of
periportal hepatic steatosis, as may be seen due to
steroid use,
trichrome stain The 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). At this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the last stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving a 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 liver of pregnancy and
Reye's syndrome are examples of severe liver disease caused by microvesicular fatty change. The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight. Defects in
fatty acid metabolism are responsible for
pathogenesis of FLD, 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 liver 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 deposit. 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 FLD may begin as excess of unmetabolized energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying cause is reduced or removed. ) Severe fatty liver is sometimes go along with
inflammation, a situation referred to as
steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or metabolic dysfunction associated steatohepatitis (MASH) 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 FLD progression. Liver 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. Liver 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 FLD, the transition to cirrhosis related to continued alcohol consumption is well-documented, but the process involved in non-alcoholic FLD is less clear. ==Diagnosis==