Journal of Liver Cancer

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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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

Advancing Korean nationwide registry for hepatocellular carcinoma: a systematic sampling approach utilizing the Korea Central Cancer Registry database: Bo Hyun Kim, E Hwa Yun, Jeong-Hoon Lee, Geun Hong, Jun Yong Park, Ju Hyun Shim, Eunyang Kim, Hyun-Joo Kong, Kyu-Won Jung, Young-Suk Lim; J Liver Cancer. 2024;24(1):57-61. Published online March 26, 2024; DOI: https://doi.org/10.17998/jlc.2024.03.03

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8 Citations

Abstract PDF Supplementary Material

Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

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Self-testing strategy to eliminate hepatitis C as per World Health Organization’s goal: Analysis of disease burden and cost-effectiveness
Gyeongseon Shin, Beom Kyung Kim, SeungJin Bae, Hankil Lee, Sang Hoon Ahn
Clinical and Molecular Hepatology.2025; 31(1): 166. CrossRef
Cytokine-Induced Killer Cell Immunotherapy Reduces Recurrence in Patients with Early-Stage Hepatocellular Carcinoma
Dong Hyun Kim, Eun Min Kim, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Gi Hong Choi, Sang Hoon Ahn, Hye Won Lee, Do Young Kim
Cancers.2025; 17(4): 566. CrossRef
Current Trends and Impact of Liver Biopsy on Survival in Hepatocellular Carcinoma: A Korean Multicenter Analysis
Seong Joon Chun, Jeong-Ju Yoo, Sang Gyune Kim, Young-Seok Kim
Diagnostics.2025; 15(7): 818. CrossRef
Hepatocellular carcinoma in Korea: an analysis of the 2016-2018 Korean Nationwide Cancer Registry
Jihyun An, Young Chang, Gwang Hyeon Choi, Won Sohn, Jeong Eun Song, Hyunjae Shin, Jae Hyun Yoon, Jun Sik Yoon, Hye Young Jang, Eun Ju Cho, Ji Won Han, Suk Kyun Hong, Ju-Yeon Cho, Kyu-Won Jung, Eun Hye Park, Eunyang Kim, Bo Hyun Kim
Journal of Liver Cancer.2025; 25(1): 109. CrossRef
Current status and future perspectives of minimally invasive liver surgery for hepatocellular carcinoma
Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Boram Lee, Yeshong Park, Hyelim Joo, Seung Yeon Lim
Journal of Liver Cancer.2025; 25(2): 233. CrossRef
Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma
Hwi Young Kim, Hye Ah Lee, Pompilia Radu, Jean-François Dufour
Scientific Reports.2024;[Epub] CrossRef
Heavy smoking increases early mortality risk in patients with hepatocellular carcinoma after curative treatment
Jaejun Lee, Jong Young Choi, Soon Kyu Lee
Journal of Liver Cancer.2024; 24(2): 253. CrossRef
Incorporating ALBI Grade with Geriatric Nutritional Risk Index Enhances Hepatocellular Carcinoma Risk Stratification
Heechul Nam, Pil Soo Sung, Sung Won Lee, Do Seon Song, Jung Hyun Kwon, Jeong Won Jang, Chang Wook Kim, Si Hyun Bae
Liver Cancer.2024; : 1. CrossRef

Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm?: Bernardo Stefanini, Luca Ielasi, Dante Pio Pallotta, Sofia Penazza, Mariarosaria Marseglia, Fabio Piscaglia; J Liver Cancer. 2024;24(1):23-32. Published online March 12, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.21

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4 Citations

Abstract PDF

This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.

Citations

Citations to this article as recorded by

Usefulness of preoperative peripheral blood GPC3‐positive circulating tumor cells in subclassification of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma: a retrospective cohort study
Yosuke Namba, Tsuyoshi Kobayashi, Yoshito Hirata, Takeshi Tadokoro, Sotaro Fukuhara, Ko Oshita, Naruhiko Honmyo, Ryosuke Nakano, Hiroshi Sakai, Seiichi Shimizu, Shintaro Kuroda, Hiroyuki Tahara, Masahiro Ohira, Kentaro Ide, Yuka Tanaka, Hideki Ohdan
Hepatology Research.2025; 55(8): 1172. CrossRef
Potential anticancer therapeutic targets of resveratrol and its role in the therapy of hepatocellular carcinoma
Wasnaa H. Mohammed, Ghassan M. Sulaiman, Hamdoon A. Mohammed
Food Bioscience.2025; 69: 106935. CrossRef
Role of immune checkpoint inhibitor combinations in resectable and unresectable, embolization-eligible hepatocellular carcinoma
Brandon M. Meyers, Howard J. Lim, Mayur Brahmania, Dave M. Liu, Vincent C. Tam, Deanna McLeod, Ravi Ramjeesingh, Jennifer J. Knox, Arndt Vogel
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
The Neoangiogenic Transcriptomic Signature Impacts Hepatocellular Carcinoma Prognosis and Can Be Triggered by Transarterial Chemoembolization Treatment
Rosina Maria Critelli, Federico Casari, Alberto Borghi, Grazia Serino, Cristian Caporali, Paolo Magistri, Annarita Pecchi, Endrit Shahini, Fabiola Milosa, Lorenza Di Marco, Alessandra Pivetti, Simone Lasagni, Filippo Schepis, Nicola De Maria, Francesco Di
Cancers.2024; 16(20): 3549. CrossRef

