ModifiedCentenePolicy N/A

Concert Genetic Testing: Gastroenterologic Disorders (Non‑Cancerous)

Defines medical necessity and investigational indications for genetic and non‑invasive serum testing for non‑cancer gastroenterology conditions (e.g., celiac disease, hereditary hemochromatosis, hereditary pancreatitis, IBD, liver fibrosis) for members of Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyGenetic testing: gastroenterologic (non-cancerous) disorders — coverage criteria

Policy CodePolicy N/A

Change TypeMultiple material revisions (added fibrosis criteria; updated HFE and hereditary IBD criteria; removed codes)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and submit clinical documentation that supports the specific medical necessity criteria (e.g., FIB‑4 >1.3 for noninvasive fibrosis tests or abnormal iron indices for HFE genotyping).

SourceLink

POLICY UPDATE CHANGES

Non-Invasive Liver Fibrosis Serum Tests criteria is new, created criteria to align coverage with guidelines.

HFE Sequencing and/or Deletion panel retitled to HFE C282Y and H63D Genotyping with associated coding changes (eg, 81256 replacing 81479 in reference table).

Hereditary Inflammatory Bowel Disease/Crohn's Disease panel criteria: age and family-history related criteria updated and expanded (eg, earlier onset thresholds, added consanguinity, hemophagocytic features).

Several CPT/PLA codes removed from Policy Reference Table for IBD prognostic/diagnostic tests (eg, PLA 0203U, CPTs 81356 and 86671, CPT 88342 removed).

Updated Background and Rationale to reflect updated Evidence Review for multiple sections including Inflammatory Bowel Disease Crohn's Disease diagnostic and prognostic algorithmic tests and others.

~6test groups

81256HFE example CPT

81222-81479panels CPT range

3 codes removedcodes removed

V1.2025policy version

Coverage Criteria for Genetic and Non‑Invasive Tests

inv-01: HLA‑DQ Genotyping Analysis (to rule out celiac disease)

Covered when ALL of the following are met

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

HLA-DQ genotyping to rule out celiac disease is investigational for all other indications.

inv-02: HFE C282Y and H63D Genotyping

Covered when ANY of the following are met

HFE C282Y and H63D genotyping: The member has abnormal serum iron indices (e.g., elevated transferrin-iron saturation and/or elevated serum ferritin concentration indicating iron overload).

HFE C282Y and H63D genotyping is investigational for all other indications, including general population screening.

inv-03: Hereditary Pancreatitis Multigene Panel

Covered when ALL of the following are met

Hereditary pancreatitis multigene panel: A. Personal history of pancreatitis; AND B. Meets at least one: unexplained acute pancreatitis in childhood (<=18 years), OR recurrent (two or more separate, documented) unexplained acute attacks, OR chronic pancreatitis of unknown cause (particularly onset before age 35 years without heavy alcohol use), OR at least one close relative with recurrent acute pancreatitis or chronic pancreatitis of unknown cause or childhood pancreatitis of unknown cause; AND C. The panel includes at minimum PRSS1, SPINK1, CFTR, and CTRC.

Hereditary pancreatitis multigene panels are investigational for other indications.

inv-04: Inflammatory Bowel Disease Diagnostic Algorithmic Tests

IBD diagnostic algorithmic tests: Inflammatory bowel disease diagnostic algorithmic tests (CPTs 81479, 82397, 83520, 86140, 88346, 88350) are considered investigational.

Refer to the policy for specific covered genetic testing indications for IBD panels.

inv-05: Inflammatory Bowel Disease Prognostic Algorithmic Tests

IBD prognostic algorithmic tests: Inflammatory bowel disease prognostic algorithmic tests (e.g., CPTs 81401, 83520, 88346, 88350) are considered investigational.

inv-06: Hereditary Inflammatory Bowel Disease Panel Tests

Covered when ALL of the following are met

Indications for hereditary IBD multigene testing: A. Diagnosed with infantile-onset IBD (onset <2 years) OR very early-onset IBD (onset <6 years) AND B. At least one additional feature such as congenital multiple intestinal atresias, congenital diarrhea, malignancy <25 years, features of inborn errors of immunity (eg, recurrent infections, abnormal immune labs), complex autoimmune features, hemophagocytic features, OR a close relative meeting these criteria; OR undergoing stem cell transplant; OR history of multiple intestinal resections.

