Skip to main content

Advertisement

SpringerLink
Log in

Pathogenesis of Portal Hypertension: Extrahepatic Mechanisms

  • Portal Hypertension (K Brown, Section Editor)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Chronic liver diseases, including hepatic cirrhosis, chronic hepatitis, alcoholic liver disease, and hepatocellular carcinoma, are one of the commonest causes of death and liver transplantation in adults worldwide. They are accompanied by profound disturbances that are not limited to the intrahepatic circulation, but involve also the splanchnic and systemic vascular beds. These hemodynamic disturbances are responsible for the development of portal hypertension, the most frequent and severe of cirrhosis. This syndrome is characterized by a pathological increase of blood pressure in the portal vein and concomitant increases in splanchnic blood flow and portosystemic collateral vessel formation. Increased blood flow in splanchnic organs draining into the portal vein augments in turn the portal venous inflow. Such increased portal venous inflow perpetuates and exacerbates portal pressure elevation and determines the formation of ascites during chronic liver disease. In addition, portosystemic collateral vessels include the gastroesophageal varices, which are particularly prone to rupture causing massive gastroesophageal bleeding. Collateral vessels are also responsible for other major consequences of chronic liver disease, including portosystemic encephalopathy and sepsis. Extrahepatic mechanisms are clearly of major importance for disease progression and aggravation of the portal hypertensive syndrome. Accordingly, most of the therapies currently used in portal hypertension do not act inside the liver but they actually target the increased splanchnic blood flow. This paper reviews the consequences of the splanchnic circulatory abnormalities in portal hypertension and the complex signals capable of increasing vasodilatation, hyporesponsiveness to vasoconstrictors and angiogenesis in the splanchnic vascular bed and the portosystemic collateral circulation in this pathological setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Sanyal AJ, Bosch J, Blei A, et al. Portal hypertension and its complications. Gastroenterology. 2008;134:1715–28.

    Article  PubMed  Google Scholar 

  2. Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. Clin Gastroenterol. 2005;39:S125–30.

    Article  Google Scholar 

  3. Bosch J, Groszmann RJ, Shah VH. Evolution in the understanding of the pathophysiological basis of portal hypertension: how changes in paradigm are leading to successful new treatments. J Hepatol. 2015;62(1 Suppl):S121–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010;362:823–32.

    Article  CAS  PubMed  Google Scholar 

  5. Gupta TK, Toruner M, Chung MK, et al. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology. 1998;28:926–31.

    Article  CAS  PubMed  Google Scholar 

  6. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rockey DC, Chung JJ. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension. Gastroenterology. 1998;114:344–51.

    Article  CAS  PubMed  Google Scholar 

  8. Vorobioff J, Bredfeldt JE, Groszmann RJ. Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension. Am J Physiol. 1983;244:G52–7.

    CAS  PubMed  Google Scholar 

  9. Vorobioff J, Bredfeldt JE, Groszmann RJ. Increased blood flow through the portal system in cirrhotic rats. Gastroenterology. 1984;87:1120–6.

    CAS  PubMed  Google Scholar 

  10. Fernandez M. Molecular pathophysiology of portal hypertension. Hepatology. 2015;61:1406–15.

    Article  PubMed  Google Scholar 

  11. Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis—current status and future directions. J Hepatol. 2014;61:912–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lebrec D, DeFleury P, Rueff B, et al. Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in patients with cirrhosis. Gastroenterology. 1980;79:1139–44.

    CAS  PubMed  Google Scholar 

  13. Garcia-Tsao G, Sanyal AJ, Grace N, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922–38.

    Article  CAS  PubMed  Google Scholar 

  14. Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med. 2001;345:669–81.

    Article  CAS  PubMed  Google Scholar 

  15. Pizcueta MP, Garcia-Pagan JC, Fernandez M, et al. Glucagon hinders the effects of somatostatin on portal hypertension: a study in rats with partial portal vein ligation. Gastroenterology. 1991;101:1710–5.

    Article  CAS  PubMed  Google Scholar 

  16. Gomis R, Fernandez-Alvarez J, Pizcueta P, et al. Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation. Hepatology. 1994;19:1257–61.

    Article  CAS  PubMed  Google Scholar 

  17. Pizcueta P, Pique JM, Fernandez M, et al. Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition. Gastroenterology. 1992;103:1909–15.

    Article  CAS  PubMed  Google Scholar 

  18. Martin PY, Gines P, Schrier RW. Mechanisms of disease: nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med. 1998;339:533–41.

    Article  CAS  PubMed  Google Scholar 

  19. Iwakiri Y, Tsai MH, McCabe TJ, et al. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. Am J Physiol Heart Circ Physiol. 2002;282:H2084–90.

    Article  CAS  PubMed  Google Scholar 

  20. Wiest R, Shah V, Sessa WC, et al. NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. Am J Physiol. 1999;276:G1043–51.

    CAS  PubMed  Google Scholar 

  21. Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology. 2002;35:478–91.

    Article  CAS  PubMed  Google Scholar 

  22. Abraldes JG, Iwakiri Y, Loureiro-Silva M, et al. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol. 2006;290:G980–7.

    Article  CAS  PubMed  Google Scholar 

  23. Hori N, Wiest R, Groszmann RJ. Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats. Hepatology. 1998;28:1467–73.

    Article  CAS  PubMed  Google Scholar 

  24. Wiest R, Cadelina G, Milstien S, et al. Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats. Hepatology. 2003;38:1508–15.

    Article  CAS  PubMed  Google Scholar 

  25. Shah V, Wiest R, Garcia-Cardena G, et al. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension. Am J Physiol Gastrointest Liver Physiol. 1999;277:G463–8.

    CAS  Google Scholar 

  26. Kwon SY, Groszmann RJ, Iwakiri Y. Increased neuronal nitric oxide synthase interaction with soluble guanylate cyclase contributes to the splanchnic arterial vasodilation in portal hypertensive rats. Hepatol Res. 2007;37:58–67.

    Article  CAS  PubMed  Google Scholar 

  27. Jurzik L, Froh M, Straub RH, et al. Up-regulation of nNOS and associated increase in nitrergic vasodilation in superior mesenteric arteries in pre-hepatic portal hypertension. J Hepatol. 2005;43:258–65.

    Article  CAS  PubMed  Google Scholar 

  28. Morales-Ruiz M, Jimenez W, Perez-Sala D, et al. Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. Hepatology. 1996;24:1481–6.

    Article  CAS  PubMed  Google Scholar 

  29. Fernandez-Varo G, Ros J, Morales-Ruiz M, et al. Nitric oxide synthase 3-dependent vascular remodeling and circulatory dysfunction in cirrhosis. Am J Pathol. 2003;162:1985–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 1998;101:2567–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Papapetropoulos A, Garcia-Cardena G, Madri JA, et al. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest. 1997;100:3131–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rudic RD, Shesely EG, Maeda N, et al. Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest. 1998;101:731–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sieber CC, Groszmann RJ. Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats. Gastroenterology. 1992;103:235–9.

    Article  CAS  PubMed  Google Scholar 

  34. Sieber CC, Sumanovski LT, Stumm M, et al. In vivo angiogenesis in normal and portal hypertensive rats: role of basic fibroblast growth factor and nitric oxide. J Hepatol. 2001;34:644–50.

    Article  CAS  PubMed  Google Scholar 

  35. Sumanovski LT, Battegay E, Stumm M, et al. Increased angiogenesis in portal hypertensive rats: role of nitric oxide. Hepatology. 1999;29:1044–9.

    Article  CAS  PubMed  Google Scholar 

  36. Fernandez M, Bonkovsky HL. Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats. Hepatology. 1999;29:1672–9.

    Article  CAS  PubMed  Google Scholar 

  37. Fernandez M, Lambrecht RW, Bonkovsky HL. Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity. J Hepatol. 2001;34:812–7.

