Journal of Liver Cancer

Review Articles

Re-evaluating DAA therapy in active hepatocellular carcinoma: from controversy to clinical considerations: So Hyun Jeon, Jeong-Ju Yoo, Sang Gyune Kim, Young-Seok Kim; Received September 21, 2025 Accepted November 16, 2025 Published online December 2, 2025; DOI: https://doi.org/10.17998/jlc.2025.11.17 [Accepted]

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Abstract PDF: Direct-acting antiviral (DAA) therapy has brought a revolution to the management of chronic hepatitis C virus (HCV) infection, but its role in patients with active hepatocellular carcinoma (HCC) remains controversial. Early observations suggested a high rate of HCC recurrence following DAA treatment, raising concerns about a potential oncogenic effect regarding rapid viral clearance. However, subsequent large-scale cohort studies and meta-analyses have not consistently confirmed this finding, leading to an overall neutral conclusion regarding the impact of DAA on HCC recurrence. International guidelines from organizations such as the American Gastroenterological Association(AGA), American Association for the Study of Liver Diseases(AASLD), European Association for the Study of the Liver(EASL), and Korean Association for the Study of the Liver(KASL) offer conflicting recommendations, underscoring the absence of a universal framework for this patient population. While the available evidence is largely heterogeneous and retrospective, current data indicate that DAA therapy can be safely integrated into HCC management without clear evidence of harm. Oncologic outcomes, particularly overall and recurrence-free survival, are most favorable when DAAs are administered in close proximity to curative procedures or in non-transplant therapeutic settings. In contrast, studies in liver transplant candidates often show a neutral effect on oncologic outcomes after adjusting for confounding variables. These findings underscore the necessity of individualized, multidisciplinary decisions based on tumor biology, hepatic reserve, and treatment intent. Prospective studies and validated biomarkers are essential to establish a more definitive framework for optimizing DAA therapy in this complex clinical context.

Management of hepatocellular carcinoma in elderly and adolescent/young adult populations: Han Ah Lee; J Liver Cancer. 2025;25(1):52-66. Published online March 20, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.28

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Hepatocellular carcinoma (HCC) presents unique challenges in both the elderly and adolescent/young adult (AYA) populations, requiring distinct management approaches. Recent epidemiological data show an increasing incidence of HCC in both age groups, with elderly cases rising significantly and AYA cases showing trends in specific regions. The clinical characteristics and treatment considerations vary substantially among these populations. Elderly patients with HCC typically present with hepatitis C virus infection, metabolic dysfunction-associated steatotic liver disease, well-differentiated tumors, and multiple comorbidities. In contrast, AYA patients with HCC often present with more aggressive tumor characteristics and predominantly with hepatitis B virus-related diseases. Treatment decisions for elderly patients with HCC require careful consideration of physiological reserves, comprehensive geriatric assessments, and potential complications. Recent studies have demonstrated that elderly patients can achieve outcomes comparable to younger patients across various treatment modalities when properly selected. While surgical outcomes are comparable to those of younger patients with proper selection, less-invasive options such as radiofrequency ablation or transarterial therapies may be more appropriate for some elderly patients. The treatment approach for AYA HCC emphasizes curative intent while considering long-term effects. AYA patients require specialized attention to their psychosocial needs, fertility preservation, and long-term health maintenance. Although data on AYA patients remain limited, they are known to have relatively favorable prognoses despite exhibiting more aggressive tumor characteristics. Management of HCC in both the elderly and AYA populations requires individualized approaches that consider age-specific factors. Both groups benefit from multidisciplinary team involvement and careful consideration of quality of life.

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Repurposing GLP-1 Receptor Agonists: A Perspective on Epigenetic Strategies to Combat Fibrosis and Hepatocellular Carcinoma in the Aged Liver
Silvia Hanna, Jason Sethiadi, Qazi Ali, Saloni Sinha
Cancers.2025; 17(16): 2600. CrossRef

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; J Liver Cancer. 2024;24(2):155-170. Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07

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Abstract PDF

Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

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A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma: Yu Rim Lee; J Liver Cancer. 2023;23(2):316-329. Published online September 22, 2023; DOI: https://doi.org/10.17998/jlc.2023.09.04

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14 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

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Original Article

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule: Sehyeon Yu, Hye-Sung Jo, Young-Dong Yu, Yoo jin Choi, Dong-Sik Kim; J Liver Cancer. 2023;23(2):377-388. Published online September 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.24

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Abstract PDF Supplementary Material

Background/Aims
Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases.
Methods
Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated.
Results
All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038).
Conclusions
Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

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Review Article

Non-alcoholic fatty liver disease-related hepatocellular carcinoma: Darine Daher, Karim Seif El Dahan, Amit G. Singal; J Liver Cancer. 2023;23(1):127-142. Published online February 9, 2023; DOI: https://doi.org/10.17998/jlc.2022.12.30

25,309 Views
426 Downloads
32 Citations

Abstract PDF

Non-alcoholic fatty liver disease (NAFLD), one of the most common causes of liver disease, is an increasingly common cause of hepatocellular carcinoma (HCC). Several demographic, clinical, and genetic factors contribute to HCC risk in NAFLD patients, which may inform risk stratification scores. Proven efficacious approaches to primary prevention approach in patients with non-viral liver disease remain an area of need. Semi-annual surveillance is associated with improved early tumor detection and reduced HCC-related mortality; however, patients with NAFLD have several challenges to effective surveillance, including under-recognition of at-risk patients, low surveillance utilization in clinical practice, and lower sensitivity of current tools for early-stage HCC detection. Treatment decisions are best made in a multidisciplinary fashion and are informed by several factors including tumor burden, liver dysfunction, performance status, and patient preferences. Although patients with NAFLD often have larger tumor burden and increased comorbidities compared to counterparts, they can achieve similar post-treatment survival with careful patient selection. Therefore, surgical therapies continue to provide a curative treatment option for patients diagnosed at an early stage. Although there has been debate about the efficacy of immune checkpoint inhibitors in patients with NAFLD, current data are insufficient to change treatment selection based on liver disease etiology.

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Scientific Reports.2023;[Epub] CrossRef

Case Report

Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma: Ahlim Lee, Jaejun Lee, Hyun Yang, Soo-Yoon Sung, Chang Ho Jeon, Su Ho Kim, Moon Hyung Choi, Young Joon Lee, Ho Jong Chun, Si Hyun Bae; J Liver Cancer. 2022;22(1):75-83. Published online March 18, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.04

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112 Downloads
6 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

Citations

Citations to this article as recorded by

Multidisciplinary treatment strategies for the assessment of immune, coagulation, and biomarker responses after transarterial chemoembolization for hepatocellular carcinoma
Tian Song, Kan-Hua Wu, Hao Yang, Wen-Li Xie, Lan Shen
World Journal of Gastrointestinal Surgery.2025;[Epub] CrossRef
Navigating the Therapeutic Pathway and Optimal First-Line Systemic Therapy for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors
Hyun Phil Shin, Moonhyung Lee
Medicina.2025; 61(12): 2164. CrossRef
Complications of immunotherapy in advanced hepatocellular carcinoma
Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Journal of Liver Cancer.2024; 24(1): 9. CrossRef
Higher objective responses by hepatic arterial infusion chemotherapy following atezolizumab and bevacizumab failure than when used as initial therapy in hepatocellular carcinoma: a retrospective study
Jae-Sung Yoo, Ji Hoon Kim, Hee Sun Cho, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Suho Kim, Jung Suk Oh, Ho Jong Chun, Pil Soo Sung
Abdominal Radiology.2024; 49(9): 3127. CrossRef
Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab
Tae Hyun Kim, Bo Hyun Kim, Yu Ri Cho, Young-Hwan Koh, Joong-Won Park
Journal of Liver Cancer.2023; 23(2): 330. CrossRef
Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Review Articles

External Beam Radiotherapy for Hepatocellular Carcinoma: a Review of the Current Guidelines in the East and the West: Sang Min Yoon; J Liver Cancer. 2021;21(1):25-33. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.25

8,478 Views
198 Downloads
5 Citations

Abstract PDF

The incidence of hepatocellular carcinoma (HCC) is geographically heterogeneous depending on the underlying liver disease. Moreover, the decisions and recommendations about standard treatments differ between countries, especially between the East and the West. Because of the complexity of treatment decisions for the management of HCC, a multidisciplinary approach is recommended to maximize the therapeutic efficacy. External beam radiotherapy (RT) has been increasingly used to manage HCC when recommended treatments cannot be applied in real-world clinical practice. However, Western guidelines for the management of HCC do not recommend RT as a treatment option due to the lack of clinical evidence. RT has often been used more in Eastern countries than in Western countries; hence, it is necessary to review both Eastern and Western guidelines for HCC treatment regarding the recommendations about RT. In this study, the comments and potential roles of external beam RT are summarized from several treatment guidelines for the management of HCC.

