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Pancreatic, hepatobiliary, and gastrointestinal manifestations of children with cystic fibrosis: A 10-year experience from a tertiary care center in southern India

Abstract

Objectives

To describe the demography and spectrum of pancreatic, hepatobiliary, and gastrointestinal (GI) manifestations in children with cystic fibrosis (CF) from the Indian subcontinent.

Methods

In this retrospective study, relevant information from the database of all children with CF below 18 years of age was collected and analyzed.

Results

Among the total 109 children, 58 (53%) were from the southern states of India. The most common manifestation was pancreatic insufficiency (PI) in 85 (83%) children. Those with PI presented at an earlier age (1.8 vs. 6.9 years). Cirrhosis with portal hypertension was documented in only one patient and meconium ileus in three (2.8%). There was significant malnutrition in the PI cohort with a mean weight-for-age Z-score of − 3.17 ± 1.79 at diagnosis. Twenty-one (19%) patients had died during the follow-up and 18 (90%) of them had PI. There was no difference in the prevalence of selected pulmonary manifestations in the PI and pancreatic sufficient (PS) groups. Among children with PI, 78 were screened for ΔF508 mutation, 16 (21%) were homozygous, and 17 (22%) were heterozygous. In the PS group, only 2 (14%) were heterozygous for ΔF508 mutation. The median duration of follow-up of the patients was 1.8 (1.5) years.

Conclusion

PI is the most common GI manifestation of children with CF and is associated with severe malnutrition and poor outcome. Timely identification and management of the comorbidities involving the digestive system are essential for better growth and quality of life in these children.

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References

  1. Voter KZ, Ren CL. Diagnosis of cystic fibrosis. Clinic Rev Allerg Immunol. 2008;35:100–6.

    CAS  Article  Google Scholar 

  2. Li L, Somerset S. Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy. Dig Liver Dis. 2014;46:865–74.

    Article  Google Scholar 

  3. Wilschanski M, Durie PR. Patterns of GI disease in adulthood associated with mutations in the CFTR gene. Gut. 2007;56:1153–63.

    CAS  Article  Google Scholar 

  4. Ahmed N, Corey M, Forstner G, et al. Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas. Gut. 2003;52:1159–64.

    CAS  Article  Google Scholar 

  5. Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in cystic fibrosis. J Cyst Fibros. 2017;16:S70–8.

    Article  Google Scholar 

  6. Freeman AJ, Ooi CY. Pancreatitis and pancreatic cystosis in cystic fibrosis. J Cyst Fibros. 2017;16:S79-86.

    Article  Google Scholar 

  7. Sathe MN, Freeman AJ. Gastrointestinal, pancreatic, and hepatobiliary manifestations of cystic fibrosis. Pediatr Clin N Am. 2016;63:679–98.

    Article  Google Scholar 

  8. Nascimento FS, Sena NA, Ferreira TDA, Marques CDF, Silva LR, Souza EL. Hepatobiliary disease in children and adolescents with cystic fibrosis. J Pediatr (Rio J). 2018;94:504–10.

  9. Sabharwal S. Gastrointestinal manifestations of cystic fibrosis. Gastroenterol Hepatol (N Y). 2016;12:43–7.

    Google Scholar 

  10. Sathe M, Houwen R. Meconium ileus in cystic fibrosis. J Cyst Fibros. 2017;16:S32–9.

    Article  Google Scholar 

  11. van der Doef HPJ, Kokke FTM, van der Ent CK, Houwen RHJ. Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation. Curr Gastroenterol Rep. 2011;13:265–70.

    Article  Google Scholar 

  12. Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. J Pediatr. 1995;127:681–4.

    CAS  Article  Google Scholar 

  13. Lopes-Pacheco M. CFTR Modulators: the changing face of cystic fibrosis in the era of precision medicine. Front Pharmacol. 2019;10:1662.

    CAS  Article  Google Scholar 

  14. Kabra SK, Kabra M, Lodha R, et al. Clinical profile and frequency of delta f508 mutation in Indian children with cystic fibrosis. Indian Pediatr. 2003;40:612–9.

    CAS  PubMed  Google Scholar 

  15. Debray D, Kelly D, Houwen R, Strandvik B, Colombo C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros. 2011;10 Suppl 2:S29–36.

