ReviewDrug-Induced Liver Injury
Section snippets
Classification
DILI is a broad term applied to any injury to the liver by a prescribed medication, over-the-counter medication, herb, or dietary supplement manifesting as a spectrum from asymptomatic liver test elevations to ALF. Epidemiologic studies and prospective registries use different, arbitrary liver biochemical thresholds to define what constitutes DILI. The first step in describing DILI is to differentiate idiosyncratic (unpredictable) DILI from intrinsic (predictable) DILI. The most common example
Risk Factors for DILI
Risk for DILI is complex and involves several interrelated factors. It has been suggested that DILI is more likely to occur in females, the elderly, and patients with chronic liver disease, HIV, and obesity. Many of these possibilities have come under scrutiny, and there is little empiric data available to support the validity of these factors.15 With the exception of the Icelandic and French epidemiologic studies, the study of risk factors for DILI is an imperfect science because the
Diagnosis
A patient with suspected DILI should have a careful evaluation for other forms of liver disease, especially viral hepatitides. Other forms of acute and chronic liver disease can be evaluated as outlined in the Figure. In most cases, the diagnostic steps are carried concurrently, especially if the suspected DILI is deemed to be severe. There are some important potential diagnostic pitfalls to consider when evaluating for other liver diseases. Nonalcoholic fatty liver disease is the most common
New Data on Individual Agents and Specific Formulations
In this section, we provide an update on individual agents that cause DILI. We would also like to direct the reader to a new website called LiverTox (www.livertox.nih.gov), which is sponsored by the National Institutes of Health and serves as a repository of information on drugs known to cause DILI. This database is searchable and is helpful when it is unclear as to whether an agent may be responsible for DILI or not. Other common drugs that can lead to DILI are listed in Table 2 with their
Treatment
Treatment for most forms of DILI is focused on supportive care and requires longitudinal monitoring of the patient and laboratory work. Discontinuation of the offending agent is the first step. Rechallenge is not recommended except under very rare scenarios with the input of a hepatologist. Once DILI has been diagnosed, it is important to list that drug as an “allergy” and to counsel the patient on the importance of avoiding that particular drug, and when appropriate, other drugs in its class.
Prognosis
For the vast majority of patients with DILI, full recovery is expected during the dechallenge. For patients with jaundice, this may take up to 30 to 40 days, and occasionally up to a year in those with severe cholestasis. In general, the hepatocellular injury phenotype carries a worse prognosis than do the cholestatic or mixed presentations. One of the oldest tools used for prognosis in DILI was developed by the famous hepatologist Hyman Zimmerman. His simple rule stated that a bilirubin level
Conclusion
The epidemiology of idiosyncratic DILI has become clearer with the addition of the Iceland study, demonstrating a crude annual incidence of 19 per 100,000 inhabitants. Idiosyncratic DILI is a serious problem, accounting for approximately 10% of the ALF cases in the United States. There is now a better understanding of drug-specific properties that result in the risk of DILI such as the interaction of drug dose and lipophilicity as well as the extent of hepatic metabolism. Specific host genetic
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