CurrentArizona Complete HealthPolicy N/A

Concert Genetic Testing: Gastroenterology(PDF)

Defines medical necessity criteria for genetic and blood-based noninvasive tests for non-cancerous gastroenterologic conditions (e.g., hereditary hemochromatosis, hereditary pancreatitis, IBD/Crohn's disease, and noninvasive liver fibrosis tests), lists example tests and billing codes, references guideline-based rationale, and provides definitions and revision history. This is part 1 of 2 of the policy.

Policy Summary

PayerArizona Complete Health

PolicyConcert Genetic Testing: Gastroenterology(PDF)

Policy CodePolicy N/A

Change TypeMultiple revisions and additions (material)

Effective Date

Next Review Date

Key ActionDocument required clinical findings per criteria (e.g., abnormal iron studies or first-degree family history for HFE genotyping; age/onset and qualifying features for hereditary IBD panels; FIB-4 thresholds and test interval for noninvasive liver tests) when requesting coverage.

SourceLink

POLICY UPDATE CHANGES

Updated HFE panel title to 'HFE C282Y and H63D Genotyping' and added first-degree relative criterion; removed broader sequencing statement.

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

Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel Tests age and criteria revised to align with updated guidelines.

MCM6 Targeted Variant Analysis criteria retired due to low order and claim volume.

Changed age at diagnosis for Crohn's disease in Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel Tests to align with updated guidelines.

Retired MCM6 Targeted Variant Analysis criteria set due to low order volume.

Moved Known Familial Variant Analysis criteria to 'Genetic Testing: General Approach to Genetic and Molecular Testing' for consolidation.

Created new Non-Invasive Liver Fibrosis Serum Tests (Blood-based Noninvasive Liver Disease Algorithmic Tests) criteria and moved FibroSure tests into this category.

Added HLA-DQA1 and HLA-DQB1 prior testing requirement to HLA-DQ Genotyping Analysis criteria.

Removed CPT 88342, PLA 0203U, CPT 81356 and CPT 86671 from Policy Reference Table and criteria.

Updated background, rationale, coding, reference table, and references; performed multiple evidence reviews (dates noted).

7Key covered gene/panel indications described

4Tests/sections labeled 'not supported' (insufficient evidence)

23Example CPT/HCPCS/ICD-10 codes listed

4CPT/PLA codes removed

1New noninvasive liver fibrosis criteria created

Coverage Summary

This policy (part 1 of 2) defines medical necessity criteria for genetic and blood-based noninvasive tests for non-cancerous gastroenterologic conditions and aligns coverage with multiple professional guidelines (e.g., ACG, AASLD, EASL, EMQN, GeneReviews, British/European pediatric gastroenterology guidance). It addresses testing categories including HFE C282Y and H63D genotyping for hereditary hemochromatosis, hereditary pancreatitis multigene panels, hereditary IBD/Crohn's multigene panels, IBD diagnostic and prognostic algorithmic tests, and blood-based noninvasive liver fibrosis (MASLD/NAFLD) algorithmic tests.

The document reflects a mixed coverage stance: it specifies medically necessary indications for select genetic and serum-based tests while noting tests or uses that are not supported by current evidence. The policy emphasizes pre- and post-test genetic counseling and consolidates known-familial variant criteria into a general genetic testing policy; new noninvasive liver fibrosis serum test criteria were also added.

Quick facts and thresholds

FIB-4 index thresholds>= 1.3 for individuals <65 years; >= 2.0 for individuals >=65 years (intermediate/high risk); <1.3 for <65 and <2.0 for >=65 considered low-risk

Key covered gene/panel indications7

Sections labeled 'not supported' (insufficient evidence)4

Policy change noteNew non-invasive liver fibrosis criteria created

Medical-Necessity Criteria

HFE C282Y and H63D Genotyping - Medically Necessary

HFE C282Y and H63D genotyping to establish a diagnosis of hereditary hemochromatosis is considered medically necessary when:

ANY of the following

The member/enrollee has abnormal serum iron indices (e.g., elevated serum transferrin-iron saturation and/or elevated serum ferritin concentration, indicating iron overload).
The member/enrollee has a first-degree relative with a diagnosis of hereditary hemochromatosis.

ALL of the following

Not supported indication: Current evidence does not support HFE C282Y and H63D genotyping to establish a diagnosis of hereditary hemochromatosis for all other indications, including general population screening for hereditary hemochromatosis.

Not Supported / Removed Tests

The policy explicitly states that Prometheus IBD diagnostic and prognostic algorithmic tests (example: Prometheus IBD sgi Diagnostic and Prometheus Crohn's Prognostic) are not supported by current evidence for all indications. Additionally, the policy notes removal of specific CPT/PLA codes from the Policy Reference Table and criteria: 88342, 0203U, 81356, and 86671 (listed under the 'Removed from Policy Reference Table / Criteria' code group).

Summary of Policy Revisions and Criteria Changes

Revisions and specific criteria updates (narrative; individual policies referenced were changed as follows):

Inflammatory Bowel Disease / Crohn's Disease Panel Tests: changed age at diagnosis for Crohn's disease to align with updated guidelines; Diagnostic Algorithmic Tests: added term 'Crohn's Disease' to criterion I and added phrase 'for all indications'; Prognostic Algorithmic Tests: evidence review update performed; removed duplicate example tests from Policy Reference Table; CPT code 88342 removed from Policy Reference Table and criteria; PLA code 0203U and CPT codes 81356 and 86671 removed from Policy Reference Table and criteria.

MCM6 Targeted Variant Analysis: retired criteria set based on rarity of testing (low order volume).

Coding

HFE C282Y and H63D Genotyping - example billing codesCPT|ICD-10

81256	HFE C282Y and H63D genotyping (example listed elsewhere as related to hereditary hemochromatosis)
E83.110	Iron overload, unspecified (example related ICD-10 code listed)
E83.118	Other hemochromatosis (example listed)
E83.119	Hemochromatosis, unspecified (example listed)
R79.0	Abnormal level of other serum enzymes (example listed)
E83.19	Other disorders of iron metabolism (example listed)
R16.0	Hepatomegaly (example listed)

Hereditary Pancreatitis Multigene Panel - example billing codesCPT|ICD-10

81222	PRSS1 single gene testing (example listed)
81223	SPINK1 gene testing (example listed)
81404	Targeted gene panel (example listed)
81405	Targeted large panel (example listed)
81479	Unlisted molecular pathology procedure (example listed)
K85.0-K85.9	Acute pancreatitis ICD-10 range (example listed)
K86.1	Other chronic pancreatitis (example listed)
Z83.79	Family history of other specified diseases and conditions (example listed)

Inflammatory Bowel Disease / Crohn's Disease Diagnostic Algorithmic Tests - example billing codesCPT|ICD-10

81479	Unlisted molecular pathology procedure (example listed)
82397	Inflammatory markers (example listed)
83520	Serum proteins testing (example listed)
86140	Assay for autoantibodies (example listed)
88346	Immunohistochemistry (example listed)
88350	Microscopic examination single specimen (example listed)
K50-K52	Crohn's and other noninfective gastroenteritis and colitis ICD-10 range (example listed)

Inflammatory Bowel Disease / Crohn's Disease Prognostic Algorithmic Tests - example billing codesCPT|HCPCS|ICD-10

81401	Targeted genomic sequence analysis panel (example listed)
83520	Serum proteins testing (example listed)
88346	Immunohistochemistry (example listed)
88350	Microscopic examination single specimen (example listed)
0203U	Proprietary prognostic test (Prometheus Crohn's Prognostic or similar - example listed)
K50-K52	Crohn's and other noninfective gastroenteritis and colitis ICD-10 range (example listed)

Hereditary Inflammatory Bowel Disease / Crohn's - example billing codesCPT|ICD-10

81321	Whole exome sequencing or multigene panel code (example listed)
81406	Large multi-gene sequencing panel (example listed)
81407	Another large panel code (example listed)
81479	Unlisted molecular pathology procedure (example listed)
K50-K52	Crohn's and other noninfective gastroenteritis and colitis ICD-10 range (example listed)

Blood-based Noninvasive Liver Disease Algorithmic Tests - example billing codesCPT|HCPCS|ICD-10|HCPCS

81596	FibroTest/FibroSure (BioPredictive S.A.S.)
81517	Enhanced Liver Fibrosis (ELF) Test (Siemens Healthcare Diagnostics)
0003M	NASH FibroSURE - proprietary code (LabCorp) (example listed)
K76.0	Fatty (change of) liver, not elsewhere classified (example listed ICD-10)
R94.5	Abnormal results of liver function studies (example listed ICD-10)

Removed from Policy Reference Table / CriteriaCPT|PLANot Covered

88342	Removed from Policy Reference Table and criteria
0203U	PLA code removed from Policy Reference Table and criteria
81356	CPT code removed from Policy Reference Table and criteria
86671	CPT code removed from Policy Reference Table and criteria

Provider Actions and Documentation Requirements

Documentation Required

Document abnormal iron studies or family history for HFE genotyping

HFE C282Y and H63D genotyping requires documentation of abnormal iron studies indicating iron overload (e.g., elevated transferrin‑iron saturation and/or elevated serum ferritin) or documentation of a first‑degree relative with hereditary hemochromatosis.

