Cell Death in Liver Disease and Liver Surgery

Author:

Stoess Christian12ORCID,Choi Yeon-Kyung13ORCID,Onyuru Janset4,Friess Helmut2,Hoffman Hal4,Hartmann Daniel2ORCID,Feldstein Ariel15

Affiliation:

1. Department of Pediatric Gastroenterology, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA

2. Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany

3. Department of Internal Medicine, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu 41404, Republic of Korea

4. Department of Pediatric Allergy, Immunology and Rheumatology, University of California San Diego, La Jolla, CA 92093, USA

5. Novo Nordisk, Global Drug Discovery, Ørestads Boulevard 108, 2300 Copenhagen, Denmark

Abstract

Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.

Funder

National Institutes of Health

German Research Foundation DFG-Grant

Publisher

MDPI AG

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