Intermediate-stage hepatocellular carcinoma (HCC) encompasses a diverse patient population that requires individualized treatment strategies and a multidisciplinary approach. Recent advancements in systemic therapy have expanded the therapeutic options for intermediate-stage HCC, allowing for combination strategies such as systemic therapy with transarterial chemoembolization (TACE) and upfront systemic therapy for individuals deemed unsuitable for TACE. Additionally, the ongoing development of treatment modalities for intermediate-stage HCC has improved the potential for curative conversion and tumor downstaging. Nevertheless, consensus on the optimal management of intermediate-stage HCC remains limited. Thus, the primary aim of this study was to develop a set of consensus guidelines for the management of intermediate-stage HCC. To address this gap, the Taiwan Liver Cancer Association (TLCA) established a working group to develop a multidisciplinary strategy for managing intermediate-stage HCC. Here, we present eight consensus statements formulated by this expert panel, which outline criteria for TACE unsuitability, treatment recommendations based on TACE eligibility, and considerations for various modalities, including conventional TACE, drug-eluting bead TACE, and transarterial radioembolization, as well as the appropriate timing for initiating systemic therapy to enable curative conversion and downstaging. These statements provide specific, evidence-based recommendations for clinicians, addressing treatment pathways based on TACE eligibility and other key considerations for intermediate-stage HCC management. The development of this consensus guideline is intended to aid clinicians in selecting the most appropriate treatment pathway for intermediate-stage HCC, support personalized treatment planning, and ultimately enhance the feasibility of achieving curative conversion.
Citations
Citations to this article as recorded by
Editorial: Tumour Burden Score and Extrahepatic Progression After TACE—Refining Risk Stratification Beyond the Liver Chien‐Wei Su Alimentary Pharmacology & Therapeutics.2026; 63(9): 1316. CrossRef
Optimal treatment selection for hepatocellular carcinoma in the era of immunotherapy Chen-Ta Chi, Yi-Hsiang Huang Journal of Gastroenterology.2026;[Epub] CrossRef
Patterns and Prognostic Stratification of Recurrence after Thermal Ablation in Patients with Hepatocellular Carcinoma Chi-Ping Tan, Teng-Yu Lee, I-Cheng Lee, Kuo-Cheng Wu, Chien-An Liu, Nai-Chi Chiu, Shao-Jung Hsu, Pei-Chang Lee, Chi-Jung Wu, Chen-Ta Chi, Jiing-Chyuan Luo, Ming-Chih Hou, Yi-Hsiang Huang Liver Cancer.2025; : 1. CrossRef
Background/Aims The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in Barcelona Clinic Liver Cancer (BCLC) stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study.
Methods We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for sustained virological response (SVR) and adjusted hazard ratio (aHR) for OS.
Results Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were include. The SVR rates were 96.6% in the HCC group and 98.8% in the non-HCC group (P<0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41; 95% CI 0.31–0.54; P<0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46; 95% CI 0.35–0.60; P<0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41; 95% CI 0.28–0.59; P<0.001). The impact of SVR on OS persisted significantly across BCLC stages 0/A and stages B/C.
Conclusions High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.
Citations
Citations to this article as recorded by
Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients: Correspondence to letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study” Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu Clinical and Molecular Hepatology.2026; 32(1): e99. CrossRef
Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage: Correspondence to editorial on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study” Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming-Lung Yu Clinical and Molecular Hepatology.2026; 32(1): e68. CrossRef
Survival impact of hepatitis C virus eradication in patients with or without active hepatocellular carcinoma: A nationwide cohort study Teng-Yu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bai European Journal of Cancer.2026; 232: 116109. CrossRef
Letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: a nationwide cohort study” Qiong Wang, Zhongqing Qian, Xiaodi Yang, Deyan Chen, Xiaojing Wang, Fuliang Chen Clinical and Molecular Hepatology.2026; 32(1): e7. CrossRef
Setting the Record Straight: Utility and Outcomes in Patients With HCV Related HCC María Fernanda Guerra‐Veloz, Sital Shah, Beatrice Emmanouil, Mia Olsen, Renita George, Sarah Selemani, Paul J. Ross, Ivana Carey, Neha Mehta, Mark Gillyon‐Powell, Kosh Agarwal Journal of Viral Hepatitis.2026;[Epub] CrossRef
Letter: Methodological Considerations in Interpreting Polygenic Risk Scores for Hepatocellular Carcinoma After SVR. Authors' Reply Yu‐Sheng Lin, Yun‐Yu Chen, Teng‐Yu Lee Alimentary Pharmacology & Therapeutics.2026; 63(10): 1439. CrossRef
Editorial: Residual HCC Risk After Hepatitis C Cure—Can Polygenic Risk Scores Refine Surveillance? Authors' Reply Yu‐Sheng Lin, Hwai‐I Yang, Teng‐Yu Lee Alimentary Pharmacology & Therapeutics.2026; 63(10): 1429. CrossRef
Desmond Y. H. Yap, Kevin S. H. Liu, Yu-Chun Hsu, Grace L. H. Wong, Ming-Chang Tsai, Chien-Hung Chen, Ching-Sheng Hsu, Yee Tak Hui, Michael K. K. Li, Chen-Hua Liu, Yee-Man Kan, Ming-Lung Yu, Man-Fung Yuen
Clin Mol Hepatol 2020;26(4):554-561. Published online August 28, 2020
Background/Aims Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV.
Methods We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment.
Results Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed.
Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.
Citations
Citations to this article as recorded by
Glecaprevir/Pibrentasvir Versus Sofosbuvir/Velpatasvir for Hepatitis C Virus Genotype 6: A Systematic Review and Meta‐Analysis Duong Hoang Huy Le, Dinh Chuong Nguyen, Sitthichai Kanokudom, Jiratchaya Puenpa, Pornjarim Nilyanimit, Anh Ngoc Tran, Sittisak Honsawek, Yong Poovorawan Reviews in Medical Virology.2025;[Epub] CrossRef
Direct-Acting Antivirals in Hepatitis C Treatment for Renal Impairment: Liver Safety Concerns and Effectiveness in Peritoneal Dialysis Hsuan-Yu Hung, Wei-Liang Hung, Ye Gu, Chung-Yu Chen Biomedicines.2024; 13(1): 55. CrossRef
The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis Ruochan Chen, Yinghui Xiong, Yanyang Zeng, Xiaolei Wang, Yinzong Xiao, Yixiang Zheng Frontiers in Public Health.2023;[Epub] CrossRef
Glecaprevir/Pibrentasvir and Renal Dysfunction in Deceased Donor Renal Transplantation: A Case Report Akari Kaba, Shigeyoshi Yamanaga, Yuji Hidaka, Mariko Toyoda, Masayuki Kashima, Yoshi Takekuma, Akito Inadome, Hiroshi Yokomizo, Akira Miyata Transplantation Proceedings.2022; 54(2): 549. CrossRef
Real-world effectiveness and safety of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for genotype 6 chronic hepatitis C Jyh-Jou Chen, Yen-Cheng Chiu, Pei-Lun Lee, Hung-Da Tung, Hung-Chih Chiu, Shih-Chieh Chien, Pin-Nan Cheng Journal of the Formosan Medical Association.2022; 121(11): 2265. CrossRef
Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5 Chen-Hua Liu, Jia-Horng Kao Hepatology International.2022; 16(5): 1001. CrossRef
Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease Ji Eun Ryu, Myeong Jun Song, Seok-Hwan Kim, Jung Hyun Kwon, Sun Hong Yoo, Soon Woo Nam, Hee Chul Nam, Hee Yeon Kim, Chang Wook Kim, Hyun Yang, Si Hyun Bae, Do Seon Song, U Im Chang, Jin Mo Yang, Sung Won Lee, Hae Lim Lee, Soon Kyu Lee, Pil Soo Sung, Jeong The Korean Journal of Internal Medicine.2022; 37(5): 958. CrossRef
Recent Information on Pan-Genotypic Direct-Acting Antiviral Agents for HCV in Chronic Kidney Disease Fabrizio Fabrizi, Federica Tripodi, Roberta Cerutti, Luca Nardelli, Carlo M. Alfieri, Maria F. Donato, Giuseppe Castellano Viruses.2022; 14(11): 2570. CrossRef
Drug-drug interactions with direct-acting antivirals — less is more Grace Lai-Hung Wong Clinical and Molecular Hepatology.2021; 27(1): 81. CrossRef
More evidence that direct acting antiviral therapy is safe and effective in cirrhosis and chronic kidney disease including peritoneal dialysis Paul Kwo, Deepti Dronamraju Clinical and Molecular Hepatology.2020; 26(4): 489. CrossRef
First
Prev
