Predictive models and clinical manifestations of intrapulmonary vascular dilatation and hepatopulmonary syndrome in patients with cirrhosis: Prospective comparative study

Figure 1 Flow diagram of patient enrollment. CE-TTE: Contrast-enhanced transthoracic echocardiography; HPS: Hepatopulmonary syndrome; IPVD: Intrapulmonary vascular dilatation.

Figure 2 Novel biomarkers for intrapulmonary vascular dilatation and hepatopulmonary syndrome in patients with cirrhosis. Comparisons among multiple groups were performed using the Kruskal-Wallis rank sum test. A: Serum sphingosine 1 phosphate concentration; B: Serum angiopoietin-2 concentration; C: Serum platelet-derived growth factor BB concentration. HPS: Hepatopulmonary syndrome; IPVD: Intrapulmonary vascular dilatation; PDGF-BB: Platelet-derived growth factor BB; S1P: Sphingosine 1 phosphate.

Figure 3 Receiver operating characteristic curves for predicting intrapulmonary vascular dilatation and hepatopulmonary syndrome by different parameters. A: Predicting intrapulmonary vascular dilatation (IPVD) in patients with cirrhosis. Area under the curve (AUC) for: Age was 0.613 (95% confidence interval [CI]: 0.546-0.679), Model for End-Stage Liver Disease (MELD) (score) 0.691 (95%CI: 0.629-0.753), arterial oxygen pressure 0.565 (95%CI: 0.496-0.633), reticulocalbin 3 0.587 (95%CI: 0.518-0.656), sphingosine 1 phosphate (S1P) 0.649 (95%CI: 0.584-0.714), angiopoietin-2 0.699 (95%CI: 0.638-0.760), and platelet-derived growth factor BB (PDGF-BB) 0.647 (95%CI: 0.583-0.711); B: Predicting hepatopulmonary syndrome (HPS) in patients with cirrhosis. AUC for age was 0.618 (95%CI: 0.542-0.693), pulmonary alveolar-arterial oxygen gradient (P(A-a)O₂) 0.837 (95%CI: 0.790-0.885), hemoglobin (HGB) 0.674 (95%CI: 0.600-0.749), total bilirubin (TBIL) 0.749 (95%CI: 0.681-0.818), albumin (ALB) 0.734 (95%CI: 0.667-0.801), S1P 0.635 (95%CI: 0.556-0.713); angiopoietin-2 0.726 (95%CI: 0.652-0.800), and PDGF-BB 0.599 (95%CI: 0.519-0.679). FPR: False-positive rate; TPR: True-positive rat.

Figure 4 Heatmap depicting the correlation between clinical parameters and biomarkers. A: The values are presented as Spearman’s correlation coefficient (r) for a sample of 320 runners. The colormap ranges from 1 to -1, with blue indicating the highest value and red indicating the lowest value; B: Heatmap of corresponding P values. The colormap ranges from 0 to 1, with blue representing the largest value and white representing the smallest value. White cells without numerical values indicate that the P value is smaller than 0.001, indicating a highly significant correlation. DBIL: Direct bilirubin; ICAM-1: Intercellular adhesion molecule-1; INR: International normalized ratio; MELD: Model for End-Stage Liver Disease; P(A-a)O₂: Alveolar-arterial oxygen gradient; PaO₂: Partial pressure of oxygen in arterial blood; PaCO₂: Partial pressure of carbon dioxide in arterial blood; PDGF-BB: Platelet-derived growth factor BB; PH: Potential of hydrogen; PT: Prothrombin time; PTA: Prothrombin time activity; S1P: Sphingosine 1 phosphate; SpO₂: Peripheral oxygen saturation; TBIL: Total bilirubin; TNF: Tumor necrosis factor; VCAM-1: Vascular cell adhesion molecule-1; VEGF-A: Vascular endothelial growth factor A; vWF: Von Willebrand factor.

Figure 5 Predictive model for intrapulmonary vascular dilatation combining clinical parameters and biomarkers. A: Nomogram of the predictive model for intrapulmonary vascular dilatation (IPVD) in patients with cirrhosis. This model integrates four clinical parameters and three biomarkers; B: Receiver operating characteristic (ROC) curve predicting IPVD in patients with cirrhosis. Area under the curve (AUC) was 0.792 (95% confidence interval [CI]: 0.737-0.847); C: Calibration curves; D: Decision curve analysis of the nomogram for the prediction of IPVD. FPR: False-positive rate; MELD: Model for End-Stage Liver Disease; P(A-a)O₂: Alveolar-arterial oxygen gradient; PDGF-BB: Platelet-derived growth factor BB; S1P: Sphingosine 1 phosphate; TPR: True-positive rate.

Figure 6 Predictive model for hepatopulmonary syndrome combining clinical parameters and biomarkers. A: Nomogram of the predictive model for hepatopulmonary syndrome (HPS) in patients with cirrhosis. This model integrates two clinical parameters and six biomarkers; B: Receiver operating characteristic (ROC) curve predicting HPS in patients with cirrhosis. Area under the curve (AUC) was 0.891 (95% confidence interval [CI]: 0.848-0.934); C: Calibration curves; D: Decision curve analysis of the nomogram for the prediction of HPS. ALB: Albumin; HGB: Hemoglobin; FPR: False-positive rate; P(A-a)O₂: Alveolar-arterial oxygen gradient; PDGF-BB: Platelet-derived growth factor BB; S1P: Sphingosine 1 phosphate; TBIL: Total bilirubin; TPR: True-positive rate.