Journal of Liver Cancer

Review Articles

Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies: Ijin Joo; J Liver Cancer. 2025;25(2):217-232. Published online July 31, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.29

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Abstract PDF: Noninvasive imaging-based diagnosis of hepatocellular carcinoma (HCC) in high-risk patients plays a central role in clinical practice. Current major guidelines typically rely on the radiologic hallmark of nonrim arterial phase hyperenhancement followed by nonperipheral washout, criteria designed to achieve both high positive predictive value and sufficient specificity when applied within well-defined target populations. Despite these criteria, false positive diagnoses still occur and can lead to unnecessary or inappropriate treatment, as various benign and non-HCC malignant lesions may exhibit vascular features that overlap with the classic appearance of HCC. Furthermore, treatment decisions are occasionally guided by imaging findings even in patients outside the target population who are being evaluated for possible HCC, in whom vascular patterns are less specific and the risk of false positive diagnosis is inherently higher. Minimizing the risk of false positive diagnosis requires not only adherence to validated imaging criteria but also clinical and contextual integration when findings are uncertain. This includes consideration of ancillary features, tumor markers, and, when appropriate, further evaluation through biopsy, additional imaging, or follow-up. This review outlines a range of HCC mimickers and provides practical strategies to support accurate imaging interpretation and reduce false positive diagnoses in clinical practice.

Public health strategies for hepatocellular carcinoma: from risk factors to prevention and control: Mei-Hsuan Lee; J Liver Cancer. 2025;25(2):204-216. Published online July 28, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.25

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86 Downloads
1 Citation

Hepatocellular carcinoma (HCC) remains a major global health burden, ranking as one of the leading causes of cancer-related deaths worldwide. This review synthesizes current evidence on HCC epidemiology, highlighting both modifiable and non-modifiable risk factors, including chronic hepatitis B and C virus infections, metabolic dysfunction-associated steatotic liver disease (MASLD), excessive alcohol consumption, aflatoxin exposure, and genetic susceptibility. These diverse etiologies reflect not only biological mechanisms but also broader social and environmental determinants of health, emphasizing the need for integrated, population-level preventive strategies. Effective strategies across all levels of prevention are reviewed. Primordial and primary prevention strategies include public health policies, health education to raise awareness, universal hepatitis B vaccination, expanded access to antiviral therapies for hepatitis B virus (HBV) and hepatitis C virus (HCV), lifestyle interventions targeting obesity and alcohol use, and environmental controls to reduce aflatoxin exposure. Secondary prevention focuses on early detection through viral hepatitis screening and routine HCC surveillance in high-risk populations. Tertiary prevention aims to reduce morbidity and mortality through timely treatment and multidisciplinary care. Despite the availability of effective tools, substantial implementation gaps remain persist. Underdiagnosis of viral hepatitis, low treatment uptake, inadequate surveillance coverage, and disparities in healthcare access continue to limit progress. Addressing these challenges requires a coordinated public health response grounded in health system strengthening, policy innovation, and equitable access to care. A renewed public health commitment -integrating prevention, early diagnosis, and continuity of care- is essential to reduce the global burden of HCC and bridge the gap between knowledge and action.

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Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
Journal of Gastroenterology and Hepatology.2025;[Epub] CrossRef

Insights into hepatocellular adenomas in Asia: molecular subtypes, clinical characteristics, imaging features, and hepatocellular carcinoma risks: Subin Heo, In Hye Song, Edouard Reizine, Maxime Ronot, Jean-Charles Nault, Hae Young Kim, Sang Hyun Choi, So Yeon Kim; J Liver Cancer. 2025;25(1):67-78. Published online March 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.06

3,878 Views
121 Downloads
1 Citation

Abstract PDF

Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.

