The effect of acetylcysteine on thiopurine use related liver injury.

Thioprunes are pivotal in the treatment of inflammatory bowel disease such as Crohn's disease and ulcerative colitis. However, toxicity is a frequent cause of therapy cessation. Hepatotoxicity due to thiopurine therapy may be initiated by an increased state of oxidative stress due to the metabolization of thiopurines on one hand and due to low availability reduced glutathion and its amino acid precursors. By supplementation of N-acetylcysteine we try to reduce oxidative stress and thereby ameliorate hepatotoxicity.

Thiopurine induced hepatotoxicity is related with an enhanced state of oxidative stress and may ameliorate after N-acetylcysteine supplementation.

Elligible patients will be screened prior to defenite inclusion. After inclusion they will be randomly assigned to one of the two groups and will visit the outpatient clinics five times with an interval of four weeks. During the first eight weeks thiopurine therapy will be continued and depending on the group patients will concomitantly receive N-acetylcysteine 2400mg daily during weeks 1 to 4 or weeks 5 to 8. Weeks 9 to 12 both thiopurine therapy and N-acetylcysteine will be withdrawn. Rechallenge of solely thiopurine therapy takes place during weeks 13 to 16.

Continuation of thiopurine treatment during eight weeks. During four weeks 600mg N-acetylcysteine effervescent tablets four times daily.