CurrentBlue KCPolicy POL-PP-309

Serum Testing for Hepatic Fibrosis in the Evaluation and Monitoring of Chronic Liver Disease

Defines reimbursement policy for serum multianalyte assays with algorithmic analysis and individual serum biomarkers used to evaluate or monitor hepatic fibrosis in chronic liver disease across Blue KC product lines. Specifies which proprietary tests may be reimbursed (FibroSURE/FibroTest, ELF/FibroTest) under certain clinical contexts and lists biomarkers/tests that do not meet coverage criteria.

Policy Summary

PayerBlue KC

PolicySerum Testing for Hepatic Fibrosis in the Evaluation and Monitoring of Chronic Liver Disease

Policy CodePolicy POL-PP-309

Change TypeAvalon 4th Quarter updates

Effective DateOct 1, 2025

Next Review DateOct 1, 2026

Key ActionEnsure the assay is ordered for one of the covered indications and document indication; reimbursement for FibroSURE/FibroTest/ELF limited to once every 6 months.

SourceLink

POLICY UPDATE CHANGES

Initial version created 07/01/2025; Avalon 4th Quarter updates on 10/01/2025 produced version 002 effective 10/01/2025.

3Primary covered indications (HBV, HCV, MASLD/MASH/alcoholic hepatitis)

>=6 monthsMinimum interval for reimbursed testing

10+Listed CPT/HCPCS/PLA/Category III codes referenced

Coverage Summary

Scope: Defines reimbursement policy for serum multianalyte assays with algorithmic analysis and individual serum biomarkers used to evaluate or monitor hepatic fibrosis in chronic liver disease across Blue KC product lines. Coverage stance: mixed — certain proprietary assays are covered in specified clinical contexts while other multianalyte assays and individual biomarkers do not meet coverage criteria. Headline covered proprietary assays and contexts: FibroSURE/FibroTest (including HBV FibroSURE, HCV FibroSURE) and ELF (ELFTM) may be reimbursed for individuals with chronic hepatitis B (HBV) or chronic hepatitis C (HCV) (testing once every 6 months), and ELF or FibroTest may be reimbursed (once every 6 months) for individuals with metabolic dysfunction-associated steatotic liver disease (MASLD, including MASH), alcoholic hepatitis, or when performed to rule out compensated advanced chronic liver disease (cACLD) in individuals with an elevated liver stiffness measurement. Policy status: CURRENT / Active. Effective date: 10/01/2025; Last review: 10/01/2025; Next review: 10/01/2026.

Testing frequency for reimbursed assaysonce every 6 months

Elevated liver stiffness measurementrequired (no numeric threshold specified)

Primary covered indications3

Medical Necessity / Reimbursement Criteria

Covered when ALL of the following are met

Reimbursement criteria for multianalyte assays ELF or FibroTest/FibroSURE

ALL of the following

Chronic viral hepatitis indication: Individual has chronic hepatitis B (HBV) or chronic hepatitis C (HCV) viral infection
For these individuals, FibroSURE (HBV FibroSURE, HCV FibroSURE), ELF (ELFTM) or FibroTest testing once every 6 months may be reimbursed
Testing frequencyonce every 6 months
Applies to FibroSURE (HBV/HCV), ELF, or FibroTest

Covered when ANY of the following are met

Reimbursement criteria for ELF or FibroTest/FibroSURE in other specified conditions

ANY of the following

MASLD/MASH: Individual has metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH)
Alcoholic hepatitis: Individual has alcoholic hepatitis
Rule out cACLD with elevated liver stiffness: Testing is performed to rule out compensated advanced chronic liver disease (cACLD) for individuals with an elevated liver stiffness measurement
ELF (ELFTM) or FibroTest testing once every 6 months may be reimbursed in these situations
Testing frequencyonce every 6 months

Not covered / Does not meet coverage criteria

Use of other multianalyte assays with algorithmic analysis or specified individual biomarkers

Not covered assays and biomarkers

Non-reimbursed multianalyte assay examples: Other multianalyte assays with algorithmic analysis (examples: ASH FibroSURE®, LIVERFAStTM, NASH FibroSURE®, OWLiver®) may not be reimbursed
Non-reimbursed individual biomarkers
- SIPA1L1: Signal-induced proliferation-associated 1 like 1 (SIPA1L1)
- miRNAs: microRNA (miRNA or miR) analysis, including but not limited to: microRNA-21 (miR-21), miRNA-29a (miR-29a), miRNA-122 (miR-122), miRNA-221 (miR-221), miRNA-222 (miR-222)

