Skip to main content

Advertisement

SpringerLink
Log in

Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Noninvasive fibrosis markers are routinely used in patients with liver disease. Magnetic resonance elastography (MRE) is recognized as a highly accurate methodology, but a reliable blood test for fibrosis would be useful. We examined performance characteristics of the Enhanced Liver Fibrosis (ELF) Index compared to MRE in a cohort including those with HCV, HIV, and HCV/HIV.

Methods

Subjects enrolled in the Miami Adult Studies on HIV (MASH) cohort underwent MRE and blood sampling. The ELF Index was scored and receiver–operator curves constructed to determine optimal cutoff levels relative to performance characteristics. Cytokine testing was performed to identify new markers to enhance noninvasive marker development.

Results

The ELF Index was determined in 459 subjects; more than half were male, non-white, and HIV-infected. MRE was obtained on a subset of 283 subjects and the group that had both studies served as the basis of the receiver–operator curve analysis. At an ELF Index of > 10.633, the area under the curve for cirrhosis (Metavir F4, MRE > 4.62 kPa) was 0.986 (95% CI 0.994–0.996; p < 0.001) with a specificity of 100%. For advanced fibrosis (Metavir F3/4), an ELF cutoff of 10 was associated with poor sensitivity but high specificity (98.9%, 95% CI 96.7–99.8%) with an AUC of 0.80 (95% CI 0.749–0.845). ELF Index performance characteristics exceeded FIB-4 performance. HCV and age were associated with increased fibrosis (p < 0.05) in a multivariable model. IP-10 was found to be a promising biomarker for improvement in noninvasive prediction algorithms.

Conclusions

The ELF Index was a highly sensitive and specific marker of cirrhosis, even among HIV-infected individuals, when compared with MRE. IP-10 may be a biomarker that can enhance performance characteristics further, but additional validation is required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Singh S, Muir AJ, Dieterich DT, Falck-Ytter YT. American Gastroenterological Association Institute technical review on the role of elastography in chronic liver diseases. Gastroenterology. 2017;152:1544–1577.

    Article  Google Scholar 

  2. Shiha G, Ibrahim A, Helmy A, et al. Asian-Pacific Association for the study of the liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update. Hepatol Int. 2017;11:1–30.

    Article  Google Scholar 

  3. Chin JL, Pavlides M, Moolla A, Ryan JD. Non-invasive markers of liver fibrosis: Adjuncts or alternatives to liver biopsy? Front Pharmacol. 2016;7:159.

    Article  Google Scholar 

  4. Dyvorne HA, Jajamovich GH, Bane O, et al. Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection. Liver Int. 2016;36:659–666.

    Article  CAS  Google Scholar 

  5. Parkes J, Roderick P, Harris S, et al. Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease. Gut. 2010;59:1245–1251.

    Article  CAS  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;43:1317–1325.

    Article  CAS  Google Scholar 

  7. Singh S, Venkatesh SK, Wang Z, et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data. Clin Gastroenterol Hepatol. 2015;13:440–451e6.

    Google Scholar 

  8. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5:1207–1213e2.

    Article  Google Scholar 

  9. Dill T. Contraindications to magnetic resonance imaging: non-invasive imaging. Heart. 2008;94:943–948.

    Article  CAS  Google Scholar 

  10. Fernandes FF, Ferraz ML, Andrade LE, et al. Enhanced liver fibrosis panel as a predictor of liver fibrosis in chronic hepatitis C patients. J Clin Gastroenterol. 2015;49:235–241.

    Article  CAS  Google Scholar 

  11. Karlas T, Dietrich A, Peter V, et al. Evaluation of transient elastography, acoustic radiation force impulse imaging (ARFI), and enhanced liver function (ELF) score for detection of fibrosis in morbidly obese patients. PloS ONE. 2015;10:e0141649.

    Article  Google Scholar 

  12. Friedrich-Rust M, Rosenberg W, Parkes J, Herrmann E, Zeuzem S, Sarrazin C. Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis. BMC Gastroenterol. 2010;10:103.

    Article  Google Scholar 

  13. Shire NJ, Rao MB, Succop P, et al. Improving noninvasive methods of assessing liver fibrosis in patients with hepatitis C virus/human immunodeficiency virus co-infection. Clinl Gastroenterol Hepatol. 2009;7:471–480, 480.e1–2.

    Google Scholar 

  14. Peters MG, Bacchetti P, Boylan R, et al. Enhanced liver fibrosis marker as a noninvasive predictor of mortality in HIV/hepatitis C virus-coinfected women from a multicenter study of women with or at risk for HIV. Aids. 2016;30:723–729.

    Article  Google Scholar 

  15. Swanson S, Ma Y, Scherzer R, et al. Association of HIV, hepatitis C virus, and Liver fibrosis severity with the enhanced liver fibrosis score. J Infect Dis. 2016;213:1079–1086.

    Article  Google Scholar 

  16. Ren X, Kennedy A, Colletti LM. CXC chemokine expression after stimulation with interferon-gamma in primary rat hepatocytes in culture. Shock. 2002;17:513–520.

    Article  Google Scholar 

  17. Zeremski M, Petrovic LM, Chiriboga L, et al. Intrahepatic levels of CXCR17-associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C. Hepatology. 2008;48:1440–1450.

    Article  CAS  Google Scholar 

  18. Wang Y, Yu W, Shen C, et al. Predictive value of serum IFN-gamma inducible protein-10 and IFN-gamma/IL-4 ratio for liver fibrosis progression in CHB patients. Sci Rep. 2017;7:40404.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by NIH/NIDA 5U01DA040381 to MB. We would like to acknowledge the Research Flow Cytometry Core at Cincinnati Children’s Hospital Medical Center, and the Digestive Health Center (NIDDK P30 DK078392); and NIH/NIBIBR37 EB001981 to RLE.

Author information

Authors and Affiliations

  1. University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0595, USA

    Kenneth E. Sherman, Enass A. Abdel-Hameed & Susan D. Rouster

  2. Mayo Clinic, Rochester, MN, USA

    Richard L. Ehman

  3. Florida International University, Miami, FL, USA

    Adriana Campa, Sabrina Sales Martinez, Yongjun Huang, Gustavo G. Zarini, Jacqueline Hernandez, Colby Teeman, Javier Tamargo, Qingyun Liu & Marianna K. Baum

  4. NIH NIDA, Bethesda, MD, USA

    Raul Mandler

Authors
  1. Kenneth E. Sherman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enass A. Abdel-Hameed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard L. Ehman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan D. Rouster
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adriana Campa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sabrina Sales Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongjun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gustavo G. Zarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jacqueline Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Colby Teeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Javier Tamargo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Qingyun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Raul Mandler
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Marianna K. Baum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth E. Sherman.

Ethics declarations

Conflict of interest

All authors have nothing to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sherman, K.E., Abdel-Hameed, E.A., Ehman, R.L. et al. Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index. Dig Dis Sci 65, 1252–1257 (2020). https://doi.org/10.1007/s10620-019-05815-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-019-05815-z

Keywords

Search

Navigation