*1.1. Liver Fibrosis*

The capacity of the liver for regeneration is unique, but repeated and chronic liver injury frequently results in liver fibrosis. Fibrosis, which often precedes cancer, is characterized by the continuous accumulation of extracellular matrix (ECM), which is extremely rich in collagen I and III, leads to the deposition of scars and progressing on liver fibrosis [3]. This disease is characterized by an excessive accumulation of extracellular matrix (ECM) in the space of Disse. The accumulation of ECM has a negative effect on diverse functions of the organ such as detoxification and other liver functions, and it disturbs the hepatic blood flow. The recruitment of inflammatory immune cells, which can also amplify tumor development, represents another key event of fibrosis [4,5]. Untreated liver fibrosis can develop into cirrhosis and is accompanied by portal hypertension, hepatic encephalopathy, liver failure, and also is associated with an increased risk for the development of hepatocellular carcinoma (HCC) [6,7]. Liver injury usually is initiated by a noxa, virtually anything which can harm or kill the sensitive hepatocytes. Disease factors are viral hepatitis, chronic alcohol abuse, cholestatic disorders, genetic heritage, and autoimmune diseases. Apparently, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) represent the major etiology of liver fibrosis. The demographic change caused by the ageing population and the growing epidemic of obesity lead to increased prevalence of liver fibrosis [8]. NAFLD is regarded as the main inducer of chronic liver disease in industrialized countries. It is assumed that NAFLD will be the leading indication for liver transplantation [9]. A significant number of as much as 20–30% of adults have NAFLD. Additional factors in disease, particularly immune cell infiltration, can lead to the progression of NAFLD to NASH and fibrosis. Fibrosis severity has been linked to mortality related to hepatic and other diseases, as evidenced in several longitudinal clinical studies and correspondingly, the effectiveness for the evaluation of drugs against NAFLD is their impact on liver fibrosis [9], which may also have a positive outcome on nonhepatic diseases [10]. It was estimated that liver-related mortality will increase dramatically in the next decade [9]. Fibrosis can be considered a dysregulated wound-healing response which leads to scarring of tissues. Different disease etiologies exhibit specific hallmarks, but advanced stages are commonly characterized by bridging fibers between portal fields [11].
