title: Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial.
abstract: The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3 x 4.5 million units IFN-alpha 2a per week), (group A), or IFN and N-acetylcysteine (N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 microg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05-5.5) of obtaining a complete response and had significantly greater reduction in viral load (P = 0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.
authors.affiliation: Department of General Internal Medicine, University of Bonn, Germany. look@uni-bonn.de
authors.forename: M P
authors.initials: MP
authors.lastname: Look
authors.forename: A
authors.initials: A
authors.lastname: Gerard
authors.forename: G S
authors.initials: GS
authors.lastname: Rao
authors.forename: T
authors.initials: T
authors.lastname: Sudhop
authors.forename: H P
authors.initials: HP
authors.lastname: Fischer
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: U
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000097:blood; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D018038:Sodium Selenite / Q000097:blood / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D016896:Treatment Outcome; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D009195:Peroxidase; D005978:Glutathione; D018038:Sodium Selenite; D000111:Acetylcysteine