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"Recurrence"

Editorial

HCC Surveillance After Curative Treatment: A New Frontier for Abbreviated MRI Editorial on: “Non-contrast MRI for Detection of Late Recurrent Hepatocellular Carcinoma After Curative Treatment: Comparison to CT”
Hyungjin Rhee, Jin-Young Choi
Received July 16, 2025  Accepted July 24, 2025  Published online July 28, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0786    [Accepted]
  • 1,363 View
  • 40 Download

Original Article

Non-contrast magnetic resonance imaging for detection of late recurrent hepatocellular carcinoma after curative treatment: a prospective multicenter comparison to contrast-enhanced computed tomography
Dong Wook Kim, Won Chang, So Yeon Kim, Young-Suk Lim, Jonggi Choi, Jungheum Cho, Jin-Wook Kim, Jai Young Cho, Sun Kyung Jeon, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Kyung-Suk Suh, Kwang-Woong Lee, Dong Ho Lee
Clin Mol Hepatol 2025;31(4):1285-1297.
Published online June 13, 2025
DOI: https://doi.org/10.3350/cmh.2025.0258
Background/Aims
Hepatocellular carcinoma (HCC) frequently recurs after curative treatment, posing challenges to long-term survival. Although contrast-enhanced multiphasic computed tomography (CECT) is commonly used for detecting recurrence, it is associated with risks such as radiation exposure and contrast agent reactions. This study aimed to compare the diagnostic performance of non-contrast magnetic resonance imaging (NC-MRI) with CECT for detecting recurrent HCC.
Methods
In this prospective multicenter intra-individual head-to-head comparison trial (study identifier: NCT05690451, KCT0006395), participants who had undergone curative treatment for HCC and remained recurrence-free for over two years were enrolled. Each participant underwent three follow-up imaging sessions at 2–6-month intervals using both CECT and NC-MRI. The primary outcome was the detection accuracy of each modality, analyzed using the generalized estimating equation analysis. Secondary outcomes included sensitivity and specificity.
Results
The study included 203 participants with a total of 528 paired imaging sessions, identifying recurrent HCC in 22 cases (10.8%). Among these, 21 cases involved intrahepatic recurrence with a median tumor size of 1.3 cm, and one case had aortocaval lymph node metastasis. NC-MRI achieved a detection accuracy of 96.6% (196/203), higher than CECT’s 91.6% (186/203) (P=0.006). NC-MRI also showed greater sensitivity (77.3% [17/22] vs. 36.4% [8/22]; P=0.012), while specificity was comparable between NC-MRI and CECT (98.9% [179/181] vs. 98.3% [178/181]; P=0.999).
Conclusions
NC-MRI demonstrated higher sensitivity and accuracy compared to CECT in detecting recurrent HCC in patients who had been disease-free for over two years following curative treatment, indicating its potential as a preferred imaging modality for this purpose.
  • 4,215 View
  • 155 Download

Correspondences

Correspondence: Response to Editorial on “GULP1, a Multifaceted Biomarker and Therapeutic Target in HCC”
Soon Sun Kim, Hyung Seok Kim, Jae Youn Cheong, Jung Woo Eun
Received March 28, 2025  Accepted April 2, 2025  Published online April 4, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0350    [Accepted]
  • 1,543 View
  • 19 Download
Correspondence to letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Received March 12, 2025  Accepted March 15, 2025  Published online March 19, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0287    [Epub ahead of print]
  • 3,798 View
  • 34 Download

Editorial

Unveiling GULP1 as a hepatocyte-specific role for recurrence: Editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
Pengde Lu, Ning Wang
Received March 11, 2025  Accepted March 15, 2025  Published online March 19, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0282    [Epub ahead of print]
  • 2,808 View
  • 30 Download

Letter to the Editor

Classification of microvascular invasion of hepatocellular carcinoma: Different standards, common goals: Letter to the editor on “Classification of microvascular invasion of hepatocellular carcinoma: Correlation with prognosis and magnetic resonance imaging”
Wei Chen, Yihui Rong, Tianshi Ma, Weiwei Shi, Wei Chen, Hang Jiang
Clin Mol Hepatol 2025;31(3):e249-e251.
Published online February 18, 2025
DOI: https://doi.org/10.3350/cmh.2025.0167
  • 6,553 View
  • 76 Download

Editorial

Hepatic neoplasm

Screening of patients at high risk of de novo recurrence in HCC: Editorial on “Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma”
Ping Huang, Shiqiao Luo, Rui Liao
Clin Mol Hepatol 2025;31(2):662-664.
Published online February 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0106
  • 4,407 View
  • 44 Download

Original Articles

GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma
Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2025;31(3):914-934.
Published online February 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1038
Background/Aims
Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC.
Methods
We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial–mesenchymal transition (EMT), ADP-ribosylation factor 6 (ARF6) activation, and β-catenin signaling.
Results
Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ARF6 activation and β-catenin signaling pathways.
Conclusions
GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.

Citations

Citations to this article as recorded by  Crossref logo
  • The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma
    Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji
    Biomarker Research.2025;[Epub]     CrossRef
  • Advances in research regarding epithelial-mesenchymal transition and prostate cancer
    Xi Wei, Rui Liu, Wei Li, Qi Yu, Qing Tao Yang, Tao Li
    Frontiers in Cell and Developmental Biology.2025;[Epub]     CrossRef
  • Correspondence: Response to the Letter Regarding "GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma"
    Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Serum Proteomic Profile Based on the TGF‐β Pathway Stratifies Risk of Hepatocellular Carcinoma
    Xiyan Xiang, Kirti Shetty, Herbert Yu, Bibhuti Mishra, Linda L. Wong, Xianghong Jasmine Zhou, Sanjaya K. Satapathy, James M. Crawford, Patricia S. Latham, Steven‐Huy Han, Brandon Mathew, Nabil N. Dagher, Lawrence Lau, Fellanza Cacaj, Anil K. Vegesna, Srin
    Liver International.2025;[Epub]     CrossRef
  • Systematic analysis of the expression profiles and prognostic values of the FAM72 family in liver cancer
    Weihao Kong, Long Teng, Kangjie Zhang, Yajun Zou, Xingyu Wang, Jianlin Zhang
    Biochemistry and Biophysics Reports.2025; 44: 102358.     CrossRef
  • 10,895 View
  • 969 Download
  • 3 Web of Science
  • Crossref

Hepatic neoplasm

Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won Kim, Jin Hyun Park, Suk Kyun Hong, Min-Hyeok Jung, Ji-One Pyeon, Jin-Young Lee, Kyung-Suk Suh, Nam-Joon Yi, YoungRok Choi, Kwang-Woong Lee, Young-Joon Kim
Clin Mol Hepatol 2025;31(2):563-576.
Published online January 13, 2025
DOI: https://doi.org/10.3350/cmh.2024.0899
Background/Aims
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
  • 6,493 View
  • 133 Download
  • 3 Web of Science

Review

Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review
Sang Jin Kim, Jong Man Kim
Clin Mol Hepatol 2022;28(4):739-753.
Published online April 26, 2022
DOI: https://doi.org/10.3350/cmh.2022.0060
Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.

Citations

Citations to this article as recorded by  Crossref logo
  • Rapamycin-loaded nanoparticles elicit local liver immunosuppressive and remote anti-tumor efficacy
    Yiyang Sun, Yanpeng Liu, Siyu Chen, Yidan Shen, Yangla Xie, Jing Zhang, Zhengxing Lian, Haiyang Xie, Sunbin Ling, Chang Xie, Haitao Hu, Huigang Li, Youqing Shen, Xiao Xu, Nasha Qiu
    Nano Today.2025; 61: 102589.     CrossRef
  • Comparative Validation of Prediction Models for HCC Outcomes in Living Donor Liver Transplantation: Superiority of Tumor Markers to Imaging Study
    Hwa‐Hee Koh, Minyu Kang, Deok‐Gie Kim, Jae Hyon Park, Eun‐Ki Min, Jae Geun Lee, Myoung Soo Kim, Dong Jin Joo
    Journal of Gastroenterology and Hepatology.2025; 40(3): 626.     CrossRef
  • Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
    Meng Sha, Jun Wang, Jie Cao, Zhi-Hui Zou, Xiao-ye Qu, Zhi-feng Xi, Chuan Shen, Ying Tong, Jian-jun Zhang, Seogsong Jeong, Qiang Xia
    Clinical and Molecular Hepatology.2025; 31(Suppl): S285.     CrossRef
  • α-Fetoprotein model versus Milan criteria in predicting outcomes after hepatic resection for hepatocellular carcinoma: multicentre study
    Chao Li, Yong-Kang Diao, Yi-Fan Li, Shao-Dong Lv, Xian-Ming Wang, Xue-Dong Wang, Qi-Xuan Zheng, Hong Wang, Han Liu, Kong-Ying Lin, Ying-Jian Liang, Ya-Hao Zhou, Wei-Min Gu, Ming-Da Wang, Lan-Qing Yao, Xin-Fei Xu, Jia-Hao Xu, Li-Hui Gu, Timothy M Pawlik, F
    BJS Open.2025;[Epub]     CrossRef
  • Comparison of initial treatments for resectable hepatocellular carcinoma within Milan criteria: an observational study based on a nationwide survey
    Sang Jin Kim, Woo Kyoung Jeong, Hyung-Joon Han, Gyu-Seong Choi, Kyun-Hwan Kim, Jongman Kim
    Annals of Surgical Treatment and Research.2025; 108(5): 279.     CrossRef
  • Traditional herbal medicine as an adjuvant therapy for preventing the recurrence of hepatocellular carcinoma after radical resection: Development and validation of a machine learning prediction model
    Xinyu Yue, Meihuan Fu, Song Yu, Huayue Shi, Simo Cheng, Xiaofeng Zhai
    European Journal of Integrative Medicine.2025; 78: 102535.     CrossRef


  • Experimental and Clinical Transplantation.2025;[Epub]     CrossRef
  • Integrating Alpha‐Fetoprotein and Protein Induced by Vitamin K Antagonist‐II as Surveillance Tools After Liver Transplantation for Hepatocellular Carcinoma: A Novel Protocol for Early Detection of Tumor Recurrence
    Jiyoung Kim, Kwang‐Woong Lee, Jae‐Yoon Kim, Jaewon Lee, Hyun Hwa Choi, Su young Hong, Jeong‐Moo Lee, Suk Kyun Hong, YoungRok Choi, Nam‐Joon Yi, Kyung‐Suk Suh
    Clinical Transplantation.2025;[Epub]     CrossRef
  • A non-invasive decision tree predicting recurrence-free survival after liver transplantation for hepatocellular carcinoma
    Mo-Dan Yang, Jian-Yong Zhuo, Guo-Ying Wang, Li Zhuang, Xiao Xu, Shu-Sen Zheng, Yang Yang, Di Lu
    Hepatobiliary & Pancreatic Diseases International.2025;[Epub]     CrossRef
  • Activating transcription factor 4-mediated upregulation of Heat Shock Protein Family A Member 4 promotes hepatocellular carcinoma progression through activation of Wnt/β-catenin/EMT signaling pathway
    Ruixi Li, Kunnan Wang, Naijing Hou, Yu Tian, Biyan Gong, Min Tang
    International Journal of Biological Macromolecules.2025; 333: 148850.     CrossRef
  • Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions
    Yang Gao, Jian-Ping Wang, De-Fei Hong, Chang Yang, Hua Naranmandura
    Bioengineering.2025; 12(11): 1206.     CrossRef
  • Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection
    Kyowon Gu, Ji Hye Min, Jeong Hyun Lee, Jaeseung Shin, Woo Kyoung Jeong, Young Kon Kim, Honsoul Kim, Sun-Young Baek, Jong Man Kim, Gyu Seong Choi, Jinsoo Rhu, Sang Yun Ha
    European Radiology.2024; 34(11): 7002.     CrossRef
  • From prediction to prevention: Machine learning revolutionizes hepatocellular carcinoma recurrence monitoring
    Mariana Michelle Ramírez-Mejía, Nahum Méndez-Sánchez
    World Journal of Gastroenterology.2024; 30(7): 631.     CrossRef
  • Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience
    Chase J. Wehrle, Roma Raj, Marianna Maspero, Sangeeta Satish, Bijan Eghtesad, Alejandro Pita, Jaekeun Kim, Mazhar Khalil, Esteban Calderon, Danny Orabi, Bobby Zervos, Jamak Modaresi Esfeh, Maureen Whitsett Linganna, Teresa Diago-Uso, Masato Fujiki, Cristi
    International Journal of Surgery.2024; 110(5): 2818.     CrossRef
  • Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?
    Nourhan Badwei
    World Journal of Transplantation.2024;[Epub]     CrossRef
  • Advances in Understanding Hepatocellular Carcinoma Vasculature: Implications for Diagnosis, Prognostication, and Treatment
    Hyungjin Rhee, Young Nyun Park, Jin-Young Choi
    Korean Journal of Radiology.2024; 25(10): 887.     CrossRef
  • An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma
    Modan Yang, Zuyuan Lin, Li Zhuang, Linhui Pan, Rui Wang, Hao Chen, Zhihang Hu, Wei Shen, Jianyong Zhuo, Xinyu Yang, Huigang Li, Chiyu He, Zhe Yang, Qinfen Xie, Siyi Dong, Junli Chen, Renyi Su, Xuyong Wei, Junjie Yin, Shusen Zheng, Di Lu, Xiao Xu
    MedComm.2024;[Epub]     CrossRef
  • New prognostic model for liver transplantation outcomes in hepatocellular carcinoma
    S. E. Voskanyan, V. S. Rudakov, A. I. Sushkov, M. V. Popov, A. N. Bashkov, K. K. Gubarev, A. I. Artemyev, I. Yu. Kolyshev, M. Muktazhan, A. N. Pashkov, E. V. Naydenov, D. S. Svetlakova
    Transplantologiya. The Russian Journal of Transplantation.2024; 16(3): 278.     CrossRef
  • Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis
    Chiyu He, Zhihang Hu, Zuyuan Lin, Hao Chen, Chenghao Cao, Jinyan Chen, Xudong Yang, Huigang Li, Wei Shen, Xuyong Wei, Li Zhuang, Shusen Zheng, Xiao Xu, Di Lu
    BMC Cancer.2024;[Epub]     CrossRef
  • Severity of microvascular invasion does matter in hepatocellular carcinoma prognosis: Editorial on “Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging”
    Abdelrahman M Attia, Hasmik Adetyan, Ju Dong Yang
    Clinical and Molecular Hepatology.2024; 30(4): 653.     CrossRef
  • Lack of progress in cancer-related outcomes after liver transplantation: Mitigating risk and identifying future needs to move this needle
    Alex Liu, Wei Rao, Kymberly D. Watt
    Liver Transplantation.2024;[Epub]     CrossRef
  • Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation
    Jianming Yang, Yewu Chen, Haobin Sun, Xijian Zhang, Jianfeng Wang, Zhixing Liang, Binsheng Fu, Tong Zhang, Shuhong Yi, Yinan Deng, Yang Yang
    Infectious Agents and Cancer.2023;[Epub]     CrossRef
  • Molecular Clues for Prediction of Hepatocellular Carcinoma Recurrence After Liver Transplantation
    Nourhan Badwei
    Journal of Clinical and Experimental Hepatology.2023; 13(5): 804.     CrossRef
  • Persistently Elevated HBV Viral-Host Junction DNA in Urine as a Biomarker for Hepatocellular Carcinoma Minimum Residual Disease and Recurrence: A Pilot Study
    Selena Y. Lin, Dina Halegoua-DeMarzio, Peter Block, Yu-Lan Kao, Jesse Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su
    Diagnostics.2023; 13(9): 1537.     CrossRef
  • Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging
    Yoon Jung Hwang, Jae Seok Bae, Youngeun Lee, Bo Yun Hur, Dong Ho Lee, Haeryoung Kim
    Clinical and Molecular Hepatology.2023; 29(3): 733.     CrossRef
  • Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients
    Xiaoning Wu, Xiaoqian Xu, Jialing Zhou, Yameng Sun, Huiguo Ding, Wen Xie, Guofeng Chen, Anlin Ma, HongXin Piao, Bingqiong Wang, Shuyan Chen, Tongtong Meng, Xiaojuan Ou, Hwai-I Yang, Jidong Jia, Yuanyuan Kong, Hong You
    Clinical and Molecular Hepatology.2023; 29(3): 747.     CrossRef
  • Sequential regorafenib or nivolumab therapy in recurrent hepatocellular carcinoma with sorafenib failure in liver transplant patients does not improve prognosis
    Jieun Kwon, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh
    Annals of Liver Transplantation.2023; 3(2): 104.     CrossRef
  • Neutrophil extracellular traps and complications of liver transplantation
    Yanyao Liu, Ping Yan, Yue Bin, Xiaoyan Qin, Zhongjun Wu
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • 9,549 View
  • 203 Download
  • 26 Web of Science
  • Crossref

Editorial

Hepatic neoplasm

Surgical resection versus ablation for early hepatocellular carcinoma: The debate is still open
Bo Hyun Kim
Clin Mol Hepatol 2022;28(2):174-176.
Published online January 26, 2022
DOI: https://doi.org/10.3350/cmh.2021.0400

