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Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients

Infection volume 47, pages 409–415 (2019)Cite this article

Abstract

Purpose

We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients.

Methods

This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves.

Results

238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography.

Conclusions

Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.

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References

  1. Tsochatzis EA, Castera L. Assessing liver disease in HIV-HCV coinfected patients. Curr Opin HIV AIDS. 2015;10:316–22.

    Article  CAS  PubMed  Google Scholar 

  2. Geng XX, Huang RG, Lin JM, et al. Transient elastography in clinical detection of liver cirrhosis: a systematic review and meta-analysis. Saudi J Gastroenterol. 2016;22:294–303.

    Article  PubMed  PubMed Central  Google Scholar 

  3. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66:153–94.

    Article  Google Scholar 

  4. European Association for Study of Liver. Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH clinical practice guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63:237–64.

    Article  Google Scholar 

  5. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.

    Article  PubMed  Google Scholar 

  6. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.

    Article  CAS  PubMed  Google Scholar 

  7. Chromy D, Schwabl P, Bucsics T, et al. Non-invasive liver fibrosis assessment and HCV treatment initiation within a systematic screening program in HIV/HCV coinfected patients. Wien Klin Wochenschr. 2017. https://doi.org/10.1007/s00508-017-1231-x.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Macías J, Girón-González JA, González-Serrano M, et al. Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes. Gut. 2006;55:409–14.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cartabellotta F, Di Marco V. RESIST-HCV. The HCV Sicily Network: a web-based model for the management of HCV chronic liver diseases. Eur Rev Med Pharmacol Sci. 2016;20:11–6.

    CAS  PubMed  Google Scholar 

  10. Calvaruso V, Cabibbo G, Cacciola I, et al. Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology. 2018;155:411–21.

    Article  CAS  PubMed  Google Scholar 

  11. Taylor KJ, Riely CA, Hammers L, et al. Quantitative US attenuation in normal liver and in patients with diffuse liver disease: importance of fat. Radiology. 1986;160:65–71.

    Article  CAS  PubMed  Google Scholar 

  12. Lim JK, Flamm SL, Singh S, et al. American gastroenterological association institute guideline on the role of elastography in the evaluation of liver fibrosis. Gastroenterology. 2017;152:1536–43.

    Article  PubMed  Google Scholar 

  13. Li J, Gordon SC, Rupp LB, et al. The validity of serum markers for fibrosis staging in chronic hepatitis B and C. J Viral Hepat. 2014;21:930–7.

    Article  CAS  PubMed  Google Scholar 

  14. Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726–36.

    Article  PubMed  Google Scholar 

  15. Castera L, Winnock M, Pambrun E, et al. Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non-invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration. HIV Med. 2014;15:30–9.

    Article  CAS  PubMed  Google Scholar 

  16. Schmid P, Bregenzer A, Huber M, et al. Progression of liver fibrosis in HIV/HCV co-infection: a comparison between non-invasive assessment methods and liver biopsy. PLoS One. 2015;10:e0138838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Merli M, Galli L, Castagna A, et al. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients. New Microbiol. 2016;39:110–3.

    CAS  PubMed  Google Scholar 

  18. Konerman MA, Mehta SH, Sutcliffe CG, et al. Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: prospective analysis of 435 liver biopsy pairs. Hepatology. 2014;59:767–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Macías J, Berenguer J, Japón MA, et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009;50:1056–63.

    Article  CAS  PubMed  Google Scholar 

  20. Vallet-Pichard A, Mallet V, Pol S. Nonalcoholic fatty liver disease and HIV infection. Semin Liver Dis. 2012;32:158–66.

    Article  CAS  PubMed  Google Scholar 

  21. Macaluso FS, Maida M, Minissale MG, et al. Metabolic factors and chronic hepatitis C: a complex interplay. Biomed Res Int. 2013;2013:564645.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ioannou GN, Bryson CL, Weiss NS, et al. The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection. Hepatology. 2013;57:249–57.

    Article  PubMed  Google Scholar 

  23. Miro JM, Montejo M, Castells L, et al. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study. Am J Transplant. 2012;12:1866–76.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Sciences for Health Promotion “G. D’Alessandro”, University of Palermo, Palermo, Italy

    Giovanni Mazzola, Lucia Adamoli, Pietro Colletti, Adriana Cervo, Marcello Trizzino & Antonio Cascio

  2. Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy

    Vincenza Calvaruso & Vito Di Marco

  3. IBD Unit, “Villa Sofia-Cervello” Hospital, Via Trabucco 180, 90146, Palermo, Italy

    Fabio Salvatore Macaluso & Ambrogio Orlando

  4. Clinical Epidemiology and Cancer Registry Unit, A.O.U.P. “Paolo Giaccone”, Palermo, Italy

    Sergio Mazzola

  5. ARNAS “Civico-Benefratelli” Hospital, Palermo, Italy

    Francesco Di Lorenzo, Chiara Iaria & Tullio Prestileo

Authors
  1. Giovanni Mazzola
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  2. Lucia Adamoli
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  3. Vincenza Calvaruso
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  4. Fabio Salvatore Macaluso
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  5. Pietro Colletti
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  6. Sergio Mazzola
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  7. Adriana Cervo
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  8. Marcello Trizzino
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  9. Francesco Di Lorenzo
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  10. Chiara Iaria
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  11. Tullio Prestileo
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  12. Ambrogio Orlando
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  13. Vito Di Marco
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  14. Antonio Cascio
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Corresponding author

Correspondence to Fabio Salvatore Macaluso.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Mazzola, G., Adamoli, L., Calvaruso, V. et al. Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients. Infection 47, 409–415 (2019). https://doi.org/10.1007/s15010-018-1258-6

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  • DOI: https://doi.org/10.1007/s15010-018-1258-6

Keywords

  • APRI
  • FIB-4
  • HIV
  • HCV
  • Noninvasive biomarkers
  • Transient elastography