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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]
  • 335 Views
  • 17 Downloads
AbstractAbstract 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.
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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
  • 3,678 Views
  • 69 Downloads
  • 4 Citations
AbstractAbstract PDFSupplementary 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.

Citations

Citations to this article as recorded by  
  • Surgical treatment of hepatocellular carcinoma: an expert consensus-based practical recommendation from the Korean Liver Cancer Association
    Min-Su Park, Jai Young Cho, Eunju Kim, Hee Young Na, YoungRok Choi, Na Reum Ki, Young-In Yoon, Boram Lee, Eun Sun Jang, Yun Kyung Jung, Kyung Sik Kim
    Annals of Surgical Treatment and Research.2025; 109(3): 123.     CrossRef
  • Surgical treatment of hepatocellular carcinoma: an expert consensus-based practical recommendation from the Korean Liver Cancer Association
    Min-Su Park, Jai Young Cho, Eunju Kim, Hee Young Na, YoungRok Choi, Na Reum Kim, Young-In Yoon, Boram Lee, Eun Sun Jang, Yun Kyung Jung, Kyung Sik Kim
    Journal of Liver Cancer.2025; 25(2): 140.     CrossRef
  • BCLC strategy for prognosis prediction and treatment recommendations: The 2025 update
    Maria Reig, Marco Sanduzzi-Zamparelli, Alejandro Forner, Jordi Rimola, Joana Ferrer-Fàbrega, Marta Burrel, Ángeles Garcia-Criado, Alba Díaz, Neus Llarch, Gemma Iserte, Meritxell Mollà, Robin K. Kelley, Peter R. Galle, Vincenzo Mazzaferro, Riad Salem, Brun
    Journal of Hepatology.2025;[Epub]     CrossRef
  • Heavy smoking increases early mortality risk in patients with hepatocellular carcinoma after curative treatment
    Jaejun Lee, Jong Young Choi, Soon Kyu Lee
    Journal of Liver Cancer.2024; 24(2): 253.     CrossRef
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Case Report
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
AbstractAbstract 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.
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Review Article
Should We Treat Patients with Massive Hepatocellular Carcinoma? Cons
Han Chu Lee
Journal of the Korean Liver Cancer Study Group. 2009;9(1):13-16.   Published online June 30, 2009
  • 1,050 Views
  • 2 Downloads
AbstractAbstract PDF
Massive hepatocellular carcinoma (HCC) is defined as a tumor(s) involving 1 segment or more, with indistinct boundary in ≥50% of margins. There have been only few studies regarding the treatment response in patients with massive HCC. Therefore, in this review, the author focused on the treatment response in HCC of ≥10 cm in size. Reported survival rates after surgical resection are 61~66% at 1 year, 38~44% at 3 years, and 28~31% at 5 years. However, surgical resection is usually performed in patients with solitary tumor and good hepatic reserve function, and without gross vascular invasion. In addition, it was reported that surgical complication rate or mortality increases in tumors of ≥10 cm. Therefore, these data do not represent the outcome after surgical resection in patients with massive HCC. Transarterial chemoembolization (TACE) can induce objective response in about 65% of patients with HCC(s) of ≥10 cm according to modified EASL criteria. However, frequent intra- and extra-hepatic metastases are unavoidable and the survival rate was 43% at 1 year and 20% at 2 years. Of note, 11% of cases suffered from serious adverse effects such as renal impairment, sepsis and/or hepatic failure after TACE. Recently, sorafenib has been shown to increase patient’s survival, but the survival benefit is not still satisfactory. Other systemic chemotherapies using various combinations of cytotoxic agents usually show 10-20% of objective response, but there has been no evidence that it can prolong overall patient’s survival. There also has been no evidence that intra-arterial chemotherapy with or without implantable drug delivery system is superior to conventional chemotherapy or can prolong patient’s survival. In summary, treatment response in large HCC(s) is not still satisfactory and treatment-related adverse effects are considerable. Therefore, treatment should be performed in well-selected patients.
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