Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations

Abstract

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease. A committee of hepatologists, gastroenterologists, pulmonologists, pharmacists, nurses, dietitians, individuals with CF, and the parents of a child with CF devised "population, intervention, comparison, and outcome" questions regarding hepatobiliary disease in CF. PubMed literature searches were performed for each population, intervention, comparison, and outcome question. Recommendations were voted on with 80% agreement required to approve a recommendation. Public comment on initial recommendations was solicited prior to the formulation of final recommendations. Thirty-one population, intervention, comparison, and outcome questions were assembled, 6401 manuscripts were title screened for relevance, with 1053 manuscripts undergoing detailed full-text review. Seven recommendations were approved for screening, 13 for monitoring of existing disease, and 14 for treatment of CF-associated hepatobiliary involvement or advanced liver disease. One recommendation on liver biopsy did not meet the 80% threshold. One recommendation on screening ultrasound was revised and re-voted on. Through a multidisciplinary committee and public engagement, we have assembled updated recommendations and guidance on screening, monitoring, and treatment of CF-associated hepatobiliary involvement and advanced liver disease. While research gaps remain, we anticipate that these recommendations will lead to improvements in CF outcomes through earlier detection and increased evidence-based approaches to monitoring and treatment.

Graphical abstract

FIGURE 1

Pathway summarizing screening and monitoring recommendations. Flow diagram summarizing hepatobiliary disease screening and monitoring recommendations, as outlined within the manuscript. Blue color indicates screening, and yellow color indicates monitoring. ¹Should be performed at the time of clinical stability. ²CFHBI includes elevation in liver enzymes above age-appropriate values for >3–6 months, abnormal liver/spleen exam, and/or abnormal US findings. ³Advanced CF Liver Disease (aCFLD) refers to having one (or more) of the following: nodular liver, advanced fibrosis (F4), multilobular cirrhosis with or without portal hypertension, or noncirrhotic portal hypertension. Abbreviations: aCFLD, advanced CF liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CF, cystic fibrosis; CFHBI, CF hepatobiliary involvement; GGT, gamma-glutamyl transferase; SWE, shear-wave elastography; TE, transient elastography; US, ultrasound.