Exploring the role of oxidative stress and the effect of N‐acetylcysteine in thiopurine‐induced liver injury in inflammatory bowel disease: A randomized crossover pilot study

Abstract

AbstractThiopurine treatment is regularly complicated by drug‐induced liver injury. It has been suggested that oxidative stress may play a synergistic role. To assess whether thiopurine‐induced liver injury coincides with increased oxidative stress and whether co‐administration with N‐acetylcysteine is protective, we performed a randomized open label crossover pilot study in inflammatory bowel disease patients with thiopurine‐induced increased serum liver tests. The study comprised four stages of 4 weeks. Patients received no additional therapy followed by N‐acetylcysteine 1200 mg twice a day, or the other way around, alongside ongoing thiopurine treatment. The third and fourth stages comprised a washout period and thiopurine reintroduction period. Nine patients completed the study, and the addition of N‐acetylcysteine decreased myeloperoxidase concentrations (33.6–24.5 pmol/L, p = 0.038). The other biomarkers remained unchanged, including thiopurine metabolites, xanthine oxidase activity, thiopurine S‐methyltransferase activity and serum liver enzyme activity tests. Reintroduction of thiopurines led to an increase of F2‐isoprostanes (101–157 ng/mmol, p = 0.038), but not of serum liver enzyme activity tests. Results suggests that thiopurines may increase oxidative stress and although the addition of N‐acetylcysteine led to a decrease in plasma myeloperoxidase concentrations, it does not protect from thiopurine‐induced increase of serum liver tests.