The natural history of drug-induced liver injury.

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.