Citations

Citations to this article as recorded by  Crossref logo
  • Partial Hepatectomy and Ablation for Survival of Early-Stage Hepatocellular Carcinoma Patients: A Bayesian Emulation Analysis
    Jiping Wang, Yunju Im, Rong Wang, Shuangge Ma
    Life.2024; 14(6): 661.     CrossRef
  • Mucins as Potential Biomarkers for Early Detection of Cancer
    Shailendra K. Gautam, Parvez Khan, Gopalakrishnan Natarajan, Pranita Atri, Abhijit Aithal, Apar K. Ganti, Surinder K. Batra, Mohd W. Nasser, Maneesh Jain
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  • Hepatocellular Carcinoma from a Hepatologist's Perspective
    Giovanni A. Roldan, Jacquelin Blomker, Elizabeth S. Aby
    Seminars in Interventional Radiology.2023; 40(06): 524.     CrossRef
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  • 131 Download
  • 3 Web of Science
  • Crossref

Review

Hepatic neoplasm

The management of post-transplantation recurrence of hepatocellular carcinoma
Luckshi Rajendran, Tommy Ivanics, Marco PAW Claasen, Hala Muaddi, Gonzalo Sapisochin
Clin Mol Hepatol 2022;28(1):1-16.
Published online October 5, 2021
DOI: https://doi.org/10.3350/cmh.2021.0217
The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.

Citations

Citations to this article as recorded by  Crossref logo
  • Recipient blood group does not affect hepatocellular carcinoma recurrence after living donor liver transplantation in Korea
    Sung-Min Kim, Shin Hwang, Gi-Won Song, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Dong-Hwan Jung, Gil-Chun Park, Young-In Yoon, Woo-Hyoung Kang, Sang-Hoon Kim, Sung-Gyu Lee
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  • Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
    Satohiro Masuda, Florian Lemaitre, Markus J. Barten, Stein Bergan, Maria Shipkova, Teun van Gelder, Sander Vinks, Eberhard Wieland, Kirsten Bornemann-Kolatzki, Mercè Brunet, Brenda de Winter, Maja-Theresa Dieterlen, Laure Elens, Taihei Ito, Kamisha Johnso
    Therapeutic Drug Monitoring.2025; 47(1): 4.     CrossRef
  • New Scenarios in Liver Transplantation for Hepatocellular Carcinoma
    Ezequiel Mauro, Manuel Rodríguez‐Perálvarez, Antonio D'Alessio, Gonzalo Crespo, Federico Piñero, Eleonora De Martin, Jordi Colmenero, David James Pinato, Alejandro Forner
    Liver International.2025;[Epub]     CrossRef
  • Analysis of treatment benefits and prognostic factors for posttransplant HCC recurrence in a large Euro-American-Asian cohort
    Zhihao Li, Itsuko Chih-Yi Chen, Leonardo Centonze, Christian T.J. Magyar, Woo Jin Choi, Sachin Shah, Grainne M. O’Kane, Arndt Vogel, Luciano De Carlis, Jan Lerut, Quirino Lai, Neil Mehta, Chao-Long Chen, Gonzalo Sapisochin
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  • Prognosis predictors of hepatocellular carcinoma after hepatectomy following conversion therapy
    Shaoru Liu, Zongfeng Wu, Chenwei Wang, Liang Qiao, Zhenkun Huang, Yichuan Yuan, Ruhai Zou, Wei He, Binkui Li, Yunfei Yuan, Jiliang Qiu
    European Journal of Surgical Oncology.2025; 51(1): 109375.     CrossRef
  • Comparative Outcome Analysis of Lenvatinib Versus Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation
    Christian T. J. Magyar, Sheron Perera, Luckshi Rajendran, Zhihao Li, Fahad A. Almugbel, Sophie Feng, Woo Jin Choi, Laia Aceituno, Arndt Vogel, Robert C. Grant, Nazia Selzner, Elmar Jaeckel, Nazanin Falla-Rad, Jennifer J. Knox, Eric X. Chen, Gonzalo Sapiso
    Transplantation.2025; 109(4): 681.     CrossRef
  • Rapamycin-loaded nanoparticles elicit local liver immunosuppressive and remote anti-tumor efficacy
    Yiyang Sun, Yanpeng Liu, Siyu Chen, Yidan Shen, Yangla Xie, Jing Zhang, Zhengxing Lian, Haiyang Xie, Sunbin Ling, Chang Xie, Haitao Hu, Huigang Li, Youqing Shen, Xiao Xu, Nasha Qiu
    Nano Today.2025; 61: 102589.     CrossRef
  • Comparative Validation of Prediction Models for HCC Outcomes in Living Donor Liver Transplantation: Superiority of Tumor Markers to Imaging Study
    Hwa‐Hee Koh, Minyu Kang, Deok‐Gie Kim, Jae Hyon Park, Eun‐Ki Min, Jae Geun Lee, Myoung Soo Kim, Dong Jin Joo
    Journal of Gastroenterology and Hepatology.2025; 40(3): 626.     CrossRef
  • Renal metastasis of hepatocellular carcinoma after living donor liver transplantation
    Yo Nakamura, Jun Kamei, Ryo Tanaka, Yoichi Yasunaga, Nobuhisa Akamatsu, Satoru Taguchi, Shigenori Kakutani, Yuta Yamada, Aya Niimi, Daisuke Yamada, Haruki Kume
    IJU Case Reports.2025; 8(2): 133.     CrossRef
  • Construction and Validation of a Novel Butyrylation-Related Gene Signature Related to Prognosis, Clinical Implications, and Immune Microenvironment Characterization of Hepatocellular Carcinoma
    Weiping Su, Yangying Zhou, Xuanxuan Li, Kuo Kang, Hui Nie
    ACS Omega.2025; 10(4): 3375.     CrossRef
  • ZNF384 and m6A methylation promote the progression of hepatocellular carcinoma by regulating the interaction between LINC00342 and DAPK1
    Shujia Kong, Jiaxun Li, Xin Pan, Chen Zhao, Yanwen Li
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Original Articles

Liver Transplantation

Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma
Incheon Kang, Jae Geun Lee, Sung Hoon Choi, Hyun Jeong Kim, Dai Hoon Han, Gi Hong Choi, Myoung Soo Kim, Jin Sub Choi, Soon Il Kim, Dong Jin Joo
Clin Mol Hepatol 2021;27(4):589-602.
Published online July 23, 2021
DOI: https://doi.org/10.3350/cmh.2021.0038
Background/Aims
This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).
Methods
The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated.
Results
The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001).
Conclusions
Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

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Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma
Ching-Chih Lin, Ta-Wei Liu, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Chung-Feng Huang, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Clin Mol Hepatol 2021;27(2):313-328.
Published online December 14, 2020
DOI: https://doi.org/10.3350/cmh.2020.0247
Background/Aims
Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.
Methods
The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.
Results
GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.
Conclusions
Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

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Letter to the Editor

Hepatic neoplasm

How long should physicians follow up with patients after curative treatment for hepatocellular carcinoma?
Bo Hyun Kim
Clin Mol Hepatol 2020;26(4):579-581.
Published online September 23, 2020
DOI: https://doi.org/10.3350/cmh.2020.0200

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  • Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
    Tae Suk Kim, Minjong Lee, Minji Park, Sae Yun Kim, Min Suk Shim, Chea Yeon Lee, Dae Hee Choi, Yuri Cho
    International Journal of Molecular Sciences.2021; 22(18): 10027.     CrossRef
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Editorial

Hepatic neoplasm

Long-term prognosis and management of hepatocellular carcinoma after curative treatment
Naoshi Nishida
Clin Mol Hepatol 2020;26(4):480-483.
Published online September 21, 2020
DOI: https://doi.org/10.3350/cmh.2020.0208

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Original Articles

Hepatic neoplasm

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients
Jihye Kim, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik
Clin Mol Hepatol 2020;26(4):516-528.
Published online September 11, 2020
DOI: https://doi.org/10.3350/cmh.2020.0016
Background/Aims
Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.
Methods
A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.
Results
During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.
Conclusions
The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

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Hepatic neoplasm

Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial
Sang Min Yoon, So Yeon Kim, Young-Suk Lim, Kang Mo Kim, Ju Hyun Shim, Danbi Lee, Jihyun An, Jinhong Jung, Jong Hoon Kim, Han Chu Lee
Clin Mol Hepatol 2020;26(4):506-515.
Published online July 10, 2020
DOI: https://doi.org/10.3350/cmh.2020.0038
Background/Aims
Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs.
Methods
A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria.
Results
Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events.
Conclusions
SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

Citations

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  • 62 Web of Science
  • Crossref

