Pharmacological decrease of liver stiffness is pressure-related and predicts long-term clinical outcome

Am J Physiol Gastrointest Liver Physiol. 2018 Oct 1;315(4):G484-G494. doi: 10.1152/ajpgi.00392.2017. Epub 2018 May 10.


Liver stiffness (LS) as measured by transient elastography is increasingly used to noninvasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, nitric oxide donors, and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n = 38 cirrhotic patients. In the animal model, cirrhosis induction resulted in a significant increase of LS and PP. After losartan or NO application, a LS decrease of 25% was strongly correlated with a concomitant decrease of mean arterial pressure (MAP) and PP. In contrast, acute propranolol administration decreased heart rate but not MAP resulting in stable LS. In the human cohort, most patients ( n = 25, 66%) showed a LS decrease after propranolol treatment initiation which significantly correlated to HVPG ( r = 0.518, P < 0.01) but was not accompanied by statistically significant changes in transaminases or model of end-stage liver disease (MELD). On multivariate analysis, patients with decreasing LS on propranolol had a decreased risk for experiencing a transplantation or death than patients with increasing LS irrespective of HVPG. In conclusion, LS changes after pharmacological interventions are influenced by hemodynamic effects on arterial and portal pressure. In humans, a LS decrease may be predictive of improved outcome irrespective of MELD scores and may serve as an additional follow-up tool in the future. NEW & NOTEWORTHY Liver stiffness (LS) is efficiently modulated by changes in portal venous and systemic pressures in an animal model of liver cirrhosis irrespective of baseline LS and portal pressure values. In humans, most patients show a decrease in LS after propranolol treatment initiation without statistically significant changes in transaminases or model of end-stage liver disease (MELD) scores. A decrease in LS may be associated with improved outcome and thus another valuable tool in the follow-up of patients after propranolol treatment initiation.

Keywords: hepatic hemodynamics; hepatic venous pressure gradient; portal hypertension; transient elastography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Arterial Pressure
  • Elasticity Imaging Techniques
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver / drug effects*
  • Liver / pathology
  • Liver Circulation*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / epidemiology
  • Losartan / pharmacology
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Nitric Oxide / pharmacology
  • Nitric Oxide / therapeutic use
  • Portal Pressure
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Rats
  • Rats, Wistar


  • Antihypertensive Agents
  • Nitric Oxide
  • Propranolol
  • Losartan