CurrentBlue KCPolicy POL-PP-309

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

Defines reimbursement coverage for serum multianalyte assays with algorithmic analysis (e.g., FibroSURE, FibroTest, ELF) and lists specific individual serum biomarkers and other multianalyte tests that are not reimbursed for evaluation and monitoring of chronic liver disease.

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 quarterly updates (Version 002)

Effective DateOct 1, 2025

Next Review DateOct 1, 2026

Key ActionDocument that the individual meets the covered indication (chronic HBV or HCV; MASLD/MASH; alcoholic hepatitis; or evaluation to rule out cACLD with elevated liver stiffness measurement).

SourceLink

POLICY UPDATE CHANGES

Version 002 reflects Avalon 4th Quarter updates.

Initial version created 07/01/2025 (001).

2Reimbursable multianalyte assays (named: FibroSURE/FibroTest, ELF)

5Named not-reimbursed proprietary multianalyte tests (examples listed)

10Individual serum biomarkers listed as not reimbursed

Coverage Summary

Scope: This policy defines reimbursement coverage for serum multianalyte assays with algorithmic analysis to evaluate and monitor chronic liver disease, and lists specific individual serum biomarkers and proprietary multianalyte tests that are not reimbursed.

Coverage stance: Mixed — certain named multianalyte assays are reimbursable for specified indications, while other proprietary panels and many individual biomarkers are not reimbursed.

Subject: Serum testing for hepatic fibrosis (multianalyte assays and individual biomarkers).

Reimbursable (when criteria met): FibroSURE/FibroTest (e.g., HCV FibroSURE™, HBV FibroSURE™) and ELF (RLFTM/ELFTM) — testing may be reimbursed once every 6 months for eligible indications.

Not reimbursed (examples): other proprietary multianalyte assays such as ASH FibroSURE® (0002M), NASH FibroSURE® (0003M), LIVERFASt™ (0166U), OWLiver® (0344U), NASHnext™/NIS4 (0468U), and unlisted multianalyte or chemistry procedures (e.g., 81599, 84999), as well as specified individual serum biomarkers unless included as components of a covered panel.

Effective date: 2025-10-01. Last review/Version: Initial 07/01/2025 (v001); updated 10/01/2025 (v002) with Avalon quarterly updates; next review: 10/01/2026.

Quick facts and thresholds

Multianalyte assay frequencyOnce every 6 months for covered indications (HBV, HCV, MASLD/MASH, alcoholic hepatitis, or to rule out cACLD with an elevated liver stiffness measurement)

Reimbursable named assays (count)2 (FibroSURE/FibroTest and ELF)

Named not-reimbursed proprietary multianalyte tests (count)5 (examples: ASH FibroSURE, NASH FibroSURE, LIVERFASt, OWLiver, NASHnext/NIS4)

Individual serum biomarkers not reimbursed (count)10 (examples listed: SIPA1L1; multiple miRNAs including miR-21/29a/122/221/222; CHI3L1; hyaluronic acid; PCIII; type IV collagen; laminin; cytokeratin-18; MFAP4)

Policy statusCurrent / Active

Effective date2025-10-01

Next review date2026-10-01

Medical-Necessity Criteria

Medically Necessary / Reimbursable Multianalyte Assays

Covered when ALL of the following are met:

Individual has chronic hepatitis B (HBV) or chronic hepatitis C (HCV) viral infection

FibroSURE (HBV FibroSURE, HCV FibroSURE), ELF (RLFTM) or FibroTest testing once every 6 months may be reimbursed

Medically Necessary / Reimbursable for MASLD, alcoholic hepatitis, or to rule out cACLD

Covered when ALL of the following are met:

Individual has metabolic dysfunction-associated steatotic liver disease (MASLD) (including MASH), or alcoholic hepatitis, or is being evaluated to rule out compensated advanced chronic liver disease (cACLD) with an elevated liver stiffness measurement

ELF (ELFTM) or FibroTest testing once every 6 months may be reimbursed

Not Reimbursed / Experimental

Not Reimbursed: Other Multianalyte Assays with Algorithmic Analysis

Not covered in ANY of the following situations unless specified above:

ASH FibroSURE®

e.g., 0002M; not reimbursed

LIVERFAStTM (LiverFASt™)

e.g., 0166U; not reimbursed

NASH FibroSURE® (NASH FibroSURE™)

e.g., 0003M; not reimbursed

OWLiver®

e.g., 0344U; not reimbursed

Other multianalyte assays with algorithmic analysis (e.g., ASH FibroSURE®, LIVERFASt™, NASH FibroSURE®, OWLiver®)

may not be reimbursed

Not Reimbursed: Individual Serum Biomarkers (Except as components of covered multianalyte assays)

