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Genetic Testing for Hereditary Pancreatitis

Policy Number: MP-590

ARCHIVED – Refer to AIM Genetic Testing Guidelines effective 3/1/20

Latest Review Date: February 2020

Category:  Laboratory   

Policy Grade:  D

POLICY:

Effective for dates of service on and after October 1, 2015:

Genetic testing for hereditary pancreatitis may be considered medically necessary in patients with pancreatitis when one or more of the following criteria are met:

  • Relatives known to carry variants associated with hereditary pancreatitis; OR
  • Idiopathic chronic pancreatitis or recurrent acute attacks of pancreatitis for which there is not identifiable cause when the onset of pancreatitis occurs before age 25; OR
  • An unexplained documented episode of pancreatitis as a child.

Genetic testing for hereditary pancreatitis in all other situations is considered not medically necessary and investigational.

Effective for dates of service prior to October 1, 2015:

Genetic testing for hereditary pancreatitis using serine protease 1 gene (PRSS1) may be considered medically necessary in patients with pancreatitis when one or more of the following criteria are met:

  • Relatives known to carry mutations associated with hereditary pancreatitis; OR
  • Idiopathic chronic pancreatitis or recurrent acute attacks of pancreatitis for which there is not identifiable cause when the onset of pancreatitis occurs before age 25; OR
  • An unexplained documented episode of pancreatitis as a child.

Genetic testing for hereditary pancreatitis in all other situations is considered not medically necessary and investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

In chronic pancreatitis (CP), recurrent attacks of acute pancreatitis evolve into a chronic inflammatory state with exocrine insufficiency, endocrine insufficiency manifested as diabetes mellitus, and increased risk for pancreatic cancer. Hereditary pancreatitis (HP) is a subset of CP defined clinically as a familial pattern of CP. Variants of several genes are associated with HP. Demonstration of a pathogenic variant in one or several of these genes can potentially be used to confirm the diagnosis of HP, provide information on prognosis and management, and/or determine the risk of CP in asymptomatic relatives of patients with HP.

Genetic Determinants

PRSS1 Variants

Whitcomb et al (2001) discovered that disease-associated variants of protease, serine, 1 (trypsin 1) (PRSS1) on chromosome 7q35 cause HP. PRSS1 encodes cationic trypsinogen. Gain of function variants of the PRSS1 gene cause HP by prematurely and excessively converting trypsinogen to trypsin, which then results in pancreatic autodigestion. Between 60% and 80% of people who have a disease-associated PRSS1-variant will experience pancreatitis in their lifetimes; 30% to 40% will develop CP. Most, but not all, people with a disease-associated variant of PRSS1 will have inherited it from one of their parents. The proportion of HP caused by a de novo variant of PRSS1 is unknown. In families with two or more affected individuals in two or more generations, genetic testing shows that most have a demonstrable disease-associated PRSS1-variant. In 60% to 100%, the variant is detected by sequencing technology (Sanger or next generation), and duplications of exons or the whole PRSS1 gene are seen in about 6%. Two PRSS1 point variants (p.Arg122His, p.Asn29Ile) are most common, accounting for 90% of disease-associated variants in affected individuals. Over 40 other PRSS1 sequence variants have been found, but their clinical significance is uncertain. Pathogenic PRSS1 variants are present in 10% or less of individuals with CP.

Targeted analysis of exons two and three, where the common disease-associated variants are found, or PRSS1 sequencing, are first-line tests, followed by duplication analysis. The general indications for PRSS1 testing and emphasis  on pre- and posttest genetic counseling have remained central features of reviews and guidelines. However, several other genes have emerged as significant contributors to both HP and CP. These include cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, serine peptidase inhibitor, Kazal Type 1 (SPINK1) gene, chymotrypsin C (CTRC) gene and claudin-2 (CLDN-2) gene.

CFTR Variants

Autosomal recessive variants of CFTR cause cystic fibrosis (CF), a chronic disease with onset in childhood that causes severe sinopulmonary disease and numerous gastrointestinal abnormalities. The signs and symptoms of CF can vary widely. On rare occasions, an affected individual may have mild pulmonary disease, pancreatic exocrine sufficiency, and may present with acute, recurrent acute, or CP. Individuals with heterozygous variants of the CFTR gene (CF carriers) have a three- to four-fold increased risk for CP. Individuals with two CFTR pathogenic variants (homozygotes or compound heterozygotes) will benefit from CFspecific evaluations, therapies, and genetic counseling.

SPINK Variants

The SPINK gene encodes a protein that binds to trypsin and thereby inhibits its activity. Variants in SPINK are not associated with acute pancreatitis but are found, primarily as modifiers, in acute recurrent pancreatitis and seem to promote the development of CP, including for individuals with compound heterozygous variants of the CFTR gene. Autosomal recessive familial pancreatitis may be caused by homozygous or compound heterozygous SPINK variants.

CTRC Variants

The CTRC gene is important for the degradation of trypsin and trypsinogen, and two variants (p.R254W and p.K247_R254del) are associated with increased risk for idiopathic CP (odds ratio [OR]= 4.6), alcoholic pancreatitis (OR=4.2), and tropical pancreatitis (OR=13.6). Tropical pancreatitis is a disease almost exclusively occurring in the setting of tropical climate and malnutrition.

CLDN2 Variants

The CLDN2 gene encodes a member of the claudin protein family, which acts as an integral membrane protein at tight junctions and has tissue-specific expression. Several single nucleotide variants in CLDN2 have been associated with CP.

KEY POINTS:

This policy was updated with literature reviews through December 9, 2019.

Summary of Evidence

For individuals who have chronic pancreatitis or recurrent acute pancreatitis who receive testing for genes associated with hereditary pancreatitis, the evidence includes cohort studies on variant detection rates and a systematic review. Relevant outcomes are test accuracy, symptoms, change in disease status, morbid events, and hospitalizations. There are studies on the detection rate of HP-associated genes in various populations. Few studies enroll patients with known HP; those doing so had reported detection rates for disease-associated variants of 52% and 62%, respectively. Other studies that tested patients with CP or ARP; the disease-associated variant detection rate varied widely across studies. There is a lack of direct evidence that, in patients with CP or ARP, management would change after genetic testing in a manner likely to improve health outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who are asymptomatic with family members with hereditary pancreatitis who receive testing for a known familial variant associated with hereditary pancreatitis, the evidence includes a very limited number of studies. Relevant outcomes are test accuracy, symptoms, change in disease status, morbid events, and hospitalizations. No direct evidence was identified that compared outcomes in patients tested for a familial variant compared with patients not tested for a familial variant. It is possible that at-risk relatives who are identified as having a familial variant may alter lifestyle factors such as diet, smoking, and alcohol use, and this may delay the onset or prevent CP. However, studies evaluating behavioral changes and impact on disease are lacking. The evidence is insufficient to determine the effects of the technology on health outcomes.

PRACTICE GUIDELINES AND POSITION STATEMENTS

American College of Gastroenterology

The American College of Gastroenterology’s 2013 guidelines on management of acute pancreatitis (AP) includes the following statement on genetic testing:

“genetic testing may be considered in young patients (<30 years old) if no cause [of AP] is evident and a family history of pancreatic disease is present (conditional recommendation, low quality of evidence).”

The American College of Gastroenterology 2015 Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes recommended genetic testing of patients with suspected familial pancreatic cancer to include analysis of BRCA1/2,CDKN2A, PALB2, and ATM. Evaluation for Peutz-Jeghers Syndrome, Lynch Syndrome, and HP-associated genes should be considered if personal and/or family history criteria are met for the syndrome.

American Pancreatic Association

In 2014, the American Pancreatic Association published Practice Guidelines in Chronic Pancreatitis: Evidence-Based Report on Diagnostic Guidelines. A classification guideline for the etiology of chronic pancreatitis includes genetic mutations in PRSS1, CFTR, SPINK1, and others.

American College of Medical Genetics and Genomics

The American College of Medical Genetics issued a policy statement on laboratory standards and guidelines for population-based cystic fibrosis (CF) carrier screening in 2001, which were updated in 2004 and reaffirmed in 2013. These guidelines provide recommendations about specific variant testing in CF, but did not specifically address genetic testing for suspected HP.

European Consensus Conference

A 2001, a European Consensus Conference developed guidelines for genetic testing of the PRSS1 gene, genetic counseling, and consent for genetic testing for HP.  The indications recommended for symptomatic patients included:

  • Recurrent (two or more separate, documented episodes with hyperamylasemia) attacks of acute pancreatitis for which there is no explanation
  • Unexplained chronic pancreatitis
  • A family history of pancreatitis in a first- or second-degree relative
  • Unexplained pancreatitis in a child that has required hospitalization

Predictive genetic testing, defined as genetic testing in an asymptomatic “at-risk” relative of an individual proven to have HP, was considered more complex. Candidates for predictive testing should be a first degree relative of an individual with a well-defined HP gene mutation [pathogenic variant], be over 16 years old and capable of making an independent and informed decision, and able to understand the (autosomal dominant) mode of inheritance and incomplete penetrance…….. of HP mutations….”

International Consensus Guidelines for Chronic Pancreatitis

In 2018, the working group for the International Consensus Guidelines for Chronic Pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group, and the European Pancreatic Club, published consensus statements on the diagnosis and management of early chronic pancreatitis. 38 It included the following recommendation:

“Genetic variants are important risk factors for Early CP and can add specificity to the likely etiology, but they are neither necessary nor sufficient to make a diagnosis. (Quality assessment: moderate; Recommendation: strong; Agreement: strong)”

International Study Group of Pediatric Pancreatitis

In 2017, the International Study Group of Pediatric Pancreatitis INSPPIRE (The International Study Group of Pediatric Pancreatitis: In search for a cuRE) consortium developed an expert consensus opinion on evaluation of children with acute recurrent and chronic pancreatitis.39 There was strong consensus that search for a genetic cause of ARP or CP should include PRSS1, SPINK1, CFTR and CTRC gene mutation testing.

American Society of Clinical Oncology

In 2018, the American Society of Clinical Oncology (ASCO) published “Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion”.  The ASCO reported that cancer-unaffected individuals should be offered genetic risk evaluation if they are: members of families with an identified pathogenic cancer susceptibility gene variant, from families that meet criteria for genetic evaluation for known hereditary syndromes that are linked to pancreatic cancer and, from families that meet criteria for familial pancreatic cancer. ASCO further considered what surveillance strategies should be used for individuals with predisposition to pancreatic ductal adenocarcinoma to screen for pancreatic and other cancers. Surveillance can be considered for individuals who are first-degree relatives of individuals with familial pancreatic cancer and/or individuals with a family history of pancreatic cancer who carry a pathogenic germline variant in genes associated with predisposition to pancreatic cancer.

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS

Not applicable.

KEY WORDS:

Hereditary Pancreatitis, PRSS1, SPINK1, CFTR, trypsin 1, CTRC, serine protease 1 gene, CLDN2, HP, Chronic Pancreatitis, Acute Recurrent Pancreatitis, ARP, Pancreatitis

APPROVED BY GOVERNING BODIES:

Testing for variants associated with HP is typically done by direct sequence analysis or next-generation sequencing (NGS). A number of laboratories offer testing for the relevant genes, either individually or as panels.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Genetic testing for hereditary pancreatitis is available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

CURRENT CODING: 

CPT Codes:

81401

Molecular pathology procedure, Level 2, (eg, 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat) - PRSS1 (protease, serine, 1 [trypsin 1]) (e.g., hereditary pancreatitis), common variants (e.g., N29I, A16V, R122H)

81404

Molecular pathology procedure, Level 5 (e.g., analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis) - PRSS1 (protease, serine, 1 [trypsin 1]) (eg, hereditary pancreatitis), full gene sequence , SPINK1 (serine peptidase inhibitor, Kazal type 1) (e.g., hereditary pancreatitis), full gene sequence

81405

Molecular pathology procedure, Level 6 (e.g. analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis - CTRC (chymotrypsin C) (e.g. hereditary pancreatitis), full gene sequence (Effective 01/01/2018)

81222

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; duplication/deletion variants

81223

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; CFTR full gene sequence

Testing for duplication/deletion variants for PRSS1 and SPINK1 would be reported with the unlisted molecular pathology code. There is no mention of CLDN2 testing in CPT, so the unlisted molecular pathology code would be reported for that testing.

Prior to 1/1/18, there was no mention of CTRC in CPT, so the unlisted molecular pathology code would be reported.  After 1/1/18, use the applicable CPT code.

81479

  Unlisted molecular pathology procedure

REFERENCES:

  1. Ambry Genetics. Pancreatitis Testing. www.ambrygen.com/tests/pancreatitis-testing. Accessed January, 2018.
  2. AmbryGenetics. PancNext. n.d.; www.ambrygen.com/clinician/genetic-testing/34/oncology/pancnext. Accessed January 9, 2018.
  3. Applebaum-Shapiro SE, Finch R, Pfutzer RH, et al. Hereditary pancreatitis in North America: the Pittsburgh- Midwest Multi-Center Pancreatic Study Group Study. Pancreatology. 2001; 1(5):439-443.
  4. Arup Laboratories LTD. Pancreatitis, Panel (CFTR, CTRC, PRSS1, SPINK1) Sequencing. ltd.aruplab.com/tests/pub/2010876.
  5. Ballard DD, Flueckiger JR, Fogel EL, et al. Evaluating Adults With Idiopathic Pancreatitis for Genetic Predisposition: Higher Prevalence of Abnormal Results With Use of Complete Gene Sequencing. Pancreas. Jan 2015; 44(1):116-121.
  6. Behrman SW, Fowler ES. Pathophysiology of Chronic Pancreatitis. Surg Clin N Am 87 (2007) 1309-1324.
  7. Bellin MD, Freeman ML, Gelrud A, et al. Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest. Pancreatology. Jan-Feb 2014; 14(1):27-35.
  8. Canto MI. Screening and surveillance approaches in familial pancreatic cancer. Gastrointest Endosc Clin N Am. Jul 2008; 18(3):535-553, x.
  9. Ceppa EP, Pitt HA, Hunter JL, et al. Hereditary pancreatitis: endoscopic and surgical management. J Gastrointest Surg. May 2013; 17(5):847-856; discussion 856-847.
  10. Chinnakotla S, Radosevich DM, Dunn TB, et al. Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis. J Am Coll Surg. Apr 2014; 218(4):530-543.
  11. Conwell DL, Lee LS, Yadav D et al. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 Nov;43(8).
  12. Culetto A, Bournet B, Haennig A, et al. Prospective evaluation of the aetiological profile of acute pancreatitis in young adult patients. Dig Liver Dis. Jul 2015; 47(7):584-589.
  13. Ellis I, Lerch MM, Whitcomb DC, et al. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology. 2001; 1(5):405-415.
  14. Fink EN, Kant JA, Whitcomb DC. Genetic counseling for nonsyndromic pancreatitis. Gastroenterol Clin North Am. Jun 2007; 36(2):325-333, ix.
  15. Gariepy CE, Heyman MB, Lowe ME, et al. Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group. J Pediatr Gastroenterol Nutr. Jan 2017;64(1):95-103.
  16. Gasiorowska A, Talar-Wojnarowska R, Czupryniak L, et al. The prevalence of cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type 1 (SPINK1) gene mutations in Polish patients with alcoholic and idiopathic chronic pancreatitis. Dig Dis Sci. Mar 2011; 56(3):894-901.
  17. Gemmel C, Eickhoff A, Helmstadter L, et al. Pancreatic cancer screening: state of the art. Expert Rev Gastroenterol Hepatol. Feb 2009; 3(1):89-96.
  18. Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med. Mar-Apr 2001; 3(2):149-154.
  19. Grody WW, Thompson BH, Gregg AR et al. ACMG position statement on prenatal/preconception expanded carrier screening. Genet. Med. 2013 Jun;15(6).
  20. Howes N, Lerch MM, Greenhalf W, et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol. Mar 2004; 2(3):252-261.
  21. Hu C, Wen L, Deng L, et al. The differential role of human cationic trypsinogen (PRSS1) p.R122H mutation in hereditary and nonhereditary chronic pancreatitis: a systematic review and meta-analysis. Gastroenterol Res Pract. Oct 8 2017; 2017:9505460.
  22. Joergensen MT, Brusgaard K, Cruger DG, et al. Genetic, epidemiological, and clinical aspects of hereditary pancreatitis: a population-based cohort study in Denmark. Am J Gastroenterol. Aug 2010; 105(8):1876-1883.
  23. Keiles S, Kammesheidt A. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. Oct 2006; 33(3):221-227.
  24. Koziel D, Gluszek S, Kowalik A, et al. Genetic mutations in SPINK1, CFTR, CTRC genes in acute pancreatitis. BMC Gastroenterol. Jun 23 2015; 15:70.
  25. Lowenfels AB, Maisonneuve P, DiMagno EP, et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst. Mar 19 1997; 89(6):442-446.
  26. Masson E, Chen JM, Audrezet MP, et al. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. PLoS One. 2013; 8(8):e73522.
  27. Morinville VD, Lowe ME, Elinoff BD, et al. Hereditary pancreatitis amlodipine trial: a pilot study of a calciumchannel blocker in hereditary pancreatitis. Pancreas. Nov 2007; 35(4):308-312.
  28. Mullhaupt B, Truninger K, Ammann R. Impact of etiology on the painful early stage of chronic pancreatitis: a long-term prospective study. Z Gastroenterol. Dec 2005; 43(12):1293-1301.
  29. Oruc N, et al. Angiotensin-converting enzyme gene DD genotype neither increases susceptibility to acute pancreatitis nor influences disease severity. HBP (Oxford) 2009; 11(1): 45-49.
  30. Paolini O, Hastier P, Buckley M, et al. The natural history of hereditary chronic pancreatitis: a study of 12 cases compared to chronic alcoholic pancreatitis. Pancreas. Oct 1998; 17(3):266-271.
  31. Poddar U, Yachha SK, Mathias A, et al. Genetic predisposition and its impact on natural history of idiopathic acute and acute recurrent pancreatitis in children. Dig Liver Dis. Apr 25 2015.
  32. Prevention Genetics. Chronic Pancreatitis NextGen Sequencing (NGS) Panel. 2014. www.preventiongenetics.com/clinical-dna-testing/test/chronic-pancreatitis-nextgen-sequencing-ngs-panel/2452/.
  33. Rai P, Sharma A, Gupta A, et al. Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci. May 21 2014.
  34. Rai P, Sharma A, Gupta A, et al. Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci. May 21 2014.
  35. Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series. Gut. Jan 2009; 58(1):97-103.
  36. Rosendahl J, Witt H, Szmola R, et al. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet. Jan 2008; 40(1):78-82.
  37. Saito N, Suzuki M, Sakurai Y, et al. Genetic analysis of Japanese children with acute recurrent and chronic pancreatitis. J Pediatr Gastroenterol Nutr. Oct 2016; 63(4):431-436.
  38. Schwarzenberg SJ, Bellin M, Husain SZ, et al. Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden. J Pediatr. Apr 2015; 166(4):890-896 e891.
  39. Solomon S, Whitcomb, D.C., LaRusch, J, et al. PRSS1-Related Hereditary Pancreatitis. GeneReviews 2012.
  40. Stoffel EM, McKernin SE, Brand R, et al. Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. J Clin Oncol. Jan 10 2019;37(2):153-164.
  41. Sultan M, Werlin S, Venkatasubramani N. Genetic prevalence and characteristics in children with recurrent pancreatitis. J Pediatr Gastroenterol Nutr. May 2012; 54(5):645-650.
  42. Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. Feb 2015;110(2):223-262; quiz 263.
  43. Teich N, Mossner J. Hereditary chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22(1):115-130.
  44. Tenner S, Baillie J, DeWitt J, et al. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. Sep 2013; 108(9):1400-1415; 1416.
  45. Truninger K, Kock J, Wirth HP, et al. Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis. Pancreas. Jan 2001; 22(1):18-23.
  46. Vue PM, McFann K, Narkewicz MR. Genetic mutations in pediatric pancreatitis. Pancreas. Aug 2016; 45(7):992-996.
  47. Wang W, Sun XT, Weng XL, et al. Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study. BMJ Open. 2013;3(9):e003150.
  48. Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med. Sep-Oct 2004; 6(5):387-391.
  49. Weiss FU, Hesselbarth N, Parniczky A, et al. Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. Pancreatology. Jun 1 2018.
  50. Werlin S, Konikoff FM, Halpern Z, et al. Genetic and electrophysiological characteristics of recurrent acute pancreatitis. J Pediatr Gastroenterol Nutr. May 2015; 60(5):675-679.
  51. Whitcomb DC, Shimosegawa T, Chari ST, et al. International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club. Pancreatology. May 21 2018.
  52. Whitcomb DC. Framework for interpretation of genetic variations in pancreatitis patients. Front Physiol. 2012; 3:440.
  53. Whitcomb DC. Value of genetic testing in the management of pancreatitis. Gut. Nov 2004; 53(11):1710-1717.
  54. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. Jun 2013; 144(6):1252-1261.
  55. Zou WB, Tang XY, Zhou DZ, et al. SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis. Clin Transl Gastroenterol. Nov 12 2018;9(11):204.

POLICY HISTORY:

Medical Policy Group, April 2011 (1): update to Policy, Key Points, Key Words and References for PRSS1

Medical Policy Group, December 2012 (3):  Coding Updates – added code 81404 and 81479

Medical Policy Panel, August 2013

Medical Policy Panel, November 2014

Medical Policy Group, January 2015 (3): Updated description for CPT code 81404

Medical Policy Group, February 2015 (3): Creation of individual policy with all references related to genetic testing for hereditary pancreatitis removed from medical policy #136; update to Description, Key Points, Governing Bodies, Key Words, Coding & References; no change to intent of policy statement; added “Genetic testing for hereditary pancreatitis in all other situations is considered not medically necessary investigational”

Medical Policy Panel, August 2015

Medical Policy Group, September 2015 (3): 2015 Updates to Description, Key Points, Key Words, Coding & References; Policy section updated to remove “using serine protease 1 gene (PRSS1)” from the coverage statement as testing for multiple mutations is allowed based on criteria

Medical Policy Group, October 2015

Available for comment October 2 through November 16, 2015

Medical Policy Group, November 2015: 2016 Annual Coding Update. Verified coding.

Medical Policy Panel, February 2017

Medical Policy Group, February 2017 (3): 2017 Updates to Description, Key Points & References; Removed strikethrough policy information from last update; No change to policy statement intent.

Medical Policy Panel, February 2018

Medical Policy Group, March 2018 (4): Updates to Description, Key Points, Coding and References. No change to policy statement.

Medical Policy Panel, February 2019

Medical Policy Group, February 2019 (9): Updates to Description, Key Points, and References. Added key words: HP, Chronic Pancreatitis, Acute Recurrent Pancreatitis, ARP, Pancreatitis. No change to policy statement.

Medical Policy Panel, February 2020

Medical Policy Group, February 2020 (9): Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

 

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.