Genetic multigene panel testing for IBD is considered investigational for all other indications.

inv-07: Non‑Invasive Liver Fibrosis Serum Tests

Covered when ALL of the following are met

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

If FIB-4 >1.3, use a combination of >=2 NITs (serum and/or imaging) for staging per guidance; these tests are investigational for other indications.

inv-08: HFE C282Y and H63D Genotyping - Initial testing

Covered when ALL of the following are met for HFE genotyping:

HFE Genotyping Coverage: Laboratory confirmation of elevated transferrin saturation (TS) and/or elevated serum ferritin AND clinical suspicion or family history of HFE hemochromatosis (eg, signs of iron overload or affected relative).TS >= 45% or elevated serum ferritin

Targeted C282Y/H63D testing (81256) preferred; population screening is not recommended.

inv-09: Hereditary Pancreatitis Multigene Panel - Indications

Covered when ANY of the following are met for hereditary pancreatitis/multigene panels:

Hereditary Pancreatitis Testing Indications: Young age of onset (eg, <30 years) with no evident cause and/or family history of pancreatic disease; chronic or recurrent unexplained pancreatitis, especially onset before age 35 without heavy alcohol use; or recurrent documented acute attacks of unexplained pancreatitis.Age thresholds: childhood onset <=18 years or chronic onset <35 years without heavy alcohol use

Panels should include PRSS1, SPINK1, CFTR, and CTRC at minimum; testing investigational for other indications.

inv-10: Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel Tests - Indications

Covered when ALL of the following are met for hereditary/monogenic IBD panel testing (very early-onset):

Monogenic IBD Testing: Onset of IBD symptoms at very early age (eg, <6 years, especially <2 years) AND presence of one or more additional features such as family history of monogenic IBD, consanguinity, recurrent infections or severe phenotype, autoimmune features, hemophagocytic features, early-onset malignancy (<25 years), congenital intestinal atresias or congenital diarrhea, or preparation for interventions with irreversible consequences (eg, stem cell transplant) or history of multiple intestinal resections.Consider age <2 years strongly; age <6 years as VEO-IBD

Genomic testing generally favored in infantile/VEO-IBD and investigational for other indications.

inv-11: Noninvasive Liver Fibrosis Serum Tests - Risk stratification

Covered when ALL of the following are met for noninvasive liver fibrosis serum tests in NAFLD/MASLD risk stratification:

NAFLD/MASLD Fibrosis Testing: Patient at increased risk for NAFLD/MASLD (eg, type 2 diabetes, obesity, metabolic syndrome) AND initial assessment with FIB-4 performed; if FIB-4 >1.3 then combination of >=2 NITs (serum and/or imaging) used for staging; liver biopsy reserved for indeterminate/discordant/alternative etiology situations.FIB-4 > 1.3

FIB-4 recommended as first-line assessment; combine additional NITs for staging per AGA/AASLD/AACE guidance.

Several tests described in this policy are explicitly designated as investigational for indications outside the specific coverage criteria. Examples include IBD diagnostic and prognostic algorithmic tests (listed CPT codes such as 81479, 82397, 83520, 86140, 88346, 88350, 81401), which the policy identifies as investigational, and targeted genotyping or multigene panels used outside of the enumerated clinical scenarios. Providers should expect that requests for testing not meeting the policy’s stated clinical criteria may be denied as investigational.

Non‑invasive liver fibrosis serum tests and HFE genotyping have specific qualifying requirements (for example, prior FIB‑4 > 1.3 for fibrosis tests and abnormal serum iron indices for HFE genotyping). Tests performed without meeting those prerequisites are considered investigational per the policy.

