Sidali Sabrina, Spaes Ylang, El Husseini Kinan, Goria Odile, Mallet Vincent, Poujol-Robert Armelle, Gervais Anne, Lannes Adrien, Thabut Dominique, Nousbaum Jean-Baptiste, Hourmand-Ollivier Isabelle, Costentin Charlotte, Heurgué Alexandra, Houssel-Debry Pauline, Hillaire Sophie, Ganne-Carrié Nathalie, Drilhon Nicolas, Valainathan Shanta Ram, Moga Lucile, Tanguy Marion, Marcault Estelle, Plessier Aurélie, Durand François, Raevens Sarah, Paradis Valérie, Cachier Agnès, Elkrief Laure, Rautou Pierre-Emmanuel
Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France.
AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France.
JHEP Rep. 2024 Dec 20;7(4):101310. doi: 10.1016/j.jhepr.2024.101310. eCollection 2025 Apr.
BACKGROUND & AIMS: Porto-sinusoidal vascular disorder (PSVD) is a rare cause of portal hypertension. Data on hepatopulmonary syndrome (HPS) in PSVD are limited. This study aimed to determine the associated factors, plasma mediators, and evolution of HPS in patients with PSVD.
Multicenter observational study of patients with PSVD with signs of portal hypertension in whom contrast-enhanced transthoracic echocardiography (CE-TTE) was performed.
Among 196 patients with PSVD who underwent CE-TTE in 17 centers, 14 (7% [95% confidence interval 3-11%]) had a confirmed diagnosis of HPS. Patients with HPS more frequently had a genetic disorder associated with PSVD (50% 6%, <0.001), especially telomere biology disorders ( <0.001). Liver function was less preserved in patients with HPS, because they had lower prothrombin index (63% 86%, = 0.04), higher serum total bilirubin (37 μmol/L 14 μmol/L, <0.001), and lower serum albumin (32 g/L 38 g/L, <0.001). HPS tended to be associated with more portal venule obliterations ( = 0.085) and with nodular liver architecture ( = 0.069). Plasma concentrations of Angiopoietin-2, ICAM3, and Tie2 were higher in patients with HPS ( = 0.02, = 0.04, = 0.01, respectively). Out of the 14 patients with HPS, five underwent liver transplantation after a median follow-up of 34 months. Overall cumulative incidence of liver-related events and of death was similar between patients with and without HPS, when considering liver transplantation for HPS as a competing risk.
HPS in patients with PSVD was associated with genetic disorders, less preserved liver function, and higher plasma concentrations of angiogenic mediators. When applying HPS model for end-stage liver disease exception policy for liver transplantation, overall survival of patients with PSVD and HPS was similar to that of patients with PSVD without HPS.
Hepatopulmonary syndrome (HPS) is a rare complication of porto-sinusoidal vascular disorder (PSVD). This multicentric study found that patients with PSVD and HPS had less preserved liver function, and harbored genetic disorders more frequently (especially telomere biology disorders) than patients without HPS. HPS did not negatively impact transplantation-free survival when applying HPS MELD exception policy for liver transplantation through a competitive risk analysis. Our findings suggest that patients with PSVD with respiratory symptoms and/or telomere biology disorders may benefit from systematic screening for HPS.
门静脉窦状隙血管疾病（PSVD）是门静脉高压的一种罕见病因。关于PSVD合并肝肺综合征（HPS）的数据有限。本研究旨在确定PSVD患者中HPS的相关因素、血浆介质及病情演变。
对有门静脉高压体征的PSVD患者进行多中心观察性研究，并进行经胸对比增强超声心动图（CE-TTE）检查。
在17个中心接受CE-TTE检查的196例PSVD患者中，14例（7%[95%置信区间3%-11%]）确诊为HPS。HPS患者更常伴有与PSVD相关的遗传性疾病（50%对6%，P<0.001），尤其是端粒生物学疾病（P<0.001）。HPS患者的肝功能保存较差，因为他们的凝血酶原指数较低（63%对86%，P=0.04），血清总胆红素较高（37μmol/L对14μmol/L，P<0.001），血清白蛋白较低（32g/L对38g/L，P<0.001）。HPS倾向于与更多的门静脉小分支闭塞相关（P=0.085）以及与结节状肝脏结构相关（P=0.069）。HPS患者血浆血管生成素-2、细胞间黏附分子3和酪氨酸激酶2的浓度较高（分别为P=0.02、P=0.04、P=0.01）。在14例HPS患者中，5例在中位随访34个月后接受了肝移植。将HPS患者的肝移植视为竞争风险时，有HPS和无HPS患者的肝脏相关事件和死亡的总体累积发生率相似。
PSVD患者中的HPS与遗传性疾病、肝功能保存较差以及血管生成介质的血浆浓度较高有关。当将HPS模型应用于肝移植的终末期肝病例外政策时，PSVD合并HPS患者的总体生存率与无HPS的PSVD患者相似。
肝肺综合征（HPS）是门静脉窦状隙血管疾病（PSVD）的一种罕见并发症。这项多中心研究发现，与无HPS的患者相比，PSVD合并HPS的患者肝功能保存较差，且更常患有遗传性疾病（尤其是端粒生物学疾病）。通过竞争风险分析，在将HPS模型应用于肝移植的HPS终末期肝病模型（MELD）例外政策时，HPS对无移植生存率没有负面影响。我们的研究结果表明，有呼吸道症状和/或端粒生物学疾病的PSVD患者可能受益于系统性的HPS筛查。
