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Cancers (Basel). 2020;12(7):cancers12071805.

Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance.

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제1저자 윤준식, 이동호 · 교신저자 조은주, 배은정

소속 (5)
  1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  2. Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Korea.
  3. Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.
  4. Division of Pediatric Cardiology, Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
  5. Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.

Abstract

Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

Keywords

Fontan-associated liver diseasehepatocellular carcinomaliver cirrhosissurveillance

Figures

Figure 1
Figure 1 The cumulative incidence rates of cirrhosis and hepatocellular carcinoma in patients after the Fontan operation. (A) The cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. The cumulative incidence rate increased gradually until 10 years after the Fontan operation and then increased rapidly thereafter. (B) The cumulative incidence rates of HCC at 10, 20, and 30 years after the Fontan operation were 0.3%, 0.8%, and 8.5%, respectively, after considering competing risk of death.
Figure 2
Figure 2 Radiologic findings in a 36-year-old male who developed hepatocellular carcinoma 15 years after the Fontan operation. (A) Contrast-enhanced arterial-phase axial CT image shows a 4-cm-sized enhancing mass in segment V of the liver (arrow). (B) The posterior portion of mass shows washout in the portal venous phase axial CT image (arrow). (C) The washout of the mass was more evident on the delayed phase image (arrow). (D) On hepatobiliary phase of gadoxetic-acid-enhanced liver MR, the mass shows low signal intensity (arrow). The serum AFP level was elevated to 274.4 ng/mL. (E) The resected specimen revealed a well-circumscribed, solid, pinkish mass. (F) Histological examination showed well-differentiated hepatocellular carcinoma with a trabecular pattern (H and E, ×40).
Figure 3
Figure 3 Imaging findings in a 22-year-old male who developed a benign arterial-phase enhancing nodule 18 years after the Fontan operation. (A) The contrast-enhanced arterial-phase axial CT image shows a 3-cm-sized enhancing mass in segment VII of the liver (arrow). (B) This mass exhibits the appearance of washout in the delayed phase image (arrow). (C) The gadoxetic-acid-enhanced arterial-phase axial MR image obtained 1 month after the CT scan also shows a 3-cm-sized enhancing mass in segment VII of the liver. (D) This mass has high signal intensity in the transitional phase image (arrow). (E) In the hepatobiliary phase image, this mass has high signal intensity (arrow), suggesting the presence of functioning hepatocytes. The serum AFP level was 4.7 ng/mL in this patient. (F) In the follow-up hepatobiliary phase of the gadoxetic-acid-enhanced MR image obtained 2 years after initial detection, the size and signal intensity of the mass were unchanged.

그림 출처: PubMed Central 공개 논문 (PMC7408507)

Conflict of interest statement

The authors declare no conflict of interest.

그 밖의 정보
출판 형태
Journal Article
저널
Cancers · ISSN 2072-6694
전자 출판
2020-07-06
연구비
Seoul National University Hospital 0420190630 · Liver Research Foundation of Korea Bio Future Strategies Research Project
참고문헌
35편