Monitoring and stopping rules for potential drug-induced liver injury (DILI) events in patients with chronic liver diseases who enter clinical trials with abnormal baseline liver tests should be based on a knowledge of the expected test fluctuations that reflect the natural history of the disease and are specific to the disease being studied.

After establishing a potentially elevated baseline value for alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, or alkaline phosphatase derived from the mean of at least two pretreatment values, the criteria for further elevations that trigger increased monitoring and holding or stopping drug should be based on multiples of the baseline value or a specific threshold value, whichever comes first, and not solely on multiples of the upper limit of normal (ULN).

For clinical trials in patients with cirrhosis from hepatitis C virus (HCV), hepatitis B virus (HBV), or nonalcoholic steatohepatitis (NASH), lesser elevations of ALT, AST; elevations of direct bilirubin and alkaline phosphatase even without significant elevations of aminotransferases; changes in the AST:ALT ratio; and changes in the international normalized ratio (INR) or model for end-stage liver disease (MELD) score may all be more sensitive measures of potential DILI events than traditional criteria of multiples of ULN of ALT, AST, total bilirubin, or alkaline phosphatase.