Cell Death in Liver Diseases: A Review

Area of Science:

• Hepatology
• Molecular Biology
• Immunology

Background:

• Regulated cell death (RCD) is integral to liver injury progression, inflammation, and fibrosis.
• Multiple RCD pathways, including apoptosis, necrosis, necroptosis, autophagy, pyroptosis, and ferroptosis, are implicated in liver disease pathogenesis.
• These pathways exhibit distinct features yet share significant crosstalk and can coexist within liver injury models.

Purpose of the Study:

• To review signaling cascades of various RCD pathways.
• To elucidate the implications of RCD in diverse liver diseases.
• To highlight common findings, controversies, and limitations in current RCD research.

Main Methods:

• Literature review of signaling pathways in RCD.
• Analysis of RCD's role in human and rodent models of liver disease.
• Focus on alcoholic liver disease, NAFLD/NASH, APAP-induced hepatotoxicity, autoimmune hepatitis, cholestatic liver disease, and viral hepatitis.

Main Results:

• Detailed description of signaling cascades for key RCD pathways.
• Examination of RCD's contribution to liver injury across multiple disease models.
• Identification of shared and distinct features among RCD subroutines.

Conclusions:

• RCD pathways are critical determinants of liver injury severity and disease outcome.
• Understanding the interplay of different RCD modes is essential for comprehending liver disease pathogenesis.
• Further research is needed to address controversies and limitations in current RCD data, particularly in human studies.