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.

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; J Liver Cancer. 2025;25(1):134-137. Published online November 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.26

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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.

Citations

Citations to this article as recorded by

Immunotherapy in Hepatocellular Carcinoma with Portal Vein Tumour Thrombosis: From Poor Prognosis to Curative-Intent Strategies
Luca Marzi, Rodolfo Sacco, Luisa Siciliani, Saveria Lory Crocè, Mauro Giuffrè, Cristina Stasi, Chiara Turri, Monica Zoeschg, Andrea Mega
Cancers.2026; 18(4): 627. CrossRef

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

7,681 Views
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12 Citations

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
Eun Sun Jang, Nae Yun Heo, Jae Yoon Jeong, Jung Gil Park, Do Seon Song, Eun Ju Cho, Chang Hun Lee, Jae Seung Lee, Jae Hyun Yoon, Seul Ki Han, Young Kul Jung
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
Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Systematic Review and Meta-Analysis
Kristina Lindsley, Margaret Burroughs, Candido Hernandez-Lopez, Yi Wang, John Marcinak, Stephanie E. Chiuve, Barbara A. Haber, Jennifer Uyei, Soodabeh Navadeh, Giuseppe De Marco, Deanna D. Hill
Infectious Diseases and Therapy.2025; 14(10): 2247. CrossRef
Recent Advances in the Treatment of Chronic Hepatitis C
Suk Bae Kim
The Korean Journal of Gastroenterology.2025; 85(4): 475. CrossRef
Comparison of Surgical Resection and Radiofrequency Ablation in Elderly Patients with Hepatocellular Carcinoma
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
Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients
Chih-Hsuan Luan, Pin-Shuo Su, Chi-Jen Chu, Chung-Chi Lin, Chien-Wei Su, Jiing-Chyuan Luo, I-Cheng Lee, Chen-Ta Chi, Shou-Dong Lee, Yuan-Jen Wang, Fa-Yauh Lee, Yi-Hsiang Huang, Ming-Chih Hou
Journal of the Chinese Medical Association.2024; 87(4): 357. CrossRef
Impacts of smoking on alcoholic liver disease: a nationwide cohort study
Jeong-Ju Yoo, Dong Hyeon Lee, Sang Gyune Kim, Jae Young Jang, Young Seok Kim, Log Young Kim
Frontiers in Public Health.2024;[Epub] CrossRef
Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals
Reem El-Shenawy, Rehab I. Moustafa, Naiera M. Helmy, Yasmine S. El-Abd, Ashraf A. Tabll, Yasser K. Elesnawy, Heba Shawky
Virology Journal.2024;[Epub] CrossRef
Addition of Kidney Dysfunction Type to MELD-Na for the Prediction of Survival in Cirrhotic Patients Awaiting Liver Transplantation in Comparison with MELD 3.0 with Albumin
Kyeong-Min Yeom, Jong-In Chang, Jeong-Ju Yoo, Ji Eun Moon, Dong Hyun Sinn, Young Seok Kim, Sang Gyune Kim
Diagnostics.2023; 14(1): 39. CrossRef
Is direct-acting antiviral treatment beneficial or harmful for patients with hepatitis C virus-related hepatocellular carcinoma?
Hye Won Lee
Journal of Liver Cancer.2022; 22(2): 91. CrossRef

Incidence and Clinical Features of Hepatitis C Virus-associated Hepatocellular Carcinoma Patients without Liver Cirrhosis in Hepatitis B Virus-endemic Area: Jongbeom Shin, Jung Hwan Yu, Young-Joo Jin, Jin-Woo Lee; J Liver Cancer. 2021;21(1):34-44. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.34

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107 Downloads
4 Citations

Abstract PDF

Background
/objective: Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC.
Methods
The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically.
Results
Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients.
Conclusions
HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.

