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:
HCV FibroSURE® (FibroTest™ in Europe) - 6 biomarkers (a2-macroglobulin, haptoglobin, bilirubin, γ-glutamyl transpeptidase (GGT), ALT, and apolipoprotein A1) yielding a prognostic algorithm scores for fibrosis and necroinflammatory activity
ASH FibroSURE® - 10 biomarkers (a2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, GGT, ALT, AST, total cholesterol, triglycerides, and fasting glucose) yielding a prognostic algorithm score for fibrosis, steatosis, and alcoholic steatohepatitis
NASH FibroSURE® - 10 biomarkers (a2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, GGT, ALT, AST, total cholesterol, triglycerides, and fasting glucose) yielding a prognostic algorithm score for fibrosis, steatosis, and nonalcoholic steatohepatitis
FibroSpect II™- 3 biomarkers (hyaluronic acid, TIMP-1, and a2-macroglobulin) that directly measure fibrogenesis of the liver with algorithmic analysis
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:
Transient Elastography (FibroScan®) - This technique transmits an elastic shear wave that propagates within the liver. The speed of the shear wave (the harder the tissue, the faster the shear propagates) is measured and quantified to determine the stage of fibrosis.
Acoustic radiation force impulses (ARFI)(e.g., Acuson S2000™) - permits evaluation of liver stiffness in a smaller region.
Real-time tissue elastography (e.g., HI VISION Preirus™) ultrasound able to display real-time elastography images.
Magnetic resonance elastography- Combines MRI imaging with sound waves to create a visual map (elastogram) showing the stiffness of body tissues.
Note: This policy does not address standard imaging with ultrasound or MRI.
Transient elastography imaging (i.e., FibroScan®) when used to evaluate and/or monitor individuals with chronic liver disease is considered medically necessary.
Transient elastography imaging (i.e., FibroScan®) when used to evaluate and/or monitor individuals with focal liver disease is considered investigational.
All other noninvasive imaging that maps the elastic properties of soft tissue to evaluate and/or monitor individuals with chronic liver disease are considered investigational. These technologies include, but are not limited to, the following:
Magnetic resonance elastography
Acoustic radiation force impulse imaging (e.g., Acuson S2000™)
Real-time tissue elastography (e.g., HI VISION Preirus™)
Multianalyte assays with algorithmic analyses (e.g., FibroSURE™, FibroSpect™) for the evaluation and/or monitoring of individuals with chronic liver disease are considered investigational.
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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 http://www.hcvguidelines.org.
American College of Radiology (2017) ACR Appropriateness Criteria® Chronic liver disease. Retrieved August 6, 2018 from www.acr.org.
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2017) Noninvasive techniques for the evaluation and monitoring of patients with chronic liver disease. (2.04.41) Retrieved August 6, 2018 from BlueWeb. (89 articles and/or guidelines reviewed)
Brener, S. (2015). Transient elastography for assessment of liver fibrosis and steatosis: an evidence-based analysis. Ontario Health Technology Assessment Series, 15 (18), 1-45. (Level 1 evidence)
De Lédinghen, V., Hiriart, J., Vergniol, J., Merrouche, W., Bedossa, P., & Paradis, V. (2017). Controlled attenuation parameter (CAP) with the XL probe of the Fibroscan: a comparative study with the M probe and liver biopsy. Digestive Diseases and Sciences, 2017 June 2. Doi: 10.1007/s10620-017-4638-3. [Epub ahead of print]. Abstract retrieved July 18, 2017 from PubMed database.
Durango, E., Dietrich, C., Seitz, H., Kunz, C., Pomier-Layrargues, G., Duarte-Rojo, A., et al. (2013). Direct comparison of the FibroScan XL and M probes for assessment of liver fibrosis in obese and nonobese patients. Hepatic Medicine: Evidence and Research, 5, 43-52. (Level 4 evidence)
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.
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 www.nice.uk/guidance.
Naveau, S., Voican, C., Lebrun, A., Gaillard, M., Lamouri, K., Njiké-Nakseu, M., et al. (2017). Controlled attenuation parameter for diagnosing steatosis in bariatric surgery candidates with suspected nonalcoholic fatty liver disease. European Journal of Gastroenterology & Hepatology, 2017 May 31. Doi: 10.1097/MEG,919. [Epub ahead of print]. Abstract retrieved July 18, 2017 from PubMed database.
Park, M., Kim, B., Cheong, J., Kim, D., Park, J., Kim, Y., et. al., (2013, February) Discordance between liver biopsy and FibroTest in assessing liver fibrosis in chronic hepatitis B. PLOS One, 8 (2): e55759. (Level 2 evidence)
Puigvehi, M., Broquetas, T., Coll, S., Garcia-Retortillo, M., Cañete, N.. Fernández, R. (2017). Impact of anthropometric features on the applicability and accuracy of FibroScan® (M and XL) in overweight/obese patients. Journal of Gastroenterology & Hepatology, 2017 Feb 15. Doi:10.1111/jgh.13762. [Epub ahead of print]. Abstract retrieved July 18, 2017 from PubMed database.
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.
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 https://www.accessdata.fda.gov.
Winifred S. Hayes, Inc. Medical Technology Directory. (2014, December; last update search November 2017) Ultrasound transient elastography for detecting hepatic fibrosis in patients with hepatitis C. Retrieved August 6, 2018 from www.Hayesinc.com (50 articles and/or guidelines reviewed)
Winifred S. Hayes, Inc. Medical Technology Directory. (2016, January; last updated search January 2018) Magnetic resonance elastography for detecting and staging liver fibrosis. Retrieved August 6, 2018 from www.Hayesinc.com (55 articles and/or guidelines reviewed)
Xu, X., Kong, H., Song, R., Zhai, Y., Wu, X., Ai, W., et al., (2013, December) 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 4 evidence)
Yin, M., Glaser, K., Talwalkar, J., Chen, J., Manduca, A., & Ehman, R. (2016, January) Hepatic Magnetic Resonance Elastography: Clinical Performance in a Series of 1,377 Consecutive Examinations. Radiology. 278(1): 114-124. (Level 3 evidence)
ORIGINAL EFFECTIVE DATE: 11/12/2016
MOST RECENT REVIEW DATE: 9/13/2018
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