Journal of Liver Cancer

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

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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

Outcomes of liver resection and transarterial chemoembolization in patients with multinodular BCLC-A hepatocellular carcinoma: Jiwon Yang, Won-Mook Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Deok-Bog Moon, Dong-Hwan Jung, Jonggi Choi; J Liver Cancer. 2024;24(2):178-191. Published online April 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.03.25

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Abstract PDF Supplementary Material

Backgrounds/Aims
This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation.
Methods
We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups.
Results
Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (P<0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS<0.05).
Conclusions
In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Citations

Citations to this article as recorded by

A Prospective, Multicenter, Randomized, Noninferiority Trial of Stopad® Versus Tachosil® for Hemostasis After Liver Resection
Seung Yeon Lim, Gi Hong Choi, Jin Hong Lim, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Boram Lee, Yeshong Park, MeeYoung Kang, Jinju Kim, Hyelim Joo, Jai Young Cho
Cancers.2025; 17(5): 757. CrossRef
Comparison of initial treatments for resectable hepatocellular carcinoma within Milan criteria: an observational study based on a nationwide survey
Sang Jin Kim, Woo Kyoung Jeong, Hyung-Joon Han, Gyu-Seong Choi, Kyun-Hwan Kim, Jongman Kim
Annals of Surgical Treatment and Research.2025; 108(5): 279. 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

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment: Sujin Jin, Won-Mook Choi, Ju Hyun Shim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jinhong Jung, Sang Min Yoon, Jonggi Choi; J Liver Cancer. 2023;23(1):177-188. Published online March 23, 2023; DOI: https://doi.org/10.17998/jlc.2023.03.04

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115 Downloads
8 Citations

Abstract PDF Supplementary Material

Background/Aim
The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C.
Methods
A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points.
Results
The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001).
Conclusions
Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

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
Efficacy and safety of image-guided hypofractionated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective, multicenter study
Sang Min Lee, Jin Hwa Choi, Jung-Hwan Yoon, Yoon Jun Kim, Su Jong Yu, Jeong-Hoon Lee, Hyun-Cheol Kang, Eui Kyu Chie, Kyung Su Kim
BMC Cancer.2025;[Epub] CrossRef
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
Journal of Liver Cancer.2024; 24(1): 102. CrossRef
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
Journal of Liver Cancer.2024; 24(1): 81. CrossRef
A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Ji W. Han, Soon K. Lee, Jung H. Kwon, Soon W. Nam, Hyun Yang, Si H. Bae, Ji H. Kim, Heechul Nam, Chang W. Kim, Hae L. Lee, Hee Y. Kim, Sung W. Lee, Ahlim Lee, U I. Chang, Do S. Song, Seok-Hwan Kim, Myeong J. Song, Pil S. Sung, Jong Y. Choi, Seung K. Yoon,
Clinical Cancer Research.2024; 30(13): 2812. CrossRef
Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma
Ye Rim Kim, Sung Won Chung, Min-Ju Kim, Won-Mook Choi, Jonggi Choi, Danbi Lee, Han Chu Lee, Ju Hyun Shim
Journal of Hepatocellular Carcinoma.2024; Volume 11: 1235. 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
How to optimize the treatment strategy for advanced-stage hepatocellular carcinoma with macrovascular invasion
Beom Kyung Kim
Journal of Liver Cancer.2023; 23(1): 121. CrossRef

Transarterial Chemoembolization versus Radiofrequency Ablation for Small Hepatocellular Carcinomas with Discrepant Features on Computed Tomography and Magnetic Resonance Imaging: Young Youn Cho, Jung Hee Kwon, Jeong-Hoon Lee, Jeong Min Lee, Jae Young Lee, Hyo-Choel Kim, Jin Wook Chung, Won-mook Choi, Eun Ju Cho, Yoon Jun Kim, Jung-Hwan Yoon, Chung Yong Kim, Hyo-Suk Lee; J Liver Cancer. 2015;15(1):19-29. Published online March 31, 2015; DOI: https://doi.org/10.17998/jlc.15.1.19

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Abstract PDF: Background/Aims
This study compared the outcomes of patients with small hepatocellular carcinomas (HCCs) who were treated using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA).
Methods
This was a post-hoc analysis of a prospective study that evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) and computed tomography (CT). We analyzed 41 small hepatic nodules in 32 patients that showed typical radiologic hallmarks on both CT and gadoxate-enhanced MRI (typical nodules) and 25 small hepatic nodules from 22 patients that showed atypical radiologic hallmarks on CT and typical radiologic hallmarks on MRI (discrepant nodules).
Results
There were no significant differences in the baseline characteristics of the patients with typical and discrepant nodules. Complete response rates 1 month after TACE or RFA were 75.0% (18/24) and 94.1% (16/17; P=0.20), respectively, for the patients with typical nodules and 58.8% (10/17) and 100% (8/8; P=0.05), respectively, for the patients with discrepant nodules. Treatment failure rates after TACE or RFA were 33.3% (8/24) and 5.8% (1/17; P=0.15), respectively, for the patients with typical nodules and 47.0% (8/17) and 0.0% (0/8; P=0.02), respectively, for the patients with discrepant nodules. Among patients achieving complete response, there were no significant differences in the risk of marginal recurrence.
Conclusions
RFA provided higher complete response rates and significantly lower treatment failure rates than TACE for patients with discrepant nodules of HCC. Therefore, a treatment modality such as RFA may be preferable for small HCCs which show discrepancy on two imaging modalities.

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