Journal of Liver Cancer

Special Contribution

Expert survey on systemic therapy indications for hepatocellular carcinoma in Korea: bridging clinical practice and reimbursement criteria: Hyun Yang, Soon Sun Kim, Seong Hee Kang, Jieun Kwon, Do Young Kim, Eunju Kim, Hyun Phil Shin, Jeong Il Yu, Jeong-Ju Yoo, Eileen L. Yoon, Sangheun Lee, Young Eun Chon, Janghan Jung, Jaekyung Cheon, Woosun Choi, Seul Ki Han, Ji Eun Han, Moon Haeng Hur, Hyun Woong Lee, Hyung Joon Kim; J Liver Cancer. 2025;25(2):160-168. Published online July 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.02

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Abstract PDF: This survey aimed to collect expert opinions from multidisciplinary specialists involved in the management of hepatocellular carcinoma (HCC) in Korea regarding real-world criteria for systemic therapy indications. In response to discrepancies between national reimbursement policies and clinical decision-making, members of the Korean Liver Cancer Association and Korean Association for the Study of the Liver participated in a web-based survey from February 4 to 14, 2025. A total of 89 respondents, primarily experienced clinicians, provided their views on major clinical scenarios including infiltrative HCC, bilobar multifocal disease, huge tumors, vascular invasion, extrahepatic metastasis, and transarterial chemoembolization (TACE) refractoriness. There was high agreement for including infiltrative HCC (69.7%), suspected portal vein invasion (70.8%), and TACE refractoriness (82.0%) as systemic therapy indications. TACE refractoriness, in particular, aligns with current guideline definitions. Additionally, over half of respondents (51.7%) supported extrahepatic metastasis under similar conditions. Notably, multidisciplinary discussion was emphasized across scenarios, but many respondents also favored allowing primary physician discretion in select cases. This report provides consolidated expert input to inform future updates to reimbursement policies and promote alignment with real-world clinical practice. These findings may help bridge the gap between national coverage criteria and clinical decision in systemic therapy for HCC.

Review Articles

Evolving roles of systemic therapy in hepatocellular carcinoma: neoadjuvant and adjuvant strategies: Ho Soo Chun, Minjong Lee, Tae Hun Kim; J Liver Cancer. 2025;25(2):178-186. Published online June 16, 2025; DOI: https://doi.org/10.17998/jlc.2025.06.13

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Abstract PDF: Surgical resection for early-stage hepatocellular carcinoma (HCC) provides the potential for long-term survival but recurrence rates within 5 years were up to 70%. Thus, neoadjuvant or adjuvant strategies can be important to improve outcomes. Previous efforts with sorafenib in the adjuvant setting failed to show significant benefits in recurrence-free survival (RFS) or overall survival. However, developments in systemic therapies such as immune checkpoint inhibitors or tyrosine kinase inhibitors have revitalized this field. Although the IMBrave050 trial failed to demonstrate a significant improvement in RFS with one year of adjuvant treatment using atezolizumab combined with bevacizumab in high-risk patients treated with resection or ablation, several other ongoing trials are investigating this promising approach. Neoadjuvant or adjuvant approach using systemic therapies is also gaining attention, supported by phase 1 or 2 clinical trials indicating high objective response rates. In addition, systemic therapies are being increasingly studied as down-staging strategies for resection or liver transplantation. The growing complexity of HCC treatment such as the integration of neoadjuvant and adjuvant strategies underscores the importance of a multidisciplinary approach to optimize therapeutic decision-making in this evolving areas.

