8. Mechanisms of Liver Injury

  1. Eugene R. Schiff MD, MACP, FRCP2,
  2. Willis C. Maddrey MD, MACP, FRCP3 and
  3. Michael F. Sorrell MD, FACP4
  1. Harmeet Malhi MD and
  2. Gregory J. Gores MD

Published Online: 31 OCT 2011

DOI: 10.1002/9781119950509.ch8

Schiff's Diseases of the Liver, Eleventh Edition

Schiff's Diseases of the Liver, Eleventh Edition

How to Cite

Malhi, H. and Gores, G. J. (2011) Mechanisms of Liver Injury, in Schiff's Diseases of the Liver, Eleventh Edition (eds E. R. Schiff, W. C. Maddrey and M. F. Sorrell), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781119950509.ch8

Editor Information

  1. 2

    Center for Liver Diseases and Schiff Liver Institute, University of Miami Miller School of Medicine, Miami, FL, USA

  2. 3

    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

  3. 4

    University of Nebraska College of Medicine, Omaha, NE, USA

Author Information

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, College of Medicine, Rochester, MN, USA

Publication History

  1. Published Online: 31 OCT 2011
  2. Published Print: 9 DEC 2011

ISBN Information

Print ISBN: 9780470654682

Online ISBN: 9781119950509

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Keywords:

  • Fas;
  • tumor necrosis factor α (TNF-α);
  • TRAIL;
  • apoptosis;
  • necrosis;
  • liver injury;
  • caspase;
  • mitochondrial permeabilization

Summary

The death of constituent cell populations of the liver is a central component of liver injury cascades. Hepatocytes are targeted by most injurious stimuli, though other cells types are affected as well. Cell death in the liver can occur via apoptosis or necrosis. Apoptosis can be initiated via death receptor-mediated pathways, the extrinsic pathway, or from intracellular perturbations, the intrinsic pathway. Mitochondrial permeabilization is required for hepatocyte apoptosis, and both intrinsic and extrinsic pathways converge on mitochondria. Effector caspases are activated downstream of mitochondria, and cleave several cellular targets to result in the characteristic apoptotic morphology. Dead cells release damage-associated molecular patterns that activate the innate immune system and downstream inflammatory cascades. Ongoing apoptosis in the liver stimulates Kupffer cells, and activates hepatic stellate cell-stimulating fibrosis. Therapies aimed at preventing hepatocyte apoptosis show promise in experimental and clinical settings.