Histopathologische inzichten in chronische leverziekten: een focus op celplasticiteit in hepatocyt- en galweggerelateerde ziekten

Chronic liver diseases refer to conditions which cause progressive damage to the liver over time, impairing the livers ability to function. These diseases can lead to serious complications such as cirrhosis, liver failure and an increased risk for the development of liver cancer. They represent a significant health burden and affect millions of people worldwide. Chronic liver diseases can be broadly categorised into hepatocyte and biliary-related diseases, depending on the type of cells that are primarily affected. In this thesis, we focused on three distinct but impactful chronic liver diseases which cover both hepatocyte and biliary diseases. These include alcohol-associated (ALD) and metabolic dysfunction-associated steatotic liver diseases (MASLD) which primarily cause damage to the hepatocyte compartment. They represent the most prominent steatotic liver diseases and are characterised by the accumulation of fat. Primary sclerosing cholangitis (PSC) is a less common chronic liver disease, but is associated with a high risk for the development into end-stage liver disease and development of cancer. PSC is a disease, which primarily affects cholangiocytes. Cell plasticity is a term describing the ability of cells to change their phenotype in response to external cues such as chronic damage. In response to liver injury, liver cells can undergo changes in an attempt to maintain liver function. This thesis aims to explore cellular plasticity in the context of various chronic liver diseases, utilising techniques such as histopathology and multiplexing to gain a deeper understanding of the underlying disease mechanisms.