Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis.
OBJECTIVE
Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease. Although usually indolent, this disease can progress to cirrhosis in some patients. There is currently no proven medical therapy for the treatment of NASH. The aim of our study was to evaluate the efficacy of combination alpha-tocopherol (vitamin E) and vitamin C in reducing histologic inflammation and fibrosis.


METHODS
This was a prospective, double-blind, randomized, placebo-controlled trial with a total enrollment of 49 patients; 45 patients completed the study. All patients were randomized to receive either vitamins E and C (1000 IU and 1000 mg, respectively) or placebo daily for 6 months, based on their initial histologic diagnosis of NASH. Additionally, all patients were given standard weight-loss counseling and encouraged to follow a low fat diet (<30 fat g/day). The pre- and posttreatment liver biopsies were reviewed by a single pathologist, who was blinded to the patient's medication. Biopsies were scored based on a modification of the scoring system published by Brunt et al. (Am J Gastroenterol 1999;94:2467-74). A score of 0-4 was possible for fibrosis, and a score of 0-6 was possible for inflammation and hepatocyte degeneration and necrosis. In addition, body mass index, glycohemoglobin, lipids, and liver enzymes were followed throughout the study.


RESULTS
Forty-five patients completed 6 months of therapy without significant side effects. Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in the doses used in this study, were well tolerated and were effective in improving fibrosis scores in NASH patients. No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy. A larger, multicenter, longer-term trial with vitamin E and vitamin C seems to be warranted.
Harrison
Stephen A
SA
Brooke Army Medical Center, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Torgerson
Sigurd
S
Hayashi
Paul
P
Ward
John
J
Schenker
Steven
S
D000704:Analysis of Variance; D000975:Antioxidants / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid