Journal of Liver Cancer

Review Article

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

Citations to this article as recorded by

Effectiveness of Downstaging Advanced Hepatocellular Carcinoma for Liver Transplantation: Insights from a Decade of Single-Center Experience
Erin M. Duggan, Nishtha Singh, Joanna K. Weeks, Adam Talenfeld, Benjamin May, Resmi Charalel, Ian Dinmore, Sarah Stucky, Tea Binder, Alexander J. Berman, Yana Glemaud, Arush Anand, Anthony Choi, Rebecca Craig-Schapiro, Dustin Carpenter, Benjamin Samstein,
Digestive Disease Interventions.2026;[Epub] CrossRef
Transarterial Chemoembolization and Immunotherapy: Another Good Marriage?
Landon L. Chan, Stephen L. Chan
Journal of Clinical Oncology.2026; 44(11): 949. CrossRef
Low Tumor Burden Predicts Benefit from Transarterial Treatment in Hepatocellular Carcinoma with Extrahepatic Metastasis: A Nationwide Cohort Study
Jaejun Lee, Hyun Yang, Keungmo Yang, Ji Won Han, Pil Soo Sung, Jeong Won Jang, Si Hyun Bae
Liver Cancer.2026; : 1. CrossRef
Expanding the path to cure - a narrative review on optimizing multimodality sequencing in HCC
Howard J. Lim, Arndt Vogel, Emma M. Dunne, Mayur Brahmania, Vincent C. Tam, Robert J. Abraham, Jennifer J. Knox, Jason K. Wong, Prosanto Chaudhury, Ravi Ramjeesingh, Peter T.W. Kim, Ilidio Martins, Leandro C. Leite, David Valenti, Gonzalo Sapisochin, Davi
Cancer Treatment Reviews.2026; 149: 103194. CrossRef
Outcomes of living donor liver transplantation in elderly Egyptian patients: a retrospective study
Ahmed Abdelrafee, Mohamed Abdelwahab, Amr Sanad, Ahmed Shehta, Mohamed Eldesoky, Mahmoud A. Ali, Mohamed A. Elmorshedi, Adel Ali Hassan, Waleed M. R. Elsarraf
Langenbeck's Archives of Surgery.2026;[Epub] 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
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
Liver Transplantation for Hepatocellular Carcinoma: A Comprehensive Review
Seok-Hwan Kim
Convergence Hepatology.2025; 1(1): 24. CrossRef
Radioembolization of primary liver tumors for patients with pre-existing ascites: beyond Child-Pugh score
Fayez J. Jabboure, Joshua A. Marlow, Wyatt D. Reed, Naganathan B. Mani, Nassir Rostambeigi
Abdominal Radiology.2025; 51(7): 3418. CrossRef

Case Reports

A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab: Hyung Jun Kim, Sang Youn Hwang, Jung Woo Im, Ki Jeong Jeon, Wan Jeon; J Liver Cancer. 2023;23(1):213-218. Published online March 9, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.23

7,051 Views
124 Downloads
5 Citations

Abstract PDF

Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.

Citations

Citations to this article as recorded by

Marked Response to Nivolumab Plus Ipilimumab After the Failure of Two Prior Immune Checkpoint Inhibitor–Based Regimens Including CTLA-4 Blockade in Advanced Hepatocellular Carcinoma
Shinichiro Minami, Wataru Sato, Kenjiro Yamamoto, Mitsuru Chiba, Kenichi Takahashi, Mari Matsuyama, Ryo Kikuchi, Yuma Sato, Hiroki Koshiishi, Katsunori Iijima
Internal Medicine.2026;[Epub] CrossRef
Beyond second-line therapy: Strategic sequencing of systemic treatments in advanced hepatocellular carcinoma
Marta Fortuny, Landon L. Chan, Leonardo G. da Fonseca, Ghassan K. Abou-Alfa, Stephen L. Chan, María Reig
Hepatology.2026; 84(4): 1078. CrossRef
Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians
Dimitrios Moris, Alessandro Martinino, Sarah Schiltz, Peter J. Allen, Andrew Barbas, Debra Sudan, Lindsay King, Carl Berg, Charles Kim, Mustafa Bashir, Manisha Palta, Michael A. Morse, Michael E. Lidsky
CA: A Cancer Journal for Clinicians.2025; 75(6): 498. CrossRef
Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update
John D. Gordan, Erin B. Kennedy, Ghassan K. Abou-Alfa, Eliza Beal, Richard S. Finn, Terence P. Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, Hang T. Hoang, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O. Kaseb, R. Kate Kelley, Jerem
Journal of Clinical Oncology.2024; 42(15): 1830. CrossRef
Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab
Jaejun Lee, Jae-Sung Yoo, Ji Hoon Kim, Dong Yeup Lee, Keungmo Yang, Bohyun Kim, Joon-Il Choi, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
Frontiers in Immunology.2024;[Epub] CrossRef

Novel management of expected post-radiotherapy complications in hepatocellular carcinoma patients: a case report: Sung Hoon Chang, Tae Suk Kim, Yong Hwan Jeon, Nuri Hyun Jung, Dae Hee Choi; J Liver Cancer. 2022;22(2):183-187. Published online August 24, 2022; DOI: https://doi.org/10.17998/jlc.2022.08.03

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73 Downloads

Abstract PDF: In recent years, radiotherapy (RT) has been used to treat hepatocellular carcinoma (HCC) at each stage. This clinical trend has developed with the increasing improvement of RT techniques, which show clinical results comparable to those of other treatment modalities. Intensity-modulated radiotherapy uses a high radiation dose to improve treatment effectiveness. However, the associated radiation toxicity can damage adjacent organs. Radiation-induced gastric damage with gastric ulcers is a complication of RT. This report presents a novel management strategy for preventing post-RT gastric ulcers. We present the case of a 53-year-old male patient diagnosed with HCC, who experienced gastric ulcer after RT. Before the second round of RT, the patient was administered a gas-foaming agent, which was effective in preventing RT complications.

A Case of Achieving Partial Remission with the Combination of Sorafenib and Nivolumab in a Patient with Hepatocellular Carcinoma Showing Disease Progression after Nivolumab Therapy: Sang Youn Hwang, Seon-Mi Lee, Jung Woo Im, Ki Jeong Jeon, Cheol-Won Choi, Kyung-Su Kim, Wan Jeon; J Liver Cancer. 2019;19(1):74-78. Published online March 31, 2019; DOI: https://doi.org/10.17998/jlc.19.1.74

5,459 Views
57 Downloads

Abstract PDF: Sorafenib is a well-known approved systemic therapeutic agent used in patients with advanced hepatocellular carcinoma (HCC). Regorafenib and nivolumab are approved as second-line therapeutic drugs in patients showing disease progression after sorafenib therapy. However, there is no established third- or fourth-line therapy in patients with progression after regorafenib or nivolumab treatment. Recently, the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs) has been attempted as a firstline treatment strategy in advanced HCC patients based on the hypothesis that combination therapy may overcome resistance in ICPI monotherapy. On the basis of this suggestion, we herein describe the case of an HCC patient demonstrating macrovascular invasion, whereby partial remission was achieved via the combination of sorafenib and nivolumab following disease progression after nivolumab therapy. Further studies on the combination of TKIs and ICPIs are necessary to determine ways to manage HCC patients showing disease progression after ICPI therapy.

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