The following individual serum biomarkers do not meet coverage criteria and may not be reimbursed:

Signal-induced proliferation-associated 1 like 1 (SIPA1L1)

microRNA (miRNA or miR) analysis, including but not limited to: miRNA-21 (miR-21), miRNA-29a (miR-29a), miRNA-122 (miR-122), miRNA-221 (miR-221), miRNA-222 (miR-222)

Chitinase 3-like 1 (CHI3L1)

Hyaluronic acid

except when included as a component of one of the multianalyte assays described above

Type III procollagen (PCIII)

Not Reimbursed: Multianalyte Assays for Liver Disease Outside Above Indications

Not covered when ALL of the following are true:

Individual has liver disease that does not meet the clinical indications described above (HBV, HCV, MASLD/MASH, alcoholic hepatitis, or rule out cACLD with elevated liver stiffness measurement)

the use of multianalyte assays with algorithmic analysis may not be reimbursed

Coding

Covered / Mentioned Proprietary Tests (may be reimbursed for specified indications)mixedCovered

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], TIMP-1), using immunoassays, serum, prognostic algorithm reported as a risk score and risk of liver fibrosis and liver-related clinical events within 5 years.
ELF	ELF (RLFTM) proprietary panel referenced in policy (no specific CPT listed)

Not Reimbursed / Other Proprietary Multianalyte AssaysmixedNot Covered

0002M	Liver disease, ten biochemical assays... 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... 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 and biometric/demographic data... algorithm reported as scores for fibrosis, necroinflammatory activity, and steatosis with a summary interpretation. Proprietary test: LiverFASt™; Lab/Manufacturer: Fibronostics.
0344U	Hepatology (NAFLD), semiquantitative evaluation of 28 lipid markers... Proprietary test: OWLiver®; Lab/Manufacturer: CIMA Sciences, LLC.
0468U	Hepatology (NASH), miR-34a5p, alpha 2-macroglobulin, YKL40, HbA1c... Proprietary test: NASHnextTM (NIS4TM).
81599	Unlisted multianalyte assay with algorithmic analysis (not reimbursed per policy)
84999	Unlisted chemistry procedure (not reimbursed per policy)

Provider Actions / Billing Impact

Documentation Required

Confirm clinical indication and liver stiffness

Document that the individual meets the covered indication (chronic HBV or HCV; MASLD/MASH; alcoholic hepatitis; or evaluation to rule out cACLD with elevated liver stiffness measurement).

Record the clinical indication: HBV, HCV, MASLD/MASH, alcoholic hepatitis, or evaluation to rule out cACLD

Billing Rule

Frequency limitation

Report covered multianalyte assays (ELF, FibroTest/FibroSURE) no more frequently than once every 6 months for eligible individuals.

once every 6 months for eligible individuals
Covered assays: ELF, FibroTest/FibroSURE

Denial Risk

Not reimbursed tests

Claims for multianalyte assays with algorithmic analysis (e.g., ASH FibroSURE®, LIVERFASt™, NASH FibroSURE®, OWLiver®) or for listed individual serum biomarkers (unless component of a covered assay) may be denied.

Affected codes: 0002M, 0003M, 0166U, 0344U, 0468U, 81599, 84999
Claims for these tests may be denied

Background

Background: Chronic liver disease (CLD) encompasses a range of liver pathologies including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatic fibrosis involves cycles of extracellular matrix deposition and degradation. Biomarkers of extracellular matrix turnover (glycoproteins, collagen family members, collagenases and their inhibitors, and cytokines) are used to directly assess fibrosis and, in theory, to monitor progression or regression. These markers may be used individually or combined into multianalyte panels that apply algorithmic analysis to generate prognostic scores.

Clinical application and coverage dependency: Multianalyte panels (and individual biomarkers) may be utilized alone or in combination to assess fibrosis, but coverage depends on the member's benefits and the date of service; the policy states that application of coverage criteria is dependent upon an individual's benefit coverage at the time of the request.

Definitions: MASLD = metabolic dysfunction-associated steatotic liver disease (including metabolic dysfunction-associated steatohepatitis [MASH]). cACLD = compensated advanced chronic liver disease.

Examples / coding context: The policy references specific CPT and proprietary tests (e.g., 81596 — FibroSURE/FibroTest; 81517; other codes and proprietary panels such as 0002M, 0003M, 0166U, 0344U, 0468U) to clarify which assays are covered or not covered per the criteria.