title: Prevalence and characterization of fibrosis in surveillance liver biopsies of patients with Fontan circulation.
abstract: The Fontan operation is a widely used palliative procedure in patients with single-ventricle anatomy that results in liver injury. As timely identification of liver fibrosis may result in management changes to Fontan patients, the aim of our study was to identify clinically meaningful semi quantitative/quantitative pathologic parameters for biopsy assessment. We performed a retrospective review of 74 liver needle biopsies from Fontan patients. Fibrosis was assessed using quantitative % collagen deposition by Sirius red image analysis, METAVIR, congestive hepatic fibrosis score, sinusoidal fibrosis score, and sinusoidal dilation score. Contemporaneous laboratory, hemodynamic, and ultrasound data were collected. Centrilobular and peri sinusoidal fibrosis was observed in all cases, with 39.2% high grade. Portal fibrosis was observed in 93.2%, with 36.2% high-grade (METAVIR F3-F4). Cirrhosis was observed in 5.4%. % Collagen deposition was increased over control tissue (P < .001) and correlated with time from Fontan (r = 0.3, P = .009) and prothrombin time (r = 0.25, P = .034). Mildly elevated prothrombin time/international normalized ratio was the only measure of liver function consistently associated with multiple high-grade fibrosis scores (METAVIR P = .046, sinusoidal fibrosis P = .018). Abnormal liver echotexture on ultrasound was associated with high-grade congestive hepatic fibrosis score (P = .03). Pathologic gradings and %CD correlated with each other (r = 0.48-0.8, P < .001). Hepatic fibrosis in Fontan patients in our study is universally present, appears to be time dependent, and correlates with few laboratory measurements of liver function. Careful assessment of needle liver biopsies lends a more meaningful measure of liver fibrosis in the Fontan patient than clinical and laboratory data, allowing for appropriate changes to patient management.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104. Electronic address: surreylf@email.chop.edu.
authors.forename: Lea F
authors.initials: LF
authors.lastname: Surrey
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Pierre
authors.initials: P
authors.lastname: Russo
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Jack
authors.initials: J
authors.lastname: Rychik
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldberg
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dodds
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's National Medical Center, Washington, DC 20010.
authors.forename: Michael L
authors.initials: ML
authors.lastname: O'Byrne
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Glatz
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Rand
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D001391:Azo Compounds; D001707:Biopsy, Needle; D002648:Child; D003094:Collagen / Q000378:metabolism; D004396:Coloring Agents / Q000627:therapeutic use; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D019934:International Normalized Ratio; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D015143:Philadelphia / Q000453:epidemiology; D011237:Predictive Value of Tests; D015995:Prevalence; D011517:Prothrombin Time; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D001391:Azo Compounds; D004396:Coloring Agents; D003094:Collagen
keywords: Congenital heart disease; Congestive hepatopathy; Fontan circulation; Liver fibrosis; Needle biopsy