Ductular reaction in non-alcoholic fatty liver disease: When Macbeth is perverted

Abstract

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatic carcinoma. NASH, characterized by hepatocyte injury, steatosis, inflammation, and fibrosis, is associated with NAFLD prognosis. Ductular reaction (DR) is a common compensatory reaction associated with liver injury, which involves the hepatic progenitor cells (HPCs), hepatic stellate cells, myofibroblasts, inflammatory cells (such as macrophages), and their secreted substances. Recently, several studies have shown that the extent of DR parallels the stage of NASH and fibrosis. This review summarizes previous research on the correlation between DR and NASH, the potential interplay mechanism driving HPC differentiation, and NASH progression.

Keywords: Ductular reaction; Non-alcoholic steatohepatitis; Hepatic progenitor cells; Cell differentiation; Inflammatory cells; Liver fibrosis

Core Tip: This is the first review focusing on recent advances in the relationship of hepatic cells with ductular reaction (DR), in fatty liver-related steatohepatitis and fibrosis. Recent advances in DR, a common compensatory reaction in liver injury, shed light on the effects of hepatic progenitor cells, hepatic stellate cells, myofibroblasts, inflammatory cells, and their secreted substance. In particular, hepatic progenitor cell differentiation was thoroughly discussed in developing steatohepatitis and fibrosis. This review summarizes the correlation between DR and steatohepatitis and fibrosis, the advanced stages of non-alcoholic fatty liver disease, or metabolic (dysfunction) related fatty liver disease.