Journal of Liver Cancer

Review Article

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.

Special Contribution

Expert survey on systemic therapy indications for hepatocellular carcinoma in Korea: bridging clinical practice and reimbursement criteria: Hyun Yang, Soon Sun Kim, Seong Hee Kang, Jieun Kwon, Do Young Kim, Eunju Kim, Hyun Phil Shin, Jeong Il Yu, Jeong-Ju Yoo, Eileen L. Yoon, Sangheun Lee, Young Eun Chon, Janghan Jung, Jaekyung Cheon, Woosun Choi, Seul Ki Han, Ji Eun Han, Moon Haeng Hur, Hyun Woong Lee, Hyung Joon Kim; J Liver Cancer. 2025;25(2):160-168. Published online July 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.07.02

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Abstract PDF: This survey aimed to collect expert opinions from multidisciplinary specialists involved in the management of hepatocellular carcinoma (HCC) in Korea regarding real-world criteria for systemic therapy indications. In response to discrepancies between national reimbursement policies and clinical decision-making, members of the Korean Liver Cancer Association and Korean Association for the Study of the Liver participated in a web-based survey from February 4 to 14, 2025. A total of 89 respondents, primarily experienced clinicians, provided their views on major clinical scenarios including infiltrative HCC, bilobar multifocal disease, huge tumors, vascular invasion, extrahepatic metastasis, and transarterial chemoembolization (TACE) refractoriness. There was high agreement for including infiltrative HCC (69.7%), suspected portal vein invasion (70.8%), and TACE refractoriness (82.0%) as systemic therapy indications. TACE refractoriness, in particular, aligns with current guideline definitions. Additionally, over half of respondents (51.7%) supported extrahepatic metastasis under similar conditions. Notably, multidisciplinary discussion was emphasized across scenarios, but many respondents also favored allowing primary physician discretion in select cases. This report provides consolidated expert input to inform future updates to reimbursement policies and promote alignment with real-world clinical practice. These findings may help bridge the gap between national coverage criteria and clinical decision in systemic therapy for HCC.

Review Article

Complications of immunotherapy in advanced hepatocellular carcinoma: Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2024;24(1):9-16. Published online November 29, 2023; DOI: https://doi.org/10.17998/jlc.2023.11.21

9,200 Views
269 Downloads
16 Citations

Abstract PDF

Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

Citations

Citations to this article as recorded by

Advances in the Therapeutic Landscape of Hepatocellular Carcinoma: Current Strategies and Future Perspectives
Asahiro Morishita, Kyoko Oura, Hiroki Tai, Rie Yano, Mai Nakahara, Tomoko Tadokoro, Koji Fujita, Shima Mimura, Joji Tani, Miwa Tatsuta, Takashi Himoto, Hideki Kobara
Cancers.2026; 18(4): 609. CrossRef
METTL3-mediated SMPDL3A promotes cell growth, metastasis and immune process of hepatocellular carcinoma by regulating LRPPRC
Weixin Xu, Miaomiao Tao, Yeqiong Liu, Jun Yan, Jiali Hu, Lei Wang
Cellular Signalling.2025; 127: 111543. CrossRef
Case Report: A rare small bowel sarcoma
Jiwu Guo, Jie Mao
Frontiers in Surgery.2025;[Epub] CrossRef
Disparate patterns of disease time burden in patients with HCC on immunotherapy or tyrosine kinase inhibitors
Rex Wan-Hin Hui, Matthew Shing-Hin Chung, Lu Li, Xianhua Mao, Chi-Leung Chiang, Carlos King-Ho Wong, Ian Chi-Kei Wong, Ka-Shing Cheung, Man-Fung Yuen, Wai-Kay Seto, Lung-Yi Mak
JHEP Reports.2025; 7(11): 101578. 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
Successful Treatment of Nivolumab Plus Ipilimumab After Progression on Durvalumab Plus Tremelimumab in Advanced Hepatocellular Carcinoma: A Case Report
Akinori Sasaki, Rika kimura, Risa Okamoto
Cureus.2025;[Epub] CrossRef
Efficacy and Safety of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Muhammad A.B. Naeem, Muhammad R. Paracha, Ahmad Noor, Muhammad H.A. Khalid, Hafiza K. Shahid, Maaz Khan, Moeaza R. Rizvi, Javeeria Arshad, Talha Abbas, Azeem Saeed, Hamza Ashraf, Minahil Ali, Mishal Asif, Aanusha Ghouri
American Journal of Clinical Oncology.2025;[Epub] CrossRef
Radiotherapy Combined with Immune Checkpoint Inhibitor on Murine Fibrosarcoma and a Narrative Review of Clinical Studies
Wonwoo Kim, Hyunkyung Kim, Won Il Jang, Mi Sook Kim, Sun Hyun Bae
Current Issues in Molecular Biology.2025; 48(1): 20. CrossRef
Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC
Jong Geun Park, Pu Reun Roh, Min Woo Kang, Sung Woo Cho, Suhyun Hwangbo, Hae Deok Jung, Hyun Uk Kim, Ji Hoon Kim, Jae-Sung Yoo, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Young Kyoung You, Ho Joong Choi, Jae Yong Ryu, Pil Soo Sung
Hepatology.2024; 80(5): 1074. CrossRef
Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis
Young-Gi Song, Kyeong-Min Yeom, Eun Ae Jung, Sang Gyune Kim, Young Seok Kim, Jeong-Ju Yoo
Liver Cancer.2024; : 1. CrossRef
Targeted therapies in hepatocellular carcinoma: past, present, and future
Rushabh Gujarathi, Joseph W. Franses, Anjana Pillai, Chih-Yi Liao
Frontiers in Oncology.2024;[Epub] CrossRef
Atezolizumab-Induced Ulcerative Colitis in Patient with Hepatocellular Carcinoma: Case Report and Literature Review
Hyuk Kim, Yoon E Shin, Hye-Jin Yoo, Jae-Young Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(9): 1422. CrossRef
A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review
Yoon-E Shin, Hyuk Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(10): 1634. CrossRef
The histopathological and molecular heterogeneity of hepatocellular carcinoma: a narrative review
Wonju Chung, Haeryoung Kim
The Ewha Medical Journal.2024;[Epub] CrossRef
Pathogenesis and management of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma: a narrative review
Han Ah Lee
The Ewha Medical Journal.2024;[Epub] 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

