FibroTest (licensed in the United States as FibroSURE™) is a serum biomarker test. It was developed to be an alternative to liver biopsy in the assessment of liver fibrosis for individuals with chronic viral hepatitis B or C, alcoholic liver disease, and metabolic steatohepatitis (for those who are overweight, have diabetes, or hyperlipidemia).
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person’s unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
Coverage is subject to the specific terms of the member’s benefit plan.
The FibroSure test to assess liver fibrosis is considered experimental/investigational, and therefore, non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.
- Experimental/Investigational (E/I) molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.
- In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.
Professional Statements and Societal Positions
- No specific evidence-based U.S. testing guidelines were identified.
- World Health Organization (2016): The recommendations in the WHO document entitled “Guidelines for the Screening, Care and Treatment of Persons with Chronic Hepatitis C Infection” differ slightly than the recommendations in the 2015 document on HBV. The 2015 document lists FibroSURE as a possibility in settings where resources are not an issue, whereas the 2016 document does not make that same recommendation:
- “Assessing degree of liver fibrosis and cirrhosis: in resource-limited settings, it is suggested that the aminotransferase/platelet ratio index (APRI) or FIB-4 tests be used for the assessment of hepatic fibrosis rather than other noninvasive tests that require more resources such as elastography or FibroTest. (Conditional recommendation, low quality of evidence)”
- World Health Organization (2015): In the WHO guidelines for chronic hepatitis B treatment, FibroSURE is listed as a possible non-invasive assessment tool for staging liver disease:
- “Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) is recommended as the preferred non-invasive test (NIT) to assess for the presence of cirrhosis (APRI score >2 in adults) in resourcelimited settings. Transient elastography (e.g., FibroScan) or FibroTest may be the preferred NITs in settings where they are available and cost is not a major constraint. (Conditional recommendation, low quality of evidence)”
- European Association for the Study of the Liver (EASL) (2015): In the guidelines entitled “Non-invasive test for evaluation of liver disease severity and prognosis,” EASL discusses the pros and cons of serum biomarkers of liver disease. The document states that “further validation is warranted.”
- World Gastroenterology Organization (2014): In recommendations on “Esophageal varices”, the WGO states that the “predictive accuracy is still unsatisfactory” for noninvasive markers such as FibroSURE.
- British HIV Association (2013): “The Writing Group suggests hepatic transient elastography (TE) (FibroScan™ or Acoustic Radiation Force Impulse [ARFI]) as the non-invasive investigation of choice (2B) but if unavailable, or when reliable TE readings are not obtained, a blood panel test (aspartate transaminase to platelet ratio index [APRI], FIB-4, enhanced liver fibrosis [ELF], Fibrometer™, Forns Index, FibroTest™) as an alternative (2C).”
- Several systematic reviews evaluating evidence of FibroSURE have pooled results of multiple studies; one review found AUROCs in the range of 0.75 to 0.84 for fibrosis; from 0.81-0.92 for cirrhosis in patients with HCV; 0.72-0.90 for detecting fibrosis; and from 0.75-0.92 for detecting cirrhosis in patients with HBV. Another systematic review reported an HSROC of 0.84 for fibrosis, and 0.87 for cirrhosis in patients with HBV. A pooled meta-analysis estimated a sensitivity of 71.2% and a specificity of 81.4% in patients with HBV. In patients with ALD, the sensitivity for detecting fibrosis was 85% and specificity was 66%; for detecting cirrhosis, sensitivity rose to 91% and specificity to 87%. Different analysis methods resulted in different AUROCs for diagnosing NAFLD; a weighting method produced an AUROC of 0.85, while a random effects model yielded an AUROC of 0.72. Despite many different types of studies and analysis methods, the diagnostic accuracy of FibroSURE seems generally seems to fall within a consistent, albeit moderate range. FibroSURE also generally seems to perform better in diagnosing cirrhosis than fibrosis.
- FibroSURE is intended as an alternative to liver biopsy, currently considered the gold standard for staging liver fibrosis and cirrhosis. As a blood-based test, FibroSURE is an appealing alternative to the invasive nature of a biopsy. However, the evidence as a whole is insufficient and does not yet fully support using FibroSURE as a stand-alone test. Furthermore, several guideline organizations have published evidence-based recommendations regarding the treatment of liver disease and do not definitively recommend FibroSURE as a first-line choice; instead, they recommend the test as an alternative after other preferred tests, or in settings where resources are not constrained.
Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.