    Article  CAS  PubMed  Google Scholar 

  38. Bolognesi M, Sacerdoti D, Piva A, et al. Carbon monoxide-activation of large-conductance calcium activated potassium channels contributes to mesenteric vasodilatation in cirrhotic rats. J Pharm Exp Ther. 2007;321:187–94.

    Article  CAS  Google Scholar 

  39. Angermayr B, Mejias M, Gracia-Sancho J, et al. Heme oygenase attenuates oxidative stress and inflammation, and increases VEGF expression in portal hypertensive rats. J Hepatol. 2006;44:1033–9.

    Article  CAS  PubMed  Google Scholar 

  40. Oberti F, Sogni P, Cailmail S, et al. Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension. Hepatology. 1993;18:621–7.

    Article  CAS  PubMed  Google Scholar 

  41. Fernandez M, Garcia-Pagan JC, Casadevall M, et al. Acute and chronic cyclooxygenase blockade in portal hypertensive rats: influence on nitric oxide biosynthesis. Gastroenterology. 1996;110:1529–35.

    Article  CAS  PubMed  Google Scholar 

  42. Rautou PE, Bresson J, Sainte-Marie Y, et al. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology. 2012;143:166–76.

    Article  CAS  PubMed  Google Scholar 

  43. Batkai S, Jarai Z, Wagner JA, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med. 2001;7:827–32.

    Article  CAS  PubMed  Google Scholar 

  44. Ros J, Claria J, To-Figueras J, et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology. 2002;122:85–93.

    Article  CAS  PubMed  Google Scholar 

  45. Huang HC, Wang SS, Hsin IF, et al. Cannabinoid receptor 2 agonist ameliorates mesenteric angiogenesis and portosystemic collaterals in cirrhotic rats. Hepatology. 2012;56:248–58.

    Article  CAS  PubMed  Google Scholar 

  46. Schepke M, Heller J, Paschke S, et al. Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism. Hepatology. 2001;34:884–8.

    Article  CAS  PubMed  Google Scholar 

  47. Hennenberg M, Trebicka J, Biecker E, et al. Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hepatology. 2007;45:495–506.

    Article  CAS  PubMed  Google Scholar 

  48. Grace JA, Klein S, Herath CB, et al. Activation of the MAS receptor by angiotensin-(1–7) in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis. Gastroenterology. 2013;145:874–84.

    Article  CAS  PubMed  Google Scholar 

  49. Ezkurdia N, Raurell I, Rodriguez S, et al. Inhibition of neuronal apoptosis and axonal regression ameliorates sympathetic atrophy and hemodynamic alterations in portal hypertensive rats. PLoS One. 2014;9:e84374.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Coll M, Genesca J, Raurell I, et al. Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension. J Hepatol. 2008;49:43–51.

    Article  CAS  PubMed  Google Scholar 

  51. Dietrich P, Moleda L, Kees F, et al. Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: impact of exogenous neuropeptide Y. J Hepatol. 2013;58:254–61.

    Article  CAS  PubMed  Google Scholar 

  52. Gerhardt H, Golding M, Fruttiger M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jakobsson L, Franco CA, Bentley K, et al. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol. 2010;12:943–53.

    Article  CAS  PubMed  Google Scholar 

  54. Eilken HM, Adams RH. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol. 2010;22:617–25.

    Article  CAS  PubMed  Google Scholar 

  55. Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell. 2011;146:873–87.

    Article  CAS  PubMed  Google Scholar 

  56. Fernandez M, Semela D, Bruix J, et al. Angiogenesis in liver disease. J Hepatol. 2009;50:604–20.

    Article  CAS  PubMed  Google Scholar 

  57. Corpechot C, Barbu V, Wendum D, et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology. 2002;35:1010–21.

    Article  CAS  PubMed  Google Scholar 

  58. Lee JS, Semela D, Iredale J, et al. Sinusoidal remodeling and angiogenesis: a new function for the liver-specific pericyte? Hepatology. 2007;45:817–25.

