*1.1. Etiology and Pathophysiology of Chronic Liver Disease (CLD)*

Chronic liver disease (CLD) affects 800 million people worldwide and accounts for approximately 2 million deaths worldwide annually, representing a global major public health issue [4–6]. Alcohol abuse and associated alcoholic liver disease (ALD), viral hepatitis, and non-alcoholic fatty liver disease (NAFLD) are the most common causes of CLD. However, inherited disorders (such as alpha antitrypsin deficiency, hemochromatosis, and cystic fibrosis), drugs, cholestatic disease (such as primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)), and immune disorders also contribute to this common pathology [4].

Alcoholic liver disease (ALD) and NAFLD share a similar pathological progression, ranging from simple steatosis to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH). fibrosis, cirrhosis, and HCC [7]. Whereas excessive alcohol consumption is the main cause of ALD, the pathogenesis of NAFLD is related with obesity, insulin resistance and/or the metabolic syndrome, gut microbiota dysbiosis, environmental or nutritional factors, and genetic and epigenetic factors (reviewed by [8]). On the other hand, cholestatic disease [such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] are associated with chronic damage to the cholangiocytes of the biliary tree, leading to reductions in the bile flow, persistent injury to the biliary epithelium and hepatocytes, inflammation, fibrogenesis and potentially carcinogenesis [4,9].
