- The liver itself through its normally functioning enzymes and processes often causes a drug to become toxic through a process known as bioactivation.
- Drug-induced liver disease occurs as several different clinical presentations: idiosyncratic reactions, allergic hepatitis, toxic hepatitis, chronic active toxic hepatitis, toxic cirrhosis, and liver vascular disorders.
- The mechanisms of drug-induced liver disease are diverse, representing many phases of biotransformation, and are susceptible to genetic polymorphism.
- A fulminant or severe drug-induced reaction within the liver usually involves the immune system and is marked by large scale cell necrosis.
- The assessment of a possible liver injury caused by drugs should include what is known in the literature, the timing involved, the clinical course, and, always, an exploration for preexisting conditions that may have encouraged the lesion's development.
- Liver enzyme assays can help to determine if a particular type of liver damage is present.
- Monitoring for drug-induced liver disease must be tailored to the drug and the patient's potential risk factors.
Upon completion of the chapter, the reader will be able to:
- 1. Discuss the various patterns and presentations associated with drug-induced liver disease.
- 2. Identify the principle mechanisms through which a drug or other agent can initiate liver disease.
- 3. Discuss the role of single nucleotide polymorphism in increasing or decreasing a personâs risk for drug-induced liver disease.
- 4. Match the results of a liver biopsy with a classic pattern of liver damage in the assessment of possible drug culprits in a patient with liver illness.
- 5. List drugs associated with a high or well known risk for drug-induced liver disease.
- 6. Detail how certain nondrug agents can increase the risk for drug-induced liver disease.
- 7. Outline the role of liver enzyme assays in identifying the type of drug-induced liver disease.
- 8. Identify the role of liver function results in determining the extent of drug-induced liver disease.
- 9. Discuss the limits of available tests and methods in the assessment of a patient with elevated liver enzymes.
- 10. Develop a monitoring plan for a patient placed on a drug with a high or well known risk for drug-induced liver disease.
The number of drugs associated with adverse reactions involving the liver is extensive.1 One of the more common reasons for the withdrawal of a drug from the marketplace is an elevation of serum concentrations of liver enzymes.2 Its impact on the pharmaceutical industry has led regulatory agencies to withdraw drugs from the market, restrict the use of certain medications, and issue black box warnings.3
Alcohol-induced liver disease is the most common type of drug-induced liver disease. All other drugs together account for less than 10% of patients hospitalized for elevated liver enzymes.4 Drug-induced liver disease accounts for as much as 20% of acute liver failure in pediatric populations and at least that many of adults with acute liver failure.5 In approximately 75% of ...