Download Serum Biomarkers for Liver Fibrosis in Persons with

Clinical Policy Title: Serum Biomarkers for Liver Fibrosis in Persons with Hepatitis C
Clinical Policy Number: 01.01.01
Effective Date:
June 1, 2014
Initial Review Date:
Most Recent Review Date:
Next Review Date:
December 18, 2013
January 21, 2015
January 2016
Policy contains:
 FIBROSpect® II (PROMETHEUS
Laboratories, San Diego, CA)

Fibrotest/FibroSURE®
(LABCORP®, Burlington, NC)
RELATED POLICIES: None
ABOUT THIS POLICY: Keystone First has developed clinical policies to assist with making coverage determinations. Keystone First’s clinical policies
are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies,
the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies
along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific
definition of “medically necessary,” and the specific facts of the particular situation are considered by Keystone First when making coverage
determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements,
the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Keystone First’s clinical policies are for informational
purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the
treatment decisions for their patients. Keystone First’s clinical policies are reflective of evidence-based medicine at the time of review. As medical
science evolves, Keystone First will update its clinical policies as necessary. Keystone First’s clinical policies are not guarantees of payment.
Coverage Policy
Keystone First considers the use of FIBROSpect® II or Fibrotest/FibroSURE® serum biomarkers for
identifying patients infected with hepatitis C who are at risk for clinically significant liver fibrosis to be
investigational and, therefore, not medically necessary.
Limitations: All other uses of FIBROSpect® II or Fibrotest/FibroSURE® serum biomarkers in persons
infected with hepatitis C are not medically necessary.
Alternative Covered Services:

•
•
•
•
Alanine transaminase (ALT) test.
Aspartate aminotransferase (AST) test.
Computed tomography (CT) scan.
Fibrogen test.
Haptoglobin test.
1
•
•
•
Liver biopsy.
Total bilirubin test.
Ultrasound.
Background
In the United States, an estimated 150,000 persons annually are diagnosed with chronic liver disease with
nearly 30,000 (20%) individuals having cirrhosis at initial presentation (Thein 2008). The development and
progression of hepatic fibrosis can mediate disease-related complications of cirrhosis. The progression of
hepatic fibrosis is a nonlinear, discontinuous process that is greatly influenced by factors such as age, sex,
race, alcohol exposure, and obesity (Thein 2008). Obtaining further information about the degree of liver
injury from hepatitis C is an important factor in deciding to pursue or defer antiviral therapy.
The gold standard for diagnosis and planning therapy in acute and chronic liver disease is histopathological
examination of a percutaneous liver biopsy, as it provides essential information regarding inflammation,
fibrosis and steatosis (Nguyen 2011). However, liver biopsy is an invasive procedure that often requires
multiple passes, has a small but significant risk for procedure-related complications, and is subject to interand intra-observer variability in biopsy interpretation. Inaccurate staging from sampling error is estimated
to occur in up to 25% of cases. Substantial discordance in fibrosis stage involving the right and left liver
lobes in the same patient may cause sampling variability. The optimal liver biopsy specimen characteristics
(≥20 mm in length with ≥11 portal tracts) have been identified to minimize the effects from sampling error,
but the typical specimen obtained in clinical practice often fails to meet these standards. Finally, patients
may be reluctant to undergo invasive testing (Nguyen 2011).
A variety of serum markers have been developed to identify patients who are at risk for clinically significant
hepatic fibrosis (defined by stages F2-F4). These markers are classified as direct (representing components
of extracellular matrix) or indirect (reflecting hepatic inflammation and function). Indirect markers may be
used alone or combined with direct markers to form panels. The practical advantages of serum fibrosis
markers include their noninvasiveness, potential for widespread availability, and reproducibility when serial
examinations are performed using the same laboratory.
Fibrotest is marketed in the U.S. as FibroSURE® by the Laboratory Corporation of America® (LabCorp,
Burlington, NC). Specifically, HCV FibroSURE® consists of a 6 biomarker index (alpha-2-macroglobulin,
haptoglobin, gamma-globulin, apolipoprotein A1, γ-Glutamyl transferase, and total bilirubin) that provides
Metavir fibrosis staging and necroinflammatory grading to monitor liver status in patients with hepatitis C
(LabCorp 2013) (Table 1).
Table 1. Metavir Scale for Monitoring Liver Status
Fibrosis stage (Fibro Test)
F0 − no fibrosis: 0.00-0.21
F0-F1: 0.21-0.27
F1 − portal fibrosis: 0.27-0.31
F1-F2: 0.31-0.48
Activity grade (ActiTest):
A0 − no activity: 0.00-0.17
A0-A1: 0.17-0.29
A1 − minimal activity: 0.29-0.36
A1-A2: 0.36-0.52
2
Fibrosis stage (Fibro Test)
F2 − bridging fibrosis with few septa: 0.48-0.58
F3 − bridging fibrosis with many septa: 0.58-0.72
F3-F4: 0.72-0.74
F4 − cirrhosis: 0.74-1.00
Source: LabCorp®
Activity grade (ActiTest):
A2 − moderate activity: 0.52-0.60
A2-A3: 0.60-0.63
A3 − severe activity: 0.63-1.00
LabCorp® is regulated under the Clinical Laboratory Improvement Amendments of 1988 and is certified to
perform high complexity testing; the U.S. Food and Drug Administration (FDA) determined that approval is
not currently required (LabCorp 2013). According to the manufacturer, HCV FibroSURE® is indicated for:




Assessment of liver status following a diagnosis of HCV.
Pretreatment baseline and/or posttreatment assessment during HCV therapy.
Liver status of patients with HIV/HCV coinfection.
Monitoring and treatment of patients with HBV.
Limitations associated with the use of HCV FibroSURE® are the possibility of false positive results
attributable to decreases in haptoglobin from hemolysis, increases in total bilirubin from conditions such as
Gilbert's syndrome and cholestasis, and increases in α2-macroglobulin and haptoglobin from systemic as
well as hepatic inflammation. Therefore, HCV FibroSURE® should not be used for patients with Gilbert
disease, hemolysis, acute hepatitis, autoimmune hepatitis, or extrahepatic cholestasis (Nguyen 2011,
LabCorp 2013). The reproducibility of noninvasive testing is an important issue in clinical practice. Because
of the variability of components in assays and analyzers, HCV FibroSURE® can only be performed in
validated reference laboratories as opposed to local outpatient or hospital-based labs where other testing
is typically performed (Nguyen 2011).
FIBROSpect® II (PROMETHEUS Laboratories, San Diego, CA) uses a quantitative analysis of hyaluronic acid
(HA), tissue inhibitor of metalloproteinase (TIMP-1), and α2-macroglobulin (AMG), which applies an
algorithm to predict the likelihood of liver fibrosis in patients with hepatitis C with no indeterminate results
(PROMETHEUS 2013). PROMETHEUS Laboratories Inc. is CLIA certified and accredited by the College of
American Pathologists; FDA approval is not required for the FIBROSpect® II test. This test is only offered at
PROMETHEUS laboratories (PROMETHEUS 2013).
The National Institutes of Health issued a consensus statement on the management of Hepatitis C that
considered the use of noninvasive tests for assessing liver fibrosis (NIH 2002). They concluded noninvasive
tests were not adequate substitutes for liver biopsy, as they were not widely available or well validated; no
single test or panel of serologic markers can provide an accurate assessment of intermediate stages of
hepatic fibrosis (NIH 2002). Since then, several organizations have issued evidence-based recommendations
and arrived at similar conclusions, despite wider availability of these tests. (Moyer 2013, CDC 2013, Rockey
2009, Ghany 2009, Mofenson 2009)
Methods
Searches:
Keystone First searched PubMed and the databases of:
 UK National Health Services Centre for Reviews and Dissemination;
3


Agency for Healthcare Research and Quality’s National Guideline Clearinghouse and other evidence-based
practice centers; and
The Centers for Medicare & Medicaid Services.
Searches were conducted on December 4, 2013 using the terms "Liver Cirrhosis"[Mesh]), "Liver
Cirrhosis/diagnosis"[Mesh]), "Hepatitis C"[Mesh]), "Hepatitis C, Chronic"[Mesh]) crossed with "Biological
Markers"[Mesh], “Fibrotest”, “FibroSURE®” and “FIBROSpect®”. The following study types published in English were
included:
 Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision
of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods
to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidencegrading hierarchies.
