The following are some of the main mechanisms of liver injury [30]:
Mitochondrial dysfunction: may be generated by the disruption of β-oxidation of lipids and oxidative energy production within the hepatocytes. Mitochondrial membrane permeabilization can lead to apoptosis, a rupture in mitochondrial membrane can lead to ATP reduction and subsequent necrosis, and an abnormal function can also lead to fat accumulation, so steatosis can be present [31].
Oxidative stress: is produced by ATP depletion accompanied by increase in intracellular calcium concentration, it can generate necrosis [28].
.5. Clinical manifestations
The mechanisms of drug-induced liver injury are related with the clinical manifestations. The main clinical-pathological manifestations of hepatotoxicity and its histological findings include [6, 24, 26, 39]
Acute hepatitis: caused by a wide variety of drugs and characterized by parenchymal inflammation, necrosis and Kupffer cells in sinusoids, which include symptoms like malaise, asthenia, anorexia, jaundice can be present but not always [15].
Chronic hepatitis: characterized by persistent biochemical abnormalities beyond 6 months; fibrosis or cirrhosis may be present.
Fulminant hepatitis: also called acute liver failure may cause death and its manifestations are necrosis and microvesicular steatosis.
Cholestatic hepatitis: manifested by mixed hepatocellular and cholestatic injury accompanied by inflammation.
Cholestasis: caused by bile plugs; include symptoms like jaundice and pruritus is characterized by minimal inflammation.
Vanishing bile duct syndrome: presented by a paucity of bile ducts; inflammation and cholestasis may appear.
Granulomatous hepatitis: presence of granulomas in portal tracts or parenchymal, accompanied with inflammation.
Steatohepatitis: is the presence of fat in hepatocytes accompanied by inflammation and fibrosis.
Macrovesicular steatosis: characterized by the presence of medium- or large-sized fat droplets in the cytoplasm of hepatocytes.
Microvesicular steatosis: characterized by the presence of small-sized fat droplets in the cytoplasm of hepatocytes.
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