Digestive Diseases and Sciences

, Volume 59, Issue 12, pp 2890–2904 | Cite as

Targeting Apoptosis in Autoimmune Hepatitis

  • Albert J. Czaja


Apoptosis is the predominant mechanism of liver cell death in autoimmune hepatitis, and interventions that can modulate this activity are emerging. The aim of this review was to describe the apoptotic mechanisms, possible aberrations, and opportunities for intervention in autoimmune hepatitis. Studies cited in PubMed from 1972 to 2014 for autoimmune hepatitis, apoptosis in liver disease, apoptosis mechanisms, and apoptosis treatment were examined. Apoptosis is overactive in autoimmune hepatitis, and the principal pathway of cell death is receptor mediated. Surface death receptors are activated by extrinsic factors including liver-infiltrating cytotoxic T cells and the cytokine milieu. The executioner caspases 3 and 7 cleave nuclear deoxyribonucleic acid, and the release of apoptotic bodies can stimulate inflammatory, immune, and fibrotic responses. Changes in mitochondrial membrane permeability can be initiated by caspase 8, and an intrinsic pathway of apoptosis can complement the extrinsic pathway. Defects in the apoptosis of activated effector cells can prolong their survival and sustain the immune response. Caspase inhibitors have been used in diverse experimental and human diseases to retard apoptosis. Oligonucleotides that inhibit the signaling of toll-like receptors can limit the presentation of auto-antigens, and inhibitors of apoptosis that extend the survival of effector cells can be blocked by antisense oligonucleotides. Mechanisms that enhance the clearance of apoptotic bodies and affect key signaling pathways are also feasible. Interventions that influence the survival of liver and effector cells by altering their apoptosis are candidates for study in autoimmune hepatitis.


Autoimmune hepatitis Pathogenesis Apoptosis Interventions 


Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Professor Emeritus of Medicine, Division of Gastroenterology and HepatologyMayo Clinic College of MedicineRochesterUSA

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