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Cystic fibrosis from the gastroenterologist's perspective

Nature Reviews Gastroenterology & Hepatology volume 13, pages 175–185 (2016)Cite this article

Subjects

Key Points

  • Cystic fibrosis is a life-limiting disease caused by different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and can vary in severity and manifestation

  • The majority of patients with cystic fibrosis survive into adulthood and transition into the care of adult gastroenterologists

  • Besides the well-known pulmonary and pancreatic consequences, cystic fibrosis is a multiorgan disease that also affects the hepatobiliary and gastrointestinal tracts

  • Adult-specific gastrointestinal complications in those with cystic fibrosis are emerging, in particular biliary and gastrointestinal tract malignancies

  • Novel therapies specifically targeting the defects in processing or function of the CFTR protein are available, providing opportunities to better understand disease mechanisms and use intestinal endpoints in clinical trials

Abstract

Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis.

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Figure 1: Gastrointestinal, hepatobiliary and pancreatic manifestations and complications of cystic fibrosis.
Figure 2: Proposed pathogenesis of liver disease related to cystic fibrosis.
Figure 3: Alterations in the intestinal milieu and the proposed pathogenic factors associated with the development of an altered intestinal microbiota (dysbiosis) in cystic fibrosis.

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Acknowledgements

C.Y.O. acknowledges the grant support received from The Cystic Fibrosis Australia Research Trust Grant and The Royal Australasian College of Physicians Research and Education Foundation Award (Servier Staff Research Fellowship).

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Authors and Affiliations

  1. Sydney Children's Hospital, School of Women's and Children's Health, High Street, Randwick, Sydney, 2031, New South Wales, Australia

    Chee Y. Ooi

  2. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada

    Peter R. Durie

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  1. Chee Y. Ooi
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  2. Peter R. Durie
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All authors contributed equally to researching data for the article, review and editing of the manuscript and discussion of content. C.Y.O. wrote the manuscript.

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Correspondence to Chee Y. Ooi.

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Competing interests

C.Y.O. received consultancy fees from Vertex. P.R.D. declares no competing interests.

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Ooi, C., Durie, P. Cystic fibrosis from the gastroenterologist's perspective. Nat Rev Gastroenterol Hepatol 13, 175–185 (2016). https://doi.org/10.1038/nrgastro.2015.226

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