PMID- 35714161
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20220719
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 6
DP  - 2022
TI  - Risk factors for Fontan-associated hepatocellular carcinoma.
PG  - e0270230
LID - 10.1371/journal.pone.0270230 [doi]
LID - e0270230
AB  - 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.
FAU - Kogiso, Tomomi
AU  - Kogiso T
AUID- ORCID: 0000-0003-1248-4324
AD  - Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's 
      Medical University, Shinjuku-ku, Tokyo, Japan.
FAU - Sagawa, Takaomi
AU  - Sagawa T
AD  - Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's 
      Medical University, Shinjuku-ku, Tokyo, Japan.
FAU - Taniai, Makiko
AU  - Taniai M
AD  - Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's 
      Medical University, Shinjuku-ku, Tokyo, Japan.
FAU - Shimada, Eriko
AU  - Shimada E
AD  - Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical 
      University, Shinjuku-ku, Tokyo, Japan.
FAU - Inai, Kei
AU  - Inai K
AD  - Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical 
      University, Shinjuku-ku, Tokyo, Japan.
FAU - Shinohara, Tokuko
AU  - Shinohara T
AUID- ORCID: 0000-0002-2268-3266
AD  - Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical 
      University, Shinjuku-ku, Tokyo, Japan.
FAU - Tokushige, Katsutoshi
AU  - Tokushige K
AD  - Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's 
      Medical University, Shinjuku-ku, Tokyo, Japan.
LA  - eng
SI  - figshare/10.6084/m9.figshare.18515690
PT  - Journal Article
DEP - 20220617
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Biomarkers
MH  - *Carcinoma, Hepatocellular/epidemiology/etiology/surgery
MH  - *End Stage Liver Disease/complications
MH  - *Esophageal and Gastric Varices/complications
MH  - Humans
MH  - *Liver Neoplasms/epidemiology/etiology/surgery
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Young Adult
PMC - PMC9205474
COIS- KT has received research funding from Sumitomo Dainippon Pharma Co., Ltd., 
      Astellas Pharma Inc., Eisai Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai 
      Pharmaceutical Co., Ltd., Daiichi Sankyo Pharmaceutical Co., Ltd., AbbVie GK, 
      Takeda Pharmaceutical Co. Ltd., Asahi Kasei Corporation. Ajinomoto Co., Inc., and 
      Otsuka Pharmaceutical Co., Ltd. The authors received no specific support for this 
      work from a commercial source. We have no declarations relating to employment, 
      consultancy, patents, products in development, marketed products, etc.
EDAT- 2022/06/18 06:00
MHDA- 2022/06/22 06:00
PMCR- 2022/06/17
CRDT- 2022/06/17 13:44
PHST- 2021/12/18 00:00 [received]
PHST- 2022/06/07 00:00 [accepted]
PHST- 2022/06/17 13:44 [entrez]
PHST- 2022/06/18 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/06/17 00:00 [pmc-release]
AID - PONE-D-21-39903 [pii]
AID - 10.1371/journal.pone.0270230 [doi]
PST - epublish
SO  - PLoS One. 2022 Jun 17;17(6):e0270230. doi: 10.1371/journal.pone.0270230. 
      eCollection 2022.