title: New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).
abstract: Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders.
authors.affiliation: a Health Policy Research Center, Building No. 2, Eighth Floor, Shiraz University of Medical Sciences, School of Medicine, Zand Avenue, P.O. Box 71345-1877, Shiraz, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Peymani
authors.affiliation: b Program in Physiology & Experimental Medicine, Hospital for Sick Children Research Institute and University of Toronto, Toronto, ON M5G 0A4, Canada.
authors.forename: Behzad
authors.initials: B
authors.lastname: Yeganeh
authors.affiliation: c Safety Promotion and Injury Prevention Research Center and Department of Clinical Epidemiology, School of Health, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Siamak
authors.initials: S
authors.lastname: Sabour
authors.affiliation: d Department of Pathology and Organ Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.affiliation: e Department of Internal Medicine and Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Fattahi
authors.affiliation: f Department of Clinical Virology, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Keyvani
authors.affiliation: g Organ Transplant Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: h Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Coombs
authors.affiliation: i Department of Human Anatomy and Cell Science, St. Boniface Research Centre, Children Hospital Research Institute of Manitoba, Biology of Breathing Theme, University of Manitoba, 745 Bannatyne Ave., Winnipeg, MB R3E 0J9, Canada.
authors.forename: Saied
authors.initials: S
authors.lastname: Ghavami
authors.affiliation: a Health Policy Research Center, Building No. 2, Eighth Floor, Shiraz University of Medical Sciences, School of Medicine, Zand Avenue, P.O. Box 71345-1877, Shiraz, Iran.
authors.forename: Kamran B
authors.initials: KB
authors.lastname: Lankarani
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism*; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load / Q000379:methods
chemical_list: D000998:Antiviral Agents; D002738:Chloroquine; D000410:Alanine Transaminase
keywords: autophagy; chloroquine; chronic hepatitis C; hépatite C chronique; non-responsive; pilot study; réponse non satisfaisante au traitement; étude pilote