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; Received October 9, 2024 Accepted December 27, 2024 Published online January 14, 2025; DOI: https://doi.org/10.17998/jlc.2024.12.27 [Accepted]

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Abstract PDF: Background/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 PCR 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.

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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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.

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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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109 Downloads
6 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

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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

Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry: Jun Sik Yoon, Han Ah Lee, Hwi Young Kim, Dong Hyun Sinn, Dong Ho Lee, Suk Kyun Hong, Ju-Yeon Cho, Jonggi Choi, Young Chang, Hyun-Joo Kong, Eunyang Kim, Young-Joo Won, Jeong-Hoon Lee; J Liver Cancer. 2021;21(1):58-68. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.58

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302 Downloads
20 Citations

Abstract PDF Supplementary Material

Background/Aims
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015.
Methods
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated.
Results
The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively.
Conclusions
In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.

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