Health Net genetic GI testing Coverage Update

Coverage Criteria and Policy Rules

inv-01: HLA-DQ Genotyping Analysis (Celiac Disease)

HLA-DQ genotyping to rule out celiac disease is considered medically necessary when ALL of the following are met:

HLA-DQ for CD: A. The member is being evaluated for celiac disease; AND B. HLA DQA1 and HLA DQB1 genotyping analysis has not been previously performed; AND (one of: 1) inconclusive serology (antibody) result; OR 2) inconclusive histology (biopsy) result; OR 3) started a gluten-free diet before evaluation

ACG guidance supports use to rule out celiac disease in serology–histology discrepancy or when a gluten-free diet was started prior to evaluation.

inv-02: HFE C282Y and H63D Genotyping

HFE C282Y and H63D genotyping (81256) to establish a diagnosis of hereditary hemochromatosis is considered medically necessary when ANY of the following are met:

HFE genotyping: A. The member has abnormal serum iron indices (e.g., elevated transferrin-iron saturation and/or elevated serum ferritin indicating iron overload); OR B. The member has a first-degree relative with a diagnosis of hereditary hemochromatosis.TS >= 45% or elevated ferritin

EMQN and ACG guidance recommend confirming elevated transferrin saturation before genetic testing and screening first-degree relatives.

inv-03: Hereditary Pancreatitis Multigene Panel

Hereditary pancreatitis multigene panel is considered medically necessary when ALL of the following are met:

Pancreatitis panel: A. The member has a personal history of pancreatitis; AND B. The member meets at least one of: 1) unexplained acute pancreatitis in childhood (≤18 years); OR 2) recurrent (≥2) documented acute attacks of pancreatitis with no explanation; OR 3) chronic pancreatitis of unknown cause, particularly with onset <35 years without heavy alcohol use; OR 4) at least one close relative with recurrent acute pancreatitis, chronic pancreatitis of unknown cause, or childhood pancreatitis of unknown cause; AND C. The panel includes at minimum PRSS1, SPINK1, CFTR, and CTRC.

ACG and GeneReviews recommend testing in young or idiopathic cases; representative CPT codes include 81222, 81223, 81404, 81405, 81479.

inv-04: Hereditary Inflammatory Bowel Disease Panel Tests

Genetic testing for inflammatory bowel disease via a multigene panel (81479, 81321, 81406, 81407) is considered medically necessary when ANY of the following are met:

Hereditary IBD panel: A. Diagnosis of infantile-onset IBD before age 2 years; OR B. Diagnosis of very early onset IBD (VEO-IBD) before age 6 years AND at least one of: congenital multiple intestinal atresias; congenital diarrhea; malignancy under age 25; features of an inborn error of immunity (eg, recurrent or severe infections with supporting lab abnormalities); complex autoimmune features; a close relative meeting any of the above; OR C. The member is undergoing stem cell transplant; OR D. The member has a history of multiple intestinal resections.age <6 years (esp <2) for consideration

British and other society guidance favor genomic panel testing in infantile/VEO-IBD and recommend offering testing only in exceptional circumstances after age 6.

inv-05: IBD Algorithmic and Prognostic Tests

Inflammatory bowel disease algorithmic diagnostic and prognostic tests are considered investigational:

IBD algorithmic/prognostic: Diagnostic algorithmic tests (e.g., CPTs 81479, 82397, 83520, 86140, 88346, 88350) and prognostic algorithmic tests (e.g., CPTs 81401, 83520, 88346, 88350) for inflammatory bowel disease are considered investigational and not medically necessary.

These algorithmic/multimarker tests lack sufficient evidence to support clinical validity and utility per policy.

inv-06: Non-Invasive Liver Fibrosis Serum Tests

Non-invasive liver fibrosis serum tests (0002M, 0003M, 84450, 84460, 85049) to rule out liver fibrosis are considered medically necessary when ALL of the following are met:

Non-invasive liver fibrosis tests: A. The member has one of: NAFLD (also known as MASLD); NASH; type 2 diabetes; obesity (BMI >25); abnormal liver function tests; or history of alcohol use; AND B. The member had prior FIB-4 testing with a score >1.3.FIB-4 > 1.3

Guideline-preferred approach uses FIB-4 as first-line risk stratification; proprietary serum biomarkers are reserved for second-line evaluation and tests are investigational for other indications.

inv-07: Covered with criteria

Covered when clinical and/or laboratory criteria specific to each disorder are met according to professional society guidance and policy criteria.

HFE C282Y and H63D Genotyping: Genotyping is indicated when there is biochemical evidence suggestive of hemochromatosis (e.g., transferrin saturation >=45% and/or elevated serum ferritin) or for screening of first-degree relatives of affected individuals.TS >=45% or elevated ferritin

EMQN and ACG recommend confirming elevated TS prior to genetic testing.

Hereditary Pancreatitis Multigene Panel: Genetic testing may be considered for patients with unexplained or recurrent pancreatitis, particularly with onset at young age (<30) or family history; panels should include at minimum PRSS1, SPINK1, CFTR, and CTRC per ACG and GeneReviews.age <30 (consideration); onset <35 for chronic pancreatitis without heavy alcohol use

Testing is investigational outside these indications.

Hereditary Inflammatory Bowel Disease (monogenic IBD) Panel:

inv-08: Notable criteria updates

Policy updates and criteria changes noted in document

Celiac HLA-DQ genotyping prerequisite: HLA DQA1 and HLA DQB1 genotyping analysis has not been previously performed

Newly added criterion requires confirmation that HLA genotyping was not previously done before coverage.

Noninvasive liver fibrosis terminology update: Noninvasive liver fibrosis serum tests criteria now include 'also known as metabolic dysfunction-associated steatotic liver disease (MASLD)'

Terminology updated to include MASLD in the liver fibrosis criteria.

Multiple tests and panels referenced in this policy are designated investigational when ordered outside the specific clinical indications and criteria set forth in the policy. Examples include algorithmic diagnostic and prognostic inflammatory bowel disease (IBD) tests and multigene panels for IBD or pancreatitis when clinical eligibility criteria are not met. See the policy sections that list required age, family history, clinical features, or prior testing for each panel; orders that do not meet those criteria are considered investigational and are not supported as medically necessary.

Specifically, diagnostic and prognostic algorithmic IBD tests (listed CPTs such as 81479, 82397, 83520, 86140, 88346, 88350, 81401 and related codes) are classified investigational due to insufficient evidence of clinical validity and utility to demonstrate improved health outcomes compared with standard care. Similarly, multigene panels for hereditary pancreatitis and hereditary IBD are medically necessary only when the policy’s detailed clinical criteria (for example, infantile/VEO-IBD age thresholds, recurrent or unexplained pancreatitis, or required gene content) are satisfied; otherwise they are investigational.

Providers should consult the policy criteria for each test group to confirm that the member’s clinical presentation and prior testing meet the coverage requirements before ordering. Claims for investigational uses are at higher risk for denial.

Algorithmic diagnostic and prognostic tests for inflammatory bowel disease (examples include Prometheus IBD sgi Diagnostic and Prometheus Crohn's Prognostic test) are treated as investigational in this policy. The Concert evidence reviews found insufficient peer‑reviewed evidence that these proprietary algorithmic tests improve health outcomes compared with current standard diagnostic and management approaches.

Professional society guidance cited in the evidence review does not endorse routine use of these algorithmic or serologic panels for diagnosis or prognostication of IBD; recommendations generally discourage routine serologic antibody testing for establishing IBD diagnosis and consider many genetic/serologic markers to remain research tools. As a result, Prometheus‑type diagnostic or prognostic assays are not supported as medically necessary by the policy.

When considering testing for IBD diagnosis or prognosis, providers should rely on guideline‑recommended clinical evaluation and document how any considered test aligns with the policy’s coverage criteria. Tests lacking demonstrated clinical utility in the literature are likely to be denied.

The policy reference table and criteria have been updated to remove certain proprietary/example codes. In particular, the PLA code 0203U and CPT codes 81356 and 86671 were removed from the Policy Reference Table and criteria. This removal implies these specific codes are no longer referenced for coverage under this policy and may affect prior authorization and claim adjudication.