81256

Documentation Required

Document pancreatitis history for hereditary pancreatitis panels

Hereditary pancreatitis multigene panel coverage requires documentation of a personal history of pancreatitis plus at least one qualifying feature such as unexplained childhood acute pancreatitis, recurrent (≥2) unexplained acute attacks, chronic unexplained pancreatitis with onset <35 without heavy alcohol use, or a close relative with similar pancreatitis history.

Background and Evidence

Background: This policy aligns coverage for genetic testing of non-cancer gastroenterologic conditions with professional society guidelines (ACG, AASLD, EASL, EMQN, GeneReviews, British/European pediatric gastroenterology). Pre- and post-test genetic counseling is strongly advised to facilitate informed decision-making and management of incidental findings.

Operational updates consolidate known-familial variant criteria into a general genetic testing policy, clarify terminology (replacing 'mutation' with 'variant'), and add criteria for blood-based noninvasive liver fibrosis serum tests (e.g., FibroSure, ELF) to align coverage with guideline-recommended risk stratification.

Evidence / Guideline	Summary/Conclusion
Concert Evidence Review - Prometheus IBD sgi Diagnostic (Published 07/01/2024)	Insufficient evidence of clinical utility to improve health outcomes; diagnostic algorithmic tests like Prometheus IBD sgi Diagnostic have INSUFFICIENT EVIDENCE versus standard care.
Concert Evidence Review - Prometheus Crohn's Prognostic (Published 07/01/2024)	Insufficient evidence of clinical utility to improve health outcomes; Prometheus Crohn's Prognostic test has INSUFFICIENT EVIDENCE to improve outcomes compared to standard care.
Guideline - ACG	ACG guidelines support confirming transferrin saturation before HFE testing and recommend using FIB-4 as a first-line test for NAFLD; they do not support routine serologic testing for IBD diagnosis.
Guideline - AASLD (2024)	AASLD suggests sequential combinations of blood-based markers may perform better than single tests for fibrosis in HCV and NAFLD; generally recommends starting with simple tests (FIB-4 or NFS) over proprietary tests.
Guideline - EASL (2021) / AGA (2023 clinical practice update)	EASL and AGA endorse noninvasive testing strategies (FIB-4 first-line) and reserve specialized blood tests (ELF, FibroTest/FibroSure) for secondary assessment when elastography is unavailable; sequential testing improves risk stratification.
Guideline incorporations / Society guidelines (EMQN, GeneReviews, British/European pediatric gastroenterology)	EMQN recommends testing p.C282Y and optionally p.H63D for HFE; GeneReviews and pediatric society guidelines support genomic testing in infantile/VEO-IBD and outline features prompting multigene testing.
Policy Evidence Summary / Guideline-based revisions	Policy revisions incorporate Concert evidence reviews (7/1/2024) and society guidelines (ACG, AASLD, EASL, EMQN) to define when HFE genotyping, pancreatitis panels, hereditary IBD panels, and noninvasive liver fibrosis tests are medically necessary versus not supported.

Definitions

Close relativesFirst-, second-, and third-degree blood relatives on the same side of the family (first-degree: parents, siblings, children; second-degree: grandparents, aunts/uncles, nieces/nephews, grandchildren, half siblings; third-degree: great grandparents, great aunts/uncles, great grandchildren, first cousins).

Infantile-onset IBDClinical manifestations and/or diagnosis when younger than 2 years of age.

VEO-IBD (Very early onset IBD)Clinical manifestations and/or diagnosis when younger than 6 years of age.

Medicare Determinations

Name	Number	Type	Effective Date
Hepatic (Liver) Function Panel	L33907	LCD

Revision History

2024-03-23revisedLatest

Updated HFE panel title to 'HFE C282Y and H63D Genotyping'; added first-degree relative criterion and removed broader sequencing statement.

2024-03-23added

Created Non-Invasive Liver Fibrosis Serum Tests (Blood-based Noninvasive Liver Disease Algorithmic Tests) criteria and moved FibroSure and other proprietary tests into this new category.

2024-03-23revised

Revised Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel Tests age and related criteria (changed age at diagnosis thresholds and added specific additional testing criteria such as family history, consanguinity, infections, autoimmune features, malignancy, intestinal atresias, etc.) to align with updated guidelines.

