title: Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C.
abstract: OBJECTIVE
  To evaluate the performance of FibroMeterVirus3Gcombined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC).
  
  
  METHODS
  First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3Gwas sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3Gand Forns plus FibroMeterVirus3Gwas evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3Gcombination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C.
  
  
  RESULTS
  Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3GAUROC was similar to APRI AUROC (0.855vs0.815,P= 0.06) but higher than Forns AUROC (0.769,P< 0.001). The best FibroMeterVirus3Gcut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population,P= 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3Gin derivation population presented similar performance compared to FibroMeterVirus3Gused alone (79%vs78%vs80%, respectively,P= 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3Gallowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3Grequirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3Gapplied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3).
  
  
  CONCLUSIONS
  The stepwise combination of APRI or Forns with FibroMeterVirus3Gmay represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Chindamo
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Jerome
authors.initials: J
authors.lastname: Boursier
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Ronir Raggio
authors.initials: RR
authors.lastname: Luiz
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fouchard-Hubert
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Vera Lúcia Nunes
authors.initials: VL
authors.lastname: Pannain
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: João Marcello
authors.initials: JM
authors.lastname: de Araújo Neto
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Henrique Sérgio Moraes
authors.initials: HS
authors.lastname: Coelho
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: de Mello Perez
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: Maria Chiara Chindamo, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Cristiane Alves Villela-Nogueira, Departament of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
authors.forename: Cristiane Alves
authors.initials: CA
authors.lastname: Villela-Nogueira
keywords: Chronic hepatitis C; Combination algorithms; FibroMeterVirus3G; Fibrosis; Liver biopsy; Non-invasive methods