Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstric...Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstriction(functional component).PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding.Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns(PAMPs)that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways.Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability:The intestinal barrier function is affected by impaired microcirculation,neoangiogenesis,and abnormal vascular and mucosal permeability.The close bidirectional relationship between the gut and the liver has been termed“gut-liver axis”.Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function,intestinal barrier integrity,as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects.The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments,however,further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed.In this review,we summarize the clinical impact of PHT on the course of liver disease,discuss the underlying pathophysiological link of PHT to gut-liver axis signaling,and provide insight into molecular mechanisms that may represent novel therapeutic targets.展开更多
After nearly a decade,the American Association for the Study of Liver Diseases has updated its guidance on the diagnosis,evaluation,and management of ascites and its complications(1).Ascites is the most common first h...After nearly a decade,the American Association for the Study of Liver Diseases has updated its guidance on the diagnosis,evaluation,and management of ascites and its complications(1).Ascites is the most common first hepatic decompensating event,thereby denoting the transition to from compensated advanced chronic liver disease(cACLD)to decompensated cirrhosis-(literally)a watershed moment in the natural history of liver disease(2).展开更多
文摘Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstriction(functional component).PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding.Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns(PAMPs)that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways.Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability:The intestinal barrier function is affected by impaired microcirculation,neoangiogenesis,and abnormal vascular and mucosal permeability.The close bidirectional relationship between the gut and the liver has been termed“gut-liver axis”.Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function,intestinal barrier integrity,as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects.The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments,however,further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed.In this review,we summarize the clinical impact of PHT on the course of liver disease,discuss the underlying pathophysiological link of PHT to gut-liver axis signaling,and provide insight into molecular mechanisms that may represent novel therapeutic targets.
文摘After nearly a decade,the American Association for the Study of Liver Diseases has updated its guidance on the diagnosis,evaluation,and management of ascites and its complications(1).Ascites is the most common first hepatic decompensating event,thereby denoting the transition to from compensated advanced chronic liver disease(cACLD)to decompensated cirrhosis-(literally)a watershed moment in the natural history of liver disease(2).