 Guidelines based on systematic reviews.
 Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies),
reporting both costs and outcomes — sometimes referred to as efficiency studies — which also rank near the top
of evidence hierarchies.
Findings
A total of six systematic reviews were identified for this policy. No economic analyses were
identified.
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
For the FIBROSpect® II test, three systematic reviews with overlapping literature found insufficient
evidence to determine either its efficacy for detecting fibrosis or disease severity in HCV-infected
populations. FIBROSpect® II has a significant false-negative rate, which indicates that it fails to detect
cases of clinically significant fibrosis detected by biopsy. Studies of FIBROSpect II generally enrolled
populations with a high prevalence of clinically significant fibrosis, which may overestimate accuracy
estimates, and used a variety of gold standards. Thus, its ‘true’ discriminative ability has not been
tested adequately. Finally, there is a lack of evidence of the effect of FIBROSpect® II testing on patient
management or patient outcomes.
For the FibroTest/FibroSURE® test, five systematic reviews with overlapping literature found
insufficient evidence to determine either its efficacy for detecting fibrosis or disease severity or impact
on patient outcomes in HCV-infected populations. Test scores at the extremes of the fibrosis measures
(e.g., FibroTest <0.20 or >0.60), which are seen in approximately 50% of patients, have acceptable
predictive values (80% range), but test scores with intermediate values are not yet accurate enough to
replace liver biopsy. Risk factors for erroneous test results include unconjugated hyperbilirubinemia
and inflammation.
Overall, the evidence of diagnostic efficacy for non-invasive biomarkers such as the FIBROSpect® II and
Fibrotest/FibroSURE® tests is limited by variability in methods and poor inter-observer agreement for
histological staging. Non-invasive biomarkers produce continuous scores that are then correlated with
categorical variables, i.e. the stage scores, which are only descriptive categories of fibrosis. There are
differences among the various histological scoring systems, and they lack an arithmetical progression.
Quantitative measurement of liver fibrosis would be a more appropriate comparator to these test scores,
but the relationship between clinical correlations and quantitative measurement of liver fibrosis has not
been extensively evaluated (Cholongitas 2010).
4
Summary of Clinical Evidence
Citation
Chou 2013
(AHRQ study)
HCV screened
populations
Hayes 2010
Hayes Brief
Cholongitas
2010
HCV recurrence
after liver
transplantation
Smith 2009
HCV or HCV/HIV
coinfection
Shaheen 2008
HCV/HIV
coinfection
Shaheen 2007
Content, Methods, Recommendations
Key Points
 Systematic review of studies of diagnostic accuracy in screened populations;
o 21 samples reported in 20 studies compared Fibrotest to liver biopsy; quality of
evidence=high
o 4 studies compared FIBROSpect to liver biopsy; quality of evidence=low
o 16 studies directly compared Aspartate Aminotransferase-Platelet Ratio Index
(APRI) to Fibrotest; quality of evidence=moderate
 Fibrotest: the median AUROC=0.79 (range 0.70 to 0.89) (METAVIR F2-F4, Ishak 3-6,
or equivalent)
 FIBROSpect: median AUROC=0.86 (range 0.82 to 0.90) (METAVIR F2-F4, Ishak 3-6,
or equivalent)
 Studies generally enrolled a broad spectrum of patients with varying severity of fibrosis
and other markers of HCV infection severity. Therefore, estimates of diagnostic
accuracy are likely to be applicable to patients identified by screening.
 Insufficient evidence to determine clinical outcomes associated with strategies
incorporating noninvasive tests for evaluating patients with HCV infection.
 Sensitivity analysis: biopsy specimen length and aminotransferase levels had no effect
on diagnostic estimates.
 Comparison APRI blood test and the Fibrotest showed similar AUROC estimates.
Key Points
 Systematic review of 5 studies.
 FIBROSpect II testing is a moderately effective method for the detection of clinically
significant fibrosis in HCV-infected patients.
 Sensitivity=67% to 81%, specificity=62% to 74%
 Limitations of evidence: high prevalence of clinically significant fibrosis, which may
overestimate accuracy estimates; lack of agreement on gold standard; lack of evidence
on patient management or patient outcomes.
