Identification of Distinguishing Features of Drug‐Induced Liver Injury and Liver Injury Associated With Sepsis

ABSTRACT Background and Aims It can be difficult to distinguish between drug‐induced liver injury (DILI) and liver injury associated with sepsis (sepsis induced liver injury, SILI). The aims of the study were to compare clinical and biochemical features between DILI and SILI and identify distinguishing characteristics that might assist in diagnosing these conditions. Methods Retrospective cohorts of all DILI cases diagnosed in Iceland 2009–2024 and SILI 2006–2024 were divided into hepatocellular and cholestatic (CS/mixed) patterns. Patients had: > 5× upper limit of normal (ULN) of ALT and/or > 2× ULN in ALP. RUCAM and expert opinion were used in the causality assessment of DILI, and SILI patients had to fulfil international consensus criteria. Results Overall 275 DILI patients (median age 59 years, 63% females), 153 with SILI (67 years, 49% females) were included. Among patients with HC type, 57% with SILI and only one (0.9%) with DILI had normal liver tests 2 weeks after the event. The peak value of AST was 1794 (IQR 931–3526) IU/L in HC type of SILI but 584 (315–1013) IU/L in DILI, p < 0.001. CS/mixed type of SILI resolved also significantly faster while CS/mixed pattern of DILI had significantly higher ALP at onset and peak ALT than SILI. SILI had 30% mortality compared to DILI (2%) p < 0.001. Conclusions Marked elevation of AST and rapid resolution with a HC pattern of liver injury favours the diagnosis of SILI. Cholestatic/mixed SILI also resolves rapidly in contrast to CS/mixed DILI that is associated with markers of more pronounced liver injury.