Drug-Induced Liver Injury: What You Need to Know
The pathogenesis of DILI is not fully understood. Potential relationships include intrinsic or direct hepatotoxicity, liver injury from activation of immunologic mechanisms, or drug-induced impairment of mitochondrial function. Personal, genetic, and environmental factors can also contribute to the development of liver injury from medications. Furthermore, patients are often taking more than one medication, and it may be the combined effect that allows liver injury to develop.
Some drugs are direct hepatotoxins; others produce an idiosyncratic reaction that causes liver injury. Most DILI is idiosyncratic and seemingly independent of dose, duration of medication use, or route of drug administration. Acetaminophen is an intrinsic hepatotoxin when taken in sufficient dosage. It is the only common pharmaceutical in use that produces direct hepatotoxicity, and it is the most frequent cause of acute liver failure in the United States and the United Kingdom.
In general, the risk for DILI is related to the class of drug, the quantity of drug consumed; the patient's age and sex; and such concurrent factors as diabetes mellitus, excessive ethanol intake, or the use of other medications. Drugs administered in higher doses are more likely to cause liver injury, especially drugs that require extensive hepatic metabolism.
Increased patient age also carries a greater risk for DILI, although children are at greater risk for injury from such medications as antibiotics. Women appear to be at higher risk from medications that produce chronic hepatitis-like manifestations, and pregnancy carries a risk for hepatotoxicity from tetracycline.
Genetic factors also influence drug metabolism and can result in more severe hepatotoxicity: for example, isoniazid in black persons and Hispanic persons. Human leukocyte antigen (HLA) subtypes are associated with hepatotoxicity, as evidenced by the liver injury that develops in patients with HLA-B*5701 with the use of flucloxacillin. Alcohol intake and malnutrition can also influence drug-induced hepatotoxicity.
The role played by environmental factors in DILI is unclear. Underlying cirrhosis does not typically increase the likelihood of idiosyncratic drug hepatotoxicity.
Medications can produce many manifestations of liver disease, including hepatocellular injury (acute hepatitis, massive liver cell necrosis, and autoimmune hepatitis-like disease), cholestasis (pure cholestasis, cholestasis and hepatitis, cholestasis with bile duct injury, and vanishing bile duct syndrome), fatty liver, peliosis, and hepatic tumors (hepatocellular carcinoma, cholangiocarcinoma, and angiosarcoma).
Pathophysiology of Drug-Induced Liver Injury
The pathogenesis of DILI is not fully understood. Potential relationships include intrinsic or direct hepatotoxicity, liver injury from activation of immunologic mechanisms, or drug-induced impairment of mitochondrial function. Personal, genetic, and environmental factors can also contribute to the development of liver injury from medications. Furthermore, patients are often taking more than one medication, and it may be the combined effect that allows liver injury to develop.
Some drugs are direct hepatotoxins; others produce an idiosyncratic reaction that causes liver injury. Most DILI is idiosyncratic and seemingly independent of dose, duration of medication use, or route of drug administration. Acetaminophen is an intrinsic hepatotoxin when taken in sufficient dosage. It is the only common pharmaceutical in use that produces direct hepatotoxicity, and it is the most frequent cause of acute liver failure in the United States and the United Kingdom.
In general, the risk for DILI is related to the class of drug, the quantity of drug consumed; the patient's age and sex; and such concurrent factors as diabetes mellitus, excessive ethanol intake, or the use of other medications. Drugs administered in higher doses are more likely to cause liver injury, especially drugs that require extensive hepatic metabolism.
Increased patient age also carries a greater risk for DILI, although children are at greater risk for injury from such medications as antibiotics. Women appear to be at higher risk from medications that produce chronic hepatitis-like manifestations, and pregnancy carries a risk for hepatotoxicity from tetracycline.
Genetic factors also influence drug metabolism and can result in more severe hepatotoxicity: for example, isoniazid in black persons and Hispanic persons. Human leukocyte antigen (HLA) subtypes are associated with hepatotoxicity, as evidenced by the liver injury that develops in patients with HLA-B*5701 with the use of flucloxacillin. Alcohol intake and malnutrition can also influence drug-induced hepatotoxicity.
The role played by environmental factors in DILI is unclear. Underlying cirrhosis does not typically increase the likelihood of idiosyncratic drug hepatotoxicity.
Medications can produce many manifestations of liver disease, including hepatocellular injury (acute hepatitis, massive liver cell necrosis, and autoimmune hepatitis-like disease), cholestasis (pure cholestasis, cholestasis and hepatitis, cholestasis with bile duct injury, and vanishing bile duct syndrome), fatty liver, peliosis, and hepatic tumors (hepatocellular carcinoma, cholangiocarcinoma, and angiosarcoma).
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