Hepatic neoplasm

Safety margin of embolized area can reduce local recurrence of hepatocellular carcinoma after superselective transarterial chemoembolization
Kittipitch Bannangkoon, Keerati Hongsakul, Teeravut Tubtawee, Teerha Piratvisuth
Clin Mol Hepatol 2019;25(1):74-85.
Published online February 28, 2019
DOI: https://doi.org/10.3350/cmh.2018.0072
Background/Aims
We aimed to determine the relationship between the safety margin of an embolized area and local tumor recurrence (LTR) of patients with hepatocellular carcinoma (HCC) who underwent superselective transarterial chemoembolization (TACE).
Methods
The medical records of 77 HCC patients with 109 HCC nodules who underwent superselective TACE were retrospectively analyzed for LTR. Univariate and multivariate analyses were performed for 16 potential factors using Cox proportional hazard regression. Iodized oil deposition on cone-beam computed tomography (CBCT) imaging was divided into three grades: A=complete tumor staining and complete circumferential safety margin, B=complete tumor staining but incomplete safety margin, C=incomplete tumor staining. The effect of a safety margin on LTR was evaluated by comparison between grade A and B group.
Results
Univariate and multivariate analyses revealed that grade A iodized oil deposition and portal vein visualization were the only two independent significant factors of LTR (P<0.001 and P=0.029, respectively). The 12- and 24-month LTR rates of tumors for grade A (n=62), grade B (n=30), and grade C (n=17) were 16% vs. 41% vs. 100% and 16% vs. 61% vs. 100%, respectively (P<0.001). The tumors in the grade A group had a 75% risk reduction in LTR (odds ratio, 0.25; 95% confidence interval, 0.10 to 0.64; P=0.004) compared to the grade B group.
Conclusions
LTR was significantly lower when a greater degree of iodized oil deposition occurred with a complete circumferential safety margin. In superselective TACE, the safety margin of the embolized areas using intraprocedural CBCT affected LTR in HCC patients.

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Liver Imaging

Hepatic neoplasm

Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma
Tae Wook Kang, Hyo Keun Lim, Dong Ik Cha
Clin Mol Hepatol 2017;23(1):95-101.
Published online March 24, 2017
DOI: https://doi.org/10.3350/cmh.2017.0006
Image-guided radiofrequency ablation (RFA) is an evolving and growing treatment option for patients with hepatocellular carcinoma (HCC) and hepatic metastasis. RFA offers significant advantages as it is less invasive than surgery and carries a low risk of major complications. However, serious complications, including aggressive tumor recurrence, may be observed during follow-up, and recently, mechanical or thermal damage during RFA has been proposed to be one of the causes of this kind of recurrence. Although the exact mechanism of this still remains unclear, physicians should be familiar with the imaging features of aggressive tumor recurrence after RFA for HCC and its risk factors. In addition, in order to prevent or minimize this newly recognized tumor recurrence, a modified RFA technique, combined RFA treatments with transarterial chemoembolization, and cryoablation can be used as alternative treatments. Ultimately, combining an understanding of this potential complication of RFA with an understanding of the possible risk factors for aggressive tumor recurrence and choosing alternative treatments are crucial to optimize clinical outcomes in each patient with HCC.

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Original Article

Hepatic neoplasm

Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma
Ju-Yeon Cho, Moon Seok Choi, Gil Sun Lee, Won Sohn, Jemma Ahn, Dong-Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik
Clin Mol Hepatol 2016;22(4):477-486.
Published online December 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0048
Background/Aims
Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated.
Methods
In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated.
Results
During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence.
Conclusions
Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.

Citations

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Reviews

Hepatic neoplasm

Current status of laparoscopic liver resection for hepatocellular carcinoma
Hanisah Guro, Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, YoungRok Choi, Mohan Periyasamy
Clin Mol Hepatol 2016;22(2):212-218.
Published online June 15, 2016
DOI: https://doi.org/10.3350/cmh.2016.0026
Laparoscopic liver resection (LLR) is becoming widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic left lateral sectionectomy and minor laparoscopic liver resection are now considered standard approaches, especially for tumors located in the anterolateral segments of the liver. Laparoscopic left lateral sectionectomy in adult donors is also gaining acceptance for child liver transplantation in many centers. Major LLRs, including left hepatectomy and right hepatectomy, have been recently attempted. Laparoscopic donor hepatectomy is becoming more popular owing to increasing demand from young living donors who appreciate its minimal invasiveness and excellent cosmetic outcomes. Several centers have performed total laparoscopic donor right hepatectomy in adult-to-adult living donor liver transplantation. Many meta-analyses have shown that LLR is better than open liver resection in terms of short-term outcomes, principally cosmetic outcomes. Although no randomized control trials have compared LLR with open liver resection, the long-term oncologic outcomes were similar for both procedures in recent case-matched studies.

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    Mohan Periyasamy, Jai Young Cho, Soyeon Ahn, Ho-Seong Han, Yoo-Seok Yoon, YoungRok Choi, Jae Seong Jang, Seong Uk Kwon, Sungho Kim, Jang Kyu Choi, Hanisah Guro
    Surgical Endoscopy.2017; 31(12): 5209.     CrossRef
  • Consensus on Stereotactic Body Radiation Therapy for Small-Sized Hepatocellular Carcinoma at the 7th Asia-Pacific Primary Liver Cancer Expert Meeting
    Zhao-Chong Zeng, Jinsil Seong, Sang Min Yoon, Jason Chia-Hsien Cheng, Ka-On Lam, Ann-Shing Lee, Ada Law, Jian-Ying Zhang, Yong Hu
    Liver Cancer.2017; 6(4): 264.     CrossRef
  • Update on current problems in colorectal liver metastasis
    Jeffrey Chakedis, Malcolm H. Squires, Eliza W. Beal, Tasha Hughes, Heather Lewis, Anghela Paredes, Mazen Al-Mansour, Steven Sun, Jordan M. Cloyd, Timothy M. Pawlik
    Current Problems in Surgery.2017; 54(11): 554.     CrossRef
  • Is laparoscopic hepatectomy superior to open hepatectomy for hepatocellular carcinoma?
    Jian-Hong Zhong, Ning-Fu Peng, Jian-Hong Gu, Ming-Hua Zheng, Le-Qun Li
    World Journal of Hepatology.2017; 9(4): 167.     CrossRef
  • Current Status of Laparoscopic Liver Resection: Experiences from Tertiary Center
    Mohan Periyasamy, Ho-Seong Han, Jai Young Cho, Yoo-Seok Yoon, Young Rok Choi, Jae Seong Jang, Seong Uk Kwon, Sungho Kim, Jang Kyu Choi, Hanisah Guro
    The Journal of Minimally Invasive Surgery.2017; 20(4): 125.     CrossRef
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Viral hepatitis

Management of viral hepatitis in liver transplant recipients
Soung Won Jeong, YoungRok Choi, Jin-Wook Kim
Clin Mol Hepatol 2014;20(4):338-344.
Published online December 24, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.4.338

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.

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  • Hepatitis E in post‐liver transplantation: is it time to routinely consider it?
    Brian B. Borg, Zongdi Feng, Truman M. Earl, Christopher D. Anderson
    Clinical Transplantation.2016; 30(9): 975.     CrossRef
  • Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus
    Neal Patel, Kian Bichoupan, Lawrence Ku, Rachana Yalamanchili, Alyson Harty, Donald Gardenier, Michel Ng, David Motamed, Viktoriya Khaitova, Nancy Bach, Charissa Chang, Priya Grewal, Meena Bansal, Ritu Agarwal, Lawrence Liu, Gene Im, Jennifer Leong, Leona
    World Journal of Gastroenterology.2016; 22(9): 2844.     CrossRef
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    Nouredine Behloul, Jiyue Wen, Xing Dai, Chen Dong, Jihong Meng
    Infection, Genetics and Evolution.2015; 34: 211.     CrossRef
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Original Articles

Could patients who underwent hepatic resection due to hepatocellular carcinoma with high alpha-fetoprotein be monitored for recurrence by alpha-fetoprotein Level?
Woo Young Shin, M.D., Kyung-Suk Suh, M.D.1, Taehoon Kim, M.D.1, Young Min Jeon, M.D.1, Nam-Joon Yi, M.D.1, Kuhn Uk Lee, M.D.1
Korean J Hepatol 2010;16(2):168-175.
Published online June 25, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.2.168
Background/Aims
The follow-up strategy after hepatectomy for hepatocellular carcinoma (HCC) usually depends on the experience of physician, resulting in frequent imaging studies, which leads to increased cost. Hence, we investigated the role of monitoring alpha-fetoprotein (AFP) levels after hepatectomy in patients with preoperative high AFP. Methods: From January 2000 to December 2004, 66 patients who underwent curative hepatectomy due to HCC with preoperative AFP level >400 ng/ml were reviewed. Changes in AFP level after the operation were investigated. The recurrence was suspected in case of two consecutive increase of AFP over cut-off value. Cut-off value was determined by ROC curve. All patients were divided into 2 groups: patients who met the definition (Group S) and those who didn`t (Group D). Results: AFP level of 20ng/ml was proposed as the cut-off value for diagnosis of recurrence by ROC curve. Thirty two patients who didn`t have the AFP level decreased below 20 ng/ml after the resection had HCC recurred, whereas 16 out of 34 patients who had AFP decreased had tumor recurrence. The AFP level of patients without recurrence was kept below 20 ng/ml during the follow-up. The AFP level of 44 out of 48 recurred patients increased over 20ng/ml upon recurrence. By definition, group D were 5 patients. In 4 patients of group D, the AFP level didn`t increase above 20 ng/ml upon recurrence. These patients had HCC and they recurred 1 year after the surgery. Conclusions: In patients with preoperative AFP level >400 ng/ml, the AFP level tended to increase above 20ng/ml at recurrence mostly within 1 year. Hence, we proposed that these patients could be monitored by only AFP until 1 year after surgery.

