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.

Original Articles

Effect of direct-acting antivirals for hepatitis C virus-related hepatocellular carcinoma recurrence and death after curative treatment: Young-Hwan Ahn, Heirim Lee, Ji Eun Han, Hyo Jung Cho, Jae Youn Cheong, Bumhee Park, Soon Sun Kim; J Liver Cancer. 2022;22(2):125-135. Published online June 28, 2022; DOI: https://doi.org/10.17998/jlc.2022.05.24

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Abstract PDF Supplementary Material

Background/Aim
There has been a long-standing debate about the association of directacting antiviral (DAA) therapy and hepatocellular carcinoma (HCC) recurrence. This study aimed to investigate the association between DAA therapy and HCC recurrence after curative therapy.
Methods
We retrospectively enrolled 1,021 patients with HCV-related (hepatitis C virus) HCC who underwent radiofrequency ablation (RFA), liver resection, or both as the first treatment modality from January 2007 to December 2016 and without a history of HCV therapy before HCC treatment from a nationwide database. The effect of HCV treatment on HCC recurrence and all-cause mortality was also investigated.
Results
Among the 1,021 patients, 77 (7.5%) were treated with DAA, 14 (1.4%) were treated with interferon-based therapy, and 930 (91.1%) did not receive HCV therapy. DAA therapy was an independent prognostic factor for lower HCC recurrence rate (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.006-0.289; P=0.001 for landmarks at 6 months after HCC treatment and HR, 0.05; 95% CI, 0.007-0.354; P=0.003 for landmarks at 1 year). Furthermore, DAA therapy was associated with lower all-cause mortality (HR, 0.049; 95% CI, 0.007-0.349; P=0.003 for landmarks at 6 months and HR, 0.063; 95% CI, 0.009-0.451; P=0.006 for landmarks at 1 year).
Conclusions
DAA therapy after curative HCC treatment can decrease HCC recurrence and all-cause mortality compared to interferon-based therapy or no antiviral therapy. Therefore, clinicians should consider administering DAA therapy after curative HCC treatment in patients with HCV-related HCC.

Citations

Citations to this article as recorded by

2025 KASL clinical practice guidelines for management of hepatitis C
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Clinical and Molecular Hepatology.2026; 32(1): 1. CrossRef
Impact of sustained virological response on prognosis after hepatectomy for hepatitis C-related hepatocellular carcinoma: a retrospective cohort study
Pei-shu Li, Guo-dong Yang, Xiu-nan Huang, Xin-yuan Wu, Yi-fan Li, Ming-jian Huang, Jie Zhang, Bang-de Xiang
BMC Infectious Diseases.2026;[Epub] CrossRef
Direct-acting antivirals lower mortality and recurrence in HCV-related hepatocellular carcinoma post liver resection: A multicenter international study
Woo Jin Choi, Tommy Ivanics, Marco Claasen, Christian T.J. Magyar, Zhihao Li, Parissa Tabrizian, Chiara Rocha, Bryan Myers, Grainne M. O'Kane, Maria Reig, Joana Ferrer Fàbrega, Victor Holgin, Neehar D. Parikh, Anjana Pillai, Thomas M. Hunold, Arndt Vogel,
Surgery.2025; 183: 109396. CrossRef
Direct-acting Antivirals Therapy for Hepatocellular Carcinoma in Hepatitis C Patients
Seul Ki Han, Soon Koo Baik, Moon Young Kim
Journal of Digestive Cancer Research.2025; 13(2): 150. CrossRef
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Infectious Diseases and Therapy.2025; 14(10): 2247. CrossRef
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Suk Bae Kim
The Korean Journal of Gastroenterology.2025; 85(4): 475. CrossRef
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Jun Il Kim, Jayoun Lee, Gi Hong Choi, Min Woo Lee, Dong Ah Park, Jeong-Ju Yoo
Digestive Diseases and Sciences.2024; 69(3): 1055. CrossRef
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Tenofovir and Entecavir Have Similar Renal Adverse Events on Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization: Young Youn Cho, Young Hwan Choi, Su Jong Yu, Eun Ju Cho, Jeong-Hoon Lee, Yoon Jun Kim, Jung-Hwan Yoon; J Liver Cancer. 2019;19(2):128-135. Published online September 30, 2019; DOI: https://doi.org/10.17998/jlc.19.2.128

