Rationality of medication based on the “ascending” pathophysiology of cholestatic liver disease

In recent years, some scholars have put forward the“ascending”pathophysiology of cholestatic liver disease, especially in primary biliary cholangitis ( PBC) and primary sclerosing cholangitis ( PSC) . According to this theory, cholestatic liver disease develops from the bottom to the top of the anatomical structure over time. Primary or early lesions are usually located in the “downstream”bile duct, with a major cause of immune-mediated biliary necrotizing inflammatory injury. When cholestasis occurs, the toxic effect mediated by bile salt will lead to the injury in the“upstream”liver parenchyma. Therefore, bile toxicity is of great importance during disease progression. According to this theory of“ascending”pathophysiology, there are different locations and causes of the disease in different disease stages, and therefore, it is necessary to establish a staging system for cholestatic liver disease and use different drugs in different stages, in order to use the existing drugs in a more effective manner and give directions for new drug development. However, there are still no early biochemical markers for cholestatic liver disease, and current clinical work should focus on the search for biomarkers with strong specificity and high sensitivity.