Inflammatory and stress responses in chronic liver diseases
Our team studies the mechanisms underlying chronic liver disease progression to cirrhosis and its complications, with an emphasis on the identification of prognosis markers and therapeutic targets for fatty liver diseases.Our research program focuses on the identification of immunometabolic targets and biomarkers of liver and systemic inflammation.
Non-alcoholic and alcoholic fatty liver diseases (NAFLD, ALD) are leading causes of liver diseases worldwide. They share common pathogenic features including steatosis and steatohepatitis (alcoholic-ASH and non-alcoholic-NASH) that lead to fibrosis and cirrhosis. Persistent inflammation is a driving force of liver fibrosis progression during NAFLD and ALD. Among patients with cirrhosis, excessive inflammation results in the development of multiorgan failure (defining acute-on-chronic liver failure, ACLF), which often leads to death. The lack of treatment highlights the urgent need for new prognosis markers and specific therapeutic targets that could limit liver injury, fibrosis, progression of cirrhosis to ACLF, and favour liver regeneration.
Ongoing studies are investigating:
i) The mechanisms underlying monocyte/macrophage reprogramming and the impact on fatty liver disease progression to fibrosis, and on liver regeneration. We target specific pathways we recently uncovered, including canonical and non canonical autophagy, macrophage apoptosis and lipid metabolic targets such as monoacylglycerol lipase. Lodder Autophagy 2015 Denaes, 2016, Sci Rep, Gual, 2017 AJP, Wan Hepatology 2014, Gandoura J Hepatol 2015, Louvet, Hepatology 2011 Mallat, J Hepatol 2013, Mallat Am J Physiol 2013, Weiss, J Hepatol 2017, Habib Gut 2018
ii) The role of adaptive immune cells (Th17) and non conventional (Mucosal-associated invariant T (MAIT) cells) T lymphocytes in the control of inflammation at sequential steps of fatty liver progression (Guillot, Hepatology 2014, Hegde Nat Com 2018)
iii) Novel biomarkers, targets and clinical studies evaluating new therapeutic strategies in NAFLD, cirrhosis and ACLF, a syndrome we characterized and in which systemic inflammation is a major trigger (Moreau, Gastroenterology 2013,Gustot Hepatology 2016, Claria J Hepatol 2016, Claria Hepatology 2018).
Networks : founding team of the European Consortium for the Study of Chronic Liver Failure (EF-CLIF), French-Indian network (LIA)), DHU Unity and RHU QUID.
Funding: Inserm, Université Paris-Diderot, Laboratory of Excellence Inflamex, National research agency (ANR), Fondation pour la Recherche médicale (FRM), french associations for the study of the liver and for digestive diseases (AFEF, SNFGE), Inserm-Transfert, Assistance Publique Hopitaux de Paris (PHRC),