Subclinical liver dysfunction (MELD-Na ≥ 12) in PAH patients was associated with higher pulmonary vascular resistance (ß = 0.5; 95% CI 0.2-0.8; p=0.005) and decreased 6-minute walk distance.
Observational (n=25)
Subclinical liver dysfunction in PAH patients without overt liver disease is associated with worse hemodynamics and functional capacity, suggesting a lung-liver axis in PAH pathogenesis.
Effect estimate: ß = 0.5 (95% CI 0.2-0.8)
p-value: p=0.005
ABSTRACT The liver's contribution to pulmonary arterial hypertension (PAH) pathogenesis remains unclear. We hypothesized that the liver promotes inflammatory injury to the pulmonary endothelium. PAH patients without liver disease with pulmonary artery endothelial cell (PAEC) biopsies were included. Unsupervised CART analysis of liver serologies identified subclinical dysfunction clusters; machine‐learning models informed differential expression and protein–protein interaction network assembly. PAEC transcriptomes were compared to liver and lung data from monocrotaline and Sugen‐Hypoxia rats. Liver fibrosis was assessed in rat and human PAH livers. Among 25 PAH patients (76% female, median age 61 30–84 years), CART identified clusters distinguished by Model for End‐Stage Liver Disease Sodium (MELD‐Na) ≥ 12, which was associated with higher Fibrosis‐4 scores and higher pulmonary vascular resistance (ß = 0.5 Wood units per point increase in MELD‐Na, 95% CI 0.2–0.8, p = 0.005) after adjustment for right atrial pressure. Subjects with MELD‐Na ≥ 12 had decreased 6‐min walk distance (353 120–576 m vs. 411 300–600 m, p = 0.03). In comparing the two clusters, a protein–protein interaction network analysis identified IL‐6 as the primary hub of a transcriptional module enriched for leukocyte chemotaxis and myeloid leukocyte migration (all FDR < 0.05) among the High‐MELD‐Na group. Rat livers demonstrated immune activation and a trend toward increased fibrosis (20.8 vs. 16.6% area stained, p = 0.09), and human PAH livers without liver disease showed an intermediate fibrotic phenotype between controls and portopulmonary hypertension, though this did not reach statistical significance. Our observations support a lung–liver axis in PAH even in the absence of liver disease, warranting further study.
Singh et al. (Fri,) conducted a observational in Pulmonary arterial hypertension (n=25). MELD-Na ≥ 12 vs. MELD-Na < 12 was evaluated on Pulmonary vascular resistance (ß = 0.5, 95% CI 0.2-0.8, p=0.005). Subclinical liver dysfunction (MELD-Na ≥ 12) in PAH patients was associated with higher pulmonary vascular resistance (ß = 0.5; 95% CI 0.2-0.8; p=0.005) and decreased 6-minute walk distance.