Original Article

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study: Sun Hong Yoo, Soon Sun Kim, Sang Gyune Kim, Jung Hyun Kwon, Han-Ah Lee, Yeon Seok Seo, Young Kul Jung, Hyung Joon Yim, Do Seon Song, Seong Hee Kang, Moon Young Kim, Young-Hwan Ahn, Jieun Han, Young Seok Kim, Young Chang, Soung Won Jeong, Jae Young Jang, Jeong-Ju Yoo; J Liver Cancer. 2023;23(1):189-201. Published online March 24, 2023; DOI: https://doi.org/10.17998/jlc.2023.03.11

4,750 Views
99 Downloads
5 Citations

Abstract PDF Supplementary Material

Background/Aim
Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity.
Methods
This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017.
Results
In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors.
Conclusions
This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Citations

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The Visualization of the Importance of Covariance Importance in a Machine Learning Model for Advanced Liver Fibrosis in a Nationally Representative Sample
Alexander A. Huang, Samuel Y. Huang
JGH Open.2025;[Epub] CrossRef
Advanced Hepatocellular Carcinoma Missed on Ultrasonography: A Case Report
Tom Ryu, Jae Young Jang, Yon Hee Kim, Young Chang, Soung Won Jeong
Clinical Ultrasound.2025; 10(2): 114. CrossRef
The Epidemiology of Hepatitis B Virus Infection in Korea: 15-Year Analysis
Log Young Kim, Jeong-Ju Yoo, Young Chang, Hoongil Jo, Young Youn Cho, Sangheun Lee, Dong Hyeon Lee, Jae Young Jang
Journal of Korean Medical Science.2024;[Epub] CrossRef
Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels
Soon Kyu Lee, Soon Woo Nam, Jeong Won Jang, Jung Hyun Kwon
Diagnostics.2024; 14(5): 495. CrossRef
Evolving epidemiology of non-alcoholic fatty liver disease in South Korea: incidence, prevalence, progression, and healthcare implications from 2010 to 2022
Jae Woo Park, Jeong-Ju Yoo, Dong Hyeon Lee, Young Chang, Hoongil Jo, Young Youn Cho, Sangheun Lee, Log Young Kim, Jae Young Jang
The Korean Journal of Internal Medicine.2024; 39(6): 931. CrossRef

Case Reports

Rare Case of Pyogenic Brain Abscess after Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma: Case Report and Literature Review: Jun-Ho Myeong, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2021;21(1):81-86. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.81

5,856 Views
78 Downloads
1 Citation

Abstract PDF

Transarterial chemoembolization (TACE) is a useful treatment option for hepatocellular carcinoma (HCC). TACE can particularly be used as a treatment for localized HCC, where surgical resection is impossible due to decreased liver function. However, TACE is associated with several complications, including vascular complications, liver failure, non-target embolization, infection, and death. The main risk factor for complications after TACE is decreased liver function. There have been only few reports of brain abscesses after TACE that are difficult to be distinguished from hepatic encephalopathy. Here, we report a rare case of brain abscess caused by Klebsiella pneumoniae that occurred after TACE.