Staging of Hepatocellular Carcinoma: Joon-Il Choi; Journal of the Korean Liver Cancer Study Group. 2011;11(1):26-32. Published online February 28, 2011

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Abstract PDF: Staging systems of HCC are very complex and disunited because multiple variables, including residual liver function, performance of patients and treatment modalities, can have influence on the survival of the patients and therefore, there is no united and generalized staging system of HCC. Staging systems of HCC can be classified as two categories; Anatomical staging systems and clinical staging systems. In anatomical staging systems, tumor factors are main elements that determine the stage of the patients and LCSGJ systems and AJCC/UICC systems are included in this category. Practice guideline and General rules of HCC by the Korean Liver Cancer Study Group adopted LCSGJ system. In clinical staging systems, not only tumor factors but also clinical factors such as liver function, performance of the patients and treatment modalities are considered to determine the stage of the patients. The BCLC system is the only system that provides treatment recommendations for each of the assigned stages based on the best treatment options currently available. Criteria for liver transplantation are on the way of expansion because of the widespread of living donor liver transplantation and several researchers presented various expanded criteria over Milan’s criteria with comparable survival data to those of Milan’s criteria. Upcoming researches of molecular biology and imaging can help the establishment of more precise and united staging systems for the patients with HCC.

Case Reports

A Patient of Hepatocellular Carcinoma Performed Hepatectomy after Tumor Downing Sizing with Transcatheter Arterial Chemoembolization: Seul Ki Min, Sang Gyune Kim, Young Seok Kim, Sae Whan Lee, Soung Won Jeong, Jae Young Jang, Hong Soo Kim, Boo Sung Kim; Journal of the Korean Liver Cancer Study Group. 2011;11(1):40-45. Published online February 28, 2011

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Abstract PDF: Hepatocellular carcinoma (HCC) is the third most common cancer in korean population. Surgical management is the mainstay of HCC. Surgical resection and liver transplantation shows the best outcomes in well-selected patients. But few patients are possible to benefit from surgical resection or liver transplantation. The majority of cases of HCC are unresectable, but there are no proven treatment modalities for these cases. In small number of articles showed the favorable result of adjuvant chemotherapy, and transcatheter arterial chemoembolization (TACE) for unresectable HCCs. But there are some drawbacks, such as small number of sample size and variablity of study design at each studies. Hereby we report a patients of HCC, who was performed hepatectomy after tumor down sizing with TACE.

From Down Staging to Curative Treatment: Based on Hepatic Arterial Infusion Chemotherapy in a Hepatocellular Carcinoma Patient: Chung-Hwa Park, Myung Joon Song, Seung Kew Yoon, Jong Young Choi, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2011;11(1):46-49. Published online February 28, 2011

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Abstract PDF: Hepatic arterial infusion chemotherapy (HAIC) is performed in patients with advanced hepatocellular carcinoma (HCC) in which locoregional therapeutic methods such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA) could not be the best choice. Sorafenib, the only approved systemic chemotherapeutic agent for HCC, improves survival rate, but is associated with a low tumor response rate. Thus combining these therapeutic modalities to treat HCC in advanced stage may help downstaging and leading to better treatment results without taking risk for hepatic failure. Here we report a case treated to a complete remission by combining HAIC, PEI and sorafenib.

A Case of Multiple Hepatocellular Carcinoma which was Performed Liver Transplantation after Down-staging by Transcatheter Arterial Chemoembolization: Hee-Jung Wang, Bong-Wan Kim, Sung-Won Cho, Je-Hwan Won; Journal of the Korean Liver Cancer Study Group. 2011;11(1):50-55. Published online February 28, 2011

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Abstract PDF: A case of multiple hepatocellular carcinoma (HCC) which was performed a living donor liver transplantation (LDLT) after down-staging by transcatheter arterial chemoembolization (TACE) is reviewed. Generally, the recommended therapeutic strategy for this kind of HCC is TACE. However, the response of multiple HCC of this 48 year-old male patient was relatively good after 4 times of TACE, and we performed LDLT on the concept of clinical trial under the informed consent of patient and his families. Although there were two times recurrences in the liver and lung, he has overcome them and is still alive 66 months after LDLT. We suggest that liver transplantation could be an alternative strategy in the multiple HCC cases who show good responses after TACE.