Citations

Citations to this article as recorded by

Serological Biomarkers Related to Non-Cirrhotic Hepatocellular Carcinoma: Promising Applications in Clinical Diagnosis and Prognosis
进玲刘
Advances in Clinical Medicine.2025; 15(02): 142. CrossRef
LI-RADS for Diagnosing Hepatocellular Carcinoma in Patients with Noncirrhotic Chronic Hepatitis C
Jihyun An, Rohee Park, Euichang Kim, Seong Kyun Na, Ha Il Kim, In-Hye Song, Young Seo Cho, Ji Hun Kang, Han Chu Lee, Seungbong Han, Jean-Charles Nault, Sang Hyun Choi, Ju Hyun Shim
Radiology.2025;[Epub] CrossRef
Comparison of Surgical Resection and Radiofrequency Ablation in Elderly Patients with Hepatocellular Carcinoma
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
Diagnostic performance of CT/MRI LI-RADS v2018 in non-cirrhotic hepatitis C virus infection
Jennie J. Cao, Andy Shon, Luke Yoon, Aya Kamaya, Justin R. Tse
Abdominal Radiology.2024; 50(4): 1615. CrossRef

Case Report

Hemangioma Diagnosed by Gadoxetate Disodium-Enhanced MRI in a Patient with Chronic Hepatitis C: Jin Won Mo, Soo Hyung Ryu, Dong Won Park, Won Jae Yoon, Jin Nam Kim, Jeong Seop Moon, Jae-Chan Shim; J Liver Cancer. 2015;15(1):36-40. Published online March 31, 2015; DOI: https://doi.org/10.17998/jlc.15.1.36

2,037 Views
40 Downloads

Abstract PDF: A hemangioma is the most common benign hepatic tumor. Many hepatic hemangioma tend to be found incidentally, but should be differentiated from malignant tumors, especially in patients with a high risk for malignancy. We presented a 52-year-old woman who diagnosed as hepatic hemangioma. The patient was a chronic alcohol abuser and diagnosed as a hepatic C virus carrier for the first time. Contrast enhanced abdominal computed tomography (CT) revealed a 4cm sized hepatic mass involving both segment 5 and 6. Abdominal CT finding suggested hepatic hemangioma, but could not rule out the malignancy. Because the patient had risk factors for hepatocellular carcinoma, abdominal ultrasonography (US) was performed for further evaluation. But abdominal US also showed atypical finding. For the confirmative diagnosis, dynamic magnetic resonance imaging using gadoxetate disodium (primovist®, Bayer HealthCare, Berlin, Germany) which is the innovative liver cell-specific contrast medium was done, and the patient was diagnosed as hepatic hemangioma.

Original Article

Cirrhosis in Surgically Resected Hepatitis C-Associated Hepatocellular Carcinoma in a Hepatitis B Endemic Area: Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Jae-Won Joh, Seung Woon Paik, Byung Chul Yoo, Cheol Keun Park; J Liver Cancer. 2014;14(2):108-114. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.108

1,612 Views
4 Downloads

Abstract PDF: Background/Aims
Cirrhosis has generally been considered a prerequisite for hepatitis C virus (HCV)-infected livers to develop hepatocellular carcinoma (HCC), but HCCs that arise in absence of cirrhosis has been reported. We assessed the prevalence and significance of cirrhosis in HCV-related HCC patients who underwent surgical resection.
Methods
A total of 78 HCC patients (65 male [83.3%]; mean age, 64.2 ± 8.6 years) were evaluated for the presence of cirrhosis. Cirrhosis was assessed based on histology, aspartate aminotransferase-to-platelet ratio index (APRI) as well as clinical criteria, such as ascites, varices, thrombocytopenia, splenomegaly, and radiographic configuration of cirrhosis.
Results
Based on histology, cirrhosis, septal fibrosis, periportal fibrosis and no fibrosis was noticed in 33.3%, 60.3%, 5.1% and 1.3% of patients, respectively. The clinical criteria of cirrhosis were present in 76.9% of patients. APRI > 1.0 was seen in 47.4% of patients. There was no evidence of cirrhosis in 18 patients (23.1%), either by histology or clinically. Cirrhosis by histology was an independent factor for overall survival [hazard ratio: 3.87 (95% CI: 1.24 – 12.00), P=0.019].
Conclusions
Quite proportion of HCC patients had no evidence of cirrhosis, either by histology or clinically. Careful follow-up for HCC may be necessary even for non-cirrhotic HCVinfected Korean patients. (J Liver Cancer 2014;14:108-114)

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