Serum markers for mitochondrial dysfunction and cell death are possible predictive indicators for drug-induced liver injury by direct acting antivirals

Aim We prospectively screened patients treated with direct-acting antivirals (DAA) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). Methods The levels of various serum markers among DILI, non-DILI and control groups were compared. The DILI group consisted of eight patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, sex and disease severity. Additionally, eight healthy volunteers were employed as the controls. Serum measurements of cytokines/chemokines, cytokeratin-18 fragment (CK-18F) and super oxidase dismutase-2 (SOD2) were evaluated on the date at which hepatitis C virus RNA was absent (baseline). For patients with DILI, serum measurements taken before treatment, 1 week before pronounced transaminase elevation (prominence-1 W) and on the date at which pronounced elevation of transaminase occurred (prominence) were also evaluated. Results All patients treated with DAA had normalized transaminase levels at baseline. In patients with DILI, interferon-inducible protein-10 (IP-10) levels were higher at prominence-1 W than at baseline. Those patients also had significantly higher levels of SOD2 and CK-18F at prominence-1 W than at baseline. Conclusion Elevated IP-10 may be a preconditioning chemokine for DAA-induced liver injury, and damage markers associated with cell death and mitochondrial dysfunction are potential predictive serum markers for DILI.