The Natural History of Drug-induced Liver Injury

Einar Björnsson, M.D., Ph.D.

Semin Liver Dis. 2009;24(9):357-363.

Abstract

The development of acute hepatocellular injury with jaundice in patients with drug-induced liver injury (DILI) has been associated with a case-fatality rate of 10 to 50%, depending on the drug involved. This observation, called "Hy's rule," is frequently used by regulatory agencies in assessing the hepatotoxic potential of drugs being tested in clinical trials. Registry studies from Sweden, Spain, and the United States have confirmed the validity of Hy's rule by demonstrating a 9 to 12% mortality rate in consecutive DILI patients. In patients with suspected DILI, the causative agent should be immediately discontinued, and hospitalized patients with severe coagulopathy or encephalopathy should be referred for potential liver transplantation. Recent studies have shown that DILI can infrequently evolve into chronic liver injury including cirrhosis and even liver-related morbidity and mortality in a minority of patients.

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Cite this: The Natural History of Drug-induced Liver Injury - Medscape - Nov 01, 2009.

Table 1. Mortality and Liver Transplantation among Patients with Hepatocellular, Cholestatic, and Mixed Types of Drug-Induced Liver Injury
Study	Severe Hepatocellular DILI (%) (Death, LT)	Severe Cholestatic DILI (%) (Death, LT)	Severe Mixed DILI (%) (Death, LT)
Ibañez et al 2002^[11]	10/56 (17.8)	4/31 (12.9)	1/20 (5)
	(7, 3)	(4, 0)	(1, 0)
Andrade et al 2005^[14]	25/258 (9.7)	5/89 (5.6)	2/99 (2)
	(18, 7)	(4, 1)	(2, 0)
Björnsson & Olsson 2005^[2]	52/409 (12.7)	16/206 (7.8)	4/165 (2.4)
	(39, 13)	(16, 0)	(4, 0)
Chalasani et al 2008^[12]	19/169 (11.2)	4/68 (5.9)	4/61 (6.6)
	(11, 8)	(4, 0)	(3, 1)

DILI, drug-induced liver injury; LT, liver transplantation.

Table 2. Drugs Associated with Development of Chronic Liver Injury and Cirrhosis
Medication	Drug Class	Reference
Isoniazid	Antituberculosis	^[33]
Nitrofurantoin	Antibiotic	^[40]
Flucloxacillin	Antibiotic	^[41]
Amiodarone	Antiarrhythmic	^[42]
Methotrexate	Anti-inflammatory	^[43]
Chlorpromazine	Antipsychotic	^[44]
Ramipril	Antihypertensive	^[45]
Diclofenac	Anti-inflammatory	^[46]

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The Natural History of Drug-induced Liver Injury

Abstract

Abstract

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Tables

References

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