Epidemiology and genomic features of biliary tract cancer and its unique features in Korea: Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon; J Liver Cancer. 2025;25(1):41-51. Published online March 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.27

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172 Downloads
3 Citations

Abstract PDF Supplementary Material

Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

Citations

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Global, regional, and national burden of gallbladder and biliary tract cancer among adults aged 55 years and older, 2010–2021
Mingjuan Li, Jiaguang Li, Shuangjiang Li, Minmin Zhang, Shuang Li, Jiahui Zhao, Tao Gan, Min Wu, Shunwen Luo, Yunying Liang, Qiuyun Li, Guangdong Pan, Jianqing Yang, Guoqing Ouyang
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Duygu Kirkik, Ayse Naz Ozabaci, Sevgi Kalkanli Tas
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A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024: Hyunjae Shin, Su Jong Yu; J Liver Cancer. 2025;25(1):19-30. Published online February 10, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.03

27,187 Views
909 Downloads
9 Citations

Abstract PDF

Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.

Citations

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Radiofrequency Ablation Technology in Liver Malignancies: A Systematic Review of Economic Evaluations
Amirreza Taherkhani, Hoornaz Molana, Mahsa Taremi, Ghader Mohammadnezhad
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In Vitro and In Vivo Efficacy of the Essential Oil from the Leaves of Annona amazonica R.E. Fries (Annonaceae) Against Liver Cancer
Maria V. L. de Castro, Milena C. F. de Lima, Gabriela A. da C. Barbosa, Sabrine G. Carvalho, Amanda M. R. M. Coelho, Luciano de S. Santos, Valdenizia R. Silva, Rosane B. Dias, Milena B. P. Soares, Emmanoel V. Costa, Daniel P. Bezerra
Molecules.2025; 30(15): 3248. CrossRef
Spectrum of therapeutic options in hepatocellular carcinoma
Hyun Phil Shin, Moonhyung Lee, Jung Won Jeon
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Re-evaluating surgical strategies in Barcelona Clinic Liver Cancer-B hepatocellular carcinoma
Ioannis Liapis, Ioannis A Ziogas, Charalampos Theocharopoulos, Dimitrios P Moris, Trevor L Nydam, Ana L Gleisner, Richard D Schulick, Georgios Tsoulfas
World Journal of Hepatology.2025;[Epub] CrossRef
Predicting early progression to atezolizumab–bevacizumab in hepatocellular carcinoma: a clinical and imaging-based scoring system
Jae Hyon Park, Myung Ji Goh, Dong Hyun Sinn, Jaeseung Shin, Hyungjin Rhee
European Radiology.2025;[Epub] CrossRef
Unraveling the role of flotillin-1 in driving hepatocellular carcinoma progression through transcription factor E3-mediated Golgi stress response
Chiara Mazziotta, John Charles Rotondo
World Journal of Gastroenterology.2025;[Epub] CrossRef
The synergistic action of HDAC inhibitor with cisplatin impedes survival and proliferation of drug-tolerant persister in gastric and liver cancer cells
Anjali Singh, Abhiram Natu, Flevia Anthony, Hemalatha Muthu, Bharat Khade, Duane T. Smoot, Hassan Ashktorab, Sanjay Gupta
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Repurposing HIV-Protease Inhibitor Precursors as Anticancer Agents: The Synthetic Molecule RDD-142 Delays Cell Cycle Progression and Induces Autophagy in HepG2 Cells with Enhanced Efficacy via Liposomal Formulation
Fabiana Crispo, Antonio Vassallo, Immacolata Faraone, Alessandro Santarsiere, Lucia Chiummiento, Mara Martinelli, Nicoletta Cascelli, Xavier Fernàndez-Busquets, Rocchina Miglionico, Ilaria Nigro, Carla Caddeo, Maria Francesca Armentano
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Angiography-Assisted Cone-Beam CT-Guided Radiofrequency Ablation for Hepatocellular Carcinoma: Single-Center Workflow and Early Outcomes
Jung Ui Hong, Soon Gu Cho, Kyu Hong Lee, Ji Hoon Noh, Ro Woon Lee
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Molecular and immune landscape of hepatocellular carcinoma for therapeutic development: Hiroyuki Suzuki, Sumit Mishra, Subhojit Paul, Yujin Hoshida; J Liver Cancer. 2025;25(1):9-18. Published online December 6, 2024; DOI: https://doi.org/10.17998/jlc.2024.12.02