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Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies
Ijin Joo
Journal of Liver Cancer.2025; 25(2): 217. CrossRef

Original Articles

Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma: Jin Sun Kim, Won-Mook Choi, Ha-Il Kim, Sung Won Chung, Jonggi Choi, Danbi Lee, Kang Mo Kim; J Liver Cancer. 2025;25(1):79-90. Published online January 14, 2025; DOI: https://doi.org/10.17998/jlc.2024.12.27

3,553 Views
95 Downloads
2 Citations

Abstract PDF

Backgrounds/Aims
Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

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Antitumor role of L-arginine and argininosuccinate synthetase 1 in hepatocellular carcinoma: direct and immunological mechanisms
Hyuk Soo Eun
Journal of Liver Cancer.2025; 25(1): 1. CrossRef
Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC
Yi Ju, Kequan Xu, Xi Chen, Tiangen Wu, Yufeng Yuan
Trends in Endocrinology & Metabolism.2025;[Epub] CrossRef

Re-assessing the diagnostic value of the enhancing capsule in hepatocellular carcinoma imaging: Jae Seok Bae, Jeong Min Lee, Bo Yun Hur, Jeongin Yoo, Sae-Jin Park; J Liver Cancer. 2024;24(2):206-216. Published online May 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.01

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1 Citation

Abstract PDF Supplementary Material

Backgrounds/Aims
The enhancing capsule (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection.
Methods
We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LI-RADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC.
Results
In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBAMRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178).
Conclusions
The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.

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Value of enhancing capsule for diagnosing hepatocellular carcinoma on MRI: implications for simplifying LI-RADS
Se Jin Choi, Hae Young Kim, So Jung Lee, So Yeon Kim, Hyung Jin Won, Yong Moon Shin, Sang Hyun Choi, Jae Ho Byun
European Radiology.2025;[Epub] CrossRef

Review Article

Multidisciplinary approach for hepatocellular carcinoma patients: current evidence and future perspectives: Joo Hyun Oh, Dong Hyun Sinn; J Liver Cancer. 2024;24(1):47-56. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.27