Policy Summary

PayerArizona Complete Health

PolicyConcert Genetic Testing: Gastroenterology(PDF)

Policy CodePolicy N/A

Change TypeMultiple revisions and additions (material)

Effective Date

Next Review Date

SourceLink

On This Page

HFE C282Y and H63D Genotyping - Not Supported

Not supported indication

Current evidence does not support HFE C282Y and H63D genotyping to establish a diagnosis of hereditary hemochromatosis for all other indications, including general population screening for hereditary hemochromatosis.

Hereditary Pancreatitis Multigene Panel - Medically Necessary

Panel analysis is medically necessary when:

ALL of the following

The member/enrollee has a personal history of pancreatitis.
AND meets at least one of
- Unexplained episode of acute pancreatitis in childhood (18 years or younger).
- Recurrent (two or more separate, documented) acute attacks of pancreatitis for which there is no explanation (i.e., anatomical anomalies, ampullary or main pancreatic strictures, trauma, viral infection, gallstones, alcohol, drugs, hyperlipidemia, etc.).
- Chronic pancreatitis of unknown cause, particularly with onset before age 35 years without a history of heavy alcohol use.
- At least one close relative with recurrent acute pancreatitis, chronic pancreatitis of unknown cause, or childhood pancreatitis of unknown cause.
The panel includes, at a minimum, the following genes: PRSS1, SPINK1, CFTR, and CTRC.

Hereditary Pancreatitis Multigene Panel - Not Supported

Not supported indication

Current evidence does not support hereditary pancreatitis multigene panel analysis to establish a diagnosis of hereditary pancreatitis for all other indications.

Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel - Medically Necessary

Genetic testing via multigene panel is medically necessary when:

ANY of the following

The member/enrollee was diagnosed with infantile-onset inflammatory bowel disease (Infantile-IBD) before age 2 years.
The member/enrollee was diagnosed with very early onset inflammatory bowel disease (VEO-IBD) before age 6 years, AND at least one of the following: congenital multiple intestinal atresias; congenital diarrhea; diagnosis of malignancy under age 25; features of an inborn error of immunity such as susceptibility to infections; complex autoimmune features; a close relative meeting any of the above criteria; undergoing stem cell transplant; or a history of multiple intestinal resections.

Hereditary Inflammatory Bowel Disease / Crohn's Disease Panel - Not Supported

Not supported indication

Current evidence does not support genetic testing for inflammatory bowel disease, including Crohn's disease, via a multigene panel for all other indications.

Inflammatory Bowel Disease / Crohn's Disease Diagnostic Algorithmic Tests

Coverage stance

Current evidence does not support inflammatory bowel disease / Crohn's disease diagnostic algorithmic tests (e.g., Prometheus IBD sgi Diagnostic) for all indications.

Inflammatory Bowel Disease / Crohn's Disease Prognostic Algorithmic Tests

Coverage stance

Current evidence does not support inflammatory bowel disease / Crohn's disease prognostic algorithmic tests (e.g., Prometheus Crohn's Prognostic) for all indications.

Blood-based Noninvasive Liver Disease Algorithmic Tests - Medically Necessary

These tests are considered medically necessary when ALL criteria below are met:

The member/enrollee does NOT have a confirmed diagnosis of liver fibrosis.

This test has NOT been performed within the last year.

AND member meets BOTH 1 and 2

1. One of the following liver disease indications
- Untreated chronic hepatitis C virus (HCV) infection.
- Suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD).
2. One of the following risk/fibrosis criteria
- FIB-4 index threshold: An intermediate or high-risk Fibrosis-4 index (FIB-4) score (>= 1.3 for individuals younger than 65 years; >= 2.0 for individuals 65 years or older).>= 1.3 for individuals <65 years; >= 2.0 for individuals >=65 years
- A low-risk Fibrosis-4 index (FIB-4) score (less than 1.3 for individuals younger than 65 years; less than 2.0 for individuals 65 years or older), AND either prediabetes/type 2 diabetes or two or more features of metabolic syndrome (e.g., abdominal obesity, high blood pressure, high triglyceride levels).<1.3 for <65 years; <2.0 for >=65 years

Blood-based Noninvasive Liver Disease Algorithmic Tests - Not Supported

Not supported indication

Current evidence does not support blood-based noninvasive liver disease algorithmic tests to rule out liver fibrosis for all other indications, including but not limited to alcohol-associated steatotic liver disease.

