title: Evidence of a significant role for Fas-mediated apoptosis in HCV clearance during pegylated interferon plus ribavirin combination therapy.
abstract: BACKGROUND
  The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection.
  
  
  METHODS
  Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy.
  
  
  RESULTS
  Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients.
  
  
  CONCLUSIONS
  Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.
authors.affiliation: Division of Gastroenterology, Hepatitis Section, Federal University of Sao Paulo, Brazil. leo-jf@uol.com.br
authors.forename: Leonardo L
authors.initials: LL
authors.lastname: Schiavon
authors.forename: Janaína L
authors.initials: JL
authors.lastname: Narciso-Schiavon
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Carvalho-Filho
authors.forename: Juliana P
authors.initials: JP
authors.lastname: Sampaio
authors.forename: Philipe N
authors.initials: PN
authors.lastname: El Batah
authors.forename: Genimari A
authors.initials: GA
authors.lastname: Silva
authors.forename: Cláudia T
authors.initials: CT
authors.lastname: Carvente
authors.forename: Antonio Eduardo B
authors.initials: AE
authors.lastname: Silva
authors.forename: Maria Lucia G
authors.initials: ML
authors.lastname: Ferraz
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019014:fas Receptor / Q000097:blood*
chemical_list: D000998:Antiviral Agents; D053222:Fas Ligand Protein; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D019014:fas Receptor; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a