Drug-induced liver injury (DILI), a relatively rare condition, is nevertheless a 
major reason for not approving a drug in development or for removing one already 
marketed. With a specific diagnostic biomarker lacking, finding elevated serum 
enzyme [alanine aminotransferase (ALT), aspartate aminotransferase and alkaline 
phosphatase] activities remains an initial signal for incipient liver injury. 
Enzyme elevations alone may not be harmful, but if caused by a drug and followed 
by jaundice (called 'Hy's law') there is a high possibility of serious DILI. In 
1997 several drugs were approved by the Food and Drug Administration (FDA) of 
the USA that were later withdrawn from the market for serious liver toxicity. 
New drugs in development are now required to be monitored for liver injury, and 
the data is to be considered in the approval decision. A program called e-DISH 
(evaluation of drug-induced serious hepatotoxicity) was introduced in 2004 to 
aid medical reviewers to select from all subjects studied those few who show 
nontrivial liver injury and estimate the most likely cause. The threshold of 
enzyme elevation comprising a warning for possibly serious DILI is uncertain, 
although generally accepted as 3-5 times the 'upper limit of normal'. The new 
direct-acting antiviral agents for treating chronic hepatitis C virus, which 
often lead to a reduction of elevated ALTs, mandate that a later increase 
without viral breakthrough be compared to the new on-treatment level of values. 
The drug may be discontinued or interrupted for evaluation to exclude other 
possible causes of liver injury. The FDA has approved no drug since 1997 that 
has been withdrawn later because of serious hepatotoxicity.