8,724 Views
557 Downloads
4 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an estimated 750,000 deaths in 2022. Recent emergence of molecular targeted agents and immune checkpoint inhibitors and their combination therapies have been transforming HCC care, but their prognostic impact in advanced-stage disease remains unsatisfactory. In addition, their application to early-stage disease is still an unmet need. Omics profiling studies have elucidated recurrent and heterogeneously present molecular aberrations involved in pro-cancer tumor (immune) microenvironment that may guide therapeutic strategies. Recurrent aberrations such somatic mutations in TERT promoter and TP53 have been regarded undruggable, but recent studies have suggested that these may serve as new classes of therapeutic targets. HCC markers such as alpha-fetoprotein, glypican-3, and epithelial cell adhesion molecule have also been explored as therapeutic targets. These molecular features may be utilized as biomarkers to guide the application of new approaches as companion biomarkers to maximize therapeutic benefits in patients who are likely to benefit from the therapies, while minimizing unnecessary harm in patients who will not respond. The explosive number of new agents in the pipelines have posed challenges in their clinical testing. Novel clinical trial designs guided by predictive biomarkers have been proposed to enable their efficient and cost-effective evaluation. These new developments collectively facilitate clinical translation of personalized molecular-targeted therapies in HCC and substantially improve prognosis of HCC patients.

Citations

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Paracancerous binuclear hepatocytes assessed by computer program is a novel biomarker for short term recurrence of hepatocellular carcinoma after surgery
Yifan Zhang, Yiquan Lu, Nan Wang, Fengjie Hao, Yongjun Chen, Xiaochun Fei, Junqing Wang
Scientific Reports.2025;[Epub] CrossRef
Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma
Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
Cancers.2025; 17(9): 1548. CrossRef
Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care
Dongming Liu, Norihiro Imai
Cancers.2025; 17(19): 3105. CrossRef
YKL-40 in Virus-Associated Liver Disease: A Translational Biomarker Linking Fibrosis, Hepatocarcinogenesis, and Liver Transplantation
Jadranka Pavicic Saric, Dinka Lulic, Dunja Rogic, Stipislav Jadrijevic, Danko Mikulic, Tajana Filipec Kanizaj, Nikola Prpic, Laura Karla Bozic, Ivona Adamovic, Iva Bacak Kocman, Zrinka Sarec, Gorjana Erceg, Mirta Adanic, Petra Ozegovic Zuljan, Filip Jadri
International Journal of Molecular Sciences.2025; 26(19): 9584. CrossRef

Case Report

Durable complete response after discontinuation of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma with portal vein tumor thrombosis: the first report: Pramod Kumar, Pradeep Krishna, Rohit Maidur, Naveen Chandrashekhar, Suresh Raghavaiah; J Liver Cancer. 2025;25(1):134-137. Published online November 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.26

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212 Downloads

Abstract PDF: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a dismal prognosis. Atezolizumab plus bevacizumab (atezo-bev) is the recommended palliative treatment, and approximately 10% of the patients may experience a complete response (CR), according to the mRECIST criteria. The treatment duration is until disease progression or unacceptable side effects occur. Long-term continuation can cause potential toxicities and a substantial financial burden, making early treatment discontinuation a viable option. This report describes durable CR after discontinuing atezo-bev treatment in three patients with HCC and PVTT.

Review Articles

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future: Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim; J Liver Cancer. 2024;24(2):171-177. Published online September 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.30

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314 Downloads
2 Citations

Abstract PDF

Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Citations

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A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024
Hyunjae Shin, Su Jong Yu
Journal of Liver Cancer.2025; 25(1): 19. CrossRef
The Lancet Commission on addressing the global hepatocellular carcinoma burden: comprehensive strategies from prevention to treatment
Stephen Lam Chan, Hui-Chuan Sun, Yang Xu, Hongmei Zeng, Hashem B El-Serag, Jeong Min Lee, Myron E Schwartz, Richard S Finn, Jinsil Seong, Xin Wei Wang, Valérie Paradis, Ghassan K Abou-Alfa, Lorenza Rimassa, Jia-Horng Kao, Bo-Heng Zhang, Josep M Llovet, Jo
The Lancet.2025; 406(10504): 731. CrossRef

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; J Liver Cancer. 2024;24(2):155-170. Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07

34,208 Views
587 Downloads
14 Citations

Abstract PDF

Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

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Genomic and transcriptomic signatures of sequential carcinogenesis from papillary neoplasm to biliary tract cancer
Taek Chung, Seungho Oh, Jeongsoo Won, Jiho Park, Jeong Eun Yoo, Ho Kyoung Hwang, Gi Hong Choi, Chang Moo Kang, Dai Hoon Han, Sangwoo Kim, Young Nyun Park
Journal of Hepatology.2025; 83(1): 119. CrossRef
A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024
Hyunjae Shin, Su Jong Yu
Journal of Liver Cancer.2025; 25(1): 19. CrossRef
Modulating Wnt/β-catenin pathway activity to enhance chemosensitivity in cholangiocarcinoma
Kevin Delgado-Calvo, Luke Boulter, Oscar Briz, Aleksandra Rozyczko, Paula Olaizola, Jose J.G. Marin, Rocio I.R. Macias, Elisa Lozano
Biomedicine & Pharmacotherapy.2025; 188: 118225. CrossRef
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Jean-Frédéric Blanc, Mohamed Bouattour, Ludovic Gauthier, Emmanuel Deshayes, Sophie Guillemard, Yann Touchefeu, Fabienne Portales, Christophe Borg, Lobna Harguem, Rosine Guimbaud, Laurent Mineur, Marc Ychou, Thibault Mazard, Eric Assenat
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Paweena Dana, Prattana Tanyapanyachon, Saksorn Klibaim, Monthira Rattanatayarom, Walailuk Chonniyom, Nattika Saengkrit
Hepatoma Research.2025;[Epub] CrossRef
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Saeed Mohammadzadeh, Alisa Mohebbi, Mehrad Zare, Faeze Salahshour, Afshin Mohammadi
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Advanced cholangiocarcinoma with human epidermal growth factor receptor 2 (HER2) amplification treated with Trastuzumab deruxtecan (T-DXd): A case report
Xiaohui Bao, Zhi Chen, Jin Xiong, Zhenzhou Yang, Ni Zhang
Medicine.2025; 104(35): e44094. CrossRef
Validation of prognostic models for predicting postsurgical outcomes in intrahepatic cholangiocarcinoma patients using a multicenter cohort
Dong Hwan Kim, Sang Hyun Choi, Sehee Kim, Woohyung Lee, Hyung-Don Kim, Hyungjin Rhee, Eun-Suk Cho, Suk-Keu Yeom, Sumi Park, Seung Soo Lee, Mi-Suk Park
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The Antibody–Drug Conjugate Sacituzumab Govitecan (IMMU-132) Represents a Potential Novel Therapeutic Strategy in Cholangiocarcinoma
Racha Hosni, Niklas Klümper, Christine Sanders, Sana Hosni, Vittorio Branchi, Alexander Semaan, Abdullah Alajati, Natalie Pelusi, Susanna S. Ng, Damian J. Ralser, Saif-Eldin Abedellatif, Hanno Matthaei, Jörg Kalff, Jasmitha Boovadira Poonacha, Veronika Lu
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Viviana A. Ruiz-Pozo, Santiago Cadena-Ullauri, Patricia Guevara-Ramírez, Rafael Tamayo-Trujillo, Elius Paz-Cruz, Alejandro Cabrera-Andrade, Ana Karina Zambrano
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Lynn Affarah, Sreelakshmi Kotha, Philip Berry
World Journal of Transplantation.2025;[Epub] CrossRef
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Yong-Zhi Zhuang, Li-Quan Tong, Xue-Ying Sun
World Journal of Hepatology.2024; 16(11): 1219. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
The Ewha Medical Journal.2024;[Epub] CrossRef
Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma.
Poowanai Sarkhampee, Weeris Ouransatien, Nithi Lertsawatvicha, Satsawat Chansitthichock, Paiwan Wattanarath
World Journal of Surgical Oncology.2024;[Epub] CrossRef

