Jose Arun, Yogeswaran Athiththan, Fuenderich Meike, Kiely David, Sweatt Andrew J, Zamanian Roham T, Hassoun Paul M, Mouawad Antoine, Balasubramanian Aparna, Wilkins Martin, Lawrie Allan, Howard Luke, Sahay Sandeep, Olschewski Horst, Kovacs Gabor, Saleh Khaled, Sabbour Hani, Eichstaedt Christina A, Grünig Ekkehard, Giannakoulas George, Arvanitaki Alexandra, Sirenko Yuriy, Torbas Olena, Cajigas Hector, Frantz Robert, Scelsi Laura, Ghio Stefano, Majeed Raphael W, Wilhelm Jochen, Ghofrani Hossein Ardeschir, Grimminger Friedrich, Tello Khodr, Elwing Jean, Seeger Werner
Division of Pulmonary & Critical Care University of Cincinnati Cincinnati Ohio USA.
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC) Member of the German Center for Lung Research (DZL) Giessen Germany.
Pulm Circ. 2025 Jul 8;15(3):e70121. doi: 10.1002/pul2.70121. eCollection 2025 Jul.
Portopulmonary hypertension (PoPH), a type of pulmonary arterial hypertension (PAH) in patients with liver disease, is associated with high morbidity and mortality. The relationship between cardiopulmonary hemodynamics, PAH therapy, and survival in PoPH remains unclear. We performed a retrospective cohort study of PoPH patients from the international pulmonary hypertension (PH) meta-registry, PVRI GoDeep. PAH was defined by a mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) > 2 Wood Units. PoPH diagnoses were assigned by each center's PH specialist based on international guidelines at the time of enrollment. 246 incident PoPH patients met eligibility criteria and were included in the analysis, equally split between males (51%) and females (49%), with a median age of 54 years. When compared to both patients with IPAH and those with other subtypes of PAH (not classified as PoPH or IPAH), those with PoPH had significantly lower 5-year survival rates (46% vs. 68% vs. 65%, log-rank < 0.001). Amongst the PoPH patients, however, there was no significant difference in 5-year survival when dichotomized by disease severity, either by a PVR of 5 Wood Units or a CI of 2.5 L/min/m. Treatment of the PoPH patients with PAH-targeted therapies was associated with significantly higher 5-year survival rates compared to those not receiving such treatments, as shown by Kaplan-Meier analysis. This survival benefit was observed for PDE5i (50% vs. 34%, log-rank = 0.029), ERA (58% vs. 34%, log-rank < 0.001), and the combination of PDE5i and/or ERA (51% vs. 22%, log-rank < 0.001), as well as any PAH-targeting treatment (50% vs. 26%, log-rank = 0.007). Corresponding survival advantage was noted when including only PoPH patients with MELD Score ≥ 13. PoPH is a disease with significantly worse long-term survival than other PAH subtypes, but targeted PAH therapy is associated with a robust survival benefit. Survival did not differ across high-risk PVR and cardiac index thresholds, suggesting the factors that influence prognosis and survival in PoPH may be unique as compared to other PAH subtypes, and warrant further investigation.
门肺高压（PoPH）是肝病患者中一种类型的肺动脉高压（PAH），与高发病率和高死亡率相关。心肺血流动力学、PAH治疗与PoPH患者生存率之间的关系仍不清楚。我们对来自国际肺动脉高压（PH）荟萃登记库PVRI GoDeep的PoPH患者进行了一项回顾性队列研究。PAH的定义为平均肺动脉压>20 mmHg、肺动脉楔压≤15 mmHg以及肺血管阻力（PVR）>2伍德单位。PoPH诊断由每个中心的PH专科医生在入组时根据国际指南进行判定。246例新发PoPH患者符合纳入标准并被纳入分析，男性（51%）和女性（49%）人数相等，中位年龄为54岁。与特发性肺动脉高压（IPAH）患者以及其他PAH亚型（未分类为PoPH或IPAH）的患者相比，PoPH患者的5年生存率显著更低（46% 对 68% 对 65%，对数秩检验<0.001）。然而，在PoPH患者中，根据疾病严重程度进行二分，无论是PVR为5伍德单位还是心脏指数为2.5 L/min/m²，5年生存率均无显著差异。与未接受此类治疗的患者相比，用PAH靶向治疗方法治疗PoPH患者的5年生存率显著更高，如Kaplan-Meier分析所示。观察到磷酸二酯酶5抑制剂（PDE5i）（50% 对 34%，对数秩检验=0.029）、内皮素受体拮抗剂（ERA）（58% 对 34%，对数秩检验<0.001）以及PDE5i和/或ERA联合使用（51% 对 22%，对数秩检验<0.001），以及任何PAH靶向治疗（50% 对 26%，对数秩检验=0.007）均有生存获益。仅纳入终末期肝病模型（MELD）评分≥13的PoPH患者时，也观察到了相应的生存优势。PoPH是一种长期生存率明显低于其他PAH亚型的疾病，但PAH靶向治疗与显著的生存获益相关。在高风险PVR和心脏指数阈值范围内，生存率没有差异，表示与其他PAH亚型相比，影响PoPH预后和生存的因素可能是独特的，值得进一步研究。
