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Drug-induced liver injury

Author
Anne M Larson, MD, FACP, FAASLD, AGAF
Section Editor
Keith D Lindor, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF

INTRODUCTION

Drug-induced liver injury can develop following the use of many drugs, both prescription and over-the-counter, through a variety of mechanisms [1-3]. A high index of suspicion is often necessary to expeditiously establish the diagnosis.

This topic will review the epidemiology, clinical manifestations, diagnosis, and management of drug-induced liver injury. The metabolism of drugs by the liver, the mechanisms by which drugs might injure the liver, and the use of medications in patients with liver disease are discussed separately. (See "Drugs and the liver: Metabolism and mechanisms of injury" and "Overview of the management of chronic hepatitis C virus infection", section on 'Dose adjustments of medications' and "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'Medication adjustments'.)

EPIDEMIOLOGY

Drug-induced liver injury (DILI) has an estimated annual incidence between 10 and 15 per 10,000 to 100,000 persons exposed to prescription medications [4-11]. DILI accounts for approximately 10 percent of all cases of acute hepatitis [12], and it is the most common cause of acute liver failure in the United States [13,14]. DILI is also the most frequently cited reason for withdrawal of medications from the marketplace [13,15]. DILI may not be detected prior to drug approval, because most new drugs are tested in fewer than 3000 people prior to drug approval. As a result, cases of DILI with an incidence of 1 in 10,000 may be missed. It has been suggested that for every 10 cases of alanine aminotransferase elevation (>10 times the upper limit of normal) in a clinical trial, there will be one case of more severe liver injury that develops once the drug is widely available [16,17].

Several risk factors have been associated with the development of DILI [18]. In general, adults are at higher risk for DILI than children (with the notable exception of DILI from valproic acid, which is more common in children). Women may be more susceptible to DILI than men, which may in part be due to their generally smaller size [9]. Alcohol abuse and malnutrition predispose to DILI in some cases, as is seen with acetaminophen toxicity. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis", section on 'Clinical factors influencing toxicity'.)

ASSOCIATED DRUGS

Over 1000 medications and herbal products have been implicated in the development of drug-induced liver injury (DILI), and the list continues to grow (table 1) [19,20]. The National Institutes of Health maintains a searchable database of drugs, herbal medications, and dietary supplements that have been associated with DILI. Herbal products associated with DILI are discussed separately. (See "Hepatotoxicity due to herbal medications and dietary supplements".)

                  

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Literature review current through: Nov 2016. | This topic last updated: Fri May 29 00:00:00 GMT+00:00 2015.
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