A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombi which was Performed Hepatectomy after Down-staging by Proton Therapy: Hee-Jung Wang, Bong-Wan Kim, Wei-Kwang Xu; Journal of the Korean Liver Cancer Study Group. 2011;11(1):56-59. Published online February 28, 2011

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Abstract PDF: A case of hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT) which was performed hepatectomy after down-staging by proton therapy is reviewed. Generally, the recommended therapeutic strategy for this kind of HCC is radiation therapy, systemic or infusion anticancer chemotherapy. However, the response of HCC and its PVTT of this 56 year-old male patient was relatively good after 22 times of proton therapy, and we performed right hemihepatectomy on the concept of clinical trial under the informed consent of patient and his families. He is still alive without recurrence 15 months after hepatectomy. We suggest that hemihepatectomy with removal of PVTT could be an alternative strategy in the PVTT accompanied HCC cases who show good responses after the above generally recommended therapies.

A Case of Hepatocellular Carcinoma with Bile Duct Invasion Surgically Resected after Transarterial Chemoembolization; Curative Resection after Tumor Downstaging: Nae-Yun Heo, Han Chu Lee, Ju Hyun Shim, Kang Mo Kim, Young Suk Lim, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh; Journal of the Korean Liver Cancer Study Group. 2011;11(1):69-74. Published online February 28, 2011

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Abstract PDF: A surgical resection is a major curative treatment of hepatocellular carcinoma (HCC) in Korea. However, the respectability of HCC at the time of diagnosis is low (10-30%) because the cancer is often identified as advanced stage. Nevertheless, some of the patients were known to have a curative resection after successful downstaging therapy. We report a HCC with bile duct invasion which was successfully downstaged by the transarterial chemoembolization and treated by surgical resection.

Review Articles

Comparative Analysis of the Variable Prognostic Staging Systems for Hepatocellular Carcinoma: Sang Hoon Park; Journal of the Korean Liver Cancer Study Group. 2008;8(1):24-27. Published online June 30, 2008

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Abstract PDF: There are several worldwide prognostic staging systems for hepatocellular carinoma (HCC) since Okuda staging system was proposed in 1985. However, there is no consensus which staging system is best in predicting the survival of patients with HCC. In this review, the author investigated the value and the usefulness of known prognostic systems using the literatures. Comparative analysis was taken with focused on 1) the status of validation (internal and/or external validation), 2) the homogeneity within classification groups (treatment, survival), 3) the adequacy of study design (prospective or retrospective, single center or multi-center, and number of patients), 4) the adequacy of statistical method and 5) the concordance of between predicted and observed outcomes between all staging systems. In overall, the CLIP, BCLC and JIS staging systems provided the good stratification of patients with HCC. Although these scoring system have been well validated by many authors, they have some problems and limitations when applied to individual HCC patients, We should try to find more simple and better discriminatory prognostic scoring systems in the future

Studies for Stage and Prognosis of Hepatocellular Carcinoma in Korea: Sang Young Han; Journal of the Korean Liver Cancer Study Group. 2008;8(1):28-31. Published online June 30, 2008

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Abstract PDF: Hepatocellular carcinoma is the fifth most common cancer in the world, and the 3rd leading cause of cancer-related death. The precise stage system of hepatocellular carcinoma, which classifies patients to the same prognosis group, is important, so that it can help to choose proper treatment strategy. Staging systems used for hepatocellular carcinoma are Okuda, TNM, CLIP, French, CUPI, JIS score and BCLC classification, these staging systems have limitations in predicting patient prognosis, because these do not include tumor morphology, characteristics, clinical variables and treatment modalities properly. The staging system of hepatocellular carcinoma is still insignificantly studied in domestic. A large scale cohort study is needed including multivariables.

Hepatic Resection Following Adjuvant Treatments in Hepatocellular Carcinoma: Sae-Byeol Choi, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2008;8(1):32-38. Published online June 30, 2008

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Abstract PDF: The optimal treatment of hepatocellular carcinoma has become increasingly complex with myriad of available treatment options. Although recently the liver transplantation has been accepted the best treatment for survival, the shortage of donor limits the extension of this procedures. As the neoadjuvant chemotherapy is being increasingly employed to downsize colorectal metastasis, the clinical trials have been extended to the hepatocellular carcinoma. Therefore we reviewed the use of liver resection following tumor downstaging with chemotherapeutic agents and Radiation therapy to treat unresectable HCC. Key Words: Hepatic resection․Downstaging․Transarterial chemoembolization․Radiation

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