Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes

• Published in: The Journal of heart and lung transplantation Vol. 34; no. 7; pp. 883 - 891
• Main Authors: Wu, Fred M., Jonas, Maureen M., Opotowsky, Alexander R., Harmon, Amy, Raza, Roshan, Ukomadu, Chinweike, Landzberg, Michael J., Singh, Michael N., Valente, Anne Marie, Egidy Assenza, Gabriele, Perez-Atayde, Antonio R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Adolescent; Adult; Adult congenital heart disease; Child; Child, Preschool; Cirrhosis; Congenital heart disease; Female; Fontan procedure; Fontan Procedure - adverse effects; Heart Defects, Congenital - complications; Heart Defects, Congenital - surgery; Heart transplant; Hepatic fibrosis; Humans; Liver - pathology; Liver Cirrhosis - epidemiology; Liver Cirrhosis - etiology; Male; Massachusetts - epidemiology; Middle Aged; Pediatric cardiology; Prevalence; Retrospective Studies; Risk Adjustment; Risk Factors; Surgery; Young Adult; Massachusetts; Hepatic fibrosis; Cirrhosis; Fontan procedure; Heart transplant; Adult congenital heart disease; Pediatric cardiology; Congenital heart disease
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2015.01.993

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. 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). 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. 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.