https://www.journal-of-hepatology.eu/article/S0168-8278(10)01066-4/pdf

Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI) The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis

/pdf/drug-induced-steatohepatitis-an-uncommon-culprit-of-a-common-1zxd5b3lkq.pdf

Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease.

Cytometric analysis for drug-induced steatosis in HepG2 cells

Nonalcoholic steatosis/steatohepatitis is the most common cause for abnormal liver chemistries. Apart from metabolic syndrome, drugs may also lead to development of steatohepatitis that may, rarely, progress to cirrhosis and portal hypertension. We discuss a case of amiodarone-induced steatohepatitis with advanced fibrosis, presenting with hepatic decompensation and portal hypertension manifesting as ascites and recurrent esophageal variceal hemorrhage. Amiodarone is a lipophilic drug that concentrates in the liver and usually, over a period of time, leads to toxicity related to drug accumulation. There is marked histological similarity between amiodarone-induced liver disease and alcoholic and nonalcoholic steatohepatitis. The clinical manifestations of amiodarone-induced hepatotoxicity and the mechanism of toxicity are also discussed.

Aaron B. Kuperman

Papers

Hepatic cirrhosis caused by low-dose oral amiodarone therapy.