Dodging death: Surprise discovery redirects efforts for treatment of liver disease

WEHI researchers have revealed that common liver diseases are not driven by inflammatory cell death as previously thought, resolving a long-standing controversy in gastroenterology and pointing to a new direction for treatment.

The research team studied liver diseases that affect billions worldwide, including non-alcoholic fatty liver disease and hepatitis B, to understand what drives their progression.

Their unexpected finding — that liver cells are unable to undergo an inflammatory form of cell death called ‘necroptosis’ — resolves crucial unanswered questions in the field and will help guide the development of new therapeutic interventions.

At a glance

  • WEHI researchers have for the first time revealed that an important type of liver cells cannot undergo necroptosis, eliminating this type of cell death as a driver of common liver diseases
  • The surprise findings define the role and relevance of necroptosis in non-cancerous liver diseases, which affect billions of people worldwide
  • The results will help to inform new strategies for the development of treatments for these liver diseases

The findings, published in Gastroenterology, offer clarity on the heavily debated role of necroptosis in the progression of liver pathologies, and provide fundamental insights to guide future pre-clinical and clinical studies in a new direction.

The study was led by chief investigator Dr Marcel Doerflinger, former WEHI PhD researcher Dr Simon Preston and principal investigator Professor Marc Pellegrini, in collaboration with researchers from the Peter Doherty Institute for Infection and Immunity and the University of Queensland.

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