BlueCross BlueShield of Tennessee Medical Policy Manual

Noninvasive Techniques for Evaluation and Monitoring of Chronic Liver Diseases


Noninvasive techniques to diagnose and monitor liver fibrosis are being investigated as alternatives to liver biopsy in individuals with chronic liver disease. Options for noninvasive monitoring include multianalyte serum assays with algorithmic analysis and specialized radiologic methods including magnetic resonance elastography, transient elastography, acoustic radiation for impulse imaging and real-time transient elastography.

Multianalyte assays with algorithmic analyses are proposed as an alternative to simple serum tests (e.g., ALT, AST, platelet count and prothrombin index). They use a combination of serum biochemical markers of liver function and age, sex, height and weight. The algorithmic analysis provides a score that purportedly correlates with the degree of liver damage in individuals with a variety of liver diseases. These lab tests include, but are not limited to:

Noninvasive imaging is proposed as an alternative to liver biopsy to diagnose and evaluate the degree of fibrosis by mapping the elastic properties of soft tissue. Imaging techniques currently being investigated include:

Note: This policy does not address standard imaging with ultrasound or MRI.




The evidence to support the use of noninvasive radiologic methods other than transient elastography for liver fibrosis measurement is limited due to varying cutoffs not prespecified or validated. The evidence is insufficient to determine the effects of the technology on health outcomes.


American Association for the Study of Liver Disease / Infectious Disease Society of America. (2018, May).   Recommendations for testing, managing, and treating hepatitis C.  Retrieved August 6, 2018 from 

BlueCross BlueShield Association. Evidence Positioning System. (11:2018) Noninvasive techniques for the evaluation and monitoring of patients with chronic liver disease. (2.04.41) Retrieved July 18, 2019 from (78 articles and/or guidelines reviewed)

Harris, R., Harman, D., Card, T., Aithal, G., & Guha, I. (2017). Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. The Lancet: Gastroenterology & Hepatology, 2 (4), 288-297. Abstract retrieved July 18, 2017 from PubMed database.

Hashemi, S., Alavian, S., Gholami-Fesharaki, M. (2016). Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Caspian Journal of Internal Medicine, 7 (4), 242-252. Abstract retrieved July 18, 2017 from PubMed database.

Houot, M., Ngo, Y., Munteanu, M., Marque, S., & Polynard, T. (2016). Systematic review with meta-analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B. Alimentary Pharmacology and Therapeutics, 43 (1), 16-29. Abstract retrieved July 18, 2017from PubMed database.

Lam, S., Nettel-Aguirre, A., Van Biervliet, S., Roeb, E.,Sadler, M., Friedrich-Rust, M., et al. (2019). Transient elastography in the evaluation of cystic fibrosis-associated liver disease: systematic review and meta-analysis. Journal of the Canadian Association of Gastroenterology, 2 (2), 71-80.  (Level 2 evidence)

Li, Y., Huang, Y., Wang, Z., Yang, Z, Sun, F., Zhan, S. (2016). Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. Alimentary Pharmacology and Therapeutics, 43 (4), 458-469. Abstract retrieved July 18, 2017 from PubMed database.

National Institute for Health and Care Excellence. (2017). Hepatitis B (chronic): diagnosis and management. Retrieved August 6, 2018 from

Roulot, D., Roudot-Thoraval, F., NKontchou, G., Kouacou, N., Costes, J., Elourimi, G., et al. (2017). Concomitant screening for liver fibrosis and steatosis in French type 2 diabetic patients using Fibroscan. Liver International, 2017 May 27. Doi: 10.1111/liv.13481. [Epub ahead of print]. Abstract retrieved July 18, 2017 from PubMed database.

Shen, Y., Wu, S.D., Wu, L., Wang, S.Q., Chen, Y., Liu, L.L., et al. (2019). The prognostic role of liver stiffness in patients with chronic liver disease: a systematic review and dose-response meta-analysis. Hepatology International, doi: 10.1007/s12072-019-09952-5. [Epub ahead of print]. Abstract retrieved July 19, 2019 from PubMed database.

U.S. Food and Drug Administration. (2013, April). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K123806 (FibroScan®). Retrieved July 18, 2017 from

Winifred S. Hayes, Inc. Medical Technology Directory. (2016, January; last update search January 2019). Magnetic resonance elastography for detecting and staging liver fibrosis. Retrieved July 18, 2019 from (55 articles and/or guidelines reviewed)

Winifred S. Hayes, Inc. Medical Technology Directory. (2019, March). Ultrasound transient elastography for detecting hepatic fibrosis in patients with hepatitis C. Retrieved July 18, 2019 from (80 articles and/or guidelines reviewed)

Xu, X., Kong, H., Song, R., Zhai, Y., Wu, X., Ai, W., et al. (2013). The Effectiveness of Noninvasive Biomarkers to Predict Hepatitis B-Related Significant Fibrosis and Cirrhosis: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy. PLOS One. 9 (6), e100182. (Level 2 evidence)




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