6,908 Views
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2 Citations

Abstract PDF

Background/Aims
Tenofovir disoproxil fumarate (TDF) is potentially nephrotoxic in chronic hepatitis B patients. Hepatocellular carcinoma (HCC) patients treated using transarterial chemoembolization (TACE) are at an increased risk of renal injury. The aim of this study was to determine whether TDF is associated with more renal adverse events than entecavir (ETV) in HCC patients treated with TACE.
Methods
In this retrospective single-center study, we selected 53 HCC patients who were treated with TDF from January 2012 to July 2013 and had their first TACE procedure in the same period. These patients were matched by age and sex to patients treated with ETV.
Results
There were no significant differences in baseline characteristics, including HCC factors, and nephrotoxic drug use, between the two groups. The median follow-up period was 17.0 and 20.0 months for the TDF and ETV groups, respectively. There was no difference during the follow-up period between the TDF and ETV groups in the increase in creatinine over 0.5 mg/dL (17.0% and 17.0%, P=1.00, respectively) and the decrease in eGFR over 25% (43.4% and 41.5%, P=0.84, respectively). Multivariate analysis revealed that Child-Pugh class over B (hazard ratio [HR], 7.30; 95% confidence interval [CI] 2.79-19.10; P<0.01) was associated with increase in creatinine, and Child-Pugh class over B (HR, 82.74; 95% CI 12.31-555.83; P<0.01) and Barcelona-Clinic Liver Cancer stage over B (HR, 14.93; 95% CI 1.60-139.51; P=0.02) were associated with decrease in eGFR.
Conclusions
TDF has comparable safety to that of ETV for HCC patients undergoing TACE.

Citations

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QuEChERS and UPLC-MS/MS-Based Quantification of Human Plasma of Eight Nucleoside Reverse Transcriptase Inhibitors and Platinum Anticancer Drugs for Hepatocellular Carcinoma
Yanan Liu, Jiangning Peng, Yan Liang, Yilin Li, Xiaolan Zhen, Hui Li
Molecules.2025; 30(10): 2204. CrossRef
Big Data Information under Proportional Hazard Mathematical Model in Analysis of Hepatitis B Virus Infection Data of Patients with Interventional Liver Cancer through Antiviral Therapy of Entecavir
Yichi Zhang, Shuai Zhao, Han Ding, Xiaoling Song, Huijie Miao, Xuya Cui, Jian Wang, Bing Han, Enas Abdulhay
Journal of Healthcare Engineering.2021; 2021: 1. CrossRef

Survival Benefit of Antiviral Agents for Hepatocellular Carcinoma Patients Treated with Sorafenib: Jeong Han Kim, Hyung Min Yu, Yong Hwang, Soon Young Ko, Won Hyeok Choe, So Young Kwon; J Liver Cancer. 2016;16(1):23-30. Published online March 31, 2016; DOI: https://doi.org/10.17998/jlc.16.1.23

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14 Downloads

Abstract PDF: Background/Aims
Nucleos(t)ide analogues (NAs) help reduce the recurrence rate after the curative treatment of hepatitis B related hepatocellular carcinoma (HCC). Sorafenib has been shown to improve survival of advanced HCC patients. Whether antiviral therapy with NAs could help such patients is unknown. Our aim is to investigate the usefulness of antiviral therapy for advanced-stage HCC treated with sorafenib.
Methods
We performed a retrospective cohort study in advanced-stage HCC patients treated with sorafenib between June 2007 and December 2013. Patients in group A (the nonantiviral therapy group) were treated with sorafenib alone. Those in group B (the antiviral therapy group) were treated with sorafenib and NAs. Progression-free survival (PS) and overall survival (OS) were compared between these two groups.
Results
Finally, 23 patients in group A and 40 patients in group B were enrolled in the study. The mean number of days of treatment with sorafenib was 79 (34-231) days and 96 (33-449) days for group A and B, respectively (P=0.286). The mean PS of group A and B was 97 (14-449) days and 51 (0-461) days, respectively (P=0.068). The OS was 154 (44-741) days in group A and 138 (30-1,025) days in group B (P=0.665). PS and OS showed no significant difference between the two groups.
Conclusions
This study shows that there was no significant survival gain of using antiviral therapy in patients with advanced-stage HCC treated with sorafenib. In consideration of costeffectiveness, antiviral therapy may be not mandatory. (J Liver Cancer 2016;16:23-30)

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