title: Features of Severe Liver Disease With Portal Hypertension in Patients With Cystic Fibrosis.
abstract: Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been characterized fully.
  
  
  
  We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013.
  
  
  
  Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 y; P = .01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88 × 10(9)/L vs 145 × 10(9)/L; P < .0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared with patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78 × 10(9)/L vs 113 × 10(9)/L; P < .0001), higher international normalized ratios (P < .0001), and lower levels of albumin (P = .0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were higher than the diagnostic thresholds for CF liver disease in 96% and in 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not.
  
  
  
  In patients with CF, severe liver disease develops early in childhood (approximately 10 years of age), and is more common in boys than in girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: Jaclyn_Stonebraker@med.unc.edu.
authors.forename: Jaclyn R
authors.initials: JR
authors.lastname: Stonebraker
authors.affiliation: Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia.
authors.forename: Chee Y
authors.initials: CY
authors.lastname: Ooi
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Rhonda G
authors.initials: RG
authors.lastname: Pace
authors.affiliation: Pediatric Pulmonology Department, Assistance Publique-Hôpitaux de Paris, Trousseau Hospital, Paris, France; Institut National de la Santé et la Recherche Médicale, Paris, France; Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
authors.forename: Harriet
authors.initials: H
authors.lastname: Corvol
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.affiliation: Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada; Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Durie
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000453:epidemiology / Q000473:pathology*; D008107:Liver Diseases / Q000150:complications* / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012737:Sex Factors; D055815:Young Adult
keywords: ALT; CFLD; INR; Phenotype; Portal Pressure