Likelihood Scoring System
Classification system for drug-induced liver injury based on published evidence and case reports
Well-Known Hepatotoxin
The drug is well known, well described and well reported to cause either direct or idiosyncratic liver injury, and has a characteristic signature; more than 50 cases including case series have been described.
Known Hepatotoxin
The drug is known or highly likely to cause idiosyncratic liver injury and has a characteristic signature; between 12 and 50 cases including small case series have been described.
Probable Hepatotoxin
The drug is probably linked to idiosyncratic liver injury, but has been reported uncommonly and no characteristic signature has been identified; less than 12 cases without significant case series.
Possible Hepatotoxin
Single case reports have appeared implicating the drug, but fewer than 3 cases have been reported in the literature, no characteristic signature has been identified, and the case reports may not have been very convincing. Thus, the agent can only be said to be a possible hepatotoxin and only a rare cause of liver injury.
Unlikely Hepatotoxin
Despite extensive use, no evidence that the drug has caused liver injury. Single case reports may have been published, but they were largely unconvincing. The agent is not believed or is unlikely to cause liver injury.
Unproven but Suspected
The drug is suspected to be capable of causing liver injury or idiosyncratic acute liver injury but there have been no convincing cases in the medical literature. In some situations cases have been reported to regulatory agencies, but the specifics and details supportive of causality assessment are not available. The agent is unproven, but suspected to cause liver injury.
Unknown
For medications recently introduced into or rarely used in clinical medicine, there may be inadequate information on the risks of developing liver injury to place it in any of the five categories, and the category is characterized as "unknown."
Important Note: High-Dose Hepatotoxicity
Some agents cause liver injury but only when given in high doses as might occur with a drug overdose. These agents are usually direct toxins. Some do not cause liver injury at normal or therapeutic doses but are quite toxic in overdoses, examples being aspirin, acetaminophen, niacin and vitamin A. These agents are categorized using [HD] after the category of A, B, C or D.