Table 4.

Factors to Consider in the Histological Evaluation of DILI

Factor	Questions
Temporal Eligibility	What agents were taken and over what time period? Do those exposures match the known risk profile of the agents?
Exclusion of Competing Causes	Given the histological pattern of injury, have all the appropriate clinical tests been performed to exclude other possibilities?
Known Potential for Injury	What is the evidence that the agents in question cause liver injury? Are the potential agents common or rare causes of injury?
Precedent for Pathologic Injury Pattern	Given the histological changes, how does that compare to the reported injury patterns of the agents in question? If the agent’s injury pattern is unknown because the agent is novel or recently introduced, can the injury pattern be explained by the agent’s mechanism of action or by relation to other agents in the same class?
De-challenge/Re-challenge	What is the natural history of the injury associated with the agents in question? Are the histological changes consistent with ongoing/resolving injury?
Toxicologic Analysis	Are there laboratory studies that can be done to check for drug levels or accumulation of toxic by-products?