{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:02Z","timestamp":1772169002915,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/hrbopenres.13065.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000}},{"DOI":"10.12688\/hrbopenres.13065.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000}}],"reference-count":23,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001631","name":"University College Dublin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001631","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRA-2014-PHR-662"],"award-info":[{"award-number":["HRA-2014-PHR-662"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["hrbopenresearch.org"],"crossmark-restriction":false},"short-container-title":["HRB Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background<\/ns4:bold>\n                    Cystic fibrosis (CF) is a multiorgan disease affecting the lungs pancreas and gastrointestinal tract. Pulmonary complications are the most common manifestation of the disease. Recent advances in the treatment of pulmonary complications have resulted in substantial improvement in life expectancy. Less than 10% of persons with CF (PWCF) develop liver disease (CFLD). There is conflicting evidence about impact of liver disease on mortality in CF, with evidence suggesting that CFLD contributes to increased mortality in CF, while other studies suggest that the impact on mortality is limited. Understanding the contribution of liver disease to mortality in CF is essential if further improvements in life expectancy are to be achieved.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Objective:<\/ns4:bold>\n                    To document the impact of liver disease on life expectancy for PWCF.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015). PubMed, Medline and Embase will be searched for English language publications (1949-2020). Studies reporting the outcome for CFLD will be included where the definition of CFLD is outlined clearly in a CF population. Studies with and without a comparator will be evaluated. Clinical trials of ursodeoxycholic acid will be excluded as well as organ transplantation outcome studies. We will examine all-cause and specific causes of mortality.We will include transplantation in our estimates of all-cause mortality. The Axis Risk of Bias Tool for Observational Studies will be used to evaluate the quality of studies. We will provide a narrative synthesis of our findings using tabular formats to highlight any impact of liver disease on mortality in CF.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion:<\/ns4:bold>\n                    It is anticipated that this review will bring clarity to the question of whether CFLD shortens life expectancy in PWCF and stimulate new approaches to the management of CFLD.\n                  <\/ns4:p>","DOI":"10.12688\/hrbopenres.13065.3","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T07:05:00Z","timestamp":1608620700000},"page":"44","update-policy":"https:\/\/doi.org\/10.12688\/hrbopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The impact of liver disease on mortality in cystic fibrosis - a systematic review protocol"],"prefix":"10.12688","volume":"3","author":[{"given":"Ao","family":"Sasame","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emer","family":"Fitzpatrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4319-8048","authenticated-orcid":false,"given":"Diarmuid","family":"Stokes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Billy","family":"Bourke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-830X","authenticated-orcid":false,"given":"Marion","family":"Rowland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"2519-31","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic 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Jackson","year":"2011","journal-title":"Thorax."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"120-6","DOI":"10.1016\/j.jcf.2014.05.013","article-title":"Outcome in patients with cystic fibrosis liver disease.","volume":"14","author":"M Rowland","year":"2015","journal-title":"J Cyst Fibros."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"461-6","DOI":"10.1097\/MCP.0b013e32834b7f51","article-title":"Liver disease in cystic fibrosis.","volume":"17","author":"M Rowland","year":"2011","journal-title":"Curr Opin Pulm Med."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"385-389","DOI":"10.1016\/j.jcf.2018.11.009","article-title":"Cirrhosis associated with decreased survival and a 10-year lower median age at death of cystic fibrosis patients in the Netherlands.","volume":"18","author":"F Pals","year":"2018","journal-title":"J Cyst Fibros."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1377-82","DOI":"10.1016\/j.jhep.2011.03.028","article-title":"Liver disease in adult patients with cystic fibrosis: a frequent and independent prognostic factor associated with death or lung transplantation.","volume":"55","author":"A Chryssostalis","year":"2011","journal-title":"J Hepatol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"1153-63","DOI":"10.1136\/gut.2004.062786","article-title":"Patterns of GI disease in adulthood associated with mutations in the CFTR gene.","volume":"56","author":"M Wilschanski","year":"2007","journal-title":"Gut."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"e11-e3","DOI":"10.1016\/j.jcf.2017.03.006","article-title":"Liver disease in cystic fibrosis presents as non-cirrhotic portal hypertension.","volume":"16","author":"P Witters","year":"2017","journal-title":"J Cyst Fibros."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1463-5","DOI":"10.1002\/lt.20571","article-title":"The role of liver transplantation in cystic fibrosis re-examined.","volume":"11","author":"M Jonas","year":"2005","journal-title":"Liver Transpl."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"S29-36","DOI":"10.1016\/S1569-1993(11)60006-4","article-title":"Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease.","volume":"10","author":"D Debray","year":"2011","journal-title":"J Cyst Fibros."