The DOI matches its Crossref record; 79 of the 82 references it cites were found in a registry or an index.
Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002–2020)
Open accessAbstract
Background & aims Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies.Methods We conducted a systematic review of phase III RCTs (2002-2020) across disease stages. A meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor (TKI)/antiangiogenic or immune checkpoint inhibitor (ICI) therapy.Results Out of 10,100 studies identified, 76 were phase III RCTs. Among them, a rigorous screening algorithm identified 49 with high quality including a total of 22,113 patients undergoing adjuvant (n = 7) and primary treatment for early (n = 2), intermediate (n = 7), and advanced (first-line, n = 21; second-line, n = 12) stages of disease. Nine of these trials were positive, 6 treatments have been adopted in guidelines (sorafenib [2 RCTs], lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab), but 2 were not (adjuvant CIK cells and sorafenib plus hepatic arterial infusion with FOLFOX). Meta-analysis of 8 trials including 3739 patients revealed ICI therapy to be significantly more effective in patients with viral hepatitis compared with nonviral-related HCC, whereas no differences related to etiology were observed in patients treated with TKI/anti-vascular endothelial growth factor.Conclusions Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results. A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“those testing such approaches in HCC after potentially curative resection or local ablation have not yielded positive results over the preceding decades11.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In summary, most of the studies failed to identify any clinical benefit and, among the positive studies, validation in trials conducted in Western countries is awaited.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In KEYNOTE-240, OS benefits seem numerically greater in patients with HBV-HCC (HR 0.57 [0.35–0.94]) treated with pembrolizumab compared to placebo, while the HR of patients with non-viral HCCs was 0.88 (0.64–1.20) [46].”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In KEYNOTE-240, OS benefits seem numerically greater in patients with HBV-HCC (HR 0.57 [0.35–0.94]) treated with pembrolizumab compared to placebo, while the HR of patients with non-viral HCCs was 0.88 (0.64–1.20) [46].”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, the HR for PFS was similar (0.70 [0.44–1.13] and 0.75 [0.56–1.01]) respectively.”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [46]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“in CheckMate-459, KEYNOTE-240, and COSMIC-312, the apparent reduced benefit from ICIs for patients with non-viral HCCs was likely a major cause for the negative OS outcomes, despite a clear benefit for patients with HBV-HCCs [27, 35, 46]”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [46]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Results from other studies suggest that a metabolic-related fatty liver disease-related aetiology might be related to a decreased response owing to unique immunological traits hampering antitumoural surveillance11,101.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [11]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Only a small number of patients with HCV-HCC were recruited (15.5% of all).”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [46]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · BMJ · doi:10.1136/bmj.b2700 · Cited by 17,648
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097
Self-citationEASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
Galle, P. R., Forner, A., Llovet, J. M., Mazzaferro, V., Piscaglia, F., Raoul, J.-L., Schirmacher, P., & Vilgrain, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.019 · Cited by 11,406
