title: HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial.
abstract: For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin. Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS Amplicor HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks. Stored specimens were tested using the Bayer VERSANT HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR; defined as undetectable HCV RNA by PCR at W72). Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive. Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P < .001) and at W20 (66% vs. 52%, P = 0.001). SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24). Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%). Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR. In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98104, USA. chihiro@u.washington.edu
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: David R
authors.initials: DR
authors.lastname: Gretch
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors
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