Original Articles

Recent update of proton beam therapy for hepatocellular carcinoma: a systematic review and meta-analysis: Sun Hyun Bae, Won Il Jang, Hanna Rahbek Mortensen, Britta Weber, Mi Sook Kim, Morten Høyer; J Liver Cancer. 2024;24(2):286-302. Published online July 4, 2024; DOI: https://doi.org/10.17998/jlc.2024.06.26

8,042 Views
207 Downloads
4 Citations

Abstract PDF Supplementary Material

Backgrounds/Aims
Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and metaanalysis to investigate the updated evidence of PBT for HCC.
Methods
The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024.
Results
A total of 1,858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range, 41-100), and the median tumor size was 3.6 cm (range, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91) and 86% (95% CI, 82-90), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66) and 46% (95% CI, 38-54), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiationinduced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively.
Conclusions
The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Citations

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A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024
Hyunjae Shin, Su Jong Yu
Journal of Liver Cancer.2025; 25(1): 19. CrossRef
Radiotherapy for Locally Advanced Pancreatic Cancer in the Modern Era: A Systematic Review and Meta-Analysis
Sun Hyun Bae, Won Il Jang, Jeong Il Yu, Hee Chul Park, Ji Eun Moon, Karin Haustermans, Marta Scorsetti, Morten Høyer, Mi Sook Kim
Cancers.2025; 17(18): 2959. CrossRef
CAPG Regulates Doxorubicin Resistance in Hepatocellular Carcinoma Cells via TGFB1/Smad/Nrf2 Signalling Pathway
Yue Shang, Jun Zhang, Tingting Liu
Journal of Cellular and Molecular Medicine.2025;[Epub] CrossRef
Navigating the Therapeutic Pathway and Optimal First-Line Systemic Therapy for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors
Hyun Phil Shin, Moonhyung Lee
Medicina.2025; 61(12): 2164. CrossRef

Cure can be achieved by conversion to microwave ablation following atezolizumab-bevacizumab therapy in unresectable hepatocellular carcinoma: Rene John D. Febro, Engelbert Simon S. Perillo, Akemi A. Kimura, Stephen N. Wong; J Liver Cancer. 2024;24(2):234-242. Published online June 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.23

7,421 Views
150 Downloads
1 Citation

Abstract PDF

Backgrounds/Aims
Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion.
Methods
Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria.
Results
Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response.
Conclusions
Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

Citations

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Curative Treatment after Immunotherapy Leads to Excellent Outcomes in Patients with Hepatocellular Carcinoma
Gwang Hyeon Choi, Hyun-Seok Kim, Michael Luu, Alexander Kuo, Walid S. Ayoub, Hirsh Trivedi, Yun Wang, Aarshi Vipani, Pin-Jung Chen, Steven A. Miles, Emily A. Kaymen, Andrew Hendifar, Tsuyoshi Todo, Todd V. Brennan, Georgios Voidonikolas, Steven A. Wisel,
Liver Cancer.2025; : 1. CrossRef

Downstaging with atezolizumab-bevacizumab: a case series: Anand V. Kulkarni, Parthasarathy Kumaraswamy, Balachandran Menon, Anuradha Sekaran, Anuhya Rambhatla, Sowmya Iyengar, Manasa Alla, Shantan Venishetty, Sumana Kolar Ramachandra, Giri V. Premkumar, Mithun Sharma, P. Nagaraja Rao, Duvvur Nageshwar Reddy, Amit G. Singal; J Liver Cancer. 2024;24(2):224-233. Published online May 27, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.12

7,203 Views
298 Downloads
7 Citations

Abstract PDF Supplementary Material

Backgrounds/Aims
Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown.
Methods
In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging.
Results
Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection.
Conclusions
Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.

