Portopulmonary hypertension correlated with portal vein overload

The interesting case reported by Qian et al. 1 Qian K. Yang N. Lin C. et al. Portopulmonary hypertension: a complex case derived from multiple penetrating trauma-induced mesenteric arteriovenous fistulae. Ann Vasc Surg. 2019; 58: 378.e11-378.e15 Abstract Full Text Full Text PDF Scopus (2) Google Scholar concerning mesenteric arteriovenous fistulae, clinically evident after the onset of a portopulmonary hypertension, deserves to be further considered also from a pathophysiological point of view. The patient’s history began with acquired mesenteric arteriovenous fistulae leading to a secondary overload of the portal vein system, demonstrated by angiography with an increased size of the portomesenteric trunk and by ultrasound with an estimated pressure value of 27 cm H2O. However, this portal hypertension was not followed by the development of portosystemic collaterals. 2 Guzman E.A. McCahile L.E. Rogers F.B. Arterioportal fistulas: introduction of a novel classification with therapeutical implications. J Gastrointest Surg. 2006; 10: 543-550 Crossref PubMed Scopus (79) Google Scholar The condition became clinically evident after 15 years for a severe pulmonary artery hypertension, without computed tomography signs of pulmonary fibrosis or embolism. This portopulmonary syndrome resolved after treatment of the mesenteric arteriovenous fistulae. 1 Qian K. Yang N. Lin C. et al. Portopulmonary hypertension: a complex case derived from multiple penetrating trauma-induced mesenteric arteriovenous fistulae. Ann Vasc Surg. 2019; 58: 378.e11-378.e15 Abstract Full Text Full Text PDF Scopus (2) Google Scholar First, we underline the peculiar acquired hemodynamics of the portal system overload, expressing with an elevated volume and pressure, easily exceeding the liver blood compliance. Surprisingly, this was not followed by a progressive fibrosis of the hepatic parenchyma evolving in cirrhosis, with consequent capillarization or neo-angiogenesis of the hepatic sinusoids. In the present case, the treatment of the arteriovenous mesenteric fistulae could have reduced, but not completely resolved the portal hypertension. 3 Zizzo M. Roncati L. Colasanto E. et al. Pancolorectal varices superimposed on arteriovenous malformations: a life-treating complex disease. Clin Res Hepatol Gastroenterol. 2016; 40: 75-76 Crossref Scopus (6) Google Scholar , 4 Da B. Koh C. Heller T. Noncirrhotic portal hypertension. Curr Opin Gastroenterol. 2018; 34: 140-145 PubMed Google Scholar Second, we interpret the pulmonary artery hypertension not like the result of a simple hemodynamic overload, sequentially involving the portal vein system, the inferior vena cava, the right heart, and the pulmonary artery, as commonly observed in the arteriovenous fistulae of the systemic circulation. This hypothesis excludes any secondary congestive hepatopathy, favored, in the reported case, by the concomitant tricuspid and pulmonary valve regurgitation. On the contrary, we suppose a more direct link between hypertension in the portal vein system and in the pulmonary artery, although not associated with liver cirrhosis. Today, this can be referred to an increased production of Endothelin-1 in the portal vein system, easily overcoming the metabolic filter of the liver and activating, through a paracrine signaling pathway, the A-vasoconstrictor receptors of the pulmonary artery tree. To a lesser extent, the same Endothelin-1 acts on the receptors of the portal vein branches by an autocrine mechanism. 5 Savale L. Watherld J. Sitbon O. Portopulmonary hypertension. Sem Resp Crit Care Med. 2017; 38: 651-661 Crossref PubMed Scopus (17) Google Scholar , 6 Rockey D.C. The molecular basis of portal hypertension. Trans Am Clin Climatol Assoc. 2017; 128: 330-345 PubMed Google Scholar , 7 Davenport A.P. Hyndman K.A. Dhaun N. et al. Endothelin Pharmacol Rev. 2016; 68: 357-418 Crossref PubMed Scopus (399) Google Scholar , 8 Huetsch J.C. Walker J. Undem C. et al. Rho kinase and Na+/H+ exchanger mediate endothelin-1 induced pulmonary arterial smooth muscle cell proliferation and migration. Physiol Rep. 2018; 6: e13698 Crossref Scopus (11) Google Scholar After surgery, both pulmonary and portal vein hypertension resolved, subsequently to an attained normal level of this vasoconstrictor. This cascade of favorable events would have been difficult to occur in case of liver cirrhosis, where a portal hypertension, although of lesser grade, would have persisted. This confirms that the humoral mechanism at the base of the portopulmonary hypertension develops in response to a portal vein hypertension, independently from a concomitant chronic liver disease, and underlines the value of an early diagnosis, before the onset of irreversible lesions, as intimal fibroelastosis and hyperplasia of the medial muscular layer in the pulmonary arterioles. 8 Huetsch J.C. Walker J. Undem C. et al. Rho kinase and Na+/H+ exchanger mediate endothelin-1 induced pulmonary arterial smooth muscle cell proliferation and migration. Physiol Rep. 2018; 6: e13698 Crossref Scopus (11) Google Scholar