Journal of Liver Cancer

Original Articles

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: Jeayeon Park, Yun Bin Lee, Yunmi Ko, Youngsu Park, Hyunjae Shin, Moon Haeng Hur, Min Kyung Park, Dae-Won Lee, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Tae-Yong Kim, Yoon Jun Kim, Tae-You Kim, Jung-Hwan Yoon; J Liver Cancer. 2024;24(1):81-91. Published online January 19, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.25

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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.

Citations

Citations to this article as recorded by

Role of Liver Function in the Multiparametric Assessment of Hepatocellular Carcinoma
Fabio Melandro, Leonardo Centonze, Ciro Celsa, Simone Famularo, Davide Ghinolfi, Silvia Nardelli, Maria Pallozzi, Ludovico Abenavoli, Fabrizio Romano, Francesca Romana Ponziani, Francesco Paolo Russo, Quirino Lai
Medicina.2026; 62(1): 138. CrossRef
Combined Transarterial Chemoembolization and External Beam Radiotherapy for Identifying Surgical Candidates for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score–Weighted Analysis
Sumin Lee, Jinhong Jung, Jonggi Choi, So Yeon Kim, Jin Hyoung Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Gi-Won Song, Jin-hong Park, Sang Min Yoon
Cancer Research and Treatment.2026; 58(1): 275. CrossRef
Immunotherapy in Hepatocellular Carcinoma with Portal Vein Tumour Thrombosis: From Poor Prognosis to Curative-Intent Strategies
Luca Marzi, Rodolfo Sacco, Luisa Siciliani, Saveria Lory Crocè, Mauro Giuffrè, Cristina Stasi, Chiara Turri, Monica Zoeschg, Andrea Mega
Cancers.2026; 18(4): 627. CrossRef
Survival Outcomes Following Yttrium-90 and Holmium-166 Transarterial Radioembolization for Hepatocellular Carcinoma
Dávid Ádám Korda, Dénes Balázs Horváthy, Sándor Czibor, Domonkos Nádasdy-Horváth, Petra Sólymos, Oszkár Háhn, Bálint Tegze, Klára Werling, Attila Jakó, Szabolcs Takács, Pál Ákos Deák, András Bibok
Cancers.2026; 18(13): 2039. CrossRef
Management strategies for advanced hepatocellular carcinoma with portal vein tumor thrombosis
Jeayeon Park, Su Jong Yu
The Ewha Medical Journal.2025;[Epub] CrossRef
Case Report: Tumor lysis syndrome in advanced, massive hepatocellular carcinoma with main portal vein invasion following atezolizumab plus bevacizumab therapy
Tien-Shin Chou, Chun-Feng Wu, Chih-Lang Lin, Chao-Wei Hsu
Frontiers in Oncology.2025;[Epub] CrossRef
Locoregional therapy combined with targeted therapy and immunotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis
Mengjie Jiang, Chao Chen, Yujie Hu, Gang Lin, Huafeng Li
Scientific Reports.2025;[Epub] CrossRef
Liver Resection versus Targeted Therapy Plus PD-1 Inhibitors in Hepatocellular Carcinoma with Type I-II Portal Vein Tumor Thrombus: A Comparative Study
Liang Li, Zhenli Li, Yibing Zhang, Shuaishuai Zhu, Yuanzhi Ni, Lindi Xu, Shixing Yan, Yufu Tang
Journal of Hepatocellular Carcinoma.2025; Volume 12: 2745. CrossRef
Prognostic Significance of Glypican-3 Expression in Hepatocellular Carcinoma Treated with Atezolizumab-Bevacizumab
Ji Hoon Kim, Ji Won Han, Hee Sun Cho, Jeong Won Jang, Kwon Yong Tak, Pil Soo Sung
Cancers.2025; 17(24): 3967. CrossRef
Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?
Walaa Abdelhamed, Hend Shousha, Mohamed El-Kassas
Liver Research.2024;[Epub] CrossRef
Reappraisal of transarterial radioembolization for liver-confined hepatocellular carcinoma with portal vein tumor thrombosis: Editorial on “Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein throm
Jin Hyoung Kim, Gun Ha Kim, Dong Il Gwon
Clinical and Molecular Hepatology.2024; 30(4): 659. CrossRef
Current perspectives on the pharmacological treatment of advanced hepatocellular carcinoma: a narrative review
Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
The Ewha Medical Journal.2024;[Epub] CrossRef

The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma: Jihyun An, Hyo Jeong Kang, Eunsil Yu, Han Chu Lee, Ju Hyun Shim; J Liver Cancer. 2022;22(1):40-50. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.06

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136 Downloads
2 Citations

Abstract PDF Supplementary Material

Background/Aim
Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC).
Methods
A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically.
Results
Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively).
Conclusions
Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

