The problem

There are multiple diseases and events which can induce severe liver injury leading to a potential life threatening loss of organ function. For most of these patients liver transplantation is the only lifesaving therapeutic option. The acute liver failure develops in patients with previously healthy liver, frequently caused by intoxications (e.g., with paracetamol or autoimmune diseases). Patients with acute-on-chronic liver failure (ACLF) have a pre-existing liver cirrhosis caused by chronic liver diseases. Certain events such as bacterial infections, harmful use of alcohol or gastrointestinal bleeding lead to a rapid decline of organ function, not only the liver, but also other organ systems.

There are three mechanisms which determine disease development and course: inflammation, cell death/tissue injury, and lack of regeneration and cellular senescence.

My research team explores disease mechanisms and new targets for diagnostic and therapeutic interventions in order to improve patients’ outcomes with liver failure.

The approach

• Understand the cellular and molecular mechanisms that regulate regeneration and senescence in liver failure; 
• identify the factors that determine and modulate liver sensitivity towards damaging events and agent; 
• decipher the role of stem and immune cells in modulating cell death, regeneration and senescence; 
• enhance liver regeneration as a therapeutic option for liver failure; and 
• evaluate biomarkers to reliably predict disease progression.

Main discoveries and innovations

• The combination of granulocye-colony stimulating factor (G-CSF) and a Toll-like receptor 4 (TLR-4) inhibitor (G-TAK) reduces organ injury and promotes regeneration in ACLF
• G-TAK is now being explored as a novel therapy for ACLF in a phase 2 clinical trial within A-TANGO, an EU-funded project