dr. Sander Lefere (MD, PhD)

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, paralleling the increasing prevalence of obesity and the metabolic syndrome. NAFLD can progress to hepatic inflammation (steatohepatitis), fibrosis and hepatocellular carcinoma (HCC). In contrast to other chronic liver diseases, HCC can develop in NAFLD patients even in the absence of liver cirrhosis.
NAFLD is characterized by structural and functional alterations in various non-parenchymal cells, such as stellate cells, endothelial cells and macrophages. Specifically, stellate cells proliferate and differentiate into activated myofibroblasts which produce collagen fibers. The resulting process of liver fibrosis creates a pro-carcinogenic environment. Endothelial cells lose their sinusoidal structure. This is accompanied by pathological angiogenesis, i.e. the formation of new yet leaky blood vessels which promote the infiltration of immune cells. Macrophages promote inflammation and fibrosis, and specific tumor-associated macrophages play key roles in tumor progression.
Our interest relates to unraveling the pathophysiological roles played by non-parenchymal cells in NAFLD and its progression to liver fibrosis and liver cancer using in vivo and in vitro models as well as patient samples.