Skip to main content
SpringerLink
Log in

Accuracy of Ultrasound and Noninvasive Markers of Fibrosis to Identify Patients with Cirrhosis

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

Abstract

Background

Accurate identification of patients with cirrhosis using noninvasive markers of fibrosis is useful for esophageal varices and hepatocellular carcinoma surveillance programs. The aims of our study were to characterize the accuracy of ultrasonography, AST-to-platelet ratio index (APRI), and FIB-4 as noninvasive markers to identify the presence of cirrhosis.

Methods

We conducted a retrospective cohort study of patients who underwent liver biopsy at a large urban safety-net institution between November 2008 and July 2011. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and overall accuracy using receiver operator characteristic curve analysis for the detection of cirrhosis were calculated for each noninvasive marker.

Results

Liver biopsy was performed in 388 patients, of whom 93 (24.0 %) had cirrhosis. C-statistics for APRI and FIB-4 predicting the presence of cirrhosis were 0.68 (95 % CI 0.63–0.74) and 0.73 (95 % CI 0.68–0.78), respectively. The c-statistic for a nodular appearance on ultrasound was 0.78 (95 % CI 0.72–0.83). The PPV of a shrunken nodular-appearing liver was 64.8 %; however, PPV was significantly higher in the subset with a cirrhotic-appearing liver and signs of portal hypertension (PPV 83.6 %, p = 0.01) as well as in the subset with a noninvasive fibrosis marker also suggesting cirrhosis (PPV 77.8 %, p < 0.001).

Conclusion

Serum and imaging noninvasive markers of fibrosis may have insufficient accuracy when used in isolation; however, a combination of markers may allow sufficient accuracy to systematically identify patients with cirrhosis.

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

Similar content being viewed by others

References

  1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: liver, biliary tract, and pancreas. Gastroenterology. 2009;136:1134–1144.

    Article  PubMed  Google Scholar 

  2. Kanwal F, Hoang T, Kramer JR, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140:1182-e1–1188-e1.

    Article  Google Scholar 

  3. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol. 2006;40:S5–S10.

    PubMed  Google Scholar 

  4. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7:122–128.

    Article  CAS  PubMed  Google Scholar 

  5. AASLD, IDSA, IAS-USA. Recommendations for testing, managin, and treating hepatitis C. http://www.hcvguidelines.org. Accessed April 24, 2014.

  6. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922–938.

    Article  CAS  PubMed  Google Scholar 

  7. Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11:e1001624.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology. 2009;49:1017–1044.

    Article  PubMed  Google Scholar 

  9. Szymczak A, Simon K, Inglot M, Gladysz A. Safety and effectiveness of blind percutaneous liver biopsy: analysis of 1412 procedures. Hepat Mon. 2012;12:32–37.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614–2618.

    Article  PubMed  Google Scholar 

  11. Leroy V, Hilleret MN, Sturm N, et al. Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C. J Hepatol. 2007;46:775–782.

    Article  PubMed  Google Scholar 

  12. 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;38:518–526.

    Article  PubMed  Google Scholar 

  13. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32–36.

    Article  CAS  PubMed  Google Scholar 

  14. Ferral H, Male R, Cardiel M, Munoz L. Quiroz y Ferrari F. Cirrhosis: diagnosis by liver surface analysis with high-frequency ultrasound. Gastrointest Radiol. 1992;17:74–78.

    Article  CAS  PubMed  Google Scholar 

  15. 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;53:726–736.

    Article  PubMed  Google Scholar 

  16. Singal AG, Yopp AC, Gupta S, et al. Failure rates in the hepatocellular carcinoma surveillance process. Cancer Prev Res. 2012;5:1124–1130.

    Article  Google Scholar 

  17. Singal AG, Yopp A, Skinner CS, Packer M, Lee WM, Tiro JA. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med. 2012;27:861–867.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Arguedas MR, McGuire BM, Fallon MB, Abrams GA. The use of screening and preventive therapies for gastroesophageal varices in patients referred for evaluation of orthotopic liver transplantation. Am J Gastroenterol. 2001;96:833–837.

    Article  CAS  PubMed  Google Scholar 

  19. Dalton-Fitzgerald E, Tiro J, Kandunoori P, Halm EA, Yopp A, Singal AG. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014. doi:10.1016/j.cgh.2014.06.031.

  20. Stravitz RT, Heuman DM, Chand N, et al. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med. 2008;121:119–126.

    Article  PubMed  Google Scholar 

  21. Finberg HJ. Whither (wither?) the ultrasound specialist? J Ultrasound Med. 2004;23:1543–1547.

    PubMed  Google Scholar 

  22. Singal AG, Conjeevaram HS, Volk ML, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev. 2012;21:793–799.

    Article  PubMed  Google Scholar 

  23. Singal AG, Nehra M, Adams-Huet B, et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol. 2013;108:425–432.

    Article  PubMed  Google Scholar 

  24. Singal AG, Thomassen LV, Gretch DR, Shuhart MC. Use of the AST to platelet ratio index in HCV/HIV co-infected patients. Aliment Pharmacol Ther. 2011;33:566–577.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Trabut JB, Mallet V, Pol S. Aspartate aminotransferase to platelet ratio index (APRI) score is inappropriate for assessment of liver fibrosis in HIV-infected patients with hazardous drinking. HIV Med. 2009;10:524; author reply 524–525.

  26. Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol. 2014;20:16820–16830.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kim BK, Kim SU, Kim HS, et al. Kim do Y. Prospective validation of FibroTest in comparison with liver stiffness for predicting liver fibrosis in Asian subjects with chronic hepatitis B. PLoS One. 2012;7:e35825.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32–40.

    Article  PubMed  Google Scholar 

  29. Barr DC, Hussain HK. Magnetic resonance imaging in cirrhosis: what’s new? Top Magn Reson Imaging. 2014;23:129–149.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was conducted with support from the National Center for Advancing Translational Sciences of the National Institutes of Health under award KL2TR001103. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

None.

Author information

Author notes

    Authors and Affiliations

    1. Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA

      Jason Martin & Amit G. Singal

    2. Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA

      Gaurav Khatri

    3. Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA

      Purva Gopal

    4. Division of Digestive and Liver Diseases, Dedman Scholar of Clinical Care, University of Texas Southwestern, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA

      Amit G. Singal

    Authors
    1. Jason Martin
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Gaurav Khatri
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Purva Gopal
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Amit G. Singal
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Amit G. Singal.

    Additional information

    Amit G. Singal and Purva Gopal have contributed equally to this manuscript and are co-senior authors for this manuscript.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Martin, J., Khatri, G., Gopal, P. et al. Accuracy of Ultrasound and Noninvasive Markers of Fibrosis to Identify Patients with Cirrhosis. Dig Dis Sci 60, 1841–1847 (2015). https://doi.org/10.1007/s10620-015-3531-1

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10620-015-3531-1

    Keywords

    Search

    Navigation