Citations

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  • Alpha-fetoprotein level to total tumor volume as a predictor of hepatocellular carcinoma recurrence after resection. A retrospective cohort study
    Hazem M. Zakaria, Anwar Mohamed, Hazem Omar, Nahla K. Gaballa
    Annals of Medicine and Surgery.2020; 54: 109.     CrossRef
  • Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection
    Yeshika Sharma, Michael J. Weaver, Daniel R. Ludwig, Kathryn Fowler, Neeta Vachharajani, William C. Chapman, Jeffrey S. Crippin
    Surgery.2018; 163(5): 1002.     CrossRef
  • Localized Uterine Recurrence of Hepatocellular Carcinoma 4 Years after Curative Resection
    Sang Jin Lee, Jung Woo Shin, Neung Hwa Park, Yang Won Nah, Hang Jo Yoo, Yoong Ki Jung, Hye Jeong Choi
    Korean Journal of Medicine.2012; 82(5): 603.     CrossRef
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Risk factors for early recurrence after surgical resection for hepatocellular carcinoma
Ui Jun Park, M.D., Yong Hoon Kim, M.D., Koo Jeong Kang, M.D., Tae Jin Lim, M.D.
Korean J Hepatol 2008;14(3):371-380.
Published online September 30, 2008
DOI: https://doi.org/10.3350/kjhep.2008.14.3.371
Background/Aims
Early recurrence (ER) after liver resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aimed to identify the factors associated with ER after curative hepatic resection for HCC. Methods: From the July 2000 to July 2006, 144 patients underwent hepatic resection for HCC at a single institution. After excluding those with ruptured HCC, combined or mixed HCC, and who died during admission, 116 patients were analyzed. Patients with ER (defined as within 1 year) were compared with those who remained free of disease for more than 1 year. Various clinical characteristics including tumor and operative factors were evaluated to determine the factors predicting postoperative ER using univariate and multivariate analyses. Results: ER occurred in 51 patients (44%). In the univariate analysis, tumor size (P=0.001), microvascular invasion (P=0.003), portal vein invasion (P=0.001), TNM stage (P=0.010), serum levels of alpha-fetoprotein (AFP) (P=0.002) and aspartate aminotransferase (AST) (P=0.011), and operative time (P=0.033) were significantly associated with ER. AFP and AST were the independent predictors of ER in the multivariate analysis (P<0.05). Conclusions: Preoperative serum AFP and AST levels were the independent risk factors for ER after surgical resection for HCC. Close postoperative surveillance is recommended for early detection of recurrence and additional treatments in patients with these factors. (Korean J Hepatol 2008;14:371-380)

Citations

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  • The impact of curative conversion therapy aimed at a cancer‐free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab
    Shigeo Shimose, Hideki Iwamoto, Tomotake Shirono, Masatoshi Tanaka, Takashi Niizeki, Masahiko Kajiwara, Satoshi Itano, Yoichi Yano, Satoru Matsugaki, Etsuko Moriyama, Yu Noda, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, Takumi Kawaguchi
    Cancer Medicine.2023; 12(11): 12325.     CrossRef
  • Prognostic Analysis of Postoperative Survival for Ruptured Hepatocellular Carcinoma with or without Cirrhosis
    Feng Xia, Peng Zhu, Xiao-Ping Chen, Bi-Xiang Zhang, Ming-Yu Zhang, Subhadeep Roy
    Journal of Oncology.2022; 2022: 1.     CrossRef
  • Hepatocellular carcinoma: preoperative gadoxetic acid–enhanced MR imaging can predict early recurrence after curative resection using image features and texture analysis
    Su Joa Ahn, Jung Hoon Kim, Sang Joon Park, Seung Tack Kim, Joon Koo Han
    Abdominal Radiology.2019; 44(2): 539.     CrossRef
  • Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm
    Chao Zhang, Xiangmei Chen, Hui Liu, Hui Li, Wei Jiang, Wenting Hou, Michael A. McNutt, Fengmin Lu, Gang Li
    International Journal of Cancer.2015; 137(8): 1818.     CrossRef
  • Metabolic profiling study of early and late recurrence of hepatocellular carcinoma based on liquid chromatography-mass spectrometry
    Lina Zhou, Yuan Liao, Peiyuan Yin, Zhongda Zeng, Jia Li, Xin Lu, Limin Zheng, Guowang Xu
    Journal of Chromatography B.2014; 966: 163.     CrossRef
  • Comparing Staging Systems for Predicting Prognosis and Survival in Patients with Hepatocellular Carcinoma in Egypt
    Asmaa Ibrahim Gomaa, Mohamed Saad Hashim, Imam Waked, Ferruccio Bonino
    PLoS ONE.2014; 9(3): e90929.     CrossRef
  • Early diffuse recurrence of hepatocellular carcinoma after percutaneous radiofrequency ablation: analysis of risk factors
    Hee Young Lee, Hyunchul Rhim, Min Woo Lee, Young-sun Kim, Dongil Choi, Min Jung Park, Young Kon Kim, Seong Hyun Kim, Hyo Keun Lim
    European Radiology.2013; 23(1): 190.     CrossRef
  • Diffusion-weighted imaging of hepatocellular carcinoma for predicting early recurrence and survival after hepatectomy
    Ali Muhi, Tomoaki Ichikawa, Utaroh Motosugi, Katsuhiro Sano, Zareen Fatima, Masanori Matsuda, Hideki Fujii, Nobuyuki Enomoto, Tsutomu Araki
    Hepatology International.2013; 7(2): 662.     CrossRef
  • Localized Uterine Recurrence of Hepatocellular Carcinoma 4 Years after Curative Resection
    Sang Jin Lee, Jung Woo Shin, Neung Hwa Park, Yang Won Nah, Hang Jo Yoo, Yoong Ki Jung, Hye Jeong Choi
    Korean Journal of Medicine.2012; 82(5): 603.     CrossRef
  • Impact of intracellular alpha fetoprotein on retinoic acid receptors‐mediated expression of GADD153 in human hepatoma cell lines
    Chaoying Li, Shanshan Wang, Wei Jiang, Hui Li, Zhongmin Liu, Chao Zhang, Michael A. McNutt, Gang Li
    International Journal of Cancer.2012; 130(4): 754.     CrossRef
  • The Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection and Cirrhosis
    Qing Zhang, Xinguo Chen, Yunjin Zang, Li Zhang, Hong Chen, Letian Wang, Yujian Niu, Xiuyun Ren, Zhongyang Shen, Lei Shang, Michael Bouchard
    PLoS ONE.2012; 7(12): e50919.     CrossRef
  • Risk Factors for Intrahepatic Recurrence after Resection of Hepatocellular Carcinomas in Patients with Hepatitis B Virus Infection
    Myung Hee Yoon, Young Il Choi, Kwang Kuk Park, Dong Hoon Shin, Chung Han Lee
    Korean Journal of Hepato-Biliary-Pancreatic Surgery.2011; 15(2): 83.     CrossRef
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Expression of vascular endothelial growth factor (VEGF) family members and prognosis after hepatic resection in HBV-related hepatocellular carcinoma
Ju Ik Moon, M.D., Jong Man Kim, M.D., Gum Oh Jung, M.D., Jae Min Chun, M.D., Gyu-Seong Choi, M.D., Jae Berm Park, M.D., Choon Hyuck David Kwon, M.D., Sung Joo Kim, M.D., Jae Won Jo, M.D.,
Korean J Hepatol 2008;14(2):185-196.
Published online June 20, 2008
DOI: https://doi.org/10.3350/kjhep.2008.14.2.185
Background/Aims
Human hepatocellular carcinoma (HCC) is a hypervascular tumor, and vascular endothelial growth factor (VEGF) plays a key role in the regulation of tumor-associated angiogenesis. In this study, we analyzed the significance of the expression of VEGF family members on the prognosis and clinicopathologic progress of HCC. Methods: Surgically resected specimens of HCC and noncancerous liver tissue were obtained from 323 patients with HCC, and VEGF mRNA was examined by quantitative reverse transcriptase-polymerase chain reactions (RT-PCRs). Patients who were seropositive for hepatitis B surface antigen were selected for the analysis (n=208). The VEGFtumor/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) tumor/VEGFnontumor/GAPDHnontumor ratio was calculated using a quantitative RT-PCR assay, and the relationships between the expressions of VEGF family members and clinicopathologic parameters were analyzed to evaluate their significance in the prognosis of HCC. Results: The disease-free survival was significantly worse in the high-VEGF-A group than in the low-VEGF-A group (P=0.035), whereas VEGF-A expression was not significantly related to overall survival (P=0.172). The factors significantly related to poor prognosis in univariate analysis were tumor size, portal vein invasion, microvascular thrombi, intrahepatic metastasis, tumor capsule invasion, liver capsule invasion, preoperative serum albumin level, and VEGF-A ratio. Multivariate analysis showed that a poor prognosis in HCC patients was significantly related to portal vein invasion (hazard ratio=3.381, P<0.001), intrahepatic metastasis (hazard ratio=2.379, P<0.001), tumor size (hazard ratio=1.834, P=0.003), and preoperative serum albumin level (hazard ratio=2.050, P=0.006). Conclusions: Our study showed that the expression of VEGF-A is positively correlated with the recurrence rate of HCC after curative resection. Therefore, a high expression of VEGF-A might be predictive of HCC recurrence after curative resection. (Korean J Hepatol 2008;14:185-196)

