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.