Providers submitting claims should ensure they use the updated, supported CPT/PLA codes listed in the policy reference table and follow payer prior authorization procedures; claims referencing the removed codes may not be covered under this policy.

Targeted genotyping for the common HFE variants C282Y and H63D (CPT 81256) is addressed as the recommended testing approach to establish hereditary hemochromatosis when policy criteria are met (for example, abnormal iron indices or an affected first‑degree relative).

Conversely, HFE C282Y and H63D genotyping is considered investigational for other indications, including routine population screening for hereditary hemochromatosis. The policy and referenced guidance recommend confirming elevated transferrin saturation (for example, TS >= 45%) or other biochemical evidence of iron overload before pursuing genetic testing.

The policy’s evidence review concluded that Prometheus IBD sgi Diagnostic and Prometheus Crohn's Prognostic tests have insufficient published evidence of clinical validity and utility to show improved health outcomes compared with standard care. Consequently, these algorithmic/promotional proprietary assays are treated as investigational and are not supported as medically necessary by this policy.

The evidence review included systematic searches and guideline assessments and found no new peer‑reviewed literature establishing clinical utility for these specific Prometheus assays during the review period cited in the policy.

This policy update included several editorial and labeling adjustments. Portions of the document were relabeled or clarified to explicitly identify certain tests or sections as investigational, and minor grammar and formatting edits were applied across multiple sections (for example, wording changes in the investigational statements for HFE genotyping and updates to test examples in the policy reference table).

These editorial changes do not alter the substantive clinical thresholds and primary coverage criteria but clarify prerequisites (for example, confirming prior HLA genotyping has not been performed) and align terminology in the criteria and reference table.

Coding and Billing Guidance

HLA-DQ Genotyping - Common CPT CodesCPT

81375	HLA-DQ genotyping (example listed)
81376	HLA-DQ genotyping (example listed)
81377	HLA-DQ genotyping (example listed)
81382	HLA-DQ genotyping (example listed)
81383	HLA-DQ genotyping (example listed)

HFE Genotyping - Common CPT CodesCPT

81256

HFE C282Y and H63D genotyping

Hereditary Pancreatitis Multigene Panel - Common CPT CodesCPT

81222	Hereditary pancreatitis multigene panel - CPT listed
81223	Hereditary pancreatitis multigene panel - CPT listed
81404	Hereditary pancreatitis multigene panel - CPT listed
81405	Hereditary pancreatitis multigene panel - CPT listed
81479	Unlisted molecular pathology procedure (used for some panels)

Hereditary IBD Panel - Common CPT CodesCPT

81321	Genetic testing - included in hereditary IBD panel listing
81406	Genetic testing - included in hereditary IBD panel listing
81407	Genetic testing - included in hereditary IBD panel listing

Inflammatory Bowel Disease Algorithmic/Diagnostic/Prognostic Tests - CPT CodesCPT

81479	Algorithmic/multigene testing (used across IBD/pancreatitis references)
82397	Protein electrophoresis or related (listed with algorithmic IBD tests)
83520	Serum marker (listed with algorithmic/prognostic IBD tests)
86140	Specific immunologic test (listed with algorithmic IBD tests)
88346	Pathology immunohistochemistry (listed with algorithmic IBD tests)
88350	Pathology special stains (listed with algorithmic IBD tests)

Non-invasive Liver Fibrosis Serum Tests - CPT CodesCPT

0002M	Non-invasive liver fibrosis serum test (code listed)
0003M	Non-invasive liver fibrosis serum test (code listed)
84450	AST
84460	ALT
85049	Platelet function/count related (listed with fibrosis tests)
81517	Enhanced Liver Fibrosis (ELF) test

Policy Reference Table coding updatesCPT

81256

HFE (general) — replaced 81479 in policy reference table

Removed proprietary/example codesmixed

0203U	Example PLA code removed from policy reference table
81356	CPT code removed from policy reference table
86671	CPT code removed from policy reference table