Citations

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  • The tumor microenvironment in the postsurgical liver: Mechanisms and potential targets of postoperative recurrence in human hepatocellular carcinoma
    Junyu Wu, Yau‐Tuen Chan, Yuanjun Lu, Ning Wang, Yibin Feng
    Medicinal Research Reviews.2023; 43(6): 1946.     CrossRef
  • Woodchuck VEGF (wVEGF) characteristics: Model for angiogenesis and human hepatocellular carcinoma directed therapies
    Huayi Huang, Oreste Salavaggione, Lee Rivera, Sarbajit Mukherjee, Rolf Brekken, Bud Tennant, Renuka Iyer, Araba Adjei
    Archives of Biochemistry and Biophysics.2019; 661: 97.     CrossRef
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    Pengyuan Yang, Geoffrey J. Markowitz, Xiao-Fan Wang
    National Science Review.2014; 1(3): 396.     CrossRef
  • HCC and angiogenesis: possible targets and future directions
    Andrew X. Zhu, Dan G. Duda, Dushyant V. Sahani, Rakesh K. Jain
    Nature Reviews Clinical Oncology.2011; 8(5): 292.     CrossRef
  • 6,495 View
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Clinical Outcome after Living Donor Liver Transplantation in Patients with Hepatitis C Virus-associated Cirrhosis
Jeong-Ik Park, M.D.1, Kun-Moo Choi, M.D.2, Sung-Gyu Lee, M.D.1, Shin Hwang, M.D.1, Ki-Hun Kim, M.D.1, Chul-Soo Ahn, M.D.1, Deok-Bog Moon, M.D.1, Young-Hwa Chung, M.D.3, Yung-Sang Lee, M.D.3, Dong-Jin Suh, M.D.3
Korean J Hepatol 2007;13(4):543-555.
Published online December 20, 2007
DOI: https://doi.org/10.3350/kjhep.2007.13.4.543
Background/Aims
Hepatitis C virus (HCV)-associated cirrhosis is an increasingly frequent indication for liver transplantation (LT). However, HCV recurrence is universal and this immediately occurs following LT, which endangers both the graft and patient survival. We investigated the frequency of posttransplant recurrence of HCV infection and the patient-graft survival, and we analyzed the responses to ribavirin and interferon therapy in the patients with recurrent HCV infection after living donor liver transplantation (LDLT). Methods: We retrospectively reviewed the clinical outcomes of 39 HCV-associated cirrhosis patients who underwent LDLT at Asan Medical Center between August 1992 and June 2006. In this study, the diagnosis of recurrent HCV was made on the basis of increased transaminases and serum HCV RNA levels greater than 10 million IU/mL because protocol liver biopsy was not performed. Results: HCV recurrence was seen in 26 of the 39 LDLT patients (66.7%). 86.7% of recurrence occurred within the first postoperative year. Antiviral treatment was used for all patients with recurrence of HCV. None of the 10 patients receiving ribavirin alone and 9 of 16 patients who received combination therapy with pegylated interferon alpha-2a plus ribavirin became HCV RNA negative and they remained persistently negative during the median follow-up of 24.9 months. Our data indicates that there is no significant factor influencing HCV recurrence except for the recipient`s age. The 2-year patient survival for the HCV patients with HCC and those patients without HCC were 81.2% and 81.3%, respectively (P=0.85) and the 2-year graft survival rates were 81.2% and 68.2%, respectively (P=0.29). No patient died from HCV recurrence during the follow-up period. Conclusions: Combination therapy with ribavirin and interferon appears to improve the outcome of recurrent HCV infected patients after LDLT. (Korean J Hepatol 2007;13:543-555)

