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Liver disease is a major cause of morbidity and mortality worldwide, and the sequent loss of liver function is a critical clinical challenge. There are many different types of liver disease, which can be broadly grouped into three categories: chronic liver disease caused by metabolic dysfunction, acute liver failure that does not damage normal tissue structure, however is related to direct injury and rapid deterioration of hepatic function. Also, chronic liver failure that is associated with widespread tissue damage and scar-based remodeling, which can eventually lead to end-stage cirrhosis and hepatocellular carcinoma 1.
Hepatic damage can be induced by several factors including viral infection (hepatitis B and C), alcohol abuse, autoimmune hepatitis and chronic cholangiopathies. Also accelerated liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is associated with obesity rates. This situation can cause chronic hepatic inflammation and deregulated wound healing process in the liver, which, if prolonged, can lead to fibrosis 2.
1. Hepatic fibrosis
Hepatic fibrosis is the main complication of chronic liver failure and characterized by the excessive accumulation of an altered extracellular matrix, that is extremely rich in type I and III collagens. Deposition of scar tissue results from a wound healing response that occurs to maintain liver integrity after several insults from various biochemical metabolites 3. However, the continuous unbalanced synthesis of matrix protein and degradation leads to an incomplete matrix remodeling and irreversible cirrhosis 4.
Cirrhosis is a late stage condition in which the architecture of the liver becomes abnormal, the function of hepatocytes is reduced, and the hepatic blood ?ow is altered due to vascularized ?brotic septa surrounding regenerating nodules. Liver cirrhosis results in multiple complications such as coagulation defect and portal hypertension, including ascites, variceal bleeding, renal failure, hepatic encephalopathy, bacterial peritonitis and finally hepatocellular carcinoma 3.
2. Architecture of the normal liver
2.1. Anatomy
The liver is the heaviest visceral organ in the body, expressing 2–5% of body weight and exhibits an iterative, multicellular architecture. The organ is divided into four lobes; yet, the liver lobule represents its functional units.
Each lobule is composed of hexagonal cords of hepatocytes arranged around a central vein that drain into the large hepatic vein. The corners of the hexagon constitute the portal triad consisting of a portal vein, hepatic artery and biliary duct (Figure 1-A). Within a lobule, two afferent vessels supply hepatic blood: the hepatic artery and the portal vein, and flows in specialized sinusoidal vessels towards the central vein 1.
The hepatic sinusoid is a complex vascular channel built from specialized fenestrated endothelial cells of the liver also it is the residence of the hepatic macrophages named Kupffer cells. Stellate cells are located in the sub-endothelial space known as the space of Disse that separates the hepatocyte cords from the blood and the sinusoids (Figure 1-B). Bile, that is produced and excreted by hepatocytes into the bile canaliculi, flows in the opposite direction to sinusoidal blood flow towards the intrahepatic bile duct, which is lined by epithelial cells called cholangiocytes 5.
2.2. Function
The liver exhibits many functions in the body, including filtration and volume regulation of the blood, endocrine control of growth signaling pathways and biliary excretion (bile salts and bicarbonate) that facilitates digestion of fats and lipids 1. The liver also provides immune system support, detoxifies chemicals such as xenobiotics, and metabolizes drugs and macronutrient supplying the body with the needed energy.
Carbohydrate storage as glycogen and glucose manufacture via the gluconeogenic pathway is the most critical liver function, in addition to cholesterol homeostasis, lipids oxidation, and storage of excess lipid in other tissues, such as adipose. Finally, the liver is a major producer of the proteins secreted in the blood, their conversion into amino acids, and removal of nitrogen in the form of urea metabolism 6.
2.3. Cells within the Liver
There are four major cell types that play different roles in order to allow the proper functioning of the liver.

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