Anton Barucha

(1) Background: The introduction of highly effective CFTR-modulating therapies (HEMT) has changed the course of the disease for many people with Cystic Fibrosis (pwCF). Attention previously focused on life-threatening conditions of the respiratory system has broadened, bringing the involvement of the digestive system into the clinical and scientific focus. This emphasized the need for sensitive tools to capture and quantify changes in abdominal symptoms (AS), ideally applying patient-reported outcome measures (PROMs). (2) Methods: The present review focuses on studies addressing AS assessment deriving from the multi-organic abdominal involvement in pwCF. Among 5224 publications retrieved until Nov. 2022, 88 were eligible, and 39 were finally included. (3) Results: The review reveals that for a long time, especially before HEMT availability, AS in pwCF were assessed by single questions on abdominal complaints or non-validated questionnaires. PROMs focusing on quality of life (QOL) including a few GI-related questions were applied. Likewise, PROMs developed and partially validated for other non-CF GI pathologies, such as chronic inflammatory bowel diseases, irritable bowel syndrome, gastroesophageal reflux, constipation, or pancreatitis, were implemented. (4) Conclusions: Only lately, CF-specific GI-PROMs have been developed and validated following FDA guidelines, showing high sensitivity to changes and capturing marked and statistically significant reductions in the burden of AS achieved with HEMT implementation.

Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores (p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 (p = 0.033) and with pancreatic insufficiency (p = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest.