Micrograph of periportal hepatic steatosis, as may be seen due to steroid use, trichrome stain Fatty change represents the intracytoplasmatic accumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus (microvesicular fatty change). In this stage,<unk>  cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring appearance (macrovesicular fatty change). These vesicles are well-delineated and optically "empty" because fats dissolve during tissue processing. Large vacuoles may coalesce and produce fatty cysts, which are irreversible lesions. Macrovesicular steatosis is the most common form and is typically associated with alcohol, diabetes, obesity, and corticosteroids. Acute fatty<unk>  of pregnancy and Reye's syndrome are examples of severe<unk>  disease caused by microvesicular fatty change. The diagnosis of steatosis is made when fat in the<unk>  exceeds 5–10% by weight. Mechanism leading to hepatic steatosis Defects in fatty acid metabolism are responsible for pathogenesis of<unk> , which may be due to imbalance in energy consumption and its combustion, resulting in lipid storage, or can be a consequence of peripheral resistance to insulin, whereby the transport of fatty acids from adipose tissue to the<unk>  is increased. Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute to fat accumulation. In addition, alcohol use disorder is known to damage mitochondria and other cellular structures, further impairing cellular energy mechanism. On the other hand, non-alcoholic<unk>  may begin as excess of unmetabolised energy in<unk>  cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying cause is reduced or removed. Micrograph of inflamed fatty<unk>  (steatohepatitis) Severe fatty<unk>  is sometimes accompanied by inflammation, a situation referred to as steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH) depends on the persistence or severity of the inciting cause. Pathological lesions in both conditions are similar. However, the extent of inflammatory response varies widely and does not always correlate with degree of fat accumulation. Steatosis (retention of lipid) and onset of steatohepatitis may represent successive stages in<unk>  progression.<unk>  disease with extensive inflammation and a high degree of steatosis often progresses to more severe forms of the disease. Hepatocyte ballooning and necrosis of varying degrees are often present at this stage.<unk>  cell death and inflammatory responses lead to the activation of hepatic stellate cells, which play a pivotal role in hepatic fibrosis. The extent of fibrosis varies widely. Perisinusoidal fibrosis is most common, especially in adults, and predominates in zone 3 around the terminal hepatic veins. The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors. In alcoholic<unk> , the transition to cirrhosis related to continued alcohol consumption is well-documented, but the process involved in non-alcoholic<unk>  is less clear.
Fatty liver disease
Wilson's disease
Alcoholic liver disease
Viral hepatitis
Alcoholic hepatitis
Primary sclerosing cholangitis
Non-alcoholic fatty liver disease
Autoimmune hepatitis