 Insufficient evidence of efficacy and impact on patient outcomes.
 Additional studies are needed to determine clinical role.
Key Points
 Systematic review identified 1 study evaluating Fibrotest in 56 patients
 No quality appraisal available.
 Discriminative ability was not good (AUROC: 0.56) with poor positive predictive value
 Only 32% had fibrosis scores >2
 Impact on clinical practice and the optimal combination with liver biopsy and
assessment of collagen content need further evaluation.
Key Points
 Systematic review included FIBROSpect II=3 studies. Fibrotest=6 studies.
 No quality appraisal available.
 Unclear % HCV/HIV patients studied.
 Fibrotest = the components of these models are not readily available and haptoglobin
and bilirubin can give false positive results.
 FIBROSpect II can differentiate mild from severe fibrosis, but is not as accurate for
intermediate fibrosis (F1-F3).
 Liver biopsy is still considered the gold standard
Key Points
 Systematic review identified 1 study (N=130) using Fibrotest
 Only scores at the extremes of these fibrosis measures (e.g., FibroTest <0.20 or >0.60)
which are seen in ~50% of patients, have acceptable predictive values (80% range).
 In individuals with intermediate values, not yet accurate enough to replace liver biopsy.
Key Points
5
Citation
HCV infection
Content, Methods, Recommendations
 Systematic review of 4 studies (N = 546). In heterogeneous analyses for significant
fibrosis, the AUCs for FibroTest =0.81 (95% CI 0.78-84)
 At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest
were 47% (35-59%) and 90% (87-92%).
 Methodological quality, the length of liver biopsy specimens, and inclusion of special
populations did not explain the observed heterogeneity.
 Diagnostic accuracy was associated with the prevalence of significant fibrosis (F2-4)
and cirrhosis in the study populations.
 CONCLUSIONS: Refinements are needed before test can replace liver biopsy.
AUROC, area under the receiver operating curve
POLICY UPDATE 2015
Findings
Searches were repeated on January 2, 2015 for articles published in English since January 1, 2014. One
systematic review update of Chou et al (Selph 2014), one cost-effectiveness analysis (Tsochatzis 2014), and
one guideline (AASLD 2014) were added to the policy. The new information does not change the previous
findings or the clinical policy.



In a previous systematic review, Chou et al. found that a significant number of studies had been
omitted from summary estimates, because they provided results for measures of diagnostic accuracy
that were discordant from 2 x 2 tables (i.e., number of true positives, false positives, true negatives,
and false negatives) calculated based on the information provided in the studies or insufficient to
construct 2 x 2 tables. Selph et al obtained unpublished data and recalculated diagnostic accuracy
estimates. The additional data had no appreciable impact on diagnostic accuracy estimates for
diagnostic tests for hepatic fibrosis.
Tsochatzis et al compared the cost-effectiveness of using noninvasive tests (NIT), including FibroTest
and FIBROSpect®II, to inform treatment decisions in adult patients with chronic hepatitis C from the
U.K. perspective using current triple therapy and with more potent antivirals. The four treatment
strategies were: testing with NITs and treating patients with fibrosis stage>/=F2; testing with liver
biopsy and treating patients with >/=F2; treat none; and treat all irrespective of fibrosis. Treating all
adult patients with chronic HCV infection, irrespective of fibrosis stage, was the most cost-effective
strategy with currently available drugs in developed countries.
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of
America (IDSA), in collaboration with the International Antiviral Society–USA (IAS–USA), recommend an
assessment of the degree of hepatic fibrosis, using noninvasive testing or liver biopsy, to determine the
urgency for treatment. Indirect serum markers, direct serum markers, and vibration-controlled
transient liver elastography may be considered. However, they acknowledge that no single method has
sufficiently high accuracy, and each test must be interpreted carefully. Based on the results of Selph et
al, these tests are, at best, only moderately useful for identifying clinically significant fibrosis or
cirrhosis. The most efficient approach to fibrosis assessment is to combine direct biomarkers and
vibration-controlled transient liver elastography. A biopsy should be considered for any patient who has
discordant results between the two modalities that would affect clinical decision making.
6
Glossary
Alanine Transaminase (ALT) - An enzyme normally present in serum and body tissues, especially in the
liver; it is released into the serum as a result of tissue injury.
Alpha2-Macroglobulin (A2M) - An antibody protein. Increased levels are seen in diabetes mellitus and
diseases of the liver and kidney.
Apolipoprotein A1 (Apo-A1) - The major protein component of high density lipoprotein (HDL) and a
relatively abundant plasma protein. Apo-A1 is instrumental in promoting the transfer of cholesterol into the
liver where it is metabolized and then excreted from the body via the intestine.
Aspartate aminotransferase (AST) Test - Blood test that measures levels of AST, which is an enzyme
released into the blood when certain organs or tissues, particularly the liver and heart, are injured.
Bilirubin - A bile pigment and natural byproduct that results from the normal breakdown of red blood cells.
Normally, bilirubin is carried in the blood and broken down by the liver; however, high blood levels may
indicate liver damage or disease.
C-Reactive Protein (CRP) - A protein secreted by the liver, usually appearing in response to injury, infection
or inflammation. A blood test can detect CRP to aid in the diagnosis of inflammatory response.
Fibrogen - A protein that originates in the liver. It is converted to fibrin during the blood clotting process
(coagulation).
Gamma globulin - A protein that serve as antibodies; immunoglobulin
Gamma-Glutamyl Transpeptidase (GGT) - An enzyme that appears in the serum of patients with several
types of liver or gallbladder disorders.
Haptoglobin - A protein produced by the liver; blood levels show how red blood cells are being destroyed
Hyaluronic acid - A viscous slippery substance that lubricates the joints, maintains the shape of the eyeballs
and is a key component of connective tissue.
Liver Fibrosis - A reaction to chronic injury to the liver; extensive scarring of the liver.
Tissue Inhibitor of Metalloproteinase (TIMP) - A family of secreted proteins. TIMP-1 affects inflammatory
processes associated with the extracellular matrix.
Related policies: Keystone First Utilization Management program description.
References
Professional society guidelines/others:
7
American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America
(ISDA). Recommendations for Testing, Managing, and Treating Hepatitis C. 2014. Available at:
http://www.hcvguidelines.org/full-report-view. Accessed January 1, 2015.
CDC Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention
and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from
the Centers for Disease Control and Prevention, the National Institutes of Health [trunc]. Atlanta, GA:
Centers for Disease Control and Prevention (CDC). 2013: Jul 8.
Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an
update. Hepatology. 2009 Apr;49(4):1335-74.
Mofenson LM, Brady MT, Danner SP, Dominguez KL, Hazra R, Handelsman E, et al. Guidelines for the
Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children:
recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the
Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American
Academy of Pediatrics. MMWR Recomm Rep. 2009 Sep 4;58(Rr-11):1-166.
Moyer VA. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force
recommendation statement. Ann Intern Med. 2013 Sep 3;159(5):349-57.
National Institutes of Health Consensus Conference Statement. Management of Hepatitis C: 2002.
Bethesda, MD. Available at: http://consensus.nih.gov/2002/2002hepatitisc2002116html.htm. Accessed
January 2, 2015.
Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology. 2009
Mar;49(3):1017-44.
Peer-reviewed references:
Cholongitas E, Tsochatzis E, Goulis J, Burroughs AK. Noninvasive tests for evaluation of fibrosis in HCV
recurrence after liver transplantation: a systematic review. Transpl Int. 2010 Sep;23(9):861-70.
Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus
infection: a systematic review. Ann Intern Med. 2013 Jun 4;158(11):807-20.
Hayes Inc. Hayes Medical Technology Report. FIBROSpect® II Test (Prometheus Laboratories Inc.) for
Diagnosis of Liver Fibrosis in Patients with Hepatitis C. Lansdale, Pa. Hayes Inc.; March 2010.
Laboratory Corporation of America® (LabCorp). Test Menu. Hepatitis C Virus (HCV) FibroSURE®. Available
at:
https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXy
M3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLA
z0Q_QjnYGKIvEqKsiNKDfUDVQEAARgwHA!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJ
8
NXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=407687#7_UE4S1I930O
GS20IS3O4N2N6680. Accessed January 2, 2015.
Nguyen D, Talwalkar JA. Noninvasive assessment of liver fibrosis. Hepatology. 2011 Jun;53(6):2107-10.