Citations

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  • Current Status and Perspectives of Living Donor Liver Transplantation
    Shin Hwang, Deok-Bog Moon, Sung-Gyu Lee
    Journal of the Korean Medical Association.2008; 51(8): 700.     CrossRef
  • Review: Clinical Outcome after Living Donor Liver Transplantation in Patients with Hepatitis C Virus-associated Cirrhosis
    Hyung Joon Kim
    The Korean Journal of Hepatology.2007; 13(4): 489.     CrossRef
  • 5,740 View
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Usefulness of Lens Culinaris Agglutinin - A Reactive Alpha - Fetoprotein for the Diagnosis of Hepatocelluar Carcinoma in Patients with Chronic Liver Disease Who Showed Significant Increment of Serum Alpha - Fetoprotein Level and No Mass Lesion in the Liver on Ultrasonogram
June Sung Lee , Jung Hwan Yoon , Hyo Suk Lee , Chung Yong Kim
Korean J Hepatol 1998;4(2):120-130.
Background/Aims
' Lens culinaris agglutinin-A reactive alpha-fetoprotein (AFP L3) has been reported to be highly specific for the diagnosis of hepatocellular carcinoma (HCC). The present study was to evaluate the clinical usefulness of AFP-L3 for the diagnosis of HCC in the patients either with chronic liver disease or with HCC in complete remission who showed significant increment of serum AFP level and no mass lesion in the liver on ultrasonography. Methods' A total numer of 34 patients (24 with chronic liver disease, 10 with HCC in complete remission) were enrolled, who showed significant increment of serum AFP level and no mass lesion in the liver on ultrasonography. Serum AFP L3 levels were analysed by AFP differentiation kit L. Abdominal spiral CT or ultrasonogram was performed at 1-3 month intervals and all of the patients were followed up for more than 6 months. Results- Among 24 patients with chronic liver disease, two were positive (higher than 15%) for AFP L3; however, HCC was not detected in these patients, while HCCs were detected in two of 22 patients negative for AFP L3 during followe-up. Eight of the 10 patients with HCC in complete remission were positive for AFP L3; recurrent HCCs were detected in 7 of those 8 patients as well as in the rest 2 patients negative for AFP L3 during follow-up. The overall sensitivity and specificity of AFP L3 measurement for the detection of HCC within 6 months of follow-up were 63.6% and 87.0%, respectively. The positive and negative predictive value for HCC in patients with chronic liver disease were O% and 90.9% and for recurrent HCC in HCC patients in remission were 87.5% and ON, respectively. Conclusion - The measurement of AFP L3 is suggested to be useful for the diagnostic strategy in patients either with chronic liver disease or hepatocellular carcinoma in complete remission, who showed progressive increment of serum AFP level and no mass lesion in liver on ultrasonogram. (Korean J Hepatol 1998;4:120 - 130)
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Treatment outcome of the patients with small hepatoma ( ≤ 5 cm in diameter ) in relation to treatment modalities and underlying liver function
Kun Hoon Song , Kwang Hyub Han , Young Myung Moon , Chae Yoon Chon , Won Choi , Kwan Sik Lee , In Suh Park , Byong Ro Kim , Jong Tae Lee
Korean J Hepatol 1996;2(2):186-197.
Background/Aims
. To compare treatment outcome of hepatocellular carcinoma(HCC) under the size of 5 cm in relation to underlying liver function and treatment modalities, analysis of data from 145 patients was performed. Methods '. In this study, the records of 145 patients with small HCC (< 5 cm in diameter determined by hepatic angiography) were reviewed. Clinical parameters were analyzed and survival rate, recurrence rate were calculated. Results '. There were 107(73.8%) men and 38 women. Mean age at diagnosis was 55.1(range .' 25 83 year-old). HBsAg was detected in 97(66.9%) patients. Seventy two(50.0%) patients showed markedly elevated(>40 ng/mL) serum alpha-fetoprotein(AFP) level. Liver cirrhosis was associated in 109(75.2%) patients. Sixty five(44.8%) patients underwent surge, 63(43.5%) underwent transarterial therapy(TAT), 8(5.5%) underwent other modalities of therapy and the remaining 9(6.2% ) patients did not receive any specific treatment for HCC. In relation to the underlying liver function, 119(82.1% ) patients belonged to the non-cirrhotic or Child-Pugh class A, 20(13.8%) to class B and 6(4.1%) to class C. The median follow-up duration was 21 months. When analyzed with respect to treatment modalities alone, median survival was 43 months for all patients, 60 months for surgery, 29 months for TAT, 20 months for other treatment and 18 months for patients who received no specific treatment. Without considering liver function, cumulative 3 year survival rate was 68.6% for surgery, 43.9% for TAT, 29.2% for other treatment and 0% for no treatment. The survival rate for the patients who underwent surgery was significantly higher than for any other treatment modalities without considering the underlying liver function or in the non-cirrhotic/Child-Pugh class A(p<0.001). In patients whose tumor size was equal to or less than 3 cm, there was no difference in survival rate in relation to the treatment modalities when not considering the underlying liver function of each patient(p>0.05). But in patients classified as the non-cirrhotic/Child-Pugh class A, better survival was observed in the surgep group than the TAT group(p<0.05). The only factor influencing survival was the pre-treatment serum AFP level(p<0.05). The overall recurrence rate was 30.3%. For the entire patients, the factor significantly influencing the recurrence rate was the presence of underlying cirrhosis. When considering only the patients in the surgery group, the different types of surgical procedures significantly influenced the recurrence rate. Conclusion .' Surgery is the treatment of choice for patients with HCC equal to or smaller than 5 cm. But for those patients whose tumor size is less than 3 cm, TAT may be a reasonable alternative to surgep when the liver function is not adequate for hepatic resection. Because overall recurrence rate exceeded 30% and median time of recurrence was only 9.5 months after definitive treatment, careful follow-up is required for all patients who undergo treatment for small HCC.
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The prognosis and effect of treatment modalities on recurrent hepatocellular carcinoma after curative resection
Chae Yoon Chon , Chan Hee Lee , Kwan Sik Lee , Jun Keun Chung , Kyung Chul Kim , Kwang Hyub Han , Young Myung Moon , In Suh Park , Byung Ro Kim
Korean J Hepatol 1996;2(2):198-208.
Background/Aims
The most effective method of improving survival in patients with HCC is early diagnosis and curative hepatic resection. However, longterm survival after curative resection remains low because of high recurrence rate after resection. The purpose of the study is to assess the prognosis and the efficacy of the various treatment modalities on recurrent HCC after curative resection. Methods:The clinical records of 50 patients with recurrent HCC were reviewed retrospectively who underwent curative surgery in Yonsei University, Severance Hospital from Jan. 1987 through Oct. 1994. The cummulative recurrent rate after resection, the response rate of treatment after resection, the median progression free survival and the survival after recurrence according to the treatment modalities were evaluated. Results:The cummulative recurrent rate after resection was 3.9% at 3 month, 8.3% at 6 month, 14.1% at 12 month, 21.5% at 24 month, 23.4% at 36 month and 24.4% at 60 month. The response rate of treatment after recurrence was 23.7% (9 patients). The median progression free survival of the patient with reoperation and hepatic embolization was 13.9 months, that of conservative treatment group was 6.8 months and that of no treatment group was 4 months(p = 0.004). The survival after recurrence of HCC was 19.7 months in reoperation and hepatic embolization group, 11.4 months in multimodality group, 16.9 months in conservative treatment group and 8.4 months in no treatment group(p=0.0998). Conclusions:Reoperation and hepatic embolization for HCC after curative resection was effective in improving progression free survival, but overall survival were not significantly different according to the treatment modalities. This results proposed that reoperation and hepatic embolization for recurrent HCC after curative resection improve progression free survival.
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Difference in Early Postoperative Recurrence Rate of Hepatocellular Carcinoma According to the Imaging Modalities Used for Preoperative Staging : Comparison Between CTAP and CTHA, Lipiodol CT and Three Phase Helical CT
Moon Seok Choi, Seung Woon Paik, Sang Goo Lee, Joon Hyoek Lee, Kwang Cheol Koh, Poong Lyul Rhee, Jae Jun Kim, Jong Chul Rhee and Kyoo Wan Choi
Korean J Hepatol 1998;4(4):358-364.
Background
/ Aims : Computed tomography during arterial portography and computed tomography during hepatic arteriography (CTAP and CTHA), one of the most sensitive method in detection of hepatocellular carcinoma (HCC) nodules , is reported to reduce unnecessary operation of HCC. However, it is not clear whet her CT AP and CT HA can reduce early post operative recurrence rate of HCC. We performed this study to find any differences in early postoperative recurrence rate of HCC according to the imaging modalities used for preoperativest aging. Methods : Ninety- seven patients with HCC who had underg one curative hepat icres ection from Dec.1994 to Mar . 1998 were included (median age = 52 years (26 - 78), M:F = 85:12). They were classified into 3 groups according to the imaging methods used for preoper ative staging: CTAP & CTHA group (n=56), Lipiodol CT group (n=24), and three phase helical CT group (n=16). No significant inter-group difference was found in preoperative status of the patients or characteristics of HCC. One-year recurrence rates were compared by log- rank test . Results : HCC recurred in 17 of 97 patients (18.7%) within 12 months. A significant difference in 1- year recurrence rate was observed between the groups: helical CT , may be a superior imaging modality for preoperative staging of HCC that can reduce early postoperative recurrence rate. (Korean J Hepatol 1998;4:358 364)
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Analysis of Recurrence and Prognostic Factors after Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma
Min Su Geum, M.D.*, Dae Hyun Kim, M.D., Won Young Tak, M.D. Young Oh Kweon, M.D., Sung Kook Kim, M.D., Yong Hwan Choi, M.D. and Joon Mo Chung, M.D.
Korean J Hepatol 2000;6(1):111-123.
Background/Aims
: Hepatocellular carcinoma (HCC) is a malignant tumor with very poor prognosis if left untreated after diagnosis. However, recent advances in digital subtraction imaging techniques and superselective catheterization seem to have somewhat increased the survival rate in patients with HCC after transarterial chemoembolization (TACE). This study analyzed the relationship between prognostic factors and recurrence after TACE, an aspect which has not attracted much attention. Methods : This investigation included 258 cases of HCC with 100% lipiodol uptake who received TACE for a duration of 13 years from 1985 to 1997. Clinical characteristics, biochemical factors, tumoral factors, angiographic characteristics, embolization technique, degree of lipiodol uptake, response, and recurrence factors were analyzed retrospectively. Results : Significant differences in survival were noted among 3 groups according to cancer-free interval (p<0.01). The different factors between early recurrence group (within 6 months) and late recurrence group (after 18 months) were initial tumor size (8.8±4.1/6.1±3.7cm, p<0.01), tumor type (multinodular,massive/single nodule, p<0.01), ill-defined margin (51.4/22.0%, p<0.01), response after TACE (NC/CR,PR, p<0.01), ALP level (196.1±124.5/144.4±72.0 IU/L, p<0.05), absence of encapsulation (42.3/25.0%, p<0.05), portal vein thrombosis (64.3/14.3%, p<0.05), nonsegmental embolization (46.6/25.0%, p<0.05), post-TACE AFP level (180.5±252.1/76.6±329.8 ng/mL, p<0.05), and recurrence pattern (revascularization of initial lesion/single nodule, p<0.05). Conclusions : Recurrence factors were significant in the survival of patients with HCC after TACE. Therefore, an understanding of the relationship between prognostic factors and recurrence is very important for early detection of recurrence and the timely provision of further TACE treatment. (Korean J Hepatol 2000;6:111－123)
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Case Reports