    Article  CAS  PubMed  Google Scholar 

  59. Tugues S, Fernandez-Varo G, Muñoz-Luque J, et al. Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. Hepatology. 2007;46:1919–26.

    Article  CAS  PubMed  Google Scholar 

  60. Mejias M, Garcia-Pras E, Tiani C, et al. Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats. Hepatology. 2009;49:1245–56.

    Article  CAS  PubMed  Google Scholar 

  61. Fernandez M, Vizzutti F, Garcia-Pagan JC, et al. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology. 2004;126:886–94.

    Article  CAS  PubMed  Google Scholar 

  62. Reiberger T, Angermayr B, Schwabl P, et al. Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats. J Hepatol. 2009;51:865–73. An important report that emphasizes antiproliferative, anti-inflammatory, and antiangiogenic effects of sorafenib in rats with portal hypertension.

    Article  CAS  PubMed  Google Scholar 

  63. Fernandez M, Mejias M, Garcia-Pras E, et al. Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats. Hepatology. 2007;46:1208–17.

    Article  CAS  PubMed  Google Scholar 

  64. Geerts AM, De Vriese AS, Vanheule E, et al. Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study. Liver Int. 2006;26:889–98.

    Article  PubMed  Google Scholar 

  65. Thabut D, Routray C, Lomberk G, et al. Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis. Hepatology. 2011;54:573–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Van Steenkiste C, Geerts A, Vanheule E, et al. Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of portal hypertension. Gastroenterology. 2009;137:2112–24. Important report which demonstrates that PlGF blocking could be an effective strategy for reducing collateral formation and lowering portal pressure.

    Article  PubMed  Google Scholar 

  67. Van Steenkiste C, Ribera J, Geerts A, et al. Inhibition of placental growth factor activity reduces the severity of fibrosis, inflammation, and portal hypertension in cirrhotic mice. Hepatology. 2011;53:1629–40.

    Article  PubMed  Google Scholar 

  68. Llovet JM, Bruix J. Testing molecular therapies in hepatocellular carcinoma: the need for randomized phase II trials. J Clin Oncol. 2009;27:833–5.

    Article  PubMed  Google Scholar 

  69. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473:298–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.

    Article  CAS  PubMed  Google Scholar 

  71. Reichenbach V, Fernandez-Varo G, Casals G, et al. Adenoviral dominant-negative soluble PDGFRβ improves hepatic collagen, systemic hemodynamics, and portal pressure in fibrotic rats. J Hepatol. 2012;57:967–73.

    Article  CAS  PubMed  Google Scholar 

  72. Failli P, DeFranco RM, Caligiuri A, et al. Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells. Gastroenterology. 2000;119:479–92.

    Article  CAS  PubMed  Google Scholar 

  73. Semela D, Das A, Langer D, et al. Platelet-derived growth factor signaling through ephrin-B2 regulates hepatic vascular structure and function. Gastroenterology. 2008;135:671–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pinter M, Sieghart W, Reiberger T, et al. The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma. A pilot study. Aliment Pharmacol Ther. 2012;35:83–91.

    Article  CAS  PubMed  Google Scholar 

  75. Chatterjee S. Reversal of vasohibin-driven negative feedback loop of vascular endothelial growth factor/angiogenesis axis promises a novel antifibrotic therapeutic strategy for liver diseases. Hepatology. 2014;60:458–60.

    Article  CAS  PubMed  Google Scholar 

  76. Coch L, Mejias M, Berzigotti A, et al. Disruption of negative feedback loop between vasohibin- 1 and VEGF decreases portal pressure, angiogenesis and fibrosis in cirrhotic rats. Hepatology. 2014;60:633–47.