The policy’s evidence review found that certain inflammatory bowel disease (IBD) diagnostic and prognostic algorithmic tests (for example, Prometheus IBD sgi Diagnostic and similar algorithmic assays) currently have insufficient evidence in peer‑reviewed publications to demonstrate improved health outcomes compared with standard evaluation. As a result, these algorithmic/prognostic IBD tests lack demonstrated clinical utility and are considered investigational.

Because the evidence is insufficient to support actionably improved outcomes, the policy indicates that coverage for these algorithmic/prognostic assays is not supported and that claims may be denied when those tests are requested to guide diagnosis or prognosis in routine IBD care.

The policy update removed several procedure identifiers from the Policy Reference Table and the criteria. Specifically, PLA code 0203U and CPT codes 81356 and 86671 were removed; CPT code 88342 was also removed from the reference table and associated criteria. Providers should not rely on these removed codes when submitting requests under this policy and should reference the current Policy Reference Table for the correct CPT/PLA coding to use.

Inflammatory bowel disease diagnostic and prognostic algorithmic tests, including multicomponent or algorithmic serologic and molecular assays assigned codes such as 81479 and other listed CPTs, are considered investigational and not medically necessary for general diagnostic or prognostic use. The policy states these tests do not have sufficient evidence of clinical utility to support routine coverage and should only be considered when specific, covered clinical indications defined elsewhere in the policy are met.

For hereditary IBD panels, the policy limits medically necessary use to well‑defined, early‑onset or syndromic presentations (see criteria); multigene IBD testing outside those criteria is considered investigational.

Targeted HFE C282Y and H63D genotyping (CPT 81256) is supported to establish hereditary hemochromatosis only when there is biochemical evidence of iron overload (for example, elevated transferrin‑iron saturation and/or elevated serum ferritin).

Per the policy, HFE genotyping is investigational for all other indications, including general population screening or use in the absence of abnormal serum iron indices.

Professional society guidance and the policy evidence review recommend against routine serologic antibody testing (for example, pANCA/ASCA‑based algorithmic panels) to establish or rule out ulcerative colitis or Crohn’s disease. The ACG guidelines specifically state they recommend against serologic antibody testing to establish or rule out a diagnosis of UC, and the policy cites insufficient evidence for routine use of these serologic/algorithmic tests in IBD diagnosis or therapy decisions.

Accordingly, routine serologic antibody testing for UC or Crohn’s disease is not recommended and lacks demonstrated clinical utility per the policy.

Coding and Billing Codes

HLA‑DQ Genotyping CodesCPTCovered

81375	HLA-DQ genotyping (listed as common CPT for HLA-DQ Genotyping Analysis)
81376	HLA-DQ genotyping
81377	HLA-DQ genotyping
81382	HLA genotyping
81383	HLA genotyping

HFE Genotyping CodesCPTCovered

81256

HFE C282Y and H63D genotyping

Hereditary Pancreatitis Multigene Panel CodesCPTCovered

81222	Hereditary pancreatitis panel / single gene
81223	Hereditary pancreatitis panel / single gene
81404	Multigene panel
81405	Multigene panel
81479	Unlisted molecular pathology procedure (used for panels)

Hereditary IBD Panel CodesCPT

81479	Unlisted molecular pathology procedure (used for IBD panels/diagnostics)
81321	Presumed IBD panel-related code as listed
81406	Multigene panel
81407	Multigene panel

IBD Algorithmic / Prognostic Test CodesCPTNot Covered

81479	Diagnostic algorithmic tests (listed for IBD diagnostics) considered investigational
82397	Assay-related CPT listed in diagnostic algorithmic tests
83520	Assay-related CPT listed in diagnostic algorithmic tests
86140	Assay-related CPT listed in diagnostic algorithmic tests
88346	Surgical pathology CPT listed in algorithmic/prognostic tests
88350	Surgical pathology CPT listed in algorithmic/prognostic tests
81401	Prognostic molecular pathology procedure (listed as investigational for prognostic IBD tests)

