title: Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial.
abstract: BACKGROUND
  The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection.
  
  
  OBJECTIVE
  To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants.
  
  
  METHODS
  Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire.
  
  
  RESULTS
  In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted.
  
  
  CONCLUSIONS
  These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.
authors.affiliation: Liver Unit, Department of Medicine, Hebrew University, Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Alla
authors.initials: A
authors.lastname: Melhem
authors.forename: Mirela
authors.initials: M
authors.lastname: Stern
authors.forename: Oren
authors.initials: O
authors.lastname: Shibolet
authors.forename: Eran
authors.initials: E
authors.lastname: Israeli
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ackerman
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.forename: Nilla
authors.initials: N
authors.lastname: Hemed
authors.forename: Mina
authors.initials: M
authors.lastname: Rowe
authors.forename: Hana
authors.initials: H
authors.lastname: Ohana
authors.forename: George
authors.initials: G
authors.lastname: Zabrecky
authors.forename: Robert
authors.initials: R
authors.lastname: Cohen
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D012367:RNA, Viral