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"281-4","DOI":"10.1136\/adc.72.4.281","article-title":"Liver Disease in Cystic Fibrosis.","volume":"72","author":"M Tanner","year":"1995","journal-title":"Arch Dis Child."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"116-24","DOI":"10.1016\/j.jcf.2012.11.010","article-title":"Cirrhosis and Other Liver Disease in Cystic 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One."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1648-1656","DOI":"10.1002\/hep.30148","article-title":"Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients.","volume":"69","author":"P Boelle","year":"2019","journal-title":"Hepatology."},{"key":"ref-22","article-title":"The Impact of liver disease on mortality in Cystic Fibrosis-A systematic review protocol-data (Version V1) [Data set]","author":"A Sasame","year":"2020"},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"e011458","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS).","volume":"6","author":"M Downes","year":"2016","journal-title":"BMJ Open."}],"container-title":["HRB Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T06:55:10Z","timestamp":1619765710000},"score":1,"resource":{"primary":{"URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":23,"URL":"https:\/\/doi.org\/10.12688\/hrbopenres.13065.3","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/hrbopenres.14345.r28561","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/hrbopenres.14345.r28561","asserted-by":"object"}]},"ISSN":["2515-4826"],"issn-type":[{"value":"2515-4826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,22]]},"assertion":[{"value":"Indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/hrbopenres.14276.r28076, Michael Wilschanski, Pediatric Gastroenterology Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel, 26 Oct 2020, version 2, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v2#referee-response-28076","order":0,"name":"referee-response-28076","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/hrbopenres.14276.r28075, Henkjan Verkade, Sanne Duursma, Department of Pediatric Gastroenterology\/Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands, 08 Dec 2020, version 2, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v2#referee-response-28075","order":1,"name":"referee-response-28075","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Marion Rowland<\/b>; \n<i>Posted: 11 Dec 2020<\/i>; We very much appreciate the reviewers taking the time to provide further very helpful comments on this protocol for a systematic review. The following is our response to Point 1  We fully concur with Dr Duursma and Prof Verkade concerns that including older studies could bias our outcome metrics due to the change in clinical practice, diagnostic investigations, and the management of both CF and CFLD.&nbsp; Having had the opportunity to appraise most of the literature we have further clarified the protocol to state that included studies must provide details of the prevalence of CFLD in the population on which the study is based (Methods Page 5 Line 11,12). &nbsp;This removes many of the older publications which we feel are giving rise to the reviewers\u2019 concerns. In addition, it also allows a better comparison of outcomes in different populations when the underlying prevalence of&nbsp; CFLD is known. As suggested by Prof Debray we will further subdivide the Tables of Evidence according to date of publication so that the reader will be clearly able to see how the mortality of both CF and CFLD has changed since the 1980s. At this stage we are not in a position to provide definite information on the earliest studies included as the review process is still ongoing, but it is expected that no &nbsp;study pre 1990 will be included. However, we do wish to reassure Dr Duursma and Prof Verkade that their concerns will be to the forefront when we are finalising the list of included studies.","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3#referee-comment-3245","order":2,"name":"referee-comment-3245","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/hrbopenres.14345.r28561, Chee Y Ooi, Discipline of Paediatrics, School of Women's and Children's Health, University of New South Wales, Sydney, Australia, 13 Jan 2021, version 3, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3#referee-response-28561","order":3,"name":"referee-response-28561","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/hrbopenres.14276.r28305, Dominique Debray, Pediatric Hepatology Unit, Reference center for Biliary Atresia and Cholestatic Genetic Diseases, APHP-H\u00f4pital Necker, Paris, France, 02 Dec 2020, version 2, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v2#referee-response-28305","order":4,"name":"referee-response-28305","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Marion Rowland<\/b>; \n<i>Posted: 11 Dec 2020<\/i>; We thank Prof Debray for her very helpful comments on this protocol. We very much agree that examining the change in outcome in mortality for CFLD since the 1980s will provide important information in the field, as well as providing a useful baseline against which to assess the impact of modulator therapies on CFLD.","URL":"https:\/\/hrbopenresearch.org\/articles\/3-44\/v3#referee-comment-3246","order":5,"name":"referee-comment-3246","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Health Research Board Ireland [HRA-2014-PHR-662].\nThis systematic review has the benefit of academic support from UCD with the provision of the services of an information specialist (DS) and access to UCD library services. In addition, MR and BB are employed by UCD with a research and clinical expertise in CFLD. UCD, as an academic institution, has no role in the conduct or developing the outputs from this SR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}