Non‑Invasive Liver Fibrosis Serum Test CodesCPTCovered

0002M	Non‑invasive liver fibrosis serum test (code listed)
0003M	Non‑invasive liver fibrosis serum test (code listed)
84450	Assay (e.g., AST) referenced in FIB‑4 panel
84460	Assay (e.g., ALT) referenced in FIB‑4 panel
85049	Assay (e.g., platelet count) referenced in FIB‑4 panel
81517	Enhanced Liver Fibrosis (ELF) test (referenced)

Referenced CPT Codes (examples updated in reference table)CPT

81256

HFE (C282Y and H63D) genotyping (note: replaced prior code 81479 in reference table)

Codes removed from Policy Reference Tablemixed

0203U	PLA code (example test removed from Policy Reference Table)
81356	Genetic test code (removed from Policy Reference Table)
86671	Immunoassay/serologic code (removed from Policy Reference Table)
88342	Immunohistochemistry code (removed from Policy Reference Table)

Removed from Policy Reference TablemixedNot Covered

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

FIB-4 index threshold

FIB-4 index thresholdFIB-4 > 1.3

Action when exceededIf FIB-4 > 1.3, combine with additional NITs (serum and/or imaging) for staging per AGA/AACE guidance

RoleFirst-line, low-cost fibrosis risk stratification tool based on AST, ALT, platelet count, and age

Recurrent pancreatitis definition

DefinitionTwo or more separate, documented acute attacks of pancreatitis

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required for Listed Genetic and Fibrosis Tests

Prior authorization is required for the specific genetic and fibrosis tests listed in the policy. Providers must obtain PA before ordering these tests to avoid claim denials.

Affected tests include HLA-DQ genotyping for celiac disease, HFE C282Y/H63D genotyping (81256), hereditary pancreatitis multigene panels (81222, 81223, 81404, 81405, 81479), IBD algorithmic tests (81479, 82397, 83520, 86140, 88346, 88350), and non-invasive liver fibrosis serum tests (0002M, 0003M, 84450, 84460, 85049).
Claims referencing removed PLA and CPT codes (PLA 0203U, CPT 81356, CPT 86671) may be denied if submitted.
Ensure PA submission reflects updated coding (eg, 81256 for HFE genotyping) and that HLA DQA1/DQB1 genotyping has not been previously performed when requesting HLA testing for celiac disease.

Billing Rule

Updated Coding Affects Prior Authorization

Background and Rationale

Genetic testing has an established role in several non‑cancer gastroenterologic conditions when used to confirm or clarify diagnoses in appropriate clinical contexts. Examples include HLA‑DQ genotyping to help rule out celiac disease when serology or histology is inconclusive or when a gluten‑free diet was started prior to testing; targeted HFE genotyping (C282Y/H63D) after biochemical evidence of iron overload to confirm hereditary hemochromatosis; and multigene panels for hereditary pancreatitis or very early‑onset inflammatory bowel disease when specific clinical criteria are met.

The policy also incorporates non‑genetic serum testing in staged risk stratification for liver disease: FIB‑4 is recommended as a first‑line test, and if FIB‑4 > 1.3 the policy supports use of additional non‑invasive serum or imaging tests to further stage fibrosis. These targeted uses of genetic and non‑invasive tests are intended to improve diagnostic precision and inform management while limiting testing unsupported by current evidence.

Definitions and Key Terms

Close relatives

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, and first cousins

ScopeDefined as blood relatives on the same side of the family; used in family-history criteria for hereditary testing

Infantile‑onset IBD (Infantile‑IBD)

DefinitionOnset of clinical manifestations and/or diagnosis younger than 2 years of age

Policy Summary

PayerCentene

PolicyGenetic testing: gastroenterologic (non-cancerous) disorders — coverage criteria

Policy CodePolicy N/A

Change TypeMultiple material revisions (added fibrosis criteria; updated HFE and hereditary IBD criteria; removed codes)

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Exclusion of causesEpisodes must be unexplained after excluding anatomical anomalies, gallstones, alcohol, drugs, hyperlipidemia, trauma, infection, and other known causes

ContextUsed as a qualifying criterion for hereditary pancreatitis multigene panel coverage

Age thresholds for hereditary pancreatitis consideration

Childhood onset thresholdOnset of acute pancreatitis at age ≤18 years

Early chronic pancreatitis thresholdChronic pancreatitis onset before age 35 years without a history of heavy alcohol use

Coverage relevanceThese age thresholds qualify members for hereditary pancreatitis multigene panel testing when other criteria are met

Transferrin saturation (TS)

Transferrin saturation (TS) threshold>= 45%

Use prior to genotypingPractice guidance recommends confirming elevated TS before HFE genetic testing

ContextTS ≥45% (and/or elevated ferritin) triggers consideration of targeted HFE C282Y/H63D genotyping per ACG algorithm

FIB-4 score

FIB-4 trigger value> 1.3 (FIB-4 > 1.3)

Next steps if >1.3Combine with additional noninvasive tests (serum and/or imaging) for staging; consider biopsy if results indeterminate or discordant

PurposeUsed to stratify risk of advanced liver fibrosis in NAFLD/MASLD and guide further testing

Updated coding affects prior authorization and claim submission. Providers must use current CPT/PLA codes as reflected in the policy and not rely on removed codes.

Use CPT 81256 for HFE C282Y and H63D genotyping where applicable.
Do not submit claims using removed codes PLA 0203U, CPT 81356, or CPT 86671 — these were removed from the Policy Reference Table and criteria.
Verify CPT mappings for multigene panels (eg, 81222, 81223, 81404, 81405, 81479) and proprietary fibrosis test codes (0002M, 0003M) when requesting PA.

Denial Risk

Removed Codes and Prior Authorization — Do Not Use Removed Codes

Removed codes should not be used; submissions referencing them may be denied. Providers must update ordering and billing systems accordingly.

PLA 0203U, CPT 81356, and CPT 86671 have been removed from the Policy Reference Table and coverage criteria.
Claims submitted with removed codes are at risk for denial; refile with current codes or contact the payer before resubmission.

Step Therapy

Stepwise Risk Stratification for Liver Fibrosis

Stepwise risk stratification is required for evaluating liver fibrosis: begin with FIB-4 and, for scores >1.3, use additional noninvasive tests or imaging as recommended.

First-line: FIB-4 index (simple, low-cost) — proceed if FIB-4 > 1.3.
Second-line: Combine two or more noninvasive tests (serum biomarkers and/or imaging-based biomarkers) such as TE, MRE, ELF, or proprietary fibrosis biomarkers when FIB-4 > 1.3.
Consider liver biopsy when noninvasive test results are indeterminate, discordant, or conflict with other clinical findings.

Documentation Required

Required Clinical Documentation

Clinical documentation must support the medical necessity criteria listed in the policy. Include specific pre-test findings and note prior testing where required.

For HLA-DQ genotyping: document evaluation for celiac disease and one of the following — inconclusive serology, inconclusive histology, or initiation of a gluten-free diet prior to evaluation; confirm HLA DQA1/DQB1 genotyping has not been previously performed.
For HFE genotyping (81256): document abnormal serum iron indices (eg, elevated transferrin saturation ≥45% and/or elevated ferritin) and/or relevant family history or clinical signs of iron overload per ACG/GeneReviews guidance.
For hereditary pancreatitis panels: document personal history of pancreatitis and at least one qualifying criterion (eg, unexplained childhood acute pancreatitis, recurrent unexplained acute attacks, chronic pancreatitis of unknown cause with early onset, or a close relative with similar history); confirm panel includes required genes (PRSS1, SPINK1, CFTR, CTRC).
For noninvasive liver fibrosis tests: document presence of risk factors (NAFLD/MASLD, NASH, type 2 diabetes, obesity, abnormal LFTs, significant alcohol history) and prior FIB-4 testing with score >1.3.

Denial Risk

Investigational Tests and Denial Risk

Certain IBD algorithmic and prognostic tests and other listed investigational indications may be denied due to insufficient evidence of clinical utility.