Citations

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Brain abscess caused by escherichia coli following embolization of a giant arteriovenous malformation. Clinical case
A.M. Netliukh, O.YA. Kobyletskyi, N.V. Aliieva, A.A. Sukhanov
Ukrainian Interventional Neuroradiology and Surgery.2023; 46(4): 63. CrossRef

Early Experience of Oncolytic Virus Injection Combined with Sorafenib in a Patient with Advanced Hepatocellular Carcinoma and Portal Vein Thrombosis: Hyun Ho Jo, Seong Joon Chun, Jeong-Ju Yoo, Min Hee Lee, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2020;20(2):177-182. Published online September 30, 2020; DOI: https://doi.org/10.17998/jlc.20.2.177

6,696 Views
80 Downloads
2 Citations

Abstract PDF

JX-594 is a modified oncolytic poxvirus designed to selectively replicate in and destroy cancer cells. In a pilot study, JX-594 injection followed by sorafenib was well-tolerated in three patients and associated with objective tumor responses. In this study, we report a case in which a patient with advanced hepatocellular carcinoma and portal vein thrombosis was treated with a combination of JX-594 and sorafenib.

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Phase Ib study of intratumoral talimogene laherparepvec (T-VEC) in combination with chemotherapy or endocrine therapy in patients with advanced HER2-negative breast cancer
Laura A. Huppert, Amelia S. Gliwa, Madeline Tait, Laura Quintal, Stephanie Starzinski, Alexander Cheung, Mark Moasser, Melanie Majure, Michelle Melisko, Pamela Munster, Hope S. Rugo, Michael Campbell, Lawrence Fong, A. Jo Chien
npj Breast Cancer.2025;[Epub] CrossRef
Recent progress in combination therapy of oncolytic vaccinia virus
Seyedeh Nasim Mirbahari, Miles Da Silva, Abril Ixchel Muñoz Zúñiga, Nika Kooshki Zamani, Gabriel St-Laurent, Mehdi Totonchi, Taha Azad
Frontiers in Immunology.2024;[Epub] CrossRef

A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Treated by Hepatic Arterial Infusion Chemotherapy and Radiotherapy: Jin Yong Lee, Jeong-Ju Yoo, Seong Joon Chun, Sun Hyun Bae, Jae Myeong Lee, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2020;20(1):78-83. Published online March 31, 2020; DOI: https://doi.org/10.17998/jlc.20.1.78

8,121 Views
108 Downloads

Abstract PDF: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Additionally, hepatic arterial infusion chemotherapy has been used as a treatment option for advanced HCC. Here, we report a case of sustained partial response in a patient with advanced HCC with PVT after hepatic arterial infusion chemotherapy and radiation therapy.

Review Article

Clinical Application of Liver Stiffness Measurement for Assessing the Risk of Hepatocellular Carcinoma: Jeong-Ju Yoo, Eun-Ae Jung, Sang Gyune Kim; J Liver Cancer. 2019;19(1):12-18. Published online March 31, 2019; DOI: https://doi.org/10.17998/jlc.19.1.12

7,472 Views
108 Downloads
1 Citation

Abstract PDF

The most significant risk factor for hepatocellular carcinoma (HCC) is the presence of cirrhosis or advanced fibrosis of the liver. Liver biopsy was traditionally considered the gold standard for assessing the liver fibrosis burden. Recently, non-invasive methods, particularly transient elastography (TE), have proven effective at measuring fibrosis and determining cirrhosis. Clinical application of TE ranges from measuring fibrosis to predicting long-term prognosis and treatment response. Here, we focus on recent studies on the prognostic value of TE for predicting HCC.

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Metabolic dysfunction associated fatty liver disease and the risk of hepatocellular carcinoma
Byeong Geun Song, Sung Chul Choi, Myung Ji Goh, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Seung Woon Paik
JHEP Reports.2023; : 100810. CrossRef

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