title: Hepatitis C minimal residual viremia (MRV) detected by TMA at the end of Peg-IFN plus ribavirin therapy predicts post-treatment relapse.
abstract: OBJECTIVE
  Around 15-25% of chronic hepatitis C patients treated with Peg-IFN plus ribavirin become HCV-RNA negative by PCR during therapy but relapse after its withdrawal. We investigated whether minimal residual viremia (MRV) might be detected in these cases by Transcription-Mediated Amplification (TMA).
  
  
  METHODS
  Two hundred and ninety-two consecutive patients (143 HCV-1, 82 HCV-2, 56 HCV-3 and 11 HCV-4) were prospectively treated with a standard schedule of Peg-IFNalpha 2b plus ribavirin combination and end-of-therapy response was assessed by conventional PCR using 2 protocol serum samples obtained 6-8h before the last two scheduled weekly injections of Peg-IFN. PCR negative samples were re-tested by TMA and the results were then correlated with the virological outcome after therapy withdrawal.
  
  
  RESULTS
  Among 208 patients who were repeatedly HCV-RNA negative by PCR at the end-of-therapy, 26 (12.5%) were found HCV-RNA positive by TMA. Twenty-two of them, (96%) were PCR-relapsers after therapy withdrawal, compared to only 14% of the 182 TMA negative patients (P<0.0001). This virological profile was more frequent in HCV-1 and HCV-3 infected patients and correlated with a slower virological response during therapy.
  
  
  CONCLUSIONS
  At the end of Peg-IFN plus ribavirin therapy, TMA is superior to PCR in identifying patients with sustained HCV-RNA clearance.
authors.affiliation: VIMM-Venetian Institute of Molecular Medicine, via Orus 2, Padua, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Gerotto
authors.forename: Francesca
authors.initials: F
authors.lastname: Dal Pero
authors.forename: Gladis
authors.initials: G
authors.lastname: Bortoletto
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrari
authors.forename: Roberta
authors.initials: R
authors.lastname: Pistis
authors.forename: Giada
authors.initials: G
authors.lastname: Sebastiani
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.forename: Alfredo
authors.initials: A
authors.lastname: Alberti
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / 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*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a