Hepatic inflammation and fibrosis: Functional links and key pathways

Authors

  • Ekihiro Seki,

    Corresponding author
    1. Departments of Medicine, University of California San Diego, La Jolla, CA
    2. Departments of Surgery, University of California San Diego, La Jolla, CA
    • 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: rfs2102@cumc.columbia.edu; 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: ekseki@ucsd.edu; fax: 858-822-5370.

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  • Robert F. Schwabe

    Corresponding author
    1. Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY
    2. Institute of Human Nutrition, Columbia University, College of Physicians and Surgeons, New York, NY
    • 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: rfs2102@cumc.columbia.edu; 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: ekseki@ucsd.edu; fax: 858-822-5370.

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  • Potential conflict of interest: Nothing to report.

  • E.S. was supported by National Institutes of Health (NIH) grants 5R01AA02017204, 5R01DK085252, and 5P42ES010337. R.F.S. was supported by NIH grants 5R01AA020211, 1U01AA021912, and 5R01DK076920.

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)

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