Alcohol abuse and overweight/obesity are the two major causes of liver diseases in western countries. ALD and MASLD share common pathophysiological mechanisms. Indeed, ALD can be considered in 3 overlapping phases with distinct pathological and clinical features: fatty liver (or steatosis), which is reversible, alcoholic hepatitis (AH) and fibrosis/cirrhosis. In parallel, MASLD also displays a wide spectrum of liver lesions ranging from steatosis to steatohepatitis (MASH) and fibrosis/cirrhosis. Both alcohol and a Western diet can impair the function of the intestinal barrier. Its increased permeability leads to the translocation to the liver of bacterial toxins, such as LPS, and bacterial metabolites from the intestinal microbiota (IM). This process has emerged as a key factor in the triggering of ALD and MASLD. To find out more about MASLD Nomenclature.
Severe AH is a specific life-threatening complication of alcohol abuse. Severe AH is characterized by a major inflammatory infiltrate into the liver leading to hepatic failure and death in 50% of patients in one month in the absence of treatment. Apart from liver transplantation, steroid therapy is the only treatment that can improve the survival of severe AH. However, many patients do not respond to steroid therapy. Recruitment and activation of inflammatory cells in the liver are key in the progression of liver disease from steatosis to inflammation and, subsequently, advanced liver lesions. Thus, a better understanding of the molecular mechanisms underlying liver homing of inflammatory cells in the context of MASLD and ALD is essential. Moreover, with a similar amount of alcohol intake or a similar weight, some patients develop liver injury whereas others remain reasonably healthy. Therefore, other factors than overweight or the amount of alcohol intake play a role in the onset and progression of the liver inflammatory process. Our team focus on the inflammatory mechanisms involved in the progression and the severity of liver injury and on the cofactors that play a role in the triggering and progression of liver lesions, especially the role of the IM.