Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 28, 2017; 9(6): 310-317
Published online Feb 28, 2017. doi: 10.4254/wjh.v9.i6.310
Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C
Maria Chiara Chindamo, Jerome Boursier, Ronir Raggio Luiz, Isabelle Fouchard-Hubert, Vera Lúcia Nunes Pannain, João Marcello de Araújo Neto, Henrique Sérgio Moraes Coelho, Renata de Mello Perez, Paul Calès, Cristiane Alves Villela-Nogueira
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
Jerome Boursier, Isabelle Fouchard-Hubert, Paul Calès, Department of Hepatology, University Hospital, 35044 Rennes, France
Jerome Boursier, Isabelle Fouchard-Hubert, Paul Calès, HIFIH Laboratory, UPRES 3859, SFR 4208, Bretagne Loire University, 35044 Rennes, France
Ronir Raggio Luiz, Institute of Public Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
Vera Lúcia Nunes Pannain, Departament of Pathology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
Renata de Mello Perez, Gastroenterology Department, University of the State of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Renata de Mello Perez, D’Or Institute for Research and Education, Rio de Janeiro 22281-100, Brazil
Author contributions: All authors equally contributed to the design of the work, critical revision of important contents of the manuscript and final approval of the version to be published; Chindamo MC conception of the study, acquisition and interpretation of data, article writing; Boursier J, de Mello Perez R, Villela-Nogueira CA analyses and interpretation of data; Luiz RR revision of statistical analysis; Fouchard-Hubert I, Calès P and Coelho HSM critical revision related to important content of the manuscript; Pannain VLN histopathological evaluation of liver biopsies samples; de Araújo Neto JM acquisition of data and liver biopsy procedure.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maria Chiara Chindamo, MD, PhD, Adjunt Professor, Department of Internal Medicine, Federal University of Rio de Janeiro, Avenida Lúcio Costa 3602, apto 1304 bloco 2, Barra da Tijuca, Rio de Janeiro 22630-010, Brazil. mchiara@terra.com.br
Telephone: +55-21-39382708 Fax: +55-21-39382708
Received: September 25, 2016
Peer-review started: September 27, 2016
First decision: November 22, 2016
Revised: December 15, 2016
Accepted: February 8, 2017
Article in press: February 13, 2017
Published online: February 28, 2017
Processing time: 154 Days and 10 Hours
Abstract
AIM

To evaluate the performance of FibroMeterVirus3G combined 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. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination 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 FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-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 FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, 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 FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3).

CONCLUSION

The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.

Keywords: Chronic hepatitis C; Fibrosis; Liver biopsy; Non-invasive methods; FibroMeterVirus3G; Combination algorithms

Core tip: Liver fibrosis assessment still poses a challenge when prioritizing hepatitis C treatment due to logistical and financial barriers in the use of direct acting antiviral drugs. We introduced a new stepwise combination of first generation fibrosis tests - aminotransferase-to-platelet ratio index (APRI) and Forns-followed by FibroMeterVirus3G whenever results remained unclassified after first generation tests to identify significant fibrosis. This combination presented similar accuracy to FibroMeterVirus3G used as the only test, reduced APRI and Forns grey zone, and spared FibroMeterVirus3G requirement in 50% of cases. This approach represents a lower-cost alternative to assess fibrosis, with no need for liver biopsy.