Unraveling the complexities of fibrosis and ductular reaction in liver disease: pathogenesis, mechanisms, and therapeutic insights

Am J Physiol Cell Physiol. 2024 Mar 1;326(3):C698-C706. doi: 10.1152/ajpcell.00486.2023. Epub 2023 Dec 18.

Abstract

Ductular reaction and fibrosis are hallmarks of many liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, alcoholic liver disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Liver fibrosis is the accumulation of extracellular matrix often caused by excess collagen deposition by myofibroblasts. Ductular reaction is the proliferation of bile ducts (which are composed of cholangiocytes) during liver injury. Many other cells including hepatic stellate cells, hepatocytes, hepatic progenitor cells, mesenchymal stem cells, and immune cells contribute to ductular reaction and fibrosis by either directly or indirectly interacting with myofibroblasts and cholangiocytes. This review summarizes the recent findings in cellular links between ductular reaction and fibrosis in numerous liver diseases.

Keywords: cholangiocytes; ductular reaction; fibrosis; liver; liver pathology.

Publication types

  • Review

MeSH terms

  • Bile Ducts / metabolism
  • Bile Ducts / pathology
  • Fatty Liver*
  • Fibrosis
  • Humans
  • Liver / metabolism
  • Liver Cirrhosis / metabolism
  • Liver Diseases* / metabolism
  • Liver Diseases* / pathology