    Article  CAS  PubMed  Google Scholar 

  77. Mejias M, Coch L, Berzigotti A, et al. Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats. Gut. 2015;64:657–66.

    Article  CAS  PubMed  Google Scholar 

  78. Vespasiani-Gentilucci U, Rombouts K. Boosting pigment epithelial-derived factor: a promising approach for the treatment of early portal hypertension. Gut. 2015;64:523–4.

    Article  CAS  PubMed  Google Scholar 

  79. Calderone V, Gallego J, Fernandez-Miranda G, et al. Sequential functions of CPEB1 and CPEB4 regulate pathologic expression of VEGF and angiogenesis in chronic liver disease. Gastroenterology. 2016;150:982–97. A noteworthy study highlighting the role of CPEB1 and CPEB4 regulating proteins in VEGF expression associated to neovascularization in chronic liver disease.

    Article  CAS  PubMed  Google Scholar 

  80. Bava FA, Eliscovich C, Ferreira PG, et al. CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature. 2013;495:121–5.

    Article  CAS  PubMed  Google Scholar 

  81. Fernandez-Miranda G, Mendez R. The CPEB-family of proteins, translational control in senescence and cancer. Ageing Res Rev. 2012;11:460–72.

    Article  CAS  PubMed  Google Scholar 

  82. Pique M, Lopez JM, Foissac S, et al. A combinatorial code for CPE-mediated translational control. Cell. 2008;132:434–48.

    Article  CAS  PubMed  Google Scholar 

  83. Mendez R, Hake LE, Andresson T, et al. Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA. Nature. 2000;404:302–7.

    Article  CAS  PubMed  Google Scholar 

  84. Mendez R, Murthy KG, Ryan K, et al. Phosphorylation of CPEB by Eg2 mediates the recruitment of CPSF into an active cytoplasmic polyadenylation complex. Mol Cell. 2000;6:1253–9.

    Article  CAS  PubMed  Google Scholar 

  85. Sarkissian M, Mendez R, Richter JD. Progesterone and insulin stimulation of CPEB- dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3. Genes Dev. 2004;18:48–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Garcia-Pras E, Gallego J, Coch L, et al. Role and therapeutic potential of vascular stem/progenitor cells in pathological neovascularisation during chronic portal hypertension. Gut. 2016. doi:10.1136/gutjnl-2015-311157. A novel and important report which identifies and describes the role of resident progenitor cells in abnormal neovessel formation during portal hypertension and contribution of CPEB4 protein in VSPC proliferation.

    PubMed  Google Scholar 

Download references

Grant Support

This study is supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO; SAF2014-55473-R), Scientific Foundation of the Spanish Association Against Cancer (AECC), and Worldwide Cancer Research Foundation. The CIBERehd is an initiative from the Instituto de Salud Carlos III.

Author information

Authors and Affiliations

  1. IDIBAPS Biomedical Research Institute, CIBERehd, University of Barcelona, Rossello 153, 08036, Barcelona, Spain

    Mercedes Fernandez, Marc Mejias, Ester Garcia-Pras, Javier Gallego, Nuria Pell, Marta Ramirez, Salvador Naranjo-Suarez & Alba Barrachina-Catala

Authors
  1. Mercedes Fernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc Mejias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ester Garcia-Pras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Javier Gallego
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nuria Pell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Ramirez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Salvador Naranjo-Suarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alba Barrachina-Catala
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Angiogenesis in Liver Disease Research Group

Corresponding author

Correspondence to Mercedes Fernandez.

Ethics declarations

Conflicts of Interest

MF, MM, EGP, JG, NP, MR, SNS, and ABC declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Portal Hypertension

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernandez, M., Mejias, M., Garcia-Pras, E. et al. Pathogenesis of Portal Hypertension: Extrahepatic Mechanisms. Curr Hepatology Rep 15, 199–207 (2016). https://doi.org/10.1007/s11901-016-0306-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-016-0306-x

Keywords

Search

Navigation