title: Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes.
abstract: BACKGROUND
  The Fontan operation redirects venous blood flow directly to the pulmonary circulation in subjects with single ventricle anatomy. Congestive hepatopathy and cirrhosis have been described in subjects with Fontan circulation, but the prevalence of and predictors for liver disease remain unknown.
  
  
  METHODS
  We performed a retrospective study of liver histopathology in Fontan subjects who had liver biopsy or autopsy. All specimens were graded using a pre-determined protocol. Additional data were collected through chart review. Among 68 subjects, specimens were obtained at a median age of 23.2 years (range 5.0 to 52.7 years). Median time since Fontan was 18.1 years (range 1.2 to 32.7 years).
  
  
  RESULTS
  Centrilobular fibrosis was seen in every specimen, with 41.2% showing Grade 4 centrilobular fibrosis. Portal fibrosis was seen in 82.3% of specimens, with 14.7% showing cirrhosis. Megamitochondria were seen in 58.8% of specimens. Centrilobular fibrosis grade was greater in those with a dominant left or right ventricle than in those with a combined right and left systemic ventricle (p = 0.008). Portal fibrosis grade correlated with alkaline phosphatase (p = 0.04) and mode of biopsy (p = 0.02). Neither centrilobular fibrosis nor portal fibrosis grade was predictive of transplant-free survival or overall survival.
  
  
  CONCLUSIONS
  Individuals with Fontan physiology have a high prevalence of hepatic fibrosis. Signs and symptoms of liver disease did not predict histopathologic findings. Few risk factors for advanced disease were identified. Histopathology findings did not predict transplant-free survival. The role of liver biopsy in this population remains uncertain.
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Electronic address: fred.wu@cardio.chboston.org.
authors: Fred M
authors: FM
authors: Wu
authors: Division of Gastroenterology, Department of Medicine, Boston Children's Hospital, Harvard Medical School.
authors: Maureen M
authors: MM
authors: Jonas
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Alexander R
authors: AR
authors: Opotowsky
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School.
authors: Amy
authors: A
authors: Harmon
authors: Division of Gastroenterology, Department of Medicine, Boston Children's Hospital, Harvard Medical School.
authors: Roshan
authors: R
authors: Raza
authors: Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Chinweike
authors: C
authors: Ukomadu
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Michael J
authors: MJ
authors: Landzberg
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Michael N
authors: MN
authors: Singh
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Anne Marie
authors: AM
authors: Valente
authors: Department of Cardiology, Boston Children's Hospital, Harvard Medical School; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.
authors: Gabriele
authors: G
authors: Egidy Assenza
authors: Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Antonio R
authors: AR
authors: Perez-Atayde
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000150:complications / Q000601:surgery*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D020379:Risk Adjustment; D012307:Risk Factors; D055815:Young Adult
keywords: Adult congenital heart disease; Cirrhosis; Congenital heart disease; Fontan procedure; Heart transplant; Hepatic fibrosis; Pediatric cardiology