Abstract
Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.
Highlights
Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD)
Effects of liraglutide on HSC phenotype were assessed in diverse pre-clinical models of CLD
The major findings of the current study are that liraglutide promotes a marked amelioration in the phenotype of activated HSC, which in a pre-clinical model of chronic liver disease leads to significant improvement in portal hypertension and liver fibrosis
Summary
Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Apart from the pancreatic islets, GLP-1 receptors are present in many other tissues and, its expression within the liver is not clear[4, 5], recent studies demonstrated efficacy of GLP-1RA in liver diseases, such as NAFLD6, 7. In this regard, studies showed other beneficial properties for this type of drugs, including anti-inflammatory and anti-oxidant[8, 9], which are important for the resolution of chronic liver disease (CLD). Novel therapeutic strategies based on EMA/FDA approved drugs with no systemic adverse effects are required to improve treatments for patients with CLD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