Citations

Citations to this article as recorded by

Efficacy of Radiotherapy in Combination with Immune Checkpoint Blockade for Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis
Yunjeong Lee, Minkyung Park, Eun Sun Jang, Gwanghyun Choi, Sook-Hyang Jeong, Jin Won Kim, Minsu Kang, Jee Hyun Kim, Changhoon Song, Kyubo Kim, Jin-Wook Kim
The Korean Journal of Medicine.2025; 100(5): 252. CrossRef
Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study
Bo Hyun Kim, Hee Chul Park, Tae Hyun Kim, Young-Hwan Koh, Jung Yong Hong, Yuri Cho, Dong Hyun Sinn, Boram Park, Joong-Won Park
JHEP Reports.2024; 6(4): 100991. CrossRef
Novel paradigm in the treatment of hepatocellular carcinoma: Anticipating breakthroughs with particle therapy
Sang Min Yoon
Clinical and Molecular Hepatology.2023; 29(4): 977. CrossRef
Loco-regional therapies competing with radiofrequency ablation in potential indications for hepatocellular carcinoma: a network meta-analysis
Ha Il Kim, Jihyun An, Seungbong Han, Ju Hyun Shim
Clinical and Molecular Hepatology.2023; 29(4): 1013. CrossRef
Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma
Chai Hong Rim
Journal of Liver Cancer.2021; 21(2): 113. CrossRef

Locoregional Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Sang Youn Hwang, Ryoung-Go Kim, Cheol-Won Choi, Sang Bu Ahn; J Liver Cancer. 2016;16(2):69-81. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.69

2,210 Views
15 Downloads
1 Citation

Abstract PDF

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) have a extremely poor prognosis. According to the Barcelona Clinic Liver Cancer guideline, sorafenib is a standard therapy in this situation, but many clinicians still select locoregional therapy (LRT) such as transarterial therapy, external beam radiation therapy (EBRT), even surgical resection (SR) or combination of LRTs because the survival improvement by sorafenib is unsatisfactory. Based on recent meta-analysis and prospective study, transarterial chemoembolization (TACE) and transarterial radioembolization seem to be effective and safe therapeutic option that have comparable outcome to sorafenib. Recently large nationwide studies demonstrated that SR can be a potentially curative treatment in selected patients. Hepatic arterial infusion chemotherapy (HAIC) can be also good option, especially in Child class B patients based on small volume prospective studies. Moreover, multidisciplinary strategies based on the combination of LRTs (SR plus TACE, TACE + EBRT, TACE + Sorafenib, HAIC + EBRT etc.) may improve survival of HCC patients with PVTT. Finally we discuss individualized and tailored treatment strategies for different clinical situations.

Citations

Citations to this article as recorded by

Progress in Non-Surgical Treatment of Primary Hepatocellular Carcinoma with Combined Portal Vein Carcinoma Thrombosis
文豪寇
Advances in Clinical Medicine.2023; 13(07): 11779. CrossRef

Case Reports

Regression of Advanced Hepatocellular Carcinoma with Lung Metastasis in Response to Sorafenib: Dae-ha Kim, Gee ho Min, Dong-won Lee, Ke Ryun Ahn, Ji Hye Kim, Snag-Jun Suh, Young Kul Jung, Hyung Joon Yim; J Liver Cancer. 2016;16(1):57-62. Published online March 31, 2016; DOI: https://doi.org/10.17998/jlc.16.1.57

1,796 Views
10 Downloads

Abstract PDF: Sorafenib is a multi-targeted tyrosine kinase inhibitor that inhibits Raf kinase and the vascular endothelial growth factor receptor intracellular kinase pathway and is the first agent to demonstrate a statistically significant improvement in overall survival for patients with advanced hepatocellular carcinoma (HCC). However, there were few cases of partial or complete response reported in the previous studies. We herein report a case of dramatic partial response in a patient who had advanced HCC with multiple lung metastasis and portal vein thrombosis treated with sorafenib.

A Case of Hepatocellular Carcinoma with Improved Decompansated Liver Cirrhosis with Combination Treatment of Transarterial Chemoembolization and Radiofrequency Ablation: Hyung Min Yu, Won Hyeok Choe, So Young Kwon, Jeong Han Kim; J Liver Cancer. 2014;14(2):131-134. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.131

1,903 Views
6 Downloads

Abstract PDF: A 54-year-old female patient with no medical history visited our hospital complaining of both pretibial pitting oedema for 6 months, and abdominal distension for 1 month. Computed tomography and magnetic resonance imaging revealed an 2.3cm sized tumour at segment 2 of the liver. Her Child-Turcotte-Pugh (CTP) class was C (score 11) at the initial visit. She was diagnosed as hepatocellular carcinoma (UICC stage II, BCLC stage D), and then she underwent conservative treatment for 1 month. After one month of conservative treatment, her liver function was improved to CTP class B (score 8), and then she underwent combination treatment of transarterial chemoembolization and radiofrequency ablation. However, her liver function was deteriorated gradually. She was transferred to other hospital for liver transplantation eventually. (J Liver Cancer 2014;14:131-134)

