title: Replication of hepatitis C virus in peripheral blood mononuclear cells in patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin.
abstract: BACKGROUND
  Hepatitis C virus (HCV) is a primarily hepatotropic virus, but hepatocytes are not the only localization of its replication. It is still unclear if extrahepatic HCV replication, measured as the detection of HCV RNA negative strand in peripheral blood mononuclear cells (PBMCs) before initiation of treatment, has an influence on therapy response. Detection of HCV RNA in extrahepatic sites for assessment of therapy efficacy is not routinely used in clinical practice. The aim of the study was to evaluate whether the replication of HCV in PBMCs affects the rate of sustained virological response (SVR).
  
  
  METHODS
  The study group comprised 55 patients with chronic hepatitis C, originally treatment naive. They were treated with pegylated interferon (PEG-IFN) alpha 2a and ribavirin, with the standard dosing schedule. Parallel serum samples for HCV RNA and PBMC samples for HCV RNA negative strand were obtained at baseline, at the end of treatment and 24 weeks after finishing therapy.
  
  
  RESULTS
  Undetectable HCV RNA in serum at the end of therapy was found in 48 patients (87.3%), while 33 patients (60.0%) achieved sustained virological response (SVR) (51% for HCV genotype 1 and 78% for genotype 3, respectively). Fifteen individuals (31.3%) were relapsers. Factors associated with significantly higher rate of SVR were young age, mild or no fibrosis and infection with HCV genotype 3. HCV RNA negative strand in PBMCs before treatment was found in 21.8% (12 out of 55 patients). HCV RNA negative strand was detected at baseline more frequently in patients who later achieved SVR. Relapse appeared significantly more often in patients with negative strand at the end of therapy: in 2 out of 15 individuals compared to 0 out of 33 patients (p=0.03).
  
  
  CONCLUSIONS
  Presence of negative HCV RNA strand in PBMCs before treatment may be suggested as a potential marker of good treatment response. Detection of negative strand at the end of therapy is a predictor of relapse.
authors.affiliation: Department of Infectious Diseases, Wrocław Medical University, 51-149 Wrocław, Poland. minglot@interia.pl
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Inglot
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pawlowski
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szymczak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Malyszczak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zalewska
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000254:growth & development*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C571406:PEG-IFN-SA; D012367:RNA, Viral; D011092:Polyethylene Glycols; D012254:Ribavirin