An update on cystic fibrosis Hepato-biliary involvement

Liver involvement among people with cystic fibrosis (PwCF) has long been recognized as clinically important. However, a lack of consistent terminology, incomplete understanding of natural history, and poor clinical trial endpoints have historically hindered clinical and research advancements in this field. Recent efforts by the CF Foundation and international gastrointestinal societies have led to a phenotype-based classification for liver involvement, now referred to as Cystic Fibrosis Hepato-Biliary Involvement (CFHBI), with the most severe form of disease termed advanced CF liver disease (aCFLD). Longitudinal studies such as PUSH, combined with national patient registry data, has greatly improved our understanding of the natural history of CFHBI. Several studies have assessed the utility of conventional serological markers of liver disease, non-invasive liver fibrosis indices, and imaging with various elastography modalities to screen for CFHBI and monitor for progression to aCFLD. This has led to the first evidence-based consensus recommendations for the screening, evaluation and management of CFHBI in children. These recommendations provide a foundation from which future research can build from. Finally, while there is emerging population-level data suggesting that modulator therapies are decreasing the rates of aCFLD, the true impact of these medications on CFHBI remains unknown. In this review we provide an overview of the recent advancements leading to the recent consensus recommendations, summarize what is known about the impact of modulator therapies on CFHBI, and discuss the outstanding questions that need to be addressed to advance our understanding of CFHBI.