Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes

doi:10.1016/j.healun.2015.01.993

The Journal of Heart and Lung Transplantation

Volume 34, Issue 7, July 2015, Pages 883-891

https://doi.org/10.1016/j.healun.2015.01.993 Get rights and content

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.

Section snippets

Study design

This was a retrospective study approved by the Boston Children’s Hospital institutional review board. Individuals with prior Fontan surgery were identified from the Boston Children’s Hospital cardiac database, and pathology slides for those in whom liver biopsy or autopsy had been performed after Fontan surgery were obtained for review. Biopsies or autopsies were primarily performed at Boston Children’s Hospital or Brigham and Women’s Hospital. Biopsies performed elsewhere were included if the

Baseline characteristics

Seventy-four subjects with Fontan circulation were identified who had liver histology. Six of these were excluded for: biopsy pre-dating Fontan surgery (1); original slides/paraffin blocks not available (4); or inadequate stain quality (1). In the end, 68 subjects (36 male) were reviewed. Of these, 5 had biopsy on more than 1 occasion; only the first biopsy was used for analysis.

Table 1 summarizes the subject characteristics. Fifty-nine had liver biopsy and 9 had autopsy. Median age at initial

Discussion

Although liver disease in subjects with Fontan circulation is increasingly recognized, its impact on clinical outcomes remains unclear.12, 13, 14, 15, 16, 17 Studies of heart failure patients have shown markers of liver disease to be independently associated with cardiovascular death, hospitalization for congestive heart failure and all-cause mortality.18, 19 Our study, reporting on the largest cohort to date of Fontan subjects with liver histopathology, suggests that, despite a high prevalence

Disclosure statement

The authors have no conflicts of interest to disclose. F.M.W., A.R.O., M.J.L., M.N.S. and A.M.V. are supported by the Dunlevie Family Fund.

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Fontan-type surgery is the final step in the sequential palliative surgical treatment of infants born with a univentricular heart. The resulting long-term haemodynamic changes promote liver damage, leading to Fontan-associated liver disease (FALD), in virtually all patients with Fontan circulation. Owing to the lack of a uniform definition of FALD and the competitive risk of other complications developed by Fontan patients, the impact of FALD on the prognosis of these patients is currently debatable. However, based on the increasing number of adult Fontan patients and recent research interest, the European Association for The Study of the Liver and the European Reference Network on Rare Liver Diseases thought a position paper timely. The aims of the current paper are: (1) to provide a clear definition and description of FALD, including clinical, analytical, radiological, haemodynamic, and histological features; (2) to facilitate guidance for staging the liver disease; and (3) to provide evidence- and experience-based recommendations for the management of different clinical scenarios.
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Nous avons réalisé une analyse rétrospective des cas de 32 adultes consécutivement soumis à un cathétérisme d’effort à la clinique Mayo, au Minnesota. Les résultats d’une surveillance hémodynamique invasive étaient corrélés à l’indice du rapport aspartate aminotransférase/plaquettes (APRI, pour aspartate transaminase to platelet ratio index) et au score Fibrosis-4 (FIB-4), deux indicateurs validés de la fibrose hépatique.
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View full text

Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes

Background

Methods

Results

Conclusions

Section snippets

Study design

Baseline characteristics

Discussion

Disclosure statement

J Am Coll Cardiol

J Hepatol

J Hepatol

Clin Liver Dis

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Am J Transplant

J Hepatol

Gastroenterology

J Heart Lung Transplant

[“Correction” of tricuspid atresia. 2 cases “corrected” using a new surgical technic]

Ann Chir Thorac Cardiovasc

Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery

Circulation

MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery

Heart

Single ventricle anatomy is associated with increased frequency of nonalcoholic cirrhosis

Int J Cardiol