Liver disease is the 5th commonest cause of death in the UK. Currently the only curative option for end-stage liver disease is liver transplantation. Donor organ availability cannot meet current demand and many patients die whilst waiting for a suitable organ. Common causes of liver disease include chronic alcohol intake, high-fat diet, viral infection, disruption of bile flow and hepatotoxic drug. Regardless of the causative factor, hepatic fibrosis is a common pathway for chronic liver disease that leads to a progressive and decline in liver function as healthy tissue is replaced with scar tissue. In some cases, this may proceed to liver cancer.
Our long term goal is to develop more sensitive and specific methods to detect changes in chronic and acute liver disease earlier and to develop cellular and molecular-based regenerative medicine therapies (RMTs) that can treat patients in the early stages of liver disease and thereby prevent them from developing irreversible liver failure. To achieve this, our research at Liverpool focusses on the following key areas:
- Identifying non-invasive biomarkers of liver toxicity and liver function. Biomarkers that can detect the onset of liver disease and toxicity will facilitate early diagnosis and allow disease progression and the efficacy of therapeutic interventions to be monitored preclinically and in man.
- Understanding the mechanisms of liver fibrosis. Knowledge of the underlying mechanisms of liver fibrosis will facilitate the development of novel RMTs that can suppress fibrosis, and thus prevent the degeneration of functional hepatic tissue.
- Evaluating the safety and efficacy of hepatic RMTs. Before novel therapies can be translated to the clinic, we need accurate information about their safety and efficacy in preclinical models in order to determine the likely risk/benefit ratio in human patients. A key objective of our work is to develop and apply novel imaging strategies that allow the safety and efficacy of RMTs to be monitored non-invasively in preclinical models.
- Understanding how RMTs ameliorate liver disease. By understanding the mechanisms whereby RMTs ameliorate disease, we will be able to refine and improve them so as to make them safer and more effective.
Key Investigators: George Bou-Gharios, Chris Goldring, Patricia Murray, Kevin Park, Takao Sakai
Cross-disciplinary collaborators: Mathias Brust, Marta Garcia-Finana, Raphael Levy, Matt Rosseinsky
Liver researchers at Liverpool participate in the following major consortia: the IMI SAFE-T biomarker consortium, the IMI MIP-DILI research programme, Stem Cells for Safer Medicines and the UKRMP Safety and Efficacy Hub.