Self-citationAtezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T.-Y., Kudo, M., Breder, V., Merle, P., Kaseb, A. O., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1915745 · Cited by 7,470
Mazzaferro, V., Regalia, E., Doci, R., Andreola, S. A., Pulvirenti, A., Bozzetti, F., Montalto, F., Ammatuna, M., Morabito, A., & Gennari, L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603143341104 · Cited by 7,173
Llovet, J. M., Kelley, R. K., Villanueva, A., Singal, A. G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J., & Finn, R. S. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00240-3 · Cited by 7,055
Self-citationCheng, A.-L., Kang, Y.-K., Chen, Z., Tsao, C.-J., Qin, S., Kim, J. S., Luo, R., Feng, J., Ye, S., Yang, T.-S., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70285-7 · Cited by 5,832
Sorafenib in Advanced Hepatocellular Carcinoma
정, 재. (2008) · Cited by 5,586
Kudo, M., Finn, R. S., Qin, S., Han, K.-H., Ikeda, K., Piscaglia, F., Baron, A., Park, J.-W., Han, G., Jassem, J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30207-1 · Cited by 5,497
Marrero, J. A., Kulik, L., Sirlin, C. B., Zhu, A. X., Finn, R. S., Abecassis, M. M., Roberts, L. R., & Heimbach, J. K. (2018) · Hepatology · doi:10.1002/hep.29913 · Cited by 4,597
Cited by
Sorted by citations
AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
Singal, A. G., Llovet, J. M., Yarchoan, M., Mehta, N., Heimbach, J. K., Dawson, L. A., Jou, J. H., Kulik, L. M., Agopian, V. G., Marrero, J. A., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000466 · Cited by 2,052
“[160] Despite higher rates of perioperative complications (post-hepatectomy liver failure, prolonged length of hospitalization) and morbidity, a meta-analysis of nine studies comparing outcomes of curative therapy in NAFLD and non-NAFLD HCC reported improved disease-free and OS after liver…”
Self-citationImmunotherapies for hepatocellular carcinoma
Llovet, J. M., Castet, F., Heikenwalder, M., Maini, M. K., Mazzaferro, V., Pinato, D. J., Pikarsky, E., Zhu, A. X., & Finn, R. S. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00573-2 · Cited by 1,843
Self-citationSingal, A. G., Kanwal, F., & Llovet, J. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00825-3 · Cited by 1,029
Self-citationEvolving therapeutic landscape of advanced hepatocellular carcinoma
Yang, C. G., Zhang, H., Zhang, L., Zhu, A. X., Bernards, R., Qin, W., & Wang, C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00704-9 · Cited by 747
The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma
Donné, R., & Lujambio, A. (2022) · Hepatology · doi:10.1002/hep.32740 · Cited by 659
Molecular pathogenesis and systemic therapies for hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Kelley, R. K., El-Khoueiry, A., Reeves, H. L., Wang, X. W., Gores, G. J., & Villanueva, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00357-2 · Cited by 498
Self-citationAdjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Yarchoan, M., Singal, A. G., Marron, T. U., Schwartz, M., Pikarsky, E., Kudo, M., & Finn, R. S. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00868-0 · Cited by 391
Self-citationCombination immunotherapy for hepatocellular carcinoma
Rimassa, L., Finn, R. S., & Sangro, B. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.003 · Cited by 377
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
Llovet, J. M., Willoughby, C. E., Singal, A. G., Greten, T. F., Heikenwälder, M., El-Serag, H. B., Finn, R. S., & Friedman, S. L. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00754-7 · Cited by 354
Self-citationLiver diseases: epidemiology, causes, trends and predictions
Gan, C., Yuan, Y., Shen, H., Gao, J., Kong, X., Che, Z., Guo, Y., Wang, H., Dong, E., & Xiao, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02072-z · Cited by 416
NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options
Foerster, F., Gairing, S. J., Müller, L., & Galle, P. R. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.09.007 · Cited by 285
CXCR2 inhibition enables NASH-HCC immunotherapy
Leslie, J., Mackey, J. B. G., Jamieson, T. J., Ramon‐Gil, E., Drake, T. M., Fercoq, F., Clark, W. A., Gilroy, K. L., Hedley, A., Nixon, C., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-326259 · Cited by 230
Self-citationCappuyns, S., Corbett, V., Yarchoan, M., Finn, R. S., & Llovet, J. M. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2023.2677 · Cited by 167
Self-citationMASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. I. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 137
Sun, Q., Xing, X., Wang, H., Wan, K., Fan, R., Liu, C., Wang, Y., Wu, W., Wang, Y., & Wang, R. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115586 · Cited by 125
Zeng, Q., Klein, C., Caruso, S., Maillé, P., Laleh, N. G., Sommacale, D., Laurent, A., Amaddeo, G., Gentien, D., Rapinat, A., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.01.018 · Cited by 129
NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy
Pinter, M., Pinato, D. J., Ramadori, P., & Heikenwalder, M. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1258 · Cited by 103
Jin, Z., Zhong, B., Chen, J.-J., Zhu, H., Sun, J., Yin, G., Ge, N., Luo, B., Ding, W., Li, W., et al. (2023) · European Radiology · doi:10.1007/s00330-023-09754-2 · Cited by 97
Iwamoto, H., Shimose, S., Shirono, T., Niizeki, T., & Kawaguchi, T. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0391 · Cited by 89
Esteban-Fabró, R., Willoughby, C. E., Piqué‐Gili, M., Montironi, C., Abril‐Fornaguera, J., Peix, J., Torrens, L., Mesropian, A., Balaseviciute, U., Miró‐Mur, F., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2517 · Cited by 83
Self-citationHatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2022) · Hepatology International · doi:10.1007/s12072-022-10358-z · Cited by 84
Pοlyzos, S. A., Chrysavgis, L., Vachliotis, I. D., Chartampilas, E., & Cholongitas, Ε. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.04.010 · Cited by 84
APASL clinical practice guidelines on systemic therapy for hepatocellular carcinoma-2024
Lau, G. K. K., Obi, S., Zhou, J., Tateishi, R., Qin, S., Zhao, H., Otsuka, M., Ogasawara, S., George, J., Chow, P. K. H., et al. (2024) · Hepatology International · doi:10.1007/s12072-024-10732-z · Cited by 90
Clinically approved combination immunotherapy: Current status, limitations, and future perspective
Lu, L., Zhan, M., Li, X.-Y., Zhang, H., Dauphars, D. J., Jiang, J., Yin, H., Li, S., Luo, S., Li, Y., et al. (2022) · Current Research in Immunology · doi:10.1016/j.crimmu.2022.05.003 · Cited by 77
Updates on Systemic Therapy for Hepatocellular Carcinoma
Ntellas, P., & Chau, I. (2024) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_430028 · Cited by 77
Jost‐Brinkmann, F., Demir, M., Wree, A., Luedde, T., Loosen, S. H., Müller, T., Tacke, F., Roderburg, C., & Mohr, R. U. (2023) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17441 · Cited by 59
Xing, X., Hu, E., Ouyang, J., Zhong, X., Wang, F., Liu, K., Cai, L., Zhou, Y., Wang, Y., Chen, G., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101315 · Cited by 59
Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future
Singal, A. G., Yarchoan, M. M., Yopp, A. C., Sapisochín, G., Pinato, D. J., & Pillai, A. A. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000430 · Cited by 55
Espinoza, M., Muquith, M., Lim, M., Zhu, H., Singal, A. G., & Hsiehchen, D. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.042 · Cited by 55
Pinato, D. J., Li, X., Mishra-Kalyani, P. S., D’Alessio, A., Fulgenzi, C. A. M., Scheiner, B., Pinter, M., Wei, G., Schneider, J., Rivera, D. R. R., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100747 · Cited by 55
Kudo, M., Montal, R., Finn, R. S., Castet, F., Ueshima, K., Nishida, N., Haber, P. K., Hu, Y., Chiba, Y., Schwartz, M., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3135 · Cited by 49
Self-citationThompson, S. M., Suman, G., Torbenson, M. S., Chen, Z. E., Jondal, D. E., Patra, A., Ehman, E. C., Andrews, J. C., Fleming, C. J., Welch, B. T., et al. (2021) · Hepatology Communications · doi:10.1002/hep4.1861 · Cited by 47
Lau, G. K. K., Abou‐Alfa, G. K., Cheng, A., Sukeepaisarnjaroen, W., Dao, T. V., Kang, Y., Thungappa, S. C., Kudo, M., Sangro, B., Kelley, R. K., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.07.017 · Cited by 45
Brandi, N., & Renzulli, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108598 · Cited by 43
Distinct alterations of gut microbiota between viral- and non-viral-related hepatocellular carcinoma
Jinato, T., Anuntakarun, S., Satthawiwat, N., Chuaypen, N., & Tangkijvanich, P. (2024) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12845-1 · Cited by 44
Xia, D., Bai, W., Wang, E., Li, J., Chen, X., Wang, Z., Huang, M., Huang, M. X., Sun, J., Weizhu, Y., et al. (2022) · Liver Cancer · doi:10.1159/000523849 · Cited by 40
Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma
Miyazaki, K., Morine, Y., Xu, C., Nakasu, C., Wada, Y., Teraoku, H., Yamada, S., Saito, Y., Ikemoto, T., Shimada, M., et al. (2023) · Cells · doi:10.3390/cells12040612 · Cited by 38
Epigenetic regulation of HBV-specific tumor-infiltrating T cells in HBV-related HCC
You, M., Gao, Y., Fu, J., Xie, R., Zhu, Z., Hong, Z., Meng, L., Du, S., Liu, J., Wang, F., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000369 · Cited by 39
Lombardi, R., Piciotti, R., Dongiovanni, P., Meroni, M., Fargion, S., & Fracanzani, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052707 · Cited by 28
Wang, W., Liu, Z., Wang, K., Yu, H., Cheng, Y., Xiang, Y., Feng, J.-K., Zhou, L., Zhou, H., Pan, W., et al. (2023) · Cancer Medicine · doi:10.1002/cam4.5880 · Cited by 35
Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms
Lugari, S., Baldelli, E., & Lonardo, A. (2023) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2022.38 · Cited by 32
MASLD-Related HCC—Update on Pathogenesis and Current Treatment Options
Leyh, C., Coombes, J. D., Schmidt, H., Canbay, A. E., Manka, P. P., & Best, J. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14040370 · Cited by 38
Fu, Y., Guo, X., Sun, L., Cui, T., Wu, C., Wang, J., Liu, Y., & Liu, L. (2024) · eLife · doi:10.7554/elife.95009 · Cited by 31
The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC
Wu, Q., Yang, Y., Lin, S., Geller, D. A., & Yan, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1569915 · Cited by 32
Tumor-associated neutrophils attenuate the immunosensitivity of hepatocellular carcinoma
Teo, J. M. N., Chen, Z., Chen, W., Tan, R. J. Y., Cao, Q., Chu, Y., Ma, D., Chen, L., Yu, H., Lam, K.-H., et al. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20241442 · Cited by 32
Shi, Y., Taherifard, E., Saeed, A., & Saeed, A. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060356 · Cited by 33
Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma
Qin, R., Jin, T., & Xu, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1326097 · Cited by 30
Pelizzaro, F., Farinati, F., & Trevisani, F. (2023) · Biomedicines · doi:10.3390/biomedicines11041020 · Cited by 28
Fang, S., Zheng, L., Chen, X., Guo, X., Ding, Y., Ma, J., Ding, J., Chen, W., Yang, Y., Chen, M., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10565-2 · Cited by 25
Inflammatory processes involved in NASH-related hepatocellular carcinoma
Cannito, S., Dianzani, U., Parola, M., Albano, E., & Sutti, S. (2023) · Bioscience Reports · doi:10.1042/bsr20221271 · Cited by 29
Efficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role?
Pinto, E., Meneghel, P., Farinati, F., Russo, F. P., Pelizzaro, F., & Gambato, M. (2023) · Digestive and Liver Disease · doi:10.1016/j.dld.2023.08.062 · Cited by 27
Vithayathil, M. K., D’Alessio, A., Fulgenzi, C. A. M., Nishida, N., Schönlein, M., von Felden, J., Schulze, K., Wege, H., Saeed, A., Wietharn, B., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10491-3 · Cited by 25
Requeijo, C., Bracchiglione, J., Meza, N., Acosta‐Dighero, R., Salazar, J., Santero, M., Meade, A.-G., Quintana, M. J., Rodríguez-Grijalva, G., Selva, A., et al. (2023) · Clinical Epidemiology · doi:10.2147/clep.s431498 · Cited by 24
Bhalodi, K., Kothari, C. S., & Butani, S. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03582-x · Cited by 24
Hatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2022) · Cancer Medicine · doi:10.1002/cam4.5337 · Cited by 24
Leslie, J., Krishnamurthy, K. A., Gopalsamy, I. K., Inácio, P., Huch, M., Gallage, S., Oakley, F., & Vacca, M. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01162-9 · Cited by 27
Camrelizumab: an investigational agent for hepatocellular carcinoma
Xu, B., & Sun, H. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2022121 · Cited by 23
Qi, S., Liu, G., Chen, J., Cao, P., Lei, X., Ding, C., Chen, G., Zhang, Y., & Wang, L. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s377080 · Cited by 23
RetractedDu, Q., Yuan, J., & Ren, Z. (2024) · Liver Cancer · doi:10.1159/000534446 · Cited by 20
Wang, Y., Wu, Y., Zhang, H., Wang, J., Song, A., Qiu, H., Yuan, X., Xiong, H., & Zou, Y. (2024) · Oncology and Translational Medicine · doi:10.1097/ot9.0000000000000064 · Cited by 21
Liu, X., Xia, F., Chen, Y., Sun, H., Yang, Z., Chen, B., Zhao, M. D., Bi, X., Peng, T., Ainiwaer, A., et al. (2024) · Liver Research · doi:10.1016/j.livres.2024.05.001 · Cited by 20
Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status
Gupta, T., & Jarpula, N. S. (2024) · World Journal of Hepatology · doi:10.4254/wjh.v16.i3.353 · Cited by 19
Verma, M., Kalman, R. S., Horrow, J. C., Gallagher, M., Woodrell, C. D., & Navarro, V. J. (2022) · Journal of Palliative Medicine · doi:10.1089/jpm.2022.0338 · Cited by 19
Abenavoli, L., Montori, M., Svegliati‐Baroni, G., Argenziano, M. E., Giorgi, F., Scarlata, G. G. M., Ponziani, F. R., & Scarpellini, E. (2023) · Medicina · doi:10.3390/medicina59081427 · Cited by 21
Wu, C.-Y., Lin, L., Lee, T., Hsu, Y., Yeh, C.-C., Chen, C., Kang, Y., & Huang, T. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000001950 · Cited by 18
Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?
Cammarota, A., Zanuso, V., Manfredi, G. F., Murphy, R., Pinato, D. J., & Rimassa, L. (2023) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359221148029 · Cited by 19
Stella, L., Pallozzi, M., Cerrito, L., Santopaolo, F., Tovoli, F., Hollande, C., Sidali, S., Stefanini, B., Campani, C., Pellegrini, E., et al. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.12.028 · Cited by 17
An overview: Management of patients with advanced hepatocellular carcinoma
Wang, J., Wu, R., Sun, J.-Y., Lei, F., Tan, H., & Lu, X. (2022) · BioScience Trends · doi:10.5582/bst.2022.01109 · Cited by 17
Li, X., Chen, Q., Liu, J., Lai, S., Zhang, M., Zhen, T., Hu, H., Gao, X., Wong, A. S. T., & Zeng, J.-Z. (2022) · Cells · doi:10.3390/cells11233870 · Cited by 17
Immune-Based Combination Therapies for Advanced Hepatocellular Carcinoma
Carloni, R., Sabbioni, S., Rizzo, A., Ricci, A. D., Palloni, A., Petrarota, C., Cusmai, A., Tavolari, S., Gadaleta‐Caldarola, G., & Brandi, G. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s390963 · Cited by 18
Molecular Testing and Targeted Therapies in Hepatobiliary Cancers
Tsilimigras, D. I., Kurzrock, R., & Pawlik, T. M. (2025) · JAMA Surgery · doi:10.1001/jamasurg.2025.0242 · Cited by 16
Exploration of Combinational Therapeutic Strategies for HCC Based on TCGA HCC Database
Yan, D., Li, C., Zhou, Y., Xue, Y., Zhi, W., Qian, H., & Han, Y. (2022) · ONCOLOGIE · doi:10.32604/oncologie.2022.020357 · Cited by 16
Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma
Peng, X., Gong, C., Zhang, W., & Zhou, A. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1091088 · Cited by 16
DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer
Bévant, K., Desoteux, M., Wahab, A. H. A. A., Abdel-Wahab, S., Metwally, A. M., & Coulouarn, C. (2021) · Cells · doi:10.3390/cells10092207 · Cited by 17
Tran, N. H. (2022) · Current Oncology Reports · doi:10.1007/s11912-021-01160-5 · Cited by 16
The rapidly evolving landscape of HCC: Selecting the optimal systemic therapy
Zanuso, V., Rimassa, L., & Braconi, C. (2023) · Hepatology · doi:10.1097/hep.0000000000000572 · Cited by 16
Jiang, P., Chen, C., Tian, J., Yang, F., Jiang, Z., Hu, A., & Liu, B. (2024) · Academic Radiology · doi:10.1016/j.acra.2024.09.061 · Cited by 15
Uluk, D., Pein, J., Herda, S., Schliephake, F., Schneider, C. V., Bitar, J., Dreher, K., Eurich, D., Zhang, I. W., Schaffrath, L., et al. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70002 · Cited by 15
Wang, K., Feng, J., Yu, H., Cheng, Y., Xiang, Y., Liu, Z., Qin, Y., Liu, E., Shan, Y., Chen, F., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02427-0 · Cited by 15
Chen, H., Shang, X., Yuan, H., Niu, Q., Chen, J., Luo, S., Li, W., & Li, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1019670 · Cited by 17
Downregulation of 15-PGDH enhances MASH-HCC development via fatty acid-induced T-cell exhaustion
Hu, X., Yasuda, T., Yasuda‐Yoshihara, N., Yonemura, A., Umemoto, T., Nakachi, Y., Yamashita, K., Semba, T., Arima, K., Uchihara, T., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100892 · Cited by 17
Zou, J., Huang, P., Ge, N., Xu, X., Wang, Y., Zhang, L., & Chen, Y. (2022) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-22-643 · Cited by 16
Chen, Q., Chen, S., Chen, M., Lyu, N., & Zhao, M. D. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2023.00403 · Cited by 14
Immune Checkpoints and the Immunology of Liver Fibrosis
Tsomidis, I., Voumvouraki, A., & Kouroumalis, E. (2025) · Livers · doi:10.3390/livers5010005 · Cited by 14
Wang, J., Liu, R., Zhao, Y., Ma, Z., Sang, Z., Wen, Z., Yang, X., & Xie, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.743055 · Cited by 14
Zhang, J., Xiao, Y., Li, Y., Zhu, Y., Li, Y., Zhao, R.-S., Jin, N., Fang, J., Li, X., & Han, J. (2023) · Integrative Cancer Therapies · doi:10.1177/15347354231210867 · Cited by 15
Shao, Y., & Akhmetzhanov, A. R. (2024) · Liver Cancer · doi:10.1159/000542576 · Cited by 15
Hsu, P., Cheng, T., Chuang, S., Chang, W., Liang, P., Hsu, C., Wei, Y., Jang, T., Yeh, M., Huang, C., et al. (2021) · Cancer Medicine · doi:10.1002/cam4.4430 · Cited by 13
Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma
Savier, É., Simón‐Gracia, L., Charlotte, F., Tufféry, P., Teesalu, T., Scatton, O., & Rebollo, A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13101631 · Cited by 13
Yang, K., Zhang, X., Yang, K., Liu, S., Zhang, J., Fu, Y., Liu, T., Wu, K., Li, J., Liu, C., et al. (2025) · Molecular Medicine · doi:10.1186/s10020-025-01263-w · Cited by 12
Wong, T. L., Kong, Y., & Ma, S. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000837 · Cited by 15
