title: Emerging therapies for portal hypertension in cirrhosis.
abstract: BACKGROUND
  Counteracting splanchnic vasodilatation and increased portal-collateral blood flow has been the mainstay for the treatment of portal hypertension (PH) over the past three decades. However, there is still large room for improvement in the treatment of PH.
  
  
  METHODS
  The basic mechanism leading to portal hypertension is the increased hepatic vascular resistance to portal blood flow caused by liver structural abnormalities inherent to cirrhosis and increased hepatic vascular tone. Molecules modulating microvascular dysfunction which have undergone preclinical and clinical trials are summarized, potential drug development issues are addressed, and situations relevant to design of clinical trials are considered.
  
  
  CONCLUSIONS
  Experimental and clinical evidence indicates that molecules modulating liver microvascular dysfunction may allow for 30-40% reduction in portal pressure. Several agents could be utilized in the earlier stages of cirrhosis (antifibrotics, antiangiogenics, etiological therapies) may allow reduction of fibrosis and halt progression of PH. This 'nip at the bud' policy, by combining therapies with existing agents used in advanced phase of cirrhosis and novel agents which could be used in early phase of cirrhotic spectrum, which are likely to hit the market soon would be the future strategy for PH therapy.
authors.affiliation: a Inselspital Universitatsspital Bern , Bern , Switzerland.
authors.forename: Harikumar
authors.initials: H
authors.lastname: Nair
authors.affiliation: a Inselspital Universitatsspital Bern , Bern , Switzerland.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Berzigotti
authors.affiliation: a Inselspital Universitatsspital Bern , Bern , Switzerland.|b Hospital Clinic de Barcelona , University of Barcelona , Barcelona , Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Bosch
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000503:physiopathology; D012107:Research Design; D014664:Vasodilation
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Hepatic vascular resistance; endothelial dysfunction; hepatic stellate cells; hepatic vein pressure gradient; liver fibrosis; liver sinusoidal endothelial cells; portal pressure; splanchnic circulation