Journal of Liver Cancer

Articles in E-pub version are posted online ahead of regular printed publication.

Review Article

A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017–2024: Hyunjae Shin, Su Jong Yu; Received December 25, 2024 Accepted February 3, 2025 Published online February 10, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.03 [Accepted]

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Abstract PDF: Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.

Original Articles

Microwave ablation versus liver resection for patients with hepatocellular carcinomas: Hyundam Gu, Yeonjoo Seo, Dong Jin Chung, Kwang Yeol Paik, Seung Kew Yoon, Jihye Lim; Received December 9, 2024 Accepted February 2, 2025 Published online February 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.02 [Accepted]

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Abstract PDF: Backgrounds/Aims
Microwave ablation (MWA) is an emerging ablative therapy that surpasses previous methods by achieving higher temperatures and creating larger ablation zones within shorter periods. This study compared the therapeutic outcomes of MWA with those of liver resection in real-world clinical practice.
Methods
A total of 178 patients with 259 nodules who underwent MWA or liver resection between January 2015 and July 2023 were enrolled. Local tumor progression-free survival (LTP), overall progression-free survival (OP), and overall survival (OS) were assessed based on the treatment modality for the index nodule.
Results
Of the 178 patients, 134 with 214 nodules underwent MWA, and 44 with 45 nodules underwent liver resection. The median follow-up period was 2.0 ± 1.5 years. The annual incidence of LTP was 3.7% for MWA and 1.4% for liver resection. Treatment modality did not significantly affect LTP-free survival (hazard ratio: 0.61, 95% confidence interval: 0.14–2.69, P = 0.511). For nodules larger than 3 cm, LTP-free survival was not affected by the treatment modality. Similarly, OP-free survival and OS were not influenced by treatment modality.
Conclusions
MWA and liver resection demonstrated comparable treatment outcomes in terms of local tumor control, overall recurrence, and survival. MWA may be an alternative treatment option for select patients; however, further studies are necessary to generalize these findings.

Enhanced Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma Post-Transarterial Chemoembolization: A Prospective Study Utilizing Twin Internally Cooled-Perfusion Electrodes: Sungjun Hwang, Jae Hyun Kim, Sae-Jin Park, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Jeong Min Lee; Received November 12, 2024 Accepted January 21, 2025 Published online February 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.01.25 [Accepted]

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Abstract PDF: Background
Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE.
Methods
Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter: 1.6 ± 0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-CT/MR fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP.
Results
The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range: 3–41 months), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 and 2 years, respectively.
Conclusions
Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.

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.

Review Article

Molecular and immune landscape of hepatocellular carcinoma for therapeutic development: Hiroyuki Suzuki, Sumit Mishra, Subhojit Paul, Yujin Hoshida; Received October 30, 2024 Accepted December 2, 2024 Published online December 6, 2024; DOI: https://doi.org/10.17998/jlc.2024.12.02 [Accepted]

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Abstract PDF: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an estimated 750,000 deaths in 2022. Recent emergence of molecular targeted agents (MTAs) and immune checkpoint inhibitors (ICIs) and their combination therapies have been transforming HCC care, but their prognostic impact in advanced-stage disease remains unsatisfactory. In addition, their application to early-stage disease is still an unmet need. Omics profiling studies have elucidated recurrent and heterogeneously present molecular aberrations involved in pro-cancer tumor (immune) microenvironment that may guide therapeutic strategies. Recurrent aberrations such somatic mutations in TERT promoter and TP53 have been regarded undruggable, but recent studies have suggested that these may serve as new classes of therapeutic targets. HCC markers such as alpha-fetoprotein (AFP), glypican-3 (GPC3), and epithelial cell adhesion molecule (EpCAM) have also been explored as therapeutic targets. These molecular features may be utilized as biomarkers to guide the application of new approaches as companion biomarkers to maximize therapeutic benefits in patients who are likely to benefit from the therapies, while minimizing unnecessary harm in patients who will not respond. The explosive number of new agents in the pipelines have posed challenges in their clinical testing. Novel clinical trial designs guided by predictive biomarkers have been proposed to enable their efficient and cost-effective evaluation. These new developments collectively facilitate clinical translation of personalized molecular-targeted therapies in HCC and substantially improve prognosis of HCC patients.

Editorial

Evolving trends in epidemiology, etiology, and treatment patterns for hepatocellular carcinoma in South Korea: Soo Young Hwang, Ju Dong Yang; Received November 30, 2024 Accepted December 4, 2024 Published online December 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.12.04 [Accepted]

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PDF

Case Report

Durable complete response after discontinuation of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma with portal vein tumor thrombosis: the first report: Pramod Kumar, Pradeep Krishna, Rohit Maidur, Naveen Chandrashekhar, Suresh Raghavaiah; Received June 14, 2024 Accepted September 26, 2024 Published online November 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.26 [Accepted]

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Abstract PDF: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a dismal prognosis. Atezolizumab plus bevacizumab (atezo-bev) is the recommended palliative treatment, and approximately 10% of the patients may experience a complete response (CR), according to the mRECIST criteria. The treatment duration is until disease progression or unacceptable side effects occur. Long-term continuation can cause potential toxicities and a substantial financial burden, making early treatment discontinuation a viable option. This report describes durable CR after discontinuing atezo-bev treatment in three patients with HCC and PVTT.

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