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Rationale: Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced BMP-9 (bone morphogenetic protein-9) in maintaining pulmonary vascular integrity. Objectives: This study aimed to investigate the involvement of BMP-9 in human and experimental HPS. Methods: Circulating BMP-9 levels were measured in 63 healthy control subjects and 203 patients with cirrhosis with or without HPS. Two animal models of portal hypertension were employed: common bile duct ligation with cirrhosis and long-term partial portal vein ligation without cirrhosis. Additionally, the therapeutic effect of low-dose BMP activator FK506 was investigated, and the pulmonary vascular phenotype of BMP-9–knockout rats was analyzed. Measurements and Main Results: Patients with HPS related to compensated cirrhosis exhibited lower levels of circulating BMP-9 compared with patients without HPS. Patients with severe cirrhosis exhibited consistently low levels of BMP-9. HPS characteristics were observed in animal models, including intrapulmonary vascular dilations and an increase in the alveolar-arterial gradient. HPS development in both rat models correlated with reduced intrahepatic BMP-9 expression, decreased circulating BMP-9 level and activity, and impaired pulmonary BMP-9 endothelial pathway. Daily treatment with FK506 for 2 weeks restored the BMP pathway in the lungs, alleviating intrapulmonary vascular dilations and improving gas exchange impairment. Furthermore, BMP-9–knockout rats displayed a pulmonary HPS phenotype, supporting its role in disease progression. Conclusions: The study findings suggest that portal hypertension–induced loss of BMP-9 signaling contributes to HPS development. [ABSTRACT FROM AUTHOR]

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features—intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

Background: One of the severe complications of liver disease is hepatopulmonary syndrome (HPS). There is paucity in literature regarding the various factors associated with the development of HPS. This study was conducted to analyze the prevalence and determinants of HPS among patients with decompensated chronic liver disease (CLD). Methods: This study was a cross-sectional–observational study conducted in a tertiary care center. Decompensated CLD patients admitted for pre-liver transplant workup were included in the study. Demographic data, clinical findings, and biochemical and hematologic parameters were collected. Pulse oximetry, arterial blood gas analysis, bubble contrast echocardiogram, diffusion capacity of the lungs for carbon monoxide (DLCO), and spirometry were done to get the needed parameters. All data were entered into a Microsoft Excel sheet and analyzed using the statistical software SPSS for Windows, version 22.0. Results: Among 64 subjects, 58 were men (90.6%). Mean age was 54.5 years. HPS was present in 26 (40.6%) patients. Platypnea and orthodeoxia were present more often in HPS patients. DLCO was significantly impaired among patients with HPS. Portopulmonary hypertension was seen in 8 (12.5%) subjects with no difference between HPS and non-HPS patients. Subjects with HPS had more severe liver disease. A model for end-stage liver disease (MELD)-Na score > 19 was associated with HPS (sensitivity 73.08%, specificity 65.79%, PPV 59.4%, and NPV 78.1%). Multivariate analysis (binary logistic regression) revealed that a higher MELD-Na score, hepatic encephalopathy, and impaired DLCO were independently associated with HPS. Conclusions: HPS is associated with more severe liver disease (as per Child-Turcotte-Pugh [CTP] stage and MELD-Na score). There was no relation between HPS and causes of CLD. Higher MELD-Na score, hepatic encephalopathy, impaired DLCO, clubbing, and spider naevi were independently associated with HPS. [ABSTRACT FROM AUTHOR]

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features-intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cook, Liu, Li, Jiang and Li.)

Summary: A 51 years old male patient was referred for dyspnoea on minimal exertion associated with a severe hypoxemia (PaO2=66mmHg) and respiratory alkalosis. Investigations led to the diagnosis of hepatopulmonary syndrome. PaO2 increased from 60 to 75mmHg after one hour of i.v. almitrine bismesylate infusion, and it remained at 85mmHg after 3 months of further per os treatment. This case of hepatopulmonary syndrome is the first to be persistently improved by almitrine bismesylate. Increase of PaO2 would at least delay the hepatic transplantation. [Copyright &y& Elsevier]

Hepatopulmonary syndrome (HPS) is a common pulmonary complication in patients with liver disease and / or portal hypertension, and is characterized by abnormal arterial oxygenation caused by intrapulmonary vascular dilatation. The pathogenesis of HPS is complex, with a low clinical early diagnosis rate and poor prognosis. HPS currently lacks effective therapeutic drugs; therefore, liver transplantation is the only fundamental treatment. This article summarizes the pathogenesis, clinical manifestations, diagnosis and treatment of HPS in order to further improve the level of clinical screening and diagnosis and treatment of HPS.