KOGISO Tomomi    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Non peer reviewed
Title	Risk factors for Fontan-associated hepatocellular carcinoma.
Journal	Formal name：PloS one Abbreviation：PLoS One ISSN code：19326203/19326203
Domestic / Foregin	Foregin
Volume, Issue, Page	17(6),pp.e0270230
Author and coauthor	KOGISO Tomomi†, SAGAWA Takaomi, TANIAI Makiko, SHIMADA ERIKO, Inai Kei, SHINOHARA Tokuko, TOKUSHIGE Katsutoshi
Authorship	Lead author
Publication date	2022/01
Summary	AIMS:The incidence of hepatocellular carcinoma (HCC) in patients with Fontan-associated liver disease (i.e., FALD-HCC) has increased over time. However, the risk factors for HCC development remain unclear. Here, we compared the levels of non-invasive markers to the survival rate of FALD-HCC patients.METHODS:From 2003 to 2021, 154 patients (66 men, 42.9%) developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 15 (9.7%) (8 men, 53.3%) at a median age of 34 years (range, 21-45 years). We compared FALD-HCC and non-HCC cases; we generated marker level cutoffs using receiver operating characteristic curves. We sought to identify risk factors for HCC and mortality.RESULTS:The incidence of HCC was 4.9% in FALD patients within 20 years after the Fontan procedure. Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. At the time of HCC development, the hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher in FALD-HCC patients than in non-HCC patients; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score [excluding the international normalized ratio (MELD-XI)] (p = 0.06) tended to be higher in FALD-HCC patients. Within approximately 20 years of the Fontan procedure, 10 patients died (survival rate, 96.9%). Kaplan-Meier curve analysis indicated that patients with T-BIL levels ≥ 2.2 mg/dL, HA levels ≥ 55.5 ng/mL, and MELD-XI scores ≥ 18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. Multivariate Cox regression analyses indicated that the complication of polysplenia [Hazard ratio (HR): 10.915] and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC.CONCLUSIONS:The complication of polysplenia and a MELD-XI score may predict HCC development and mortality in FALD patients.
DOI	10.1371/journal.pone.0270230
PMID	35714161