Liver resection and transplantation in the era of checkpoint inhibitors
Tabrizian, P., Marino, R., & Chow, P. K. H. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101181 · Cited by 15
Self-citationHepatocellular carcinoma systemic treatment update: From early to advanced stage
Teng, W., Wu, T.-C., & Lin, S. (2024) · Biomedical Journal · doi:10.1016/j.bj.2024.100815 · Cited by 14
Iwamoto, H., Niizeki, T., Nagamatsu, H., Ueshima, K., Tani, J., Kuzuya, T., Kasai, K., Kooka, Y., Hiraoka, A., Sugimoto, R., et al. (2022) · Cancers · doi:10.3390/cancers14194873 · Cited by 12
Yang, C., Huang, C., Hu, C.-H., Fang, J., Chen, T., Lin, Y., & Lin, C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280023 · Cited by 13
Féray, C., Campion, L., Mathurin, P., Archambreaud, I., Mirabel, X., Bronowicki, J., Rio, E., Perret, C., Mineur, L., Oberti, F., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100689 · Cited by 12
Toshida, K., Itoh, S., Yoshiya, S., Nagao, Y., Tomino, T., Izumi, T., Iseda, N., Toshima, T., Ninomiya, M., & Yoshizumi, T. (2023) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16441 · Cited by 12
Jin, J., Cheng, K., Chen, M., Liang, H., & Zhang, W. (2025) · International Journal of Biological Sciences · doi:10.7150/ijbs.117394 · Cited by 13
Kong, Y., Zhu, X., Zhang, X., Li, Z., Yin, Y., Wang, J., & Jia, H. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18591 · Cited by 11
Cammarota, A., Zanuso, V., D’Alessio, A., Pressiani, T., Personeni, N., & Rimassa, L. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2032641 · Cited by 11
Metadata
- Authors
- Haber, P. K., Puigvehí, M., Castet, F., Lourdusamy, V., Montal, R., Tabrizian, P., Buckstein, M., Kim, E., Villanueva, A., Schwartz, M., & Llovet, J. M.
- Affiliations
- Tisch Cancer Institute (US)
- Universitat Autònoma de Barcelona (ES)
- Hospital Clínic de Barcelona (ES)
- Hospital Universitari Arnau de Vilanova (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Llovet, Josep M.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 161
- Issue
- 3
- Pages
- 879-898
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC12276942
- OpenAlex
- W3169705253
- Cited by
- 248
- References
- 82
- Citations by year
- 2026: 33 · 2025: 42 · 2024: 52 · 2023: 67 · 2022: 39 · 2021: 13
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion)
- Funders
- U.S. Department of Defense (CA150272P3)
- National Cancer Institute (P30 CA19652, R01 CK 128289-01)
- Samuel Waxman Cancer Research Foundation
- California Department of Fish and Game
- Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR-1358)
- Ministerio de Ciencia e Innovación (SAF-2016-76390)
- Deutsche Forschungsgemeinschaft (HA 8754/1-1)
- Fundación Científica Asociación Española Contra el Cáncer
- Generalitat de Catalunya
- Asociación Española para el Estudio del Hígado
- Cancer Research UK
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Keywords
- hepatocellular carcinoma, systemic therapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, viral hepatitis etiology, sorafenib, lenvatinib, atezolizumab, bevacizumab, regorafenib, cabozantinib, ramucirumab, adjuvant therapy, treatment response
- MeSH terms
- Progression-Free Survival, Immune Checkpoint Inhibitors, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Hepatocellular, Humans, Immunotherapy, Liver Neoplasms, Neoplasm Staging, Time Factors, Randomized Controlled Trials as Topic, Chemoembolization, Therapeutic, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Disease Progression, Radiopharmaceuticals, Evidence-Based Medicine, Neoadjuvant Therapy, Ablation Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