Coding

Covered / Described proprietary tests and associated codesCPTCovered

81596	Infectious disease, chronic hepatitis C virus (HCV) infection, six biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, and haptoglobin) utilizing serum, prognostic algorithm reported as scores for fibrosis and necroinflammatory activity in liver. Proprietary test: HCV FibroSURE™, FibroTest™. Laboratory/Manufacturer: BioPredictive S.A.S.
81517	Liver disease, analysis of 3 biomarkers (hyaluronic acid [HA], procollagen III amino terminal peptide [PIIINP], tissue inhibitor of metalloproteinase 1 [TIMP-1]), using immunoassays, utilizing serum, prognostic algorithm reported as a risk score and risk of liver fibrosis and liver-related clinical events within 5 years.
0002M	Liver disease, ten biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, haptoglobin, AST, glucose, total cholesterol and triglycerides) utilizing serum, prognostic algorithm reported as quantitative scores for fibrosis, steatosis and alcoholic steatohepatitis (ASH). Proprietary test: ASH FibroSURE™. Laboratory/Manufacturer: BioPredictive S.A.S.
0003M	Liver disease, ten biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, haptoglobin, AST, glucose, total cholesterol and triglycerides) utilizing serum, prognostic algorithm reported as quantitative scores for fibrosis, steatosis and nonalcoholic steatohepatitis (NASH). Proprietary test: NASH FibroSURE™. Laboratory/Manufacturer: BioPredictive S.A.S.
0166U	Liver disease, 10 biochemical assays (α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, GGT, ALT, AST, triglycerides, cholesterol, fasting glucose) and biometric and demographic data, utilizing serum, algorithm reported as scores for fibrosis, necroinflammatory activity, and steatosis with a summary interpretation. Proprietary test: LiverFASt™. Lab/Manufacturer: Fibronostics.
0344U	Hepatology (nonalcoholic fatty liver disease [NAFLD]), semiquantitative evaluation of 28 lipid markers by liquid chromatography with tandem mass spectrometry (LC-MS/MS), serum, reported as at-risk for nonalcoholic steatohepatitis (NASH) or not NASH. Proprietary test: OWLiver®. Lab/Manufacturer: CIMA Sciences, LLC.
0468U	Hepatology (nonalcoholic steatohepatitis [NASH]), miR-34a5p, alpha 2-macroglobulin, YKL40, HbA1c, serum and whole blood, algorithm reported as a single score for NASH activity and fibrosis. Proprietary test: NASHnext™ (NIS4™).
81599	Unlisted multianalyte assay with algorithmic analysis.
84999	Unlisted chemistry procedure.
0000	Placeholder/unlisted code referenced in source content; use only when no specific CPT code accurately describes the proprietary multianalyte assay being billed. Billing with 0000 requires documentation of test methodology, analytes included, algorithm description, and justification that no existing specific code applies.

Unlisted / Not-specific codes used for non-covered assaysCPT

81599	Unlisted multianalyte assay with algorithmic analysis.
84999	Unlisted chemistry procedure.

Provider Actions & Billing Guidance

Prior Authorization

Reimbursement limited to specified clinical indications

Ensure the ordered assay is for one of the covered clinical indications (chronic HBV or HCV; MASLD/MASH; alcoholic hepatitis; or to rule out compensated advanced chronic liver disease [cACLD] in individuals with an elevated liver stiffness measurement). Reimbursement for FibroSURE/FibroTest/ELF is limited to testing performed for these indications and to a frequency of once every 6 months.

Affected codes: 81596
Affected codes: 0166U
Affected codes: 81517

Billing Rule

Do not bill non-reimbursed multianalyte assays

Do not bill for other multianalyte assays with algorithmic analysis or the listed individual biomarkers when they are not part of an approved reimbursable assay. Examples such assays (e.g., ASH FibroSURE®, LIVERFAStTM, NASH FibroSURE®, OWLiver®) and services billed with unlisted codes (81599, 84999) may be denied if representing non-covered tests.

Affected codes: 81599
Affected codes: 84999
Affected codes: 0002M
Affected codes: 0003M
Affected codes: 0166U
Affected codes: 0344U
Affected codes: 0468U
Potential denial risk for other/unlisted codes representing non-covered assays

Documentation Required

Document clinical rationale and prior liver stiffness

Maintain documentation that supports the covered indication for testing to support reimbursement. Documentation should show the clinical rationale (diagnosis or reason) and, when applicable, prior elevated liver stiffness measurement if testing is to rule out cACLD.

Examples of acceptable documentation: diagnosis of chronic HBV or HCV
Diagnosis of MASLD/MASH
Diagnosis of alcoholic hepatitis
Prior elevated liver stiffness measurement when testing to rule out cACLD

Background

Background: Biomarkers of extracellular matrix turnover (glycoproteins, collagen family members, collagenases and their inhibitors, and fibrogenic cytokines) are used to assess hepatic fibrosis and may be utilized individually or in panel combinations. The policy distinguishes reimbursable proprietary multianalyte assays — specifically FibroSURE/FibroTest and ELF (ELFTM) — which may be reimbursed in specified clinical contexts and at a frequency of once every 6 months, from other algorithmic multianalyte tests and individual serum biomarkers that do not meet coverage criteria due to insufficient published evidence.

Non-reimbursable algorithmic multianalyte assays (examples) include ASH FibroSURE®, LIVERFAStTM, NASH FibroSURE®, OWLiver®, LiverFASt™ and other tests described by unlisted codes; these and other multianalyte assays with algorithmic analysis may not be reimbursed except when they are components of one of the approved reimbursable assays. Individual serum biomarkers listed in the policy (e.g., hyaluronic acid, type III procollagen [PCIII], type IV collagen, laminin, miRNA analyses, CHI3L1, MFAP4, plasma caspase-generated cytokeratin-18, SIPA1L1) do not meet coverage criteria when used outside the context of an approved multianalyte assay because of a lack of published evidence supporting clinical utility.

Definitions:

MASLD: Metabolic dysfunction-associated steatotic liver disease (includes MASH).

cACLD: Compensated advanced chronic liver disease.

ELF: Enhanced Liver Fibrosis test (ELFTM).

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