Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2020; 26(32): 4833-4845
Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4833
Features of extrahepatic metastasis after radiofrequency ablation for hepatocellular carcinoma
Jae H Yoon, Young J Goo, Chae-Jun Lim, Sung K Choi, Sung B Cho, Sang S Shin, Chung H Jun
Jae H Yoon, Young J Goo, Chae-Jun Lim, Sung K Choi, Department of Gastroenterology, Chonnam National University Hospital and Medical School, Gwangju 61469, South Korea
Sung B Cho, Department of Gastroenterology, Hwasun Chonnam National University Hospital and Medical School, Hwasun 58128, South Korea
Sang S Shin, Department of Radiology, Chonnam National University Hospital and Medical School, Gwangju 61469, South Korea
Chung H Jun, Department of Internal Medicine, Mokpo Hankook Hospital, Mokpo 58643, South Korea
Author contributions: Yoon JH and Jun CH designed and performed the research and wrote the paper; Choi SK designed the research and supervised the report; Lim CJ and Goo YJ contributed to the analysis; Cho SB and Shin SS provided clinical advice.
Supported by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation, No. KASLKLF2019-06.
Institutional review board statement: The study protocol was approved by the Institutional Review Board of Chonnam National University Hospital (CNUH-2019-203). Research was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments.
Informed consent statement: Informed consent requirement was waived because the patient data were de-identified.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Chung H Jun, MD, Doctor, Professor, Department of Internal Medicine, Mokpo Hankook Hospital, 483 Yeongsan-ro, Mokpo 58643, South Korea.
Received: April 2, 2020
Peer-review started: April 2, 2020
First decision: April 29, 2020
Revised: May 4, 2020
Accepted: August 12, 2020
Article in press: August 12, 2020
Published online: August 28, 2020

Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) is associated with poor outcomes. However, the clinical features and risk factors of EHM of HCC after radiofrequency ablation (RFA) remain unclear.


To elucidate the characteristics and risk factors of EHM after RFA for HCC.


From January 2008 to December 2017, we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals. The inclusion criteria were age ≥ 18 years, a diagnosis of HCC, and treatment-naivety. Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo. Univariate analyses were performed using the chi-squared test or Student’s t-test, and univariate and multivariate analyses were performed via logistic regression, as appropriate.


EHM was diagnosed in 44 patients (6.7%) during a median follow-up period of 1204 days. The 10-year cumulative rate of HCC recurrence and EHM was 92.7% and 33.7%, respectively. Initial recurrence was most often intrahepatic, and the rate of extrahepatic recurrence at initial recurrence was only 1.2%. The median time to the diagnosis of EHM was 2.68 years, and 68.2% of patients developed EHM within 2 years of the first recurrence, regardless of recurrence-free survival and 75.0% of patients developed EHM within 5 years after first recurrence. EHM was mostly diagnosed via abdominal CT/MRI in 33 (75.0%) and 38 of 44 patients (86.4%) with EHM had either positive abdominal CT scan results or serum AFP level elevation. In multivariate analysis, recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL were associated with a high EHM risk.


EHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance. Patients especially with high-risk factors require close follow-up for EHM.

Keywords: Hepatocellular carcinoma, Metastasis, Radiofrequency ablation, Surveillance, Risk factor

Core tip: Extrahepatic metastasis (EHM) after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) takes place in substantial clinical situations and EHM of HCC is related with dismal prognosis. Our study provides characteristics and risk factors for EHM after RFA of HCC. EHM after RFA at the time of the first recurrence is rare; however, cumulative EHM frequently occurs following multiple intrahepatic recurrences. Most of the patients (86.4%) had either positive contrast-enhanced computed tomography scan results or serum alpha-fetoprotein level elevation at EHM. EHM turned out to be related with recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL.