Normal histology	Histopathology	Pathological basis of disease	Clinical findings	
Tissue architecture:
•	The hepatocytes are arranged into lobules which are bounded by thin septa of collagenous supporting tissue.
•	The hepatic lobules are hexagonal in shape.
•	Terminal branches of the hepatic artery & hepatic portal vein are located at the angles of the lobule boundaries in portal tracts.
•	Blood from the portal tracts converges upon a terminal hepatic venule (centrilobular venule) of each lobule via sinusoids which pass between plates of hepatocytes.
•	The terminal hepatic venules drain to the hepatic vein. 

Portal triad:
•	Hepatic portal vein has a very thin wall lined by flattened endothelial cells.
•	Bile collecting ducts are lined by simple cuboidal or columnar cells.
•	Surrounding the portal tract are anastomosing plates of hepatocytes.
•	Between them are hepatic sinusoids receiving blood from both the hepatic portal & hepatic arterial systems. 

Cellular characteristics:
•	Hepatocytes are large polyhedral cells with large round nuclei (polypoid), dispersed chromatin & prominent nucleoli.
•	Hepatocytes store glycogen & lipids.
•	The cytoplasm is strongly eosinophilic due to numerous mitochondria with a fine basophilic granularity due to extensive free ribosomes.
•	Sinusoid lining cells: flattened condensed nuclei & poorly stained cytoplasm.
•	Kupffer cells: scattered among endothelial cells are large plump phagocytic cells with ovoid nuclei.	Abnormal histology:
•	Hepatocytes are filled with fats, presented as cytoplasmic vacuoles, usually displacing the nucleus to one side.
•	Ballooning degeneration: hepatocytes undergo hydropic degeneration & become swollen & vacuolated.
•	Centrilobular hepatocytes exhibits extensive accumulation of fats while there is lesser degree in periportal hepatocytes.
•	General architecture of hepatic lobular system is preserved. 
•	At first centrilobular, it may involve the entire lobule over time.
•	The liver becomes enlarged & is soft & yellow.
•	With prolonged alcohol abuse there is progressive fibrosis due to hepatocyte necrosis & regeneration of liver cells which can develop into alcoholic cirrhosis. 	Causes:
•	Alcoholism (developed countries)
•	Kwashiorkor (developing countries)
•	Diabetes mellitus
•	Obesity
•	Severe gastrointestinal malabsorption

Drug-induced hepatocellular damage:
•	Microvesicular fatty change: tetracycline, salicylates, yellow phosphorus.
•	Macrovesicular fatty change: ethanol, methotrexate, amiodarone

Pathogenesis:
•	Alcohol, the most common cause, is a hepatotoxin that interferes with microsomal & mitochondrial function in hepatocytes, leading to an accumulation of lipids.
•	Steatosis results from shunting of substrates towards lipid biosynthesis, impaired lipoprotein assembly & secretion, & increased peripheral catabolism of fat. 	Clinical course:
•	Asymptomatic or mild elevation of serum bilirubin & alkaline phosphatase; reversible.
•	Lead eventually to hepatic cirrhosis & failure.