Abstract Body (Do not enter title and authors here): Abstract
Background: Mounting evidence indicates that non-invasive liver fibrosis scores (LFs) are associated with various cardiovascular diseases, but their role in pulmonary arterial hypertension (PAH) is not yet clear. This study aims to explore the relationship between LFs and PAH.
Methods: The study enrolled 1048 patients with PAH from January 2017 to January 2021, comprising individuals with idiopathic PAH and PAH related to congenital heart disease. Fibrosis-5 score (FIB-5), fibrosis-4 score (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI) and Forns score (FC) were used to evaluate the degree of liver fibrosis in patients with PAH. The association of ILs with European Society of Cardiology (ESC) risk stratification was evaluated using one-way ANOVA. The correlation between LFs and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. Subgroup analyses, predicated on age, sex, World Health Organization functional class and body mass index, were carried out to evaluated interaction effects.
Results: During a mean of 40.8 months’ follow-up, 283 participants experienced all-cause death or worsening condition. With higher ESC risk stratification, PAH patients had significantly lower FIB-5 (4.563±4.118 vs. 3.475±10.693 vs. 2.444±5.454 vs. 0.924±4.10, P=0.003) and higher FC (5.661±1.762 vs. 5.983±1.897 vs. 6.506±1.919 vs. 7.230±1.900，P<0.001). After adjusting for confounding factors, multivariable Cox regression models indicated that FIB-5 (hazard ratio [HR] 0.968, 95% confidence interval [CI] 0.949-0.988, P = 0.005) and FIB-4 (HR 1.905, 95% CI 1.388-2.614, P＜0.001) independently predicted adverse outcomes. The highest predictive performance was observed for FIB-5 compared to other LFSs. No significant interaction effect was observed in the subgroup analysis.
Conclusions: Liver fibrosis was associated with disease severity and long-term prognosis in patients with PAH. The markers FIB-5 and FIB-4 serve as independent predictors of clinical deterioration in patients with PAH.