The Different Effects of Direct Bilirubin on Portopulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension

Background. To observe different roles of direct bilirubin (Dbil) on portopulmonary hypertension (POPH) and idiopathic pulmonary arterial hypertension (IPAH). Methods. Thirty incident patients with POPH and 180 with IPAH (matched by the WHO functional classification in a 1:6 ratio) between March 2010 and December 2020 were included. The receiver operating curve and Kaplan-Meier method were applied to estimate the ability to distinguish between the two and survival, respectively. Univariate and forward multiple stepwise regression analyses were performed to access the relationship between pulmonary vascular resistance (PVR) and clinical indices. Results. Compared to IPAH, the POPH group had better hemodynamics including PVR (7.08 +/- 3.95 vs. 14.89 +/- 7.11, P<0.001) and higher total bilirubin (Tbil) and Dbil. Tbil and Dbil had a negative correlation with PVR in the POPH group (r=-0.394, P=0.031; r=-0.364, P=0.048, respectively) but positive correlation in the IPAH group (r=0.218, P=0.003; r=0.178, P=0.018, respectively). Increased neutrophil counts (r=0.394, P=0.031) and elevated NT-proBNP (r=0.433, P<0.001) would help predict the elevation of PVR in POPH and IPAH groups independent of Dbil, respectively. Dbil could distinguish POPH from IPAH (AUC=0.799, P=0.009), and the ability was elevated when taking aspartate aminotransferase together (AUC=0.835, P<0.001). The overall survival was better in POPH than in IPAH (7 dead cases of POPH and 96 of IPAH, P=0.002). Survival was better in POPH than in IPAH in the group of Dbil 7 mu mol/L (P=0.001) but showed no significant difference between POPH and IPAH in the group of Dbil <7mol/L (P=0.192). Conclusions. The POPH group had a better hemodynamic profile than IPAH. Dbil was associated oppositely with the elevation of PVR in POPH and IPAH. Patients with POPH had better survival than those with IPAH in the total cohort and in the group of Dbil >= 7 mu mol/L, but limited dead cases of POPH should be noted.