Drug-induced liver injury (DILI)
Drug-induced liver injury (DILI) is liver damage from a prescription, over-the-counter, or herbal agent, ranging from asymptomatic transaminase elevation to acute liver failure. Diagnosis rests on excluding other causes and a temporal drug link; management is prompt discontinuation of the offending agent, with N-acetylcysteine for acetaminophen toxicity.
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What this article covers
- Overview
What it is: drug-induced liver injury (DILI) is hepatic damage from a prescription, over-the-counter, or herbal or dietary supplement product, ranging from asymptomatic aminotransferase elevation to acute liver failure (ALF).
- Epidemiology
Typical patient: anyone exposed to a new prescription drug, over-the-counter product, or supplement in the preceding 6 months; risk tracks with exposure, not a fixed demographic.
- Risk factors
Chronic alcohol use: induces hepatic cytochrome P450 enzymes, so chronic drinkers can develop acetaminophen hepatotoxicity even at therapeutic doses.
- Pathophysiology
Intrinsic, dose-dependent injury: cytochrome P450 enzymes convert acetaminophen to the reactive metabolite N-acetyl-p-benzoquinone imine, which depletes glutathione; once glutathione is exhausted…
- Clinical features
Time course: intrinsic acetaminophen injury develops over hours to days after a toxic ingestion, while idiosyncratic reactions typically emerge days to a few months after starting the agent, most within 6 months.
- Differential diagnosis
Viral hepatitis (A through E): shares fatigue, jaundice, and a hepatocellular pattern, but is distinguished by positive viral serologies rather than a temporal drug relationship.
- Diagnosis
What establishes the diagnosis: DILI is a diagnosis of exclusion, established by a plausible temporal link to a drug, exclusion of viral, autoimmune, biliary, ischemic, and metabolic causes, a…
- Management
First, stop the offending agent: this is the essential step in nearly all DILI, intrinsic or idiosyncratic, and no drug substitutes for it; review the full medication and supplement list and discontinue every plausible cause.
- Complications
Acute liver failure: the most feared complication, defined by encephalopathy and INR 1.5 or higher within 26 weeks; DILI causes roughly 50% of ALF, with mortality up to 14% once the bilirubin/ALT severity threshold above is met.
- Prognosis
Most cases resolve within weeks to a few months of withdrawal: injury typically normalizes once the drug is stopped, and this course supports the diagnosis.
- Prevention
Avoid rechallenge: never re-expose a patient to a drug that previously caused DILI.
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Related articles
- Acute liver failure
Acute liver failure is the abrupt onset of hepatic synthetic dysfunction, defined by coagulopathy with an INR of 1.5 or higher plus any grade of hepatic encephalopathy, occurring within 26 weeks of illness onset in a patient without preexisting liver disease. Acetaminophen overdose is the leading cause in the United States, and management centers on N-acetylcysteine when acetaminophen is implicated, intensive supportive care, and early referral to a liver transplant center.
- Autoimmune hepatitis
Autoimmune hepatitis is a chronic inflammatory hepatitis, four times more common in women, marked by elevated aminotransferases, autoantibodies, and hypergammaglobulinemia, confirmed by liver biopsy after excluding other causes. Treatment is immunosuppression with prednisone, usually combined with azathioprine, continued for at least 2 to 3 years before withdrawal is considered.
- Evaluation of abnormal liver function tests (LFTs)
Abnormal liver chemistries are evaluated by first classifying the pattern as hepatocellular (AST/ALT predominant), cholestatic (ALP/bilirubin predominant), or isolated hyperbilirubinemia, then pursuing an ordered, pattern-specific workup for viral, autoimmune, metabolic, toxic, infiltrative, and obstructive causes.
- Alcohol-associated hepatitis
Alcohol-associated hepatitis is an acute steatohepatitic syndrome, fever, tender hepatomegaly, jaundice, and leukocytosis, arising on a background of heavy chronic alcohol use. Severity is graded by the Maddrey discriminant function and the Model for End-Stage Liver Disease score, and severe disease is treated with prednisolone after infection and bleeding are excluded, guided by the day-7 Lille score.
- Cirrhosis
Cirrhosis is end-stage hepatic fibrosis with regenerative nodules, staged as compensated or decompensated by the onset of ascites, variceal hemorrhage, encephalopathy, or jaundice. Severity is graded by Child-Pugh class and MELD, and management centers on treating the underlying cause, surveillance for varices and hepatocellular carcinoma, and timely transplant referral once decompensation appears.