Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR.

BACKGROUND: The effects of lumacaftor-ivacaftor on cystic fibrosis transmembrane conductance regulator (CFTR)-associated liver disease remain unclear. The objective of the study was to describe the effect of this treatment on features of liver involvement in a cystic fibrosis (CF) adolescent population homozygous for F508del. METHODS: Clinical characteristics, liver blood tests, abdominal ultrasonography (US), and pancreas and liver proton density fat fraction (PDFF) by magnetic resonance imaging, were obtained at treatment initiation and at 12 months for all patients. Biomarkers of CFTR activity (sweat chloride test, nasal potential difference, and intestinal current measurement) were assessed at initiation and at 6 months therapy. RESULTS: Of the 37 patients who started ivacaftor/lumacaftor treatment, 28 were eligible for analysis. In this group, before treatment initiation, 4 patients were diagnosed with multinodular liver and portal hypertension, 19 with other forms of CF liver involvement, and 5 with no signs of liver involvement. During treatment, no hepatic adverse reactions were documented, and no patient developed liver failure. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. This was not correlated with changes in clinical status, liver and pancreas US and PDFF, fecal elastase, or lumacaftor-ivacaftor serum levels. The most "responsive" patients demonstrated a significant increase in biomarkers of CFTR activity. CONCLUSIONS: These results may suggest a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies.

Plasma citrulline concentration reflects enterocyte mass in children with short bowel syndrome.

Plasma citrulline was recently shown to reflect the residual functional enterocyte mass in various situations characterized by intestinal failure. However, few data are available in children with short bowel syndrome. The objective of this study was to assess the value of citrulline assays in this situation. Prospective plasma citrulline assays were performed in 31 children with short bowel syndrome. Median age was 16 mo (range, 1 mo to 15 y), and median follow-up was 14 mo (6-40 mo). The energy supplied by parenteral nutrition (PN), served to assess intestinal failure severity. Plasma citrulline at inclusion showed a positive correlation with residual short bowel length. Subsequent values correlated negatively with intestinal failure severity. Plasma citrulline increased over time during or after weaning from PN (from 15.8 +/- 11.5 microM to 19.3 +/- 3.8 microM) but remained stable and low in patients who continued to need PN (6.5 +/- 3.0 microM at inclusion and 7.7 +/- 6.0 microM at last follow-up). No weaned patients had a residual short bowel length less than 40 cm and plasma citrulline less than 11 microM. Our findings constitute the first evidence that serial plasma citrulline assays help to monitor residual small bowel adaptation in children.

Diffuse lymphoplasmacytic bronchiolitis in cartilage-hair hypoplasia.

Three children with cartilage-hair hypoplasia presented with chronic obstructive symptoms and bronchiolar wall thickening on high-resolution computed tomography scanning. In all children, surgical lung biopsy demonstrated diffuse dilated lymphoplasmacytic bronchiolitis. The bronchiolar wall was infiltrated by a lymphocyte sheath with plasma cell differentiation and dispersed secondary follicles. Clarithromycin substantially improved respiratory symptoms and pulmonary function, allowing children to return home.