Known Familial Variant Analysis for Gastroenterologic Conditions: criteria moved to separate policy 'Genetic Testing: General Approach to Genetic and Molecular Testing' to consolidate known familial variant test criteria.

Non-Invasive Liver Fibrosis Serum Tests: new criteria created (also referred to as Blood-based Noninvasive Liver Disease Algorithmic Tests); FibroSure tests moved into this new coverage criteria; added note 'also known as metabolic dysfunction-associated steatotic liver disease (MASLD)'.

HLA-DQ Genotyping Analysis (Celiac Disease): added prior testing requirement that 'HLA-DQA1 and HLA-DQB1 genotyping analysis has not been previously performed.'; updated allele naming to 'HLA-DQA1 and HLA-DQB1'.

Hereditary Pancreatitis Multigene Panel: updated GeneReviews copyright dates in Reference list.

Other Not Covered Gastroenterologic Disorders Tests: FibroSure moved to new Non-invasive Liver Fibrosis Serum Tests; remaining tests moved to General Genetic and Molecular Testing policy for consolidation.

HFE C282Y and H63D Genotyping: minor grammar/formatting changes to investigational section and policy reference table; streamlined background and rationale.

General: Minor rewording for clarity throughout; coding, reference-table, background and references updated; multiple evidence review updates performed (references to Evidence Review PDFs dated 7/1/2024).

Documentation Required

Document age of onset and qualifying features for hereditary IBD panels

Hereditary IBD/Crohn's multigene testing requires documentation of infantile‑onset IBD (<2 years) or very early‑onset IBD (<6 years) plus at least one additional qualifying feature (e.g., congenital multiple intestinal atresias, congenital diarrhea, malignancy <25, inborn error of immunity features, complex autoimmune features, a close relative meeting criteria, stem cell transplant candidate, or history of multiple intestinal resections).

81321
81406
81407
81479

Documentation Required

FIB-4 and test interval requirements for noninvasive liver tests

Blood‑based noninvasive liver disease algorithmic tests are allowed only when there is no confirmed liver fibrosis, the same test has not been performed within the past year, a qualifying liver indication is documented (untreated chronic HCV or suspected/confirmed MASLD), and the FIB‑4 score meets the policy thresholds; for low FIB‑4 with metabolic risk, document prediabetes/type 2 diabetes or ≥2 metabolic syndrome features.

81517
81596
0003M
Requirements: The member does NOT have a confirmed diagnosis of liver fibrosis.
Requirements: The test has NOT been performed within the last year.
Requirements: Document liver disease indication (untreated chronic HCV infection OR suspected/confirmed MASLD).
Requirements: FIB-4 thresholds — >=1.3 for individuals <65 years; >=2.0 for individuals >=65 years (intermediate/high risk); <1.3 for <65 and <2.0 for >=65 considered low risk.
Requirements: For low FIB-4 with metabolic risk, document prediabetes/type 2 diabetes OR two or more features of metabolic syndrome.

Documentation Required

Prior testing requirement for HLA-DQ genotyping

HLA‑DQA1 and HLA‑DQB1 genotyping analysis must not have been previously performed for the added coverage criterion to apply.

HLA‑DQA1/DQB1 genotyping must not have been previously performed.

Note

Consolidation of known familial variant testing

Known familial variant analysis criteria for gastroenterologic conditions have been moved to the separate policy 'Genetic Testing: General Approach to Genetic and Molecular Testing'; providers should reference that policy for preauthorization and documentation requirements for known familial variant testing.

FIB-4 indexBlood test that calculates the probability of advanced liver fibrosis based on AST, ALT, platelets, and age; thresholds defined in policy.

NAFLD Fibrosis Score (NFS)Blood test that calculates the probability of advanced liver fibrosis based on AST, ALT, albumin, age, BMI, platelet count, and presence of impaired fasting glucose or diabetes.

2024-04removed

Retired MCM6 Targeted Variant Analysis criteria set due to low order and claim volume.

2024-03-23revised

Moved Known Familial Variant Analysis criteria to the 'Genetic Testing: General Approach to Genetic and Molecular Testing' policy for consolidation of known-familial variant test criteria.

2024-03-23added

Added HLA-DQA1 and HLA-DQB1 prior testing requirement to HLA-DQ Genotyping Analysis criteria and standardized allele naming.

2024-07-01revised

Removed CPT 88342, PLA 0203U, CPT 81356 and CPT 86671 from Policy Reference Table and criteria related to IBD/Crohn's diagnostic and prognostic algorithmic tests following evidence review updates.