Citations

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The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review
Amirhosein Sabaghian, Shahnam Shamsabadi, Saghar Momeni, Mobina Mohammadikia, Kiarash Mohebbipour, Samira Sanami, Sajjad Ahmad, Nahid Akhtar, Neeta Raj Sharma, Raja Babu Singh Kushwah, Yash Gupta, Ajit Prakash, Hamidreza Pazoki-Toroudi
Journal of Cancer Metastasis and Treatment.2024;[Epub] CrossRef
Recent Advances in Immune-based Therapy for Hepatocellular Carcinoma
Kyung Won Park, Tae Hoon Park, Eun Ji Jang, Pil Soo Sung
Journal of Digestive Cancer Research.2024; 12(2): 115. CrossRef

Review Article

Advances in immune checkpoint inhibitors for hepatocellular carcinoma: Ji Won Han, Su-Hyung Park; J Liver Cancer. 2021;21(2):139-145. Published online September 30, 2021; DOI: https://doi.org/10.17998/jlc.2021.09.24

11,165 Views
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9 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

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Vaccines.2026; 14(2): 189. CrossRef
Design, synthesis, and mechanistic study of bispecific small molecules-based phenyl pyrazolopyrimidinone scaffold as dual-targeting VEGFR and PD-L1 immune checkpoint in hepatocellular carcinoma
Esraa.M.M. Hassoub, Bahgat R.M. Hussein, Mamdouh F.A. Mohamed, El-Shimaa M.N. Abdelhafez
Bioorganic Chemistry.2026; 175: 109789. CrossRef
Immunology, immunotherapy, and the tumor microenvironment in hepatocellular carcinoma: a comprehensive review
Miho Akabane, Yuki Imaoka, Ghee Rye Lee, Timothy M. Pawlik
Expert Review of Clinical Immunology.2025; 21(10): 1403. CrossRef
Complete response and HBsAg clearance of advanced hepatocellular carcinoma associated with hepatitis B by DEB−TACE combined systematic therapy: a case report
Baiguo Xu, Yufeng Cui, Hao Cui, Ning Wang, Zhongsong Gao, Qing Ye
Frontiers in Immunology.2025;[Epub] CrossRef
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Journal of Liver Cancer.2024; 24(2): 243. CrossRef
Dynamic Peripheral T-Cell Analysis Identifies On-Treatment Prognostic Biomarkers of Atezolizumab plus Bevacizumab in Hepatocellular Carcinoma
Ji Won Han, Min Woo Kang, Soon Kyu Lee, Hyun Yang, Ji Hoon Kim, Jae-Sung Yoo, Hee Sun Cho, Eun Ji Jang, Deok Hwa Seo, Jung Hyun Kwon, Soon Woo Nam, Si Hyun Bae, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung
Liver Cancer.2024; : 1. CrossRef
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Logan Muzyka, Nicolas K. Goff, Nikita Choudhary, Michael T. Koltz
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Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11517. CrossRef
Editorial on Immune Checkpoint Inhibitors in the Treatment of Hepatocellular Carcinoma
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Original Article

Infiltration of T Cells and Programmed Cell Death Ligand 1-expressing Macrophages as a Potential Predictor of Lenvatinib Response in Hepatocellular Carcinoma: Pil Soo Sung, Sung Woo Cho, Jaejun Lee, Hyun Yang, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2020;20(2):128-134. Published online September 30, 2020; DOI: https://doi.org/10.17998/jlc.20.2.128

7,228 Views
113 Downloads
8 Citations

Abstract PDF

Background/Aims
Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity.
Methods
Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy.
Results
Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05).
Conclusions
Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.

Citations

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Ganghui Ye
American Journal of Cancer Research.2024; 14(9): 4113. CrossRef
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Kyung Won Park, Tae Hoon Park, Eun Ji Jang, Pil Soo Sung
Journal of Digestive Cancer Research.2024; 12(2): 115. CrossRef
Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang, Pil Soo Sung
Diagnostics.2023; 13(8): 1453. CrossRef
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Pil Soo Sung, Dong Jun Park, Pu Reun Roh, Kyoung Do Mun, Sung Woo Cho, Gil Won Lee, Eun Sun Jung, Sung Hak Lee, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Jonghwan Choi, Jaegyoon Ahn, Seung Kew Yoon
Journal for ImmunoTherapy of Cancer.2022; 10(5): e003618. CrossRef
Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
Pil Soo Sung
Clinical and Molecular Hepatology.2022; 28(3): 333. CrossRef
Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go
Pil Soo Sung, Isaac Kise Lee, Pu Reun Roh, Min Woo Kang, Jaegyoon Ahn, Seung Kew Yoon
Frontiers in Oncology.2022;[Epub] CrossRef
Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection
Pil Soo Sung, Eui-Cheol Shin
Journal of Clinical Medicine.2021; 10(2): 221. CrossRef
Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma
Dong-Jun Park, Pil-Soo Sung, Gil-Won Lee, Sung-Woo Cho, Sung-Min Kim, Byung-Yoon Kang, Won-Hee Hur, Hyun Yang, Soon-Kyu Lee, Sung-Hak Lee, Eun-Sun Jung, Chang-Ho Seo, Joseph Ahn, Ho-Joong Choi, Young-Kyoung You, Jeong-Won Jang, Si-Hyun Bae, Jong-Young Cho
International Journal of Molecular Sciences.2021; 22(9): 4710. CrossRef

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