Hepatic inflammation and fibrosis: Functional links and key ... : Hepatology (original) (raw)
New Horizons
1Departments of MedicineUniversity of California San DiegoSchool of MedicineLa JollaCA
2Departments of SurgeryUniversity of California San DiegoSchool of MedicineLa JollaCA
3Department of MedicineColumbia University, College of Physicians and SurgeonsNew YorkNY
4Institute of Human NutritionColumbia University, College of Physicians and SurgeonsNew YorkNY
*Address reprint requests to: Robert F. Schwabe, M.D., Department of Medicine, Columbia University, College of Physicians and Surgeons, Russ Berrie Pavilion, Room 415, 1150 St. Nicholas Avenue, New York, NY 10032. E‐mail: [email protected]; fax: 212‐851‐5461 or Ekihiro Seki, M.D., Ph.D., Department of Medicine, University of California San Diego, School of Medicine, 9500 Gilman Drive, MC#0063, LBR 118B, La Jolla, CA. E‐mail: [email protected]; fax: 858‐822‐5370.
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. (Hepatology 2015;61:1066–1079)
© 2014 by the American Association for the Study of Liver Diseases