7,712 Views
300 Downloads
20 Citations

Abstract PDF

Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

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Feng Ye, Qiang Cai, Xiaoyong Gong, Jiajun Ren, Ruixin Sun, Chang Liu, Xiaoli Wang, Yuan Qiao
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Soo Young Hwang, Pojsakorn Danpanichkul, Vatche Agopian, Neil Mehta, Neehar D. Parikh, Ghassan K. Abou-Alfa, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2025; 31(Suppl): S228. CrossRef
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Mahmoud Diab, Mindy X. Wang, Aarya Ramprasad, Ann A. Shi, Imran Ahmed, Sergio Klimkowski, Vincenzo K. Wong, Khaled M. Elsayes
Abdominal Radiology.2025;[Epub] CrossRef
Multidisciplinary Team Management of Hepatocellular Carcinoma in the MENA Region: Current Practices, Challenges, and Gaps
Mohamed El-Kassas, Rofida Khalifa, Khalid AlNaamani, Hend Shousha, Yusuf Yilmaz, Faisal Sanai, Maen Almattooq, Asma Labidi, Maisam Akroush, Nabil Debzi, Mohamed Abdelmalek, Nermeen Abdeen, Ali Tumi, Mohamed Elbadry, Amr El Fouly, Eman Marwan, Jassim Al Su
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Rashmita Kumari Mohapatra, Lochan Jolly, Sarada Prasad Dakua
Computational Biology and Chemistry.2025; 119: 108599. CrossRef
Primary small cell-like hepatocellular carcinoma arising in a patient with fatty liver disease without cirrhosis: a case report and literature review
Hyun Bin Choi, Jeong-Ju Yoo, Susie Chin, Sang Gyune Kim, Young-Seok Kim
Gastroenterology Report.2025;[Epub] CrossRef
Advancements in nanoultrasonics technology for the diagnosis and treatment of liver cancer: discussion on medical ethics and hospital management issues
Weiping Wan, Fan Yang, Yenan Zhang, Jie Wang, Xin Xie, Fangming Guo, Li Han
Nanomedicine.2025; 20(21): 2627. CrossRef
Impact of the 2024 medical-policy conflict on hepatocellular carcinoma management in Korea
Soon Sun Kim, Hyun Yang, Jieun Kwon, Eunju Kim, Jeong Il Yu, Janghan Jung, Woosun Choi, Ji Eun Han, Moon Haeng Hur, Bo Hyun Kim, Sung Hyun Kim, Jeong Han Kim, Haeryoung Kim, Pyoung-Jae Park, Hyun Phil Shin, Su Jong Yu, Ki Tae Yoon, Sang Min Yoon, Minjong
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Effectiveness of Nursing Care Intervention Among Patients With Hepatocellular Carcinoma Undergoing Surgery: A Systematic Review and Meta‐Analysis
Wei Geng, Danling Wang, Xinwei Feng
International Journal of Nursing Practice.2025;[Epub] 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
First-in-India experience with 90Y-BhabhaSphere: an indigenous 90Y-TheraSphere biosimilar for transarterial radioembolization of hepatic malignancies
Ashish Kumar Jha, Ameya D Puranik, Kunal Bharat Gala, K V Vimalnath Nair, Ardhi Rajeswari, Sharad P Lohar, Aaditya Shah, Amala M Mathai, Bikash K Tiwary, Nitin Sudhakar Shettye, Anupam Mathur, Usha Pandey, Sudipta Chakraborty, Nilendu Purandare, Suyash Ku
British Journal of Radiology.2025;[Epub] CrossRef
CTRP6 in Cancer: Mechanistic Insights and Therapeutic Potential
Muhammad Zubair Mehboob, Xia Lei
Cancers.2025; 17(21): 3409. CrossRef
Asian Conference on Tumor Ablation Guidelines for Hepatocellular Carcinoma
Shuichiro Shiina, Ryosuke Tateishi, Joon Il Choi, So Yeon Kim, Zhiqiang Meng, Lujun Shen, Sheng-Nan Lu, Jen-I. Hwang, Maki Tobari, Hitoshi Maruyama, Terguunbileg Batsaikhan, Qing Deng, Lariza Marie Canseco, Yoshinari Asaoka, Shi-Ming Lin, Kai-Wen Huang, H
Liver Cancer.2025; 14(5): 651. CrossRef
Applying quality indicators and multidisciplinary team care to improve long-term survival in early-stage hepatocellular carcinoma
Hui-Ling Huang, Kuan-Chen Pan, Te-Sheng Chang, Shu-Chen Chen, Hsing-Ju Lu, Sheng-Nan Lu
Asia-Pacific Journal of Oncology Nursing.2025; 12: 100804. CrossRef
Overview of the multidisciplinary team activity in patients with hepatocellular carcinoma and their survival outcomes
V. Guarini, C. Garzòn, D. Casado, M. Casanova, P. Villarejo, I. Azinovic, E. Crespo, I. Fernandez, M. Lopez, M.M. de Bourio, M. Moran, M. Jimenez, G. Medrano, V. Castellano, A. Lamarca
ESMO Gastrointestinal Oncology.2025; 10: 100263. CrossRef
Exploring the role of liver resection as a first-line treatment option for multinodular BCLC-A hepatocellular carcinoma
Joo Hyun Oh, Dong Hyun Sinn
Journal of Liver Cancer.2024; 24(2): 126. CrossRef
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Original Article

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

7,564 Views
284 Downloads
4 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.