Inflammatory bowel disease diagnostic and prognostic algorithmic tests (eg, Prometheus IBD sgi Diagnostic and related CPTs 81479, 82397, 83520, 86140, 88346, 88350) are considered investigational and may be denied.
Genetic testing for IBD via multigene panels is limited to specified early-onset or complex presentations; all other indications are investigational.
Tests lacking sufficient peer-reviewed evidence to improve health outcomes (eg, certain proprietary Prometheus tests) may be denied.

Documentation Required

Pre-test Biochemical and Family-history Documentation

Pre-test biochemical and family-history documentation expectations must be met for HFE testing and hereditary condition panels.

For HFE genotyping: document transferrin saturation and ferritin results; reference ACG suggested thresholds (TS ≥45% and/or elevated SF) and GeneReviews recommendations when submitting for PA.
For hereditary pancreatitis and hereditary IBD panels: provide phenotype details and relevant family history to support medical necessity per policy criteria.

Documentation Required

Updated Documentation Expectations

Updated documentation expectations reflect Evidence Review updates and policy clarifications; ensure prior testing is noted and that submitted panels match policy-required gene content.

Confirm HLA DQA1/DQB1 genotyping has not been previously performed before requesting HLA testing for celiac disease.
Ensure multigene panels for hereditary pancreatitis include at minimum PRSS1, SPINK1, CFTR, and CTRC as required by the policy.
When PA is requested, include prior test dates/results and rationale tying the requested test to the policy's listed medical necessity criteria.

Note

Provider Action Placeholder

Provider action placeholder.

Qualifying indication for infantile‑onset hereditary IBD panel testing

DistinctionConsidered more severe/early phenotype than VEO‑IBD

Very early onset IBD (VEO‑IBD)

DefinitionOnset of clinical manifestations and/or diagnosis younger than 6 years of age

UseQualifies as very early onset IBD (VEO‑IBD) for consideration of monogenic/hereditary IBD panel testing

Relation to infantile‑IBDIncludes infantile‑IBD (<2 years) as a subset of VEO‑IBD

FIB‑4

DefinitionA blood test estimating probability of advanced liver fibrosis based on AST, ALT, platelet count, and age

RoleRecommended as first-line, simple, low-cost assessment for fibrosis risk stratification in NAFLD/MASLD

Threshold linked to actionFIB-4 >1.3 prompts additional noninvasive tests per guideline-based stepwise approach

HFE C282Y and H63D Genotyping (definition)

DefinitionTargeted genotyping for common HFE variants p.C282Y and p.H63D

Recommended contextPerformed after confirming biochemical evidence of iron overload (eg, TS >=45% and/or elevated ferritin) per EMQN/ACG guidance

Screening stancePopulation screening for p.C282Y is not recommended; testing is targeted to those with clinical/biochemical suspicion or affected family members

Noninvasive Tests (NITs) / FIB-4

DefinitionSerum-based fibrosis prediction calculations (eg, FIB-4) and other noninvasive biomarkers used to assess risk of advanced liver fibrosis

Role in care pathwayUsed as first-line assessment (FIB-4) with additional NITs (serum and/or imaging) when FIB-4 >1.3 to stage fibrosis and guide biopsy decisions

ExamplesProprietary tests (FibroTest/FibroSure, ELF) and imaging elastography may be used as second-line confirmatory tests

MASLD

AliasMetabolic dysfunction-associated steatotic liver disease (MASLD)

ContextMASLD is used interchangeably with NAFLD in the policy criteria for noninvasive liver fibrosis serum testing

Coverage relevancePatients with MASLD/NAFLD are included among indications warranting NITs when FIB-4 >1.3

Requirement that HLA DQA1 and HLA-DQB1 genotyping has not been previously performed

RequirementHLA DQA1 and HLA-DQB1 genotyping analysis has not been previously performed for celiac HLA-DQ genotyping requests

PurposeEnsures HLA testing is not duplicated when used to rule out celiac disease after inconclusive serology/histology or prior gluten-free diet

DocumentationRequest should indicate that prior HLA-DQ genotyping (DQA1/DQB1) has not been performed