The ability of a wide range of medications to cause drug-induced liver disease (LD) is well-known to the medical community. Familiar examples include acetaminophen, methotrexate and statins. The liver is one of the principle sites of drug metabolism and detoxification in the body, with many medications passing thru the liver and concentrated there, leading to local higher concentrations of potentially hepatotoxic medications. People are genetically diverse, which affects the way each of us metabolize drugs and other chemicals. Liver toxicity of medication should be taken in the context of the increasing number of different medications available, the rising number of medications individual patients are concurrently taking, the complexity of drug-drug interactions, and the toxicity of drug metabolites.
Drug-induced LD is a relatively uncommon but severe cause of idiosyncratic liver damage, and requires special consideration as a safety problem. There are approximately 2000 cases of acute liver failure each year in the U.S., and medications account for perhaps 25 - 50% of these. Thirty-nine percent are due to acetaminophen, and 13% are idiosyncratic reactions due to other medications. Drug-induced LD accounts for 2-5% of cases of patients hospitalized with jaundice, approximately 10% of all cases of acute hepatitis and up to a quarter of all cases of chronic hepatitis. Drug-induced LD has become the leading cause of acute liver failure among patients presenting for evaluation at liver transplant centers in the United States, and the leading single cause for having to remove approved drugs from the market.
There are many different ways to categorize drug-induced LD, and this two-part module presents an overview of the major classification systems. There are overlaps and not many absolutes. The major advantage of having so many different schema is that they present various approaches to organizing and understanding specific patients, and the different processes by which drugs may cause liver injury.
Following are some interesting facts concerning drug-induced LD:
- Drug-induced LD may occur unrelated to pre-existing liver diseases.
- Symptoms can be non-specific, such as nausea, fever, rash
- On aggravation of symptoms, it can be very difficult to differentiate between the deterioration or complication of underlying liver disease and new or worsening drug-induced LD
- Our understanding at any given time of the potential for new drugs to cause liver toxicity is based upon limited data from licensing trials. It is best advised that new drugs should be used under careful observation until patient data is available for large populations.
Risk factors for drug-induced LD can be grouped in terms of specific medications. Specific groups of medications are known to have increased risk for hepatotoxicity depending on factors such as sex, age, nutritional state, body mass index, presence of underlying diseases (diabetes, renal failure, infection with HIV or hepatitis virus), and preexisting liver disease.
In summary, there are many different ways in which to categorize drug-induced LD. Following are common schema in use that you may find helpful:
- By risk factors,
- By what is known about specific medications,
- By whether the reaction is symptomatic.
- By pathologic (liver biopsy) presentation,
- By whether the presentation was predictable (dose related) or unpredictable,
- By whether there are extrahepatic / systemic manifestations.
|
