title: [To consider negative viral loads below the limit of quantification can lead to errors in the diagnosis and treatment of hepatitis C virus infection].
abstract: BACKGROUND
  For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions.
  
  
  OBJECTIVE
  To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative.
  
  
  METHODS
  We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable» and those classified as «<1.50E+01IU/mL» (BLOQ).
  
  
  RESULTS
  We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained.
  
  
  CONCLUSIONS
  This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ.
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario de Girona Doctor Josep Trueta, España. doroteoacero@yahoo.es
authors.forename: Doroteo
authors.initials: D
authors.lastname: Acero Fernández
authors.forename: María José
authors.initials: MJ
authors.lastname: Ferri Iglesias
authors.forename: Carme
authors.initials: C
authors.lastname: López Nuñez
authors.forename: René
authors.initials: R
authors.lastname: Louvrie Freire
authors.forename: Xavier
authors.initials: X
authors.lastname: Aldeguer Manté
mesh_terms: D000328:Adult; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D019562:Viral Load / Q000706:statistics & numerical data*
chemical_list: D012367:RNA, Viral
keywords: ADVP:; ARN virus hepatitis C; CAP-CTM HCV:; COBAS AMPLIPREP™/COBAS-TaqMan™; Carga viral hepatitis C; HAC:; HCC:; Hepatitis C viral load; Hepatitis C virus RNA; LD:; LIC:; LSC:; Limit of detection; Limit of quantification; Límite de cuantificación; Límite de detección; PCR-RT:; PR:; RVP:; RVR:; RVS:; VHC:; VIH:; adictos a drogas por vía parenteral; hepatitis aguda C; hepatitis crónica C; interferón-pegilado y ribavirina; límite de detección; límite inferior de cuantificación; límite superior de cuantificación; reacción en cadena de la polimerasa en tiempo real; respuesta viral precoz; respuesta viral rápida; respuesta viral sostenida; virus de la hepatitis C.; virus de la inmunodeficiencia humana