Hepatic inflammation and fibrosis: functional links and key pathways

Hepatology. 2015 Mar;61(3):1066-79. doi: 10.1002/hep.27332. Epub 2015 Jan 28.

Abstract

Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty, and autoimmune origin. Inflammation is typically present in all disease stages and associated with the development of fibrosis, cirrhosis, and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T and B lymphocytes, natural killer cells and platelets, as well as key effectors, such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of antifibrogenic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Blood Platelets / physiology
  • Cytokines / physiology
  • Dendritic Cells / physiology
  • Hepatic Stellate Cells / physiology
  • Hepatitis / complications*
  • Hepatocytes / physiology
  • Humans
  • Liver Cirrhosis / etiology*
  • Lymphocytes / physiology
  • Macrophages / physiology
  • Microbiota / physiology
  • Toll-Like Receptors / physiology

Substances

  • Cytokines
  • Toll-Like Receptors