Yoon Jun Sik, Lee Dong Ho, Cho Eun Ju, Song Mi Kyoung, Choi Young Hun, Kim Gi Beom, Lee Yun Bin, Lee Jeong-Hoon, Yu Su Jong, Kim Haeryoung, Kim Yoon Jun, Yoon Jung-Hwan, Bae Eun Jung
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Korea.
Cancers (Basel). 2020 Jul 6;12(7):1805. doi: 10.3390/cancers12071805.
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 ( = 0.006), long time elapsed since the initial Fontan operation ( = 0.04), large nodule size ( = 0.03), and elevated serum α-fetoprotein (AFP) level ( < 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.
肝硬化和肝细胞癌（HCC）是Fontan手术后可能出现的严重晚期并发症。本研究旨在调查肝硬化和HCC的累积发病率，并确定区分HCC与Fontan手术后出现的良性动脉期强化（APHE）结节的特定特征。我们回顾性纳入了313例Fontan手术后的患者，这些患者随访时间超过5年，且在2000年1月至2018年8月期间接受了肝脏超声或计算机断层扫描（CT）检查。肝硬化通过影像学诊断。Fontan手术后5年、10年、20年和30年的肝硬化估计累积发病率分别为1.3%、9.2%、56.6%和97.9%。多期CT显示，18例患者有大小≥1 cm的APHE结节，在门静脉期（PVP）/延迟期出现消退，符合当前非侵入性HCC诊断标准。其中，只有7例患者（38.9%，7/18）被诊断为HCC。肝硬化发生后，HCC的年发病率为1.04%。PVP出现消退（P = 0.006）、距首次Fontan手术时间较长（P = 0.04）、结节较大（P = 0.03）以及血清甲胎蛋白（AFP）水平升高（P < 0.001）与HCC显著相关。总之，肝硬化是Fontan手术后常见的晚期并发症，尤其是在10年后，而HCC在肝硬化发生后并非罕见并发症。HCC的诊断不应仅基于当前的影像学标准，PVP的消退和临床特征可能有助于将HCC结节与良性APHE结节区分开来。