Citations

Citations to this article as recorded by

Management strategies for advanced hepatocellular carcinoma with portal vein tumor thrombosis
Jeayeon Park, Su Jong Yu
The Ewha Medical Journal.2025;[Epub] 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

Review Article

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist: Mina Komuta; J Liver Cancer. 2024;24(1):17-22. Published online January 3, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.11

10,067 Views
372 Downloads
6 Citations

Abstract PDF

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

Citations

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Trends and Disparities in Intrahepatic Cholangiocarcinoma-related Mortality in the United States from 1999 to 2020
Obaid Ur Rehman, Malik Saad Hayat, Muhammad Mukarram Shoaib, Eeman Ahmad, Zain Ali Nadeem, Ahmad Zain
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Small but significant: Prognostic value of the small duct type in intrahepatic cholangiocarcinoma
Jiyun Kim, Joon Young Park, So Young Kim, Sejin Jung, Joo-Young Na, Hyun Jung Lee, Dong Hoon Shin, Jung Hee Lee
Annals of Diagnostic Pathology.2025; 79: 152515. CrossRef
From barriers to solutions: an expert-based algorithm for cholangiocarcinoma and other biliary tract cancers testing in the Era of precision oncology
Albrecht Stenzinger, Nicola Normanno, Angela Lamarca, Lorenza Rimassa, Fréderic Bibeau, Philippe Taniere, Arndt Vogel, Antoine Hollebecque
Expert Review of Molecular Diagnostics.2025; 25(8): 495. CrossRef
Refinement of histologic subtypes and identification of biomarkers linked to unfavorable prognosis in cholangiocarcinoma: The ENSCCA registries’ framework for digital twin advancement
Guido Carpino, Diletta Overi, Rocio I.R. Macias, Vincenzo Cardinale, Laura Izquierdo-Sanchez, Pilar Acedo, Marco Rengo, Michail Doukas, Timothy J. Kendall, Julien Calderaro, Lara R. Heij, Konrad Reichel, Stefano Leone, Paolo Onori, Barbara Franceschini, C
Hepatology.2025;[Epub] CrossRef
Role of Radiation Therapy for Biliary Tract Cancers
Molly A. Chakraborty, Ritesh Kumar, Brett L. Ecker, Haejin In, Russell C. Langan, Mariam Eskander, Salma K. Jabbour
Current Oncology.2025; 32(10): 545. 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

Original Article

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

5,884 Views
134 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

Case Reports

A Case of Metastatic Melanoma in the Liver Mimicking Hepatocellular Carcinoma: Jae-Kyoung So, Ji-Yun Hong, Min-Woo Chung, Sung-Bum Cho; J Liver Cancer. 2021;21(1):92-96. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.92

12,067 Views
312 Downloads
4 Citations

Abstract PDF

The liver is one of the most common sites of metastasis. Although most metastatic liver cancers are hypovascular, some hypervascular metastases, such as those from melanoma, need to be differentiated from hepatocellular carcinoma (HCC) because they may show similar radiologic findings due to their hypervascularity. We encountered a case of multinodular liver masses with hyperenhancement during the arterial phase and washout during the portal venous and delayed phases, which were consistent with imaging hallmarks of HCC. The patient had a history of malignant melanoma and had undergone curative resection 11 years earlier. We performed a liver biopsy for pathologic confirmation, which revealed a metastatic melanoma of the liver. Metastatic liver cancer should be considered if a patient without chronic liver disease has a history of other primary malignancies, and caution should be exercised with hypervascular cancers that may mimic HCC.

Citations

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Tumor‐Derived Exosomes Enriched by miRNA‐211a Promote Antitumor Immune Response in B16F10 Tumor‐Bearing Mice
Mohammad Reza Ataollahi, Mohammad Reza Atashzar, Ali Ghanbari Asad, Mohammad Mahdi Mokhtari Tabar, Davar Amani
APMIS.2025;[Epub] CrossRef
Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM)
Katarzyna Adamiak-Nikolouzou, Andrzej T. Słomiński, Zofia Skalska, Iwona Inkielewicz-Stępniak
Cancers.2025; 17(18): 3037. CrossRef
A case of metastatic melanoma in the liver mimicking colorectal cancer with synchronous liver metastasis
E.A. Warshowsky, M. McCarthy, K. Wells, A. Arcidiacono, L. Csury, J.R. Nitzkorski
International Journal of Surgery Case Reports.2024; 119: 109686. CrossRef
The importance of ultrasound-guided biopsy: lesson from a case of liver metastasis from uveal melanoma
Maria Boe, Susanna Vicari, Andrea Boccatonda, Fabio Piscaglia
Journal of Ultrasound.2024; 27(4): 927. CrossRef