  16. Indian Academy of Pediatrics Growth Charts Committee, Khadilkar V, Yadav S, et al. Revised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian children. Indian Pediatr. 2015;52:47–55.

  17. Moran A, Pillay K, Becker D, Granados A, Hameed S, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes. 2018;19 Suppl 27:64–74.

    Article  Google Scholar 

  18. Patel AR, Patel AR, Singh S, Singh S, Khawaja I. Diagnosing allergic bronchopulmonary aspergillosis: a review. Cureus. 2019;11:e4550.

    PubMed  PubMed Central  Google Scholar 

  19. Ivanov M, Matsvay A, Glazova O, et al. Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis. BMC Med Genomics. 2018;11 Suppl 1:13.

    Article  Google Scholar 

  20. Indika NLR, Vidanapathirana DM, Dilanthi HW, Kularatnam GAM, Chandrasiri NDPD, Jasinge E. Phenotypic spectrum and genetic heterogeneity of cystic fibrosis in Sri Lanka. BMC Med Genet. 2019;20:89.

    Article  Google Scholar 

  21. Lamireau T, Monnereau S, Martin S, Marcotte J-E, Winnock M, Alvarez F. Epidemiology of liver disease in cystic fibrosis: a longitudinal study. J Hepatol. 2004;41:920–5.

    Article  Google Scholar 

  22. Ahuja AS, Kabra SK. Cystic fibrosis: Indian experience. Indian Pediatr. 2002;39:813–8.

    CAS  PubMed  Google Scholar 

  23. Turck D, Braegger CP, Colombo C, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr. 2016;35:557–77.

    Article  Google Scholar 

  24. Steinkamp G, Wiedemann B. Relationship between nutritional status and lung function in cystic fibrosis: cross sectional and longitudinal analyses from the German CF quality assurance (CFQA) project. Thorax. 2002;57:596–601.

    CAS  Article  Google Scholar 

  25. Ferrari M, Cremonesi L. Genotype-phenotype correlation in cystic fibrosis patients. Ann Biol Clin (Paris). 1996;54:235–41.

    CAS  Google Scholar 

  26. Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PSN. Characterisation of mutations and genotype–phenotype correlation in cystic fibrosis: experience from India. J Cyst Fibros. 2008;7:110–5.

    CAS  Article  Google Scholar 

  27. Kabra SK, Kabra M, Lodha R, Shastri S. Cystic fibrosis in India. Pediatr Pulmonol. 2007;42:1087–94.

    CAS  Article  Google Scholar 

  28. Kobelska-Dubiel N, Klincewicz B, Cichy W. Liver disease in cystic fibrosis. Prz Gastroenterol. 2014;9:136–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kayani K, Mohammed R, Mohiaddin H. Cystic fibrosis-related diabetes. Front Endocrinol (Lausanne). 2018;9:20.

    Article  Google Scholar 

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Acknowledgements

1. Department of Medical Genetics of Christian Medical College, Vellore, for providing the facility for CFTR genetic testing.

2. Cystic Fibrosis Foundation (CFF), United States of America (USA), for providing grant which was used for CFTR mutation analysis and confirmation of diagnosis.

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Authors and Affiliations

Authors

Contributions

Conceptualized and designed the study, collected and analyzed data, reviewed literature, and prepared initial draft of the manuscript: L.T., M.K., A.P.L., S.V. Data analysis and manuscript preparation: G.R., S.V. All authors critically revised and approved the final version of the manuscript.

Corresponding author

Correspondence to B. Arul Premanand Lionel.

Ethics declarations

Conflict of interest

LT, MK, BAPL, SV, and GR declare that they have no conflict of interest.

Ethics approval

IRB approval number: 13029 dated 24.06.2020.

Ethics statement

The study was performed conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

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Thomas, L., Kumar, M., Lionel, B.A.P. et al. Pancreatic, hepatobiliary, and gastrointestinal manifestations of children with cystic fibrosis: A 10-year experience from a tertiary care center in southern India. Indian J Gastroenterol 41, 266–272 (2022). https://doi.org/10.1007/s12664-021-01225-0

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Keywords

  • Cystic fibrosis
  • Exocrine pancreatic insufficiency
  • Genotype
  • India
  • Liver diseases
  • Malnutrition
  • Meconium ileus
  • Mutation
  • Pancreatitis
  • Pediatrics