A Case of Postoperative Recurrence of Heatocelluar Carcinoma in Pelvic Bone without Intrahepatic Metastasis Eight Year After
Deok-Kyu Cho, M.D., Kwang Hyub Han, M.D., Jae Youn Cheong, M.D., Do Yun Lee, M.D.*, Se Hoon Kim, M.D.†, and Young Nyun Park, M.D.†
Korean J Hepatol 2001;7(3):315-319.
In hepatocellular carcinoma distant metastasis after curative surgical resection without intrahepatic metastasis is very rare. A 55-year old man presented with a huge pelvic bone mass. Eight years ago he underwent posterior hepatic segmentectomy following diagnosis of hepatocelluar carcinoma. He has received regular check-ups with abdominal ultrasonography and serum alpha-fetoprotein. On admission an MRI on the pelvic area showed an 18×10cm sized lobulated mass invading the pelvic bone and acetabulum. Microscopic examination revealed that the tumor was a well differentiated hepatocellular carcinoma. There was no evidence of intrahepatic recurrence. He was treated with transarterial chemoembolization, external radiotherapy(total 3750 cGy), and systemic chemotherapy using 5-fluorouracil. (Korean J Hepatol 2001;7:315-319)
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A Case of Needle Tract Seeding of Hepatocllular Carcinoma after Percutaneous Ethanol Injection Therapy ; Needle Tract Seeding after Percutaneous Ethanol Injection Therapy
Sung Wuk Song, M.D., So Young Kwon, M.D., Yang Wook Kang, M.D., Jin Neyn Kim, M.D., Tae Hoon Kim, M.D., Myoung Oh, M.D., Bong Ki Chung, M.D., Hye Seung Yu, M.D., and Hee Jin Chang, M.D.*
Korean J Hepatol 2001;7(3):325-329.
The tumor seeding after percutaneous ethanol injection (PEI) therapy has been considered to be a rare complication in hepatocellular carcinoma. We report a case of needle tract implantation of hepatocellular carcinoma following PEI manifested as subcutaneous nodule. A 57-years old male patient had been treated with PEI for hepatocellular carcinoma. Thirteen months after completion of the PEI session, a subcutaneous nodule was palpated at the site of the needle puncture. A CT scan showed that the subcutaneous nodule was 1.7 cm in size and enhanced in the early phase. The nodule was surgieally removed. Microscopic examination showed hepatocellular carcinoma. (Korean J Hcpatol 2001;7:325 329)
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Original Articles
Recurrence and Management of Hepatitis C after Liver Transplantation
Ki Bong Oh, M.D., Sung Gyu Lee, M.D., Young Joo Lee, M.D., Kwang Min Park, M.D., Shin Hwang, M.D., Ki Hun Kim, M.D., Chul Soo Ahn, M.D., Deok Bog Moon, M.D., Chong Woo Chu, M.D., Hyun Seung Yang, M.D., Tae Yong Ha, M.D. and Sung Hoon Cho, M.D.
Korean J Hepatol 2003;9(3):180-187.
Background/Aims
End-stage liver disease caused by viral hepatitis C has been increasing recently in Korea. In this study, we investigated the clinical progress, recurrence, and management of hepatitis C patients who underwent liver transplantation, Methods: We retrospectively reviewed the clinical progress and management of 16 patients (2.7%) with hepatitis C among 587 liver transplant patients from August 1992 to August 2002. Results: Eleven cases among 16 patients were males. The median age was 56±6(42-62) years and the median follow-up period was 6±13 (1-41) months. Thirteen cases underwent living donor liver transplantation and three had cadaveric whole liver transplantation. Clinical recurrence occurred in nine cases (56.3%) and mean time of recurrence was 5.2 months, Histological recurrence cases were eight (50%). A positive result of HCV RNA PCR was found in 90.9%, and all cases of clinical and histological recurrence in groups in the same periods were PCR-positive. Among eight cases showing histological recurrence five patients were managed by ribavirin monotherapy, two patients received interferon and ribavirin combination therapy, and one patient was not treated at all, The serum serum aminotransferase level was normalized in six cases (75%) of them. Conclusions: We observed that the HCV reinfection rate of a transplanted liver was high in this study, as in other reports in the literature, The prevention of HCV recurrence and the management of post-recurrent cirrhotic change are crucial for graft and patient survival. We think customized protocols are needed for every situation of recurrent hepatitis C.(Korean J Hepatol 2003;9:180-187)
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The Comparative Results of Radiofrequency Ablation versus Surgical Resection for the Treatment of Hepatocellular Carcinoma
Chang-Min Cho, M.D., Won-Young Tak, M.D., Young-Oh Kweon, M.D., Sung-Kook Kim, M.D., Yong-Hwan Choi, M.D., Yoon-Jin Hwang, M.D.1 and Yang-Il Kim, M.D.1
Korean J Hepatol 2005;11(1):59-71.
Background/Aims
Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC. Methods: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups. Results: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups. Conclusions: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results. (Korean J Hepatol 2005;11:59-71)
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Change of Hepatitis B Virus DNA Status in Anti-HBc Positive Liver Graft
Choon Hyuck Kwon, M.D., Kyung-Suk Suh, M.D., Ph.D., Jai Young Cho, M.D., Nam-Joon Yi, M.D., Ph.D., Ja-June Jang, M.D., Ph.D.1, and Kuhn Uk Lee, M.D., Ph.D., FACS
Korean J Hepatol 2006;12(2):191-200.
Background/Aims
Many patients with positive anti-HBc, but negative HBsAg, are known to harbor occult HBV infection, which may transmit the virus through the graft in liver transplantation. We examined the change of HBV DNA within the liver allograft tissue of the donor with positive anti-HBc, but negative HBsAg, before and after the transplantation and assessed its significance. Methods: Twenty-eight patients with available posttransplant biopsies that received anti-HBc positive liver allografts between April 2000 and November 2003 were enrolled in the study. Intraoperative wedge biopsy of donor liver and needle biopsy of the recipient around the 12th postoperative day were used. HBV DNA within the liver tissue was identified by polymerase chain reaction technique using paraffin-embedded liver tissue. Results: Among 13 patients that showed positive amplification before transplantation, 10 turned negative and 3 remained positive after transplantation. One patient, who was negative, became positive after transplantation. Three patients had recurrent HBV infection, but none had positive PCR before or after transplantation and recurrence was not associated with PCR results. Donors with low anti-HBs titer were more likely to be PCR positive compared to donors with high anti-HBs serology (P<0.05). Conclusions: Under adequate prophylactic measures, the presence of HBV DNA within the liver tissue does not affect recurrence and most allografts harboring HBV DNA before transplantation will eventually show viral clearance. However, many anti-HBc positive allografts are infected by HBV at subclinical level so vigilant surveillance is essential. (Korean J Hepatol 2006;12: 191-200)
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Clinical Outcomes of Lamivudine Therapy in HBeAg Positive Chronic Hepatitis B with Minimally Elevated ALT
Dong Ha Han , Neung Hwa Park , Jung Woo Shin , Seok Won Jung , Young Tae Hwang , Hyun Soo Kim , In Du Jeong , Sung Jo Bang , Do Ha Kim
Korean J Hepatol 2007;13(2):146-156.
Background/Aims
The aim of this study was to compare the efficacy of lamivudine therapy between chronic hepatitis B (CHB) patients, whose ALT levels less than 2 times the upper limit of normal (ULN) and patients whose ALT levels are more than 2 times ULN. Methods: We retrospectively analyzed 508 consecutive patients with HBeAg-positive CHB who were treated with lamivudine for 1 year or more. Forty-six patients (Group A) with pretreatment ALT levels less than 2 times ULN were retrospectively compared with 462 patients (Group B) whose ALT levels are more than 2 times ULN. Results: HBeAg seroconversion was achieved in 15 (32.6%) of group A and 162 (35.1%) of group B. The cumulative rates of HBeAg seroconversion in group A and B were 19% and 21% at 12 months; 35% and 31% at 24 months; and 38% and 39% at 36 months, respectively. HBV breakthrough was observed in 20 (43.5%) of group A and 192 (41.6%) of group B. The cumulative breakthrough rates of group A and B were 18% and 12% at 12 months; 33% and 29 % at 18 months; 45% and 42% at 24 months, respectively. Post-treatment relapse in group A and B occurred in 56% (5/9) and 41% (44/108), respectively. Therefore, the rates of the HBeAg seroconversion, breakthrough, and post-treatment relapse were not significantly different between these two groups. Conclusions: Lamivudine therapy in HBeAg-positive CHB patients whose ALT levels are minimally elevated is as effective as in treatment of the patients whose pretreated ALT levels are twice more than ULN. (Korean J Hepatol 2007;13:146-156)
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CMH : Clinical and Molecular Hepatology
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