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Review Article

Current perspectives on radiotherapy in hepatocellular carcinoma management: a comprehensive review: Dowook Kim, Jun-Sang Kim; J Liver Cancer. 2024;24(1):33-46. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.26

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Abstract PDF

This review examines the transformative role of external beam radiotherapy (EBRT) in managing hepatocellular carcinoma (HCC), spotlighting the progression from traditional EBRT techniques to advanced modalities like intensity-modulated radiotherapy (RT), stereotactic body RT (SBRT), and innovative particle therapy, including proton beam therapy and carbon ion RT. These advancements have significantly improved the precision and efficacy of RT, marking a paradigm shift in the multimodal management of HCC, particularly in addressing complex cases and enhancing local tumor control. The review underscores the synergistic potential of integrating RT with other treatments like transarterial chemoembolization, systemic therapies such as sorafenib, and emerging immunotherapies, illustrating enhanced survival and disease control outcomes. The efficacy of RT is addressed for challenging conditions, including advanced HCC with macrovascular invasion, and RT modalities, like SBRT, are compared against traditional treatments like radiofrequency ablation for early-stage HCC. Additionally, the review accentuates the encouraging outcomes of particle therapy in enhancing local control and survival rates, minimizing treatment-related toxicity, and advocating for continued research and clinical trials. In conclusion, the integration of RT into multimodal HCC treatment strategies, coupled with the emergence of particle therapy, is crucial for advancing oncologic management, emphasizing the need for relentless innovation and personalized treatment approaches.

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Original Articles

Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis: Manuel Lim, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh; J Liver Cancer. 2024;24(1):102-112. Published online February 14, 2024; DOI: https://doi.org/10.17998/jlc.2024.01.31

4,817 Views
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2 Citations

Abstract PDF

Background/Aim
Hepatocellular carcinoma (HCC) tumor thrombi located in the first branch of the portal vein (Vp3) or in the main portal trunk (Vp4) are associated with poor prognosis. This study aimed to investigate the clinicopathological characteristics and risk factors for HCC recurrence and mortality following liver resection (LR) in patients with Vp3 or Vp4 HCC.
Methods
The study included 64 patients who underwent LR for HCC with Vp3 or Vp4 portal vein tumor thrombosis (PVTT).
Results
Fifty-eight patients (90.6%) had Vp3 PVTT, whereas the remaining six patients exhibited Vp4 PVTT. The median tumor size measured 8 cm, with approximately 36% of patients presented with multiple tumors. Fifty-four patients (84.4%) underwent open LR, whereas 10 patients underwent laparoscopic LR. In the Vp4 cases, combined LR and tumor thrombectomy were performed. The 3-year cumulative disease-free survival rate was 42.8% for the Vp3 group and 22.2% for the Vp4 group. The overall survival (OS) rate at 3 years was 47.9% for the Vp3 group and 60.0% for the Vp4 group. Intrahepatic metastasis has been identified as an important contributor to HCC recurrence. High hemoglobin levels are associated with high mortality.
Conclusion
LR is a safe and effective treatment modality for selected patients with Vp3 or Vp4 HCC PVTT. This suggests that LR is a viable option for these patients, with favorable outcomes in terms of OS.

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7,926 Views
287 Downloads
6 Citations

Abstract PDF Supplementary Material

Background/Aim
Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT).
Methods
We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1.
Results
A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74).
Conclusion
The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

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Review Article

Complications of immunotherapy in advanced hepatocellular carcinoma: Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2024;24(1):9-16. Published online November 29, 2023; DOI: https://doi.org/10.17998/jlc.2023.11.21

7,806 Views
257 Downloads
13 Citations

Abstract PDF

Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

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