hemoglobin, gamma glutamyl transferase, and liver elastography. Age at FO was inversely correlated with Sirius red % staining.

Liver fibrosis in FC progresses with duration of exposure, independent of venous pressure, suggesting ongoing fibrogenesis even at acceptable hemodynamics. Younger age at FO is associated with greater fibrosis severity and may represent a modifiable factor influencing liver health.