Malignant Hepatic Solitary Fibrous Tumor: Hong Il Kim, Seok Kyung In, Hyung Suk Yi, Min Jeong Lee, Hyo Young Kim; J Liver Cancer. 2019;19(2):143-148. Published online September 30, 2019; DOI: https://doi.org/10.17998/jlc.19.2.143

5,694 Views
62 Downloads
1 Citation

Abstract PDF

Hepatic solitary fibrous tumors (SFTs) are mostly benign and rare because of information regarding the clinical symptoms, treatment, and prognosis of their malignant forms is currently lacking. A literature review concerning malignant SFTs revealed that there were a few cases where patients experienced abdominal right upper quadrant (RUQ) pain as their first clinical symptom, and metastases were found after being diagnosed with hepatic SFT. Here, we report a patient who was previously healthy without any clinical symptoms such as RUQ pain or weight loss, but had the appearance of a metastatic mass as the first clinical presentation before a primary hepatic SFT was detected.

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A Case of Hepatic Malignant Solitary Fibrous Tumor: A Case Report and Review of the Literature
Zhiyan Fu, Evita B. Henderson-Jackson, Barbara A. Centeno, Gregory Y. Lauwers, Mihaela Druta, Daniel A. Anaya, Yukihiro Nakanishi, Samir Sami Amr
Case Reports in Pathology.2023; 2023: 1. CrossRef

Original Article

Academic Trend and Clinical Status of Radiotherapy for Hepatobiliary Cancer Over the Past 20 Years in Korea: Won IL Jang, Yong-Seok Seo, Mi-Sook Kim, Heejin Kim; J Liver Cancer. 2015;15(2):100-105. Published online September 30, 2015; DOI: https://doi.org/10.17998/jlc.15.2.100

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Abstract PDF: Background/Aims
To analyze the future trends through the status of radiotherapy in the hepatobiliary cancer in Korea and related articles published in the world.
Methods
Science citation index (SCI) and science citation index expanded (SCIE) articles, published in the 20 years from 1995 until 2014, were searched that contain the keywords related hepatobiliary cancer and radiotherapy using the Scopus. The incidence of hepatobiliary cancer was analyzed using annual reports from the Korea Central Cancer Registry. The status of radiotherapy was analyzed using data obtained form the Korean Society for Radiation Oncology and the National Health Insurance Service.
Results
Total 2,302 papers related radiotherapy for hepatobiliary cancer were searched in the world. By 2014, the cumulative number of papers published by domestic authors was a total 221 pieces. In 1999, total 16,305 hepatobiliary cancer patients were developed, of which 729 patients have been treated with radiotherapy. In 2013, it was expected that total 22,482 hepatobiliary cancer patients would be developed, of which 3,075 patients have been treated with radiotherapy.
Conclusions
Over the past 20 years, South Korea has made clinically and academically remarkable advances in the area of radiotherapy for hepatobiliary cancer. The researchers will continue to announce the results such as an objective status data and published papers in the future. (J Liver Cancer 2015;15:100-105)

Review Articles

Clinical Safety and Efficacy of JX-594, a Targeted Multi-Mechanistic Oncolytic Pox Virus in Advanced Hepatocellular Carcinoma: Jeong Heo; Journal of the Korean Liver Cancer Study Group. 2011;11(2):149-154. Published online September 30, 2011

