Fig. 2.

Algorithm for monitoring and management of potential DILI signals in phase II–III clinical trials in patients with HCV with normal or elevated baseline ALT. ^aBaseline ALT is derived from an average of two pretreatment ALT measurements 2 weeks apart. Elevated baseline is defined as ALT ≥ 1.5 × ULN. ^bSymptoms may be liver related (e.g., severe fatigue, nausea, vomiting, right upper quadrant pain) or immunologic reaction (e.g., rash, > 5% eosinophilia). ^cFor patients with Gilbert’s syndrome or hemolysis. ^dIn patients with a sizable stable early decrease in ALT during treatment (> 50% of baseline value), a new baseline, corresponding to the ALT nadir, should be established on an individual basis for subsequent determination of a DILI signal. ^eThe specific interval between the tests should be determined based on the patient’s clinical condition. ALP alkaline phosphatase, ALT alanine aminotransferase, AST aspartate aminotransferase, DB direct bilirubin, DILI drug-induced liver injury, HBcAb+ hepatitis B core antibody positive, HBV hepatitis B virus, HCV hepatitis C virus, TBL total bilirubin, ULN upper limit of normal