Pathophysiological-based treatments of complications of cirrhosis

摘要

Detailed knowledge and understanding of the pathophysiological mechanisms and changes in hepatic and splanchnic function leading to the development of haemodynamic changes and portal hypertension in patients with cirrhosis are essential since it guides the search for targets to ameliorate liver-related abnormalities. Recent research has focused on the gut-liver axis, changes in intestinal permeability, translocation of bacterial products, and inflammation as important drivers of haemodynamic alterations and thereby targets for treatment. Additionally, treatment strategies should focus on micro-biotic modulation, antiangiogenics, anti-inflammatory strategies, and modulation of bile acid metabolism. This paper aims to review contemporary pathophysiological-based treatment principles of the major complications of cirrhosis and portal hypertension and future targets for treatment.Abbreviations: ACLF: acute-on-chronic liver failure; AKI: acute kidney injury; ALD: alcoholic liver disease; CSPH: clinical significant portal hypertension; eNOS: endothelial nitric oxide synthase; ET: endo-thelin; FXR: famesoid X-receptor; HBF: hepatic blood flow; HPS: hepatopulmonary syndrome; HRS: hepatorenal syndrome; HSC: hepatic stellate cell; HVPG: hepatic venous pressure gradient; IHVR: intra-hepatic vascular resistance; IL: interleukin; LPS: lipopopysaccaride; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; NO: nitric oxide; PAMPs: pathogen-associated molecular patterns; PoPH: portopulmonary hypertension; RAAS: renin-angiotensin-aldosterone system; SEC: sinusoidal endothelial cell; SIRS: systemic inflammatory response syndrome; SNS: sympathetic nervous system; T2D: type 2 diabetes mellitus; TIMP: Tissue inhibitor metalloproteinase; TIPS: transjugular intrahepatic porto-systemic shunt; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor; vWF: von Willebrand factor