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Abstract PDF: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ras pathway activation. Direct oncolysis plus granulocyte macrophage-colony stimulating factor (GM-CSF) expression is accompanied by tumor vascular shutdown and anti-tumoral immunity. In a Phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, anti-cancer immunity, decreased tumor perfusion and tumor necrosis. JX-594 has been shown to be well-tolerated by intravenous (IV) infusion and intratumoral (IT) injection and JX-594 is being developed as a novel therapy for patients with refractory or advanced HCC. Synergistic anti-tumor effects are predicted with JX-594 and sorafenib due to acute vascular shut down effect and tumor-specific antibody formation of JX-594 and chronic anti-angiogenic effects of sorafenib. JX-594 shows promise as a novel agent for the treatment of advanced HCC.

Multistep Carcinogenesis of Hepatocellular Carcinoma: Ja-June Jang; Journal of the Korean Liver Cancer Study Group. 2008;8(1):39-46. Published online June 30, 2008

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Abstract PDF: Epidemiological and experimental data have demonstrated that the process of carcinogenesis is progressive and multistage in nature. Model systems in animals exhibit this property of cancer development for several organ systems. The rat liver is one of the most extensively studied models of carcinogenesis. Multiple formats have been described for the analysis of cancer development in this organ, including the resistant hepatocyte selection regimens, the neonatal rat model and the partial hepatectomy model. The evolution of hepatic neoplasia is a slow process leading from the normal state via preneoplasia to benign and malignant neoplasia. On the histological level, hepatic preneoplasia usually emerges as foci of altered hepatocytes (FAH) which are perfectly integrated in the normal liver parenchyma and have no obvious neoplastic nature. The early emergence of FAH seems to be a general phenomenon of hepatocarcinogenesis in all species, no matter how this process has been elicited. The hallmark for the definition and detection of hepatic preneoplasia are biochemical and morphological changes in the hepatocellular phenotypes, which are neither uniform nor stable. In rodent liver treated with various chemical carcinogens, most of phenotypes have been shown to represent successive stages in an ordered sequence of cellular changes, progressing from glycogenic, clear and eosinophilic cell foci, through intermediate, mixed and basophilic cell populations, to hepatocellular adenomas and carcinomas, the fast growing variants of which consist of glycogen-poor, basophilic (ribosome-rich) cells. The identification of the placental isozyme of glutathione S-transferase (GST-P) as a highly expressed cytoplasmic protein during early carcinogenesis has led to its use as a marker of hepatic tumor development in early focal lesions, nodules and carcinomas. Different lesions have been suggested to represent preneoplastic conditions in human liver. They include large-cell change, small-cell change, foci of altered hepatocytes and dysplastic nodules. Experimental results suggest that multiple progressive factors are also involved in human hepatocarcinogenesis.

Case Report

Hepatoid Adenocarcinoma of the Stomach with Liver Metastasis Mimicking Hepatocellular Carcinoma: Se Hyung Kim, Byung Ihn Choi; Journal of the Korean Liver Cancer Study Group. 2003;3(1):65-68. Published online July 31, 2003

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Abstract PDF: We describe a case of hepatoid adenocarcinoma of the stomach with liver metastasis mimicking hepatocellular carcinoma (HCC). Ultrasonography demonstrated an ill-defined heterogeneous hyperechoic mass at right lobe of the liver and high echoic thrombi that filled both portal veins. Contrast enhanced CT scan revealed an ill-defined low attenuated lesion in right lobe of the liver and left portal vein and posterior branch of right portal vein that were filled with low attenuated tumor thrombi. Diffuse and irregular wall thickening with enhancement was also visualized on the posterior wall of the stomach from cardia to angle. Endoscopic biopsy for gastric lesion and US-guided percutaneous core biopsy for hepatic mass were performed. Microscopic examination and immunohistochemical staining revealed aFP-producing hepatoid adenocarcinoma of the stomach and metastatic tumor of the liver.

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