Other CPT codes referencedCPT

86140	Serologic test code referenced in updates (example)
88342	Pathology/micro code referenced as removed/modified in reference table

Removed CPT/PLA CodesmixedNot Covered

0203U	PLA code (removed from Policy Reference Table and criteria)
81356	CPT (removed from Policy Reference Table and criteria)
86671	CPT (removed from Policy Reference Table and criteria)

FIB-4 index — threshold value

FIB-4 index threshold> 1.3

Context for thresholdFIB-4 >1.3 is the trigger for further noninvasive fibrosis testing per policy (e.g., proprietary biomarkers or imaging)

Related codesApplicable CPT/PLA examples for noninvasive fibrosis tests: 0002M, 0003M, 84450, 84460, 85049

Obesity BMI — BMI threshold referenced

Obesity BMI threshold

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for the listed genetic and fibrosis tests. Providers must obtain prior authorization per Health Net processes before submitting claims for covered tests in the policy reference table.

Affected codes include those in the Policy Reference Table (see policy coding section); providers should check payer portals for the current authorized code list and submit PA requests accordingly.

Prior Authorization

Prior Authorization After Code Updates

Providers should follow standard payer prior authorization procedures after any code updates. If a test’s CPT/PLA codes change, obtain authorization based on the updated code(s) before performing the test.

When codes are updated or removed from the policy reference table, confirm current acceptable codes and prior authorization requirements via Health Net provider resources.

Background and Rationale

Genetic testing can confirm diagnoses for a range of non‑cancerous gastrointestinal disorders and may affect management or avoid further invasive testing. Examples addressed in this policy include: HLA‑DQ genotyping to help rule out celiac disease when serology or histology is inconclusive or when a gluten‑free diet was started before diagnostic evaluation; targeted HFE genotyping for suspected hereditary hemochromatosis after biochemical evidence of iron overload; and multigene panels for hereditary pancreatitis or monogenic forms of inflammatory bowel disease when strict clinical criteria are met.

The policy emphasizes targeted approaches and alignment with professional guidance: perform HFE C282Y/H63D genotyping (81256) only after biochemical confirmation (e.g., elevated transferrin saturation such as TS >= 45% or elevated ferritin) or for screening first‑degree relatives of affected individuals, and restrict multigene panel testing for hereditary pancreatitis and hereditary IBD to the specified age, clinical, and family history criteria. Noninvasive liver fibrosis serum tests are added for risk stratification in NAFLD/MASLD following guideline‑recommended pathways that use FIB‑4 > 1.3 as a threshold to trigger further evaluation.

Overall, the background rationale supports using genetic and serum testing selectively—when test results will affect clinical decision making—and cautions against routine or population screening without appropriate clinical indication.

Key Definitions and Terms

Close relatives — first/second/third-degree definitions

First-degree relativesParents, siblings, and children

Second-degree relativesGrandparents, aunts, uncles, nieces, nephews, grandchildren, and half-siblings

Third-degree relativesGreat grandparents, great aunts, great uncles, great-grandchildren, and first cousins

Infantile-IBD / VEO-IBD — age-based definitions

Infantile-onset IBD (Infantile-IBD)Clinical manifestations or diagnosis before age 2 years

Very early onset IBD (VEO-IBD)Clinical manifestations or diagnosis before age 6 years

Policy Revision History

2025-11operationalLatest

Updated Background and Rationale, evidence review dates, and removed PLA code 0203U and CPT codes 81356 and 86671 from the Policy Reference Table and criteria; added MASLD terminology to non-invasive liver fibrosis criteria; added requirement that HLA DQA1 and HLA DQB1 genotyping has not been previously performed for celiac HLA-DQ testing.

2024-10operational

Replaced HFE sequencing with targeted HFE C282Y and H63D genotyping; replaced wording 'coverage criteria' with 'criteria' throughout; updated Policy Reference Table coding (replaced some 81479 references with 81256) and refined hereditary pancreatitis and IBD criteria wording.

2024-03

OpenPayer

Genetic Testing: Gastroenterologic Disorders (Non-Cancerous)