title: Assessment, by transcription-mediated amplification, of virologic response in patients with chronic hepatitis C virus treated with peginterferon alpha-2a.
abstract: Transcription-mediated amplification (TMA) is an isothermal, autocatalytic target amplification method which has the potential to detect less than 50 hepatitis C virus (HCV) RNA copies/ml (10 IU/ml). The TMA assay was used to assess the presence of residual HCV RNA in plasma from patients treated with polyethylene glycol-modified interferon alpha-2a (peginterferon alpha-2a) who showed a virologic relapse after the end of therapy. Stored end-of-treatment and end-of-follow-up plasma samples from 177 of 267 patients treated with peginterferon alpha-2a (S. Zeuzem et al., N. Engl. J. Med. 343:1666--1672, 2000) were available for retesting by TMA. Plasma samples from patients in the same study who exhibited virologic relapse after treatment with standard interferon alpha-2a served as controls. Virologic response during the trial was defined as HCV RNA that was undetectable using a PCR-based test system with a sensitivity of 50 IU/mL (Cobas Amplicor HCV version 2.0) and was compared with TMA-based retesting results (VERSANT HCV RNA Qualitative Assay). Residual HCV RNA was detected in 4 of 60 cases (7%) by the TMA technology in end-of-treatment plasma samples from patients who relapsed after receiving peginterferon alpha-2a and in 6 of 18 patients (33%) following therapy with standard interferon alpha-2a. For peginterferon alpha-2a-treated patients with sustained virologic response, HCV RNA was detectable by TMA in end-of-treatment samples in 3 of 78 cases but in none of the end-of-follow-up samples. For all end-of-treatment and end-of-follow-up plasma samples of virologic nonresponders, a complete concordance between the PCR-based assay and TMA was observed. In conclusion, in patients with virologic relapse after the end of therapy, according to PCR, who were treated with peginterferon alpha-2a or standard interferon alpha-2a, residual HCV RNA was detectable in end-of-treatment samples by the TMA-based assay in 7 or 33% of cases, respectively. The lower rate of residual HCV RNA detection by TMA for patients treated with peginterferon alpha-2a than that for patients treated with standard interferon alpha-2a may be due to the maintained antiviral pressure of the long-acting peginterferon alpha-2a at the end-of-treatment visit.
authors.affiliation: Medizinische Klinik II, Johann Wolfgang Goethe-Universität, 60590 Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sarrazin
authors.forename: D A
authors.initials: DA
authors.lastname: Hendricks
authors.forename: F
authors.initials: F
authors.lastname: Sedarati
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D016174:Hepacivirus / Q000302:isolation & purification* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a