PROMETHEUS Laboratories. PROMETHEUS® FIBROSpect® II. Product Description. Available at:
http://www.prometheuslabs.com/Resources/Fibrospect/Fibrospect_II_Product_Detail.pdf. Accessed
January 2, 2015.
Selph S CR. Impact of Contacting Study Authors on Systematic Review Conclusions: Diagnostic Tests for
Hepatic Fibrosis. Research White Paper (Prepared by the Pacific Northwest Evidence-based Practice Center
under Contract No. 290-2012-00014-I). AHRQ Publication No. 14-EHC004-EF. Rockville, MD: Agency for
Healthcare Research and Quality. April 2014. Available at:
www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed December 31, 2014.
Shaheen AA, Myers RP. Systematic review and meta-analysis of the diagnostic accuracy of fibrosis marker
panels in patients with HIV/hepatitis C coinfection. HIV Clin Trials. 2008 Jan-Feb;9(1):43-51.
Shaheen AA, Wan AF, Myers RP. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a
systematic review of diagnostic test accuracy. Am J Gastroenterol. 2007 Nov;102(11):2589-600.
Smith JO, Sterling RK. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C.
Aliment Pharmacol Ther. 2009 Sep 15;30(6):557-76.
Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic
hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology. 2008 Aug;48(2):418-31.
Tsochatzis EA, Crossan C, Longworth L, et al. Cost-effectiveness of noninvasive liver fibrosis tests for
treatment decisions in patients with chronic hepatitis C. Hepatology (Baltimore, Md.). 2014;60(3):832-843.
Clinical trials:
Searched clinicaltrials.gov on January 2, 2015 using terms fibrotest OR fibrosure | Open Studies
3 relevant clinical trials
Non Invasive Assessment of Liver Fibrosis in Children: Comparison of ShearWave Elastography, Fibrotest
and Liver Biopsy. http://ClinicalTrials.gov/show/NCT02041780.
Patients With Chronic Hepatitis B and Low Viremia Not Receiving Antiviral Therapy.
http://ClinicalTrials.gov/show/NCT01090531.
9
Screening for Liver Fibrosis by Using Non-invasive Methods in Patients With Diabetes. A Prospective Study
(DIABSCAN). http://ClinicalTrials.gov/show/NCT01306110.
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
None identified
Local Coverage Determinations
None identified
Commonly Submitted Codes:
Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not
an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill in
accordance with those manuals.
CPT Code
0001M
00702
Description
INFECTIOUS DISEASE, HCV, SIX BIOCHEMICAL ASSAYS (ALT, A2MACROGLOBULIN, APOLIPOPROTEIN A-1, TOTAL BILIRUBIN,
GGT, AND HAPTOGLOBIN) UTILIZING SERUM, PROGNOSTIC
ALGORITHM REPORTED AS SCORES FOR FIBROSIS AND
NECROINFLAMMATORY ACTIVITY IN LIVER
ANESTHESIA FOR PROCEDURES ON UPPER ANTERIOR
ABDOMINAL WALL; PERCUTANEOUS LIVER BIOPSY
Comment
Not covered
Covered
47000
BIOPSY OF LIVER, NEEDLE; PERCUTANEOUS
Covered
47001
BIOPSY OF LIVER, NEEDLE; WHEN DONE FOR INDICATED
PURPOSE AT TIME OF OTHER MAJOR PROCEDURE (LIST
SEPARATELY IN ADDITION TO CODE FOR PRIMARY PROCEDURE)
Covered
47100
BIOPSY OF LIVER, WEDGE
Covered
76705
ULTRASOUND, ABDOMINAL, REAL TIME WITH IMAGE
DOCUMENTATION; LIMITED (EG, SINGLE ORGAN, QUADRANT,
FOLLOW-UP)
Covered
ICD-9 Code
70.54
70.70
70.51
ICD-10
Code
B18.2
B19.2
Description
Comment
Chronic hepatitis C without mention of hepatic coma
Unspecified viral hepatitis C without hepatic coma
Hepatitis C
Description
Comment
Chronic viral hepatitis C
Unspecified viral hepatitis C
10
HCPCS
Level II
Description
Comment
11