Review Articles

Directions for Future Hepatocellular Carcinoma Treatment Guidelines; Hepatologist’s Perspective: Systemic Approach to Multidisciplinary Treatment: Soo Young Park, Won Young Tak; Journal of the Korean Liver Cancer Study Group. 2013;13(1):8-13. Published online February 28, 2013; DOI: https://doi.org/10.17998/jlc.13.1.8

1,622 Views
6 Downloads

Abstract PDF: Hepatocellular carcinoma is one of the most important malignancies in Korea with high mortality rates. Although current guidelines define treatment algorithm by performance status, underlying liver function, size and number of hepatocellular carcinoma, those are not fully reflect the complexities of patients’ characteristics and recently advanced available therapeutic options. Treatment can be optimized by available therapeutic options based on the patients’ characteristics. Because of the heterogeneity in presentation among patients, it is now widely accepted that management of hepatocellular carcinoma requires multimodality and multidisciplinary treatment approaches involving hepatologists, surgeons, interventional radiologists, and radiation oncologists. These approaches are important in improving the survival of patients with hepatocellular carcinoma.

Treatment Response Evaluation of Hepatocellular Carcinoma: Joon-Il Choi; Journal of the Korean Liver Cancer Study Group. 2012;12(1):16-22. Published online February 28, 2012

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Abstract PDF: The most important and primary endpoint in oncology research is overall survival. However, other endpoints such as time-to-progression, time-to-recurrence and response rate have their roles in oncology trials and these endpoints are assessed by the imaging evaluation of tumor burden. Recently published the revised version (version 1.1) of response evaluation criteria in solid tumors (RECIST) is now the standards for the tumor response evaluation after treatment, and especially for cytotoxic agents. However, the problems are more complicated for hepatocellular carcinoma (HCC). RECIST are mainly used for the response evaluation of chemotherapeutic agents. However, for the treatment of HCC, there are some locoregional treatments and molecular targeted agents, and after these treatments, tumor necrosis remains as non-enhanced tumor areas, whereas viable tumor parts can be noted by the enhanced areas. However, these necrotic areas should be included as being tumor when we adopt the pure anatomical criteria such as RECIST and this can distort the results of the response evaluation. For overcoming this problem, some new criteria were introduced and their principle is the measurement of enhancing portion of the tumor only. However, these new criteria still have limitations and functional imaging is thought to be the future problem-solving tool for the evaluation of response for molecular targeted agents.

Case Reports

Two Cases of Small (< 1 cm) Hepatocellular Carcinoma: Jin Yong Jung, Sun Young Yim, Chang Ha Kim, Jin Dong Kim, Yeon Seok Seo, Hyung Joon Yim, Ho Sang Ryu, Min Ju Kim, Beom Jin Park, Soon Ho Um; Journal of the Korean Liver Cancer Study Group. 2012;12(1):37-41. Published online February 28, 2012

1,062 Views
2 Downloads

Abstract PDF: Tumor size is one of the most important factors for decision of therapeutic plan and prognosis of hepatocellular carcinoma (HCC). If the diagnosis of HCC is made earlier in its small size, the prognosis is better. However the diagnosis of small HCC is not easy because small HCC lacks the typical clinical and radiologic feature. We experienced two cases of small HCC less than 1 cm that was confirmed after first treatment.

A Case of Small Hepatocellular Carcinoma Less Than 1 cm: Yun Jeong Jo, Young Kul Jung, Dong Hae Chung, Oh Sang Kwon, Yun Soo Kim, Duck Joo Choi, Ju Hyun Kim; Journal of the Korean Liver Cancer Study Group. 2012;12(1):42-46. Published online February 28, 2012

1,207 Views
3 Downloads

Abstract PDF: Hepatocellular carcinoma (HCC) is one of the most important causes of cancer death in South Korea. Approximately two thirds of the patients are diagnosed in the advanced stage with multiple metastasis and underlying liver dysfunction, so they are not suitable to undergo curative resection. Small HCC has no consensus about diagnostic criteria but became known early stage HCC that means good prognosis. Cases of small HCC have been increasing with the progress of diagnostic methods. We experienced a case of incidentally found small HCC less than 1 cm from liver cirrhosis by liver dynamic imaging, so reported it.

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