Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine.
OBJECTIVE
Glutathione depletion might be one reason for the low rate of response of patients with chronic hepatitis C to treatment with interferon. The aim of the present study was to document the thiol status of patients with chronic hepatitis C and the effects of N-acetylcysteine, a precursor for glutathione synthesis, on the concentrations of total cysteine, glutathione and homocysteine during treatment of chronic hepatitis C with interferon.


METHODS
Total cysteine, glutathione and homocysteine in plasma were measured by high performance liquid chromatography, following reduction of disulfides and derivatization of thiols with monobromobimane in a group of 36 patients with chronic hepatitis C, who participated in a multicenter, double-blind, randomized, placebo-controlled clinical trial studying the effect of supplementation with N-acetylcysteine (600 mg three times daily) on the response to treatment with interferon-a (3 MU three times per week) for 6 months.


RESULTS
The concentrations of total cysteine (367.0+/-43.9 vs 360.4+/-33.5 nmol/ml, mean+/-95% confidence interval), glutathione (12.5+/-1.6 vs 14.1+/-1.3 nmol/ml) and homocysteine (21.2+/-4.5 vs 19.6+/-5.2 nmol/ml) were similar in patients with chronic hepatitis C and healthy control subjects Supplementation with N-acetylcysteine resulted in measurable concentrations of N-acetylcysteine in plasma, but did not significantly increase the concentrations of cysteine, glutathione or homocysteine. There was no difference between the two treatment groups with regard to transaminases and clearance of HCV RNA.


CONCLUSIONS
Circulating concentrations of total cysteine, glutathione and homocysteine are normal in patients with chronic hepatitis C. Supplementation with N-acetylcysteine did not increase the circulating concentrations of total cysteine, glutathione and homocysteine.
Bernhard
M C
MC
Department of Clinical Pharmacology, University of Bern, Switzerland.
Junker
E
E
Hettinger
A
A
Lauterburg
B H
BH
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003545:Cysteine / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D013997:Time Factors
D000998:Antiviral Agents; D016898:Interferon-alpha; D006710:Homocysteine; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine