Background: Mac-2 binding protein glycosylation isomer (M2BPGi) is a validated biomarker for liver fibrosis in chronic liver disease. We investigated the clinical significance of serum M2BPGi concentrations in patients with Fontan circulation.
Methods and results: We prospectively measured serum M2BPGi concentrations in 426 consecutive Fontan patients (mean [±SD] age 23±10 years) and analyzed their associations with patients' pathophysiology, including Fontan-associated liver disease (FALD), as well as all-cause unplanned hospitalization (UPH) and mortality. M2BPGi concentrations were associated with a wide range of Fontan-related pathophysiological features, including characteristic Fontan hemodynamics, total bile acid concentrations, FALD indices such as hepatic fibrosis markers and ultrasonographic image abnormalities, and impaired renal function. Among these variables, older age at Fontan operation, hypoxemia, C-reactive protein, total bile acid levels, and indices of hepatic fibrosis were independently associated with higher M2BPGi concentrations (P<0.05-0.001). During follow-up after the M2BPGi evaluation, 68 patients experienced UPH and 14 patients died. Elevated M2BPGi concentrations were associated with a higher risk of UPH and all-cause mortality (P<0.0001 for both), independent of elevated B-type natriuretic peptide levels.
Conclusions: Serum M2BPGi concentrations reflect both FALD pathophysiology and hemodynamic burden, serving as a strong prognostic biomarker. M2BPGi can be a valuable tool for risk stratification in patients with Fontan failure, including those with FALD.
Keywords: Fontan-associated liver disease; Hemodynamics; Liver fibrosis; Mac-2 binding protein glycosylation isomer (M2BPGi); Mortality.