title: Long-term administration of interferon-alpha in non-responder patients with chronic hepatitis C: follow-up of liver fibrosis over 5 years.
abstract: In chronic hepatitis C, previous data have shown that short-term treatment with interferon-alpha (IFN-alpha) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non-responder patients, the long-term effect of IFN-alpha on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non-responder patients with chronic hepatitis C retreated with successive courses of IFN-alpha. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN-alpha treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN-alpha therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow-up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow-up period in all patients (P = 0.045). Long-term treatment with IFN-alpha is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Laboratoire Marcel Mérieux, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Guerret
authors.forename: A
authors.initials: A
authors.lastname: Desmoulière
authors.forename: P
authors.initials: P
authors.lastname: Chossegros
authors.forename: A M
authors.initials: AM
authors.lastname: Costa
authors.forename: C
authors.initials: C
authors.lastname: Badid
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: J A
authors.initials: JA
authors.lastname: Grimaud
authors.forename: M
authors.initials: M
authors.lastname: Chevallier
mesh_terms: D000328:Adult; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load
chemical_list: D016898:Interferon-alpha; D003094:Collagen