lumacaftor--ivacaftor-drug-combination and Liver-Diseases

Several new therapeutic modalities have recently become available to be used in patients with cystic fibrosis such as potentiators, modulators, and probiotics. Although the effects on pulmonary function have been well documented, gastrointestinal outcomes have been addressed only rarely.. Both the potentiator (ivacaftor) and the potentiator/modulator combination (ivacaftor/lumacaftor) that are currently on the market have a positive effect on BMI. Young patients (2-5 years of age) with a gating mutation may show improvement of exocrine pancreatic function on ivacaftor. In this specific patient population this agent also seems to improve intestinal pH and reflux. The effect of these medications on other gastrointestinal outcomes, such as intestinal inflammation and cystic fibrosis liver disease, has not been described so far. Furthermore, the results of several trials suggest that probiotics might reduce intestinal inflammation. Finally, organoids might be used to predict in vitro the clinical effect of potentiators and modulators.. The effect of new interventions on the gastrointestinal outcomes studied so far is favourable. Future studies should address the effect on other gastrointestinal parameters.

Topics: Aminophenols; Aminopyridines; Benzodioxoles; Body Mass Index; Chloride Channel Agonists; Cystic Fibrosis; Digestive System; Drug Combinations; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Intestinal Diseases; Liver Diseases; Probiotics; Quinolones; Treatment Outcome; Weight Gain

To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD).. The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed.. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

Topics: Aftercare; Aminophenols; Aminopyridines; Benzodioxoles; Chloride Channel Agonists; Cholagogues and Choleretics; Cystic Fibrosis; Drug Combinations; Elasticity Imaging Techniques; Humans; Liver Diseases; Liver Transplantation; Quinolones; Ursodeoxycholic Acid