Liver Cancer最新文献

{"title":"Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in the Era of Systemic Therapies (2020-2025).","authors":"Qi-Feng Chen, Song Chen, Xiongying Jiang, Jiongliang Wang, Ming Zhao","doi":"10.1159/000551934","DOIUrl":"10.1159/000551934","url":null,"abstract":"<p><strong>Background: </strong>Management of advanced hepatocellular carcinoma (HCC) has evolved rapidly in recent years. Following the publication of the IMbrave150 study in 2020, which established atezolizumab-bevacizumab as first-line therapy, multiple systemic therapies have been approved and incorporated into global clinical guidelines. However, outcomes remain suboptimal in high-risk cases (e.g., extensive tumor burden, macrovascular invasion).</p><p><strong>Summary: </strong>This review examines the role of hepatic arterial infusion chemotherapy (HAIC) in the context of modern systemic therapy for advanced HCC. A literature search (2020-2025) was conducted employing a PICO framework (Patients: advanced HCC; Intervention: HAIC; Comparison: any or no alternative therapy; Outcomes: efficacy and safety). HAIC is a regional chemotherapy approach delivered via the hepatic artery, allowing high intratumoral drug concentration with manageable systemic toxicity. It is popularly used in East Asia and has demonstrated promising survival benefits in patients with portal vein tumor thrombosis (PVTT) or large tumors - subgroups where systemic therapies or transarterial chemoembolization frequently fail. HAIC is an integral modality for advanced HCC, especially for patients with extensive liver tumors or PVTT. It provides critical bridge-to-curative options by downsizing tumors and improving systemic treatment effects. To integrate HAIC into global practice, standardization of techniques, patient selection, biomarkers, and confirmatory trials in non-Asian populations is needed. HAIC can change the standard of care by improving outcomes in patient subsets poorly served by current therapies.</p><p><strong>Key messages: </strong>Paradigm shift to synergy: HAIC has transitioned from a palliative locoregional tool to a central pillar of \"triple therapy\" (HAIC + tyrosine kinase inhibitor + immune checkpoint inhibitor), leveraging immunogenic cell death to improve systemic treatment efficacy. Superiority in high-risk subsets: This modality demonstrates exceptional survival benefits in patients with high tumor burden and major PVTT (Vp4 PVTT) - subgroups where standard systemic monotherapies frequently fail. A bridge to cure: HAIC-based combination regimens significantly increase conversion-to-surgery rates by inducing rapid tumor necrosis and downstaging, thereby providing curative opportunities for initially unresectable patients. Global standardization needs: Future adoption relies on international consensus to standardize delivery protocols and biomarker-driven model validation for precise patient selection.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on the Article \"Prognostic Usefulness of Clinical Complete Response after PD-1 Inhibitor-Based Combination Therapy for Unresectable Hepatocellular Carcinoma\".","authors":"Mulin Liu, Qin Zheng, Juan Fu","doi":"10.1159/000551853","DOIUrl":"10.1159/000551853","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Comparison of First-Line Atezolizumab plus Bevacizumab and Durvalumab plus Tremelimumab for Unresectable Hepatocellular Carcinoma.","authors":"Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Takashi Nishimura, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Atsushi Naganuma, Hisashi Kosaka, Tomomitsu Matono, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Takanori Matsuura, Yoshihide Ueda, Soo Ki Kim, Hideko Ohama, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Shinya Fukunishi, Kazunari Tanaka, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Jumpei Okamura, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada","doi":"10.1159/000550924","DOIUrl":"10.1159/000550924","url":null,"abstract":"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab (Atez/Bev) was the first immune checkpoint inhibitor regimen approved in 2020 for unresectable hepatocellular carcinoma (uHCC), followed by durvalumab plus tremelimumab (Dur/Tre) in 2023. There is very little data available comparing the efficacy and safety of Atez/Bev with those of Dur/Tre. This study aimed to clarify the therapeutic outcomes and safety of Atez/Bev and Dur/Tre.</p><p><strong>Methods: </strong>We retrospectively analyzed patients with uHCC (BCLC-B/C and Child-Pugh class A) treated with Atez/Bev (<i>n</i> = 302) or Dur/Tre (<i>n</i> = 129) as first-line systemic therapy across multiple institutions between 2023 and 2025. A retrospective comparison of the treatment outcomes and safety of Atez/Bev and Dur/Tre was conducted.</p><p><strong>Results: </strong>The objective response rate and disease control rate were comparable between the Atez/Bev and Dur/Tre groups (31.8%/71.9% vs. 28.7%/63.6%, <i>p</i> = 0.570/<i>p</i> = 0.110, respectively). Median progression-free survival (PFS) was longer with Atez/Bev (9.1 vs. 5.0 months, <i>p</i> = 0.002), while OS was comparable (25.6 vs. 22.1 months, <i>p</i> = 0.172). Similar results were shown after adjusting with inverse probability weighting (IPW). Grade 5 immune-related adverse events occurred in 0.3% (<i>n</i> = 1, interstitial pneumonia) of the patients receiving Atez/Bev and 0.8% (<i>n</i> = 1, colitis) of those receiving Dur/Tre. In the Cox hazard analysis adjusted with IPW, Dur/Tre demonstrated a favorable trend in OS (hazard ratio [HR] <0.75) in patients with elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 0.72, interaction <i>p</i> = 0.006) or double positive elevation of tumor marker (AFP and des-gamma-carboxy prothrombin [≥100 mAU/mL]) (HR 0.66, interaction <i>p</i> = 0.005).</p><p><strong>Conclusion: </strong>Although Atez/Bev was associated with a longer PFS, OS did not differ significantly between Atez/Bev and Dur/Tre. This dissociation between PFS and OS may reflect differences in disease biology, treatment sequencing, and post-progression management rather than intrinsic superiority of either regimen. These findings highlight the importance of individualized treatment selection and careful consideration of tumor characteristics and hepatic reserve when choosing first-line immunotherapy for uHCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trajectory Modelling of Prognostic Biomarkers Linked to Liver Cancer Risk: A Systematic Review.","authors":"Bashayr Aldawsari, Laura J Bonnett, Maria Sudell, Philip Johnson, David M Hughes","doi":"10.1159/000551202","DOIUrl":"10.1159/000551202","url":null,"abstract":"<p><strong>Introduction: </strong>Liver cancer ranks as the third leading cause of cancer-related mortality. We review studies that used longitudinal clustering methods to identify trajectories of risk factors associated with risk of developing liver cancer.</p><p><strong>Methods: </strong>A systematic search of articles was conducted across three databases (MEDLINE, PubMed, and Scopus). Articles using any longitudinal clustering methods to identify trajectories of risk factors linked to liver cancer risk were considered. The review is registered on PROSPERO (CRD 42023406334).</p><p><strong>Results: </strong>Twenty-four studies were included. The people at higher risk of developing liver cancer in the general population are individuals with increasing body mass index, increasing metabolic syndrome, higher C-reactive protein, low or rare physical activity, high fasting blood glucose, and high smoking rate. Individuals with elevated risk of liver cancer in populations with liver disease had higher alcohol consumption, De Ritis ratio, AFP, FIB-4, liver fibrosis score, and stable HBsAg. Patients who already had liver cancer with increasing AFP and decreasing HBV DNA had lower survival probabilities. Three longitudinal clustering methods were identified: latent class growth modelling, Gaussian mixture models, and joint latent class modelling.</p><p><strong>Conclusion: </strong>This is the first systematic review of longitudinal clustering methods for prognostic risk factors linked to liver cancer risk. The study highlights the utility of longitudinal data in predicting liver cancer outcomes.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncological Outcomes and Treatment Strategies for Borderline Resectable Hepatocellular Carcinoma Based on the Oncological Resectability Classification.","authors":"Takashi Hamada, Akihiko Soyama, Hajime Matsushima, Ayaka Kinoshita, Kazushige Migita, Hajime Imamura, Shun Nakamura, Ayaka Satoh, Kohki Kurotaki, Tomohiko Adachi, Ryu Sasaki, Hisamitsu Miyaaki, Susumu Eguchi","doi":"10.1159/000551047","DOIUrl":"10.1159/000551047","url":null,"abstract":"<p><strong>Background: </strong>Although hepatic resection is the most effective curative treatment for hepatocellular carcinoma (HCC) in selected patients, survival outcomes can vary significantly depending on tumor burden and biology. To provide a standardized framework, the oncological resectability classification introduced in 2023 stratifies patients into resectable (R), borderline resectable 1 (BR1), or borderline resectable 2 (BR2). However, the optimal management of patients with BR1 and BR2 in the era of novel systemic therapies remains uncertain. The present study evaluated the surgical validity and treatment strategies for patients with BR1 and BR2, based on this classification.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 184 patients who underwent initial hepatic resection for HCC at Nagasaki University Hospital between 2014 and 2024. Clinical variables, perioperative outcomes, the recurrence-free survival (RFS), and the overall survival (OS) were then compared across the 3 groups: R (<i>n</i> = 149), BR1 (<i>n</i> = 21), and BR2 (<i>n</i> = 14). Subgroup analyses were performed to assess the impact of vascular invasion and preoperative systemic therapy.</p><p><strong>Results: </strong>The 5-year RFS rates were 43.9% for R, 39.3% for BR1, and 20.0% for BR2 (<i>p</i> < 0.001). The 5-year OS rates were 75.1% for R, 76.9% for BR1, and 33.8% for BR2 (<i>p</i> < 0.001). Among BR1 patients without vascular invasion, no cancer-related deaths occurred, and recurrence was largely controllable with repeated hepatectomy, radiofrequency ablation, transarterial chemoembolization, or stereotactic radiotherapy in patients even with recurrence. Conversely, BR1 patients with vascular invasion who underwent upfront surgery exhibited poor survival outcomes, whereas those received preoperative systemic therapy demonstrated at least comparable survival outcomes despite a higher tumor burden, with a lower incidence of cancer-related death. BR2 patients had uniformly poor results regardless of vascular invasion. However, two cases who received systemic therapy before surgery achieved a long-term survival, including one with complete pathological necrosis.</p><p><strong>Conclusions: </strong>BR1 patients, particularly those without vascular invasion, may achieve survival comparable to that of R. In contrast, BR2 patients generally show dismal outcomes with surgery alone, underscoring the necessity of systemic or multimodal approaches. Tailored strategies are essential for optimizing outcomes in patients with borderline resectable HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b Study of Botensilimab and Balstilimab in Treatment-Refractory Hepatocellular Carcinoma.","authors":"Anthony B El-Khoueiry, Christopher H Lieu, Ghassan K Abou-Alfa, Apostolia M Tsimberidou, Daruka Mahadevan, Diana L Hanna, Bruno Bockorny, Breelyn A Wilky, Alexis Leal, Justin Stebbing, Manushak Avagyan, Wei Wu, Dhan Chand, Joseph E Grossman, Benny Johnson, Andrea J Bullock","doi":"10.1159/000551630","DOIUrl":"10.1159/000551630","url":null,"abstract":"<p><strong>Introduction: </strong>Botensilimab (BOT) is a fragment crystallizable (Fc)-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody with differentiated mechanisms of action, designed to extend therapy to cold/poorly immunogenic solid tumors. Patients with hepatocellular carcinoma (HCC) who progress on or after first-line immunotherapy have limited treatment options. Here, we report findings from a phase 1b study of BOT plus balstilimab (BAL; anti-programmed cell death protein 1 [PD-1] antibody) in previously treated patients with HCC.</p><p><strong>Methods: </strong>This is an open-label, nonrandomized, phase 1b, multicenter study of BOT±BAL in patients with advanced solid tumors. The study began with dose escalation (3 + 3 design) then dose expansion with multiple disease-specific cohorts. An expanded cohort of 19 patients with HCC who progressed on or after prior immunotherapy (primarily atezolizumab/bevacizumab) are included in this analysis. Patients with HCC received BOT intravenously at 1 or 2 mg/kg once every 6 weeks for up to 2 years plus BAL intravenously 3 mg/kg once every 2 weeks, for up to 2 years. Endpoints included safety, objective response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS). Overall survival (OS) was an exploratory endpoint.</p><p><strong>Results: </strong>Among 18 efficacy evaluable patients (with ≥1 post-baseline 6-week imaging scan), ORR was 17% (3/18; 95% CI: 4-41), and 18-week clinical benefit rate (a complete or partial response or stable disease) 50% (9/18; 95% CI: 26-74). Median PFS was 4.4 months (95% CI: 1.4-6.9), and median OS was 12.3 months (95% CI: 8.4-21.4). Thirteen patients (68%) experienced any-grade immune-mediated treatment-related adverse events (TRAEs), with 37% (7/19) grade 3. The most common immune-mediated TRAEs included diarrhea/colitis (37% [7/19]; 16% grade 3 [3/19]), hepatitis (21% [4/19]; 16% grade 3 [3/19]), and dermatologic events (21% [4/19]; 5% grade 3 [1/19]). There were no treatment-related deaths or new safety signals outside of the class.</p><p><strong>Conclusions: </strong>The BOT+BAL combination demonstrated durable responses and manageable safety in treatment-refractory patients with HCC previously treated with immunotherapy, supporting further investigation in randomized studies. Despite the small sample size and high percentage of patients with albumin-bilirubin grade 2 liver disease, these results provide early evidence of antitumor activity in a difficult-to-treat disease setting.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging-Based Liver Transplant Eligibility in Hepatocellular Carcinoma: Analysis of 1,094 Patients Using Liver Imaging Reporting and Data System and Asia-Pacific Guideline-Based Criteria.","authors":"Yeongseok Hwang, Subin Heo, Jihyun An, Seong Kyun Na, Seon-Ok Kim, In-Hye Song, Jean-Charles Nault, Gi-Won Song, Sang Hyun Choi, Ju Hyun Shim","doi":"10.1159/000551666","DOIUrl":"10.1159/000551666","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate imaging diagnosis is essential for evaluating liver transplantation (LT) eligibility in hepatocellular carcinoma (HCC) patients. This study investigated whether pre-transplant imaging assessment using the Liver Imaging Reporting and Data System (LI-RADS) and Asia-Pacific guideline-based criteria could effectively predict long-term prognosis when determining LT eligibility.</p><p><strong>Methods: </strong>From a prospective registry, we analyzed 1,094 patients with a preoperative HCC diagnosis who had dynamic CT available within 1 month before LT. LT eligibility was assessed with Milan criteria (MC) and Up-to-Seven criteria (UTS). Imaging evaluation was performed using the LI-RADS, Asian Pacific Association for the Study of the Liver, Japan Society of Hepatology, and Korean Liver Cancer Association-National Cancer Center guidelines. We compared HCC-related mortality using competing risk analysis, overall survival, and prognostic performance between imaging-based and pathologic assessments.</p><p><strong>Results: </strong>The cohort comprised 158 (14.4%) anti-HCC treatment naïve patients and 936 (85.6%) patients who received anti-HCC treatments in the pre-LT setting. No significant difference in HCC-related mortality was observed between patients meeting imaging-based MC and pathological MC (5-year HCC-related mortality: 8.6-8.7% vs. 6.6%; all <i>p</i> > 0.05). Prognostic performance, assessed by 5-year area under the precision-recall curve and integrated Brier score, showed no significant differences between imaging-based MC and pathological MC groups (all <i>p</i> > 0.05). Similar results were observed for overall survival, UTS-based analyses, and pre-LT treatment subgroup analyses. Concordance between imaging-based MC and pathology-based MC was 84.0-84.4%.</p><p><strong>Conclusion: </strong>Although some discordance between imaging-based and pathology-based LT eligibility criteria was observed, pre-transplant imaging provided prognostic stratification comparable to pathology. Given that comprehensive pathological assessment is unattainable before LT, imaging-based evaluation using both LI-RADS and Asia-Pacific guidelines represents a practical and clinically relevant approach for determining LT eligibility.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Nivolumab plus Ipilimumab in Advanced Hepatocellular Carcinoma with and without High-Risk Features: An International Multicenter Study.","authors":"Jung Sun Kim, San-Chi Chen, Jeffrey Sum Lung Wong, Beodeul Kang, Ho Yeong Lim, Ilhwan Kim, Hyeyeong Kim, Chansik An, Su Jin Jang, Masatoshi Kudo, David Tai, Chan Kim, Thomas Yau, Hong Jae Chon","doi":"10.1159/000551631","DOIUrl":"10.1159/000551631","url":null,"abstract":"<p><strong>Introduction: </strong>The phase 1/2 CheckMate-040 and the phase 3 CheckMate-9DW trials consistently demonstrated meaningful activity of nivolumab plus ipilimumab (Nivo/Ipi) in previously treated and treatment-naïve patients with advanced HCC. However, patients with ≥50% liver involvement, Vp4 portal vein tumor thrombosis (PVTT), or bile duct invasion were excluded from these trials. We aimed to assess the real-world efficacy and safety of Nivo/Ipi in this high-risk population.</p><p><strong>Methods: </strong>This international, multicenter, retrospective study was conducted in patients with advanced HCC who received Nivo/Ipi at six hospitals in Korea, Hong Kong, Singapore, and Taiwan between 2016 and 2024. Patients with Child-Pugh B/C or ECOG >2 were excluded.</p><p><strong>Results: </strong>Of the 206 patients assessed for eligibility, 145 were included in the final analysis: 44 classified as high risk (Vp4 PVTT, <i>n</i> = 10; ≥50% liver involvement, <i>n</i> = 34; bile duct invasion, <i>n</i> = 7) and 101 as non-high risk. Baseline characteristics were comparable, aside from differences in liver function and high-risk features. Nivo/Ipi was administered as third-line or later-line therapy in 76.6% of patients. The high-risk group exhibited a significantly lower objective response rate (ORR) (12.8% vs. 34.3%) and shorter median progression-free survival (PFS) (1.2 vs. 2.9 months) and overall survival (OS) (3.6 vs. 16.5 months). Among the high-risk features, ≥50% liver involvement was strongly associated with inferior ORR, PFS, and OS, whereas Vp4 PVTT and bile duct invasion alone were not significantly associated with outcomes. A higher intrahepatic tumor burden was also inversely associated with treatment response and survival. Adverse events were more frequent in high-risk patients, particularly hyperbilirubinemia (36.4% vs. 13.9%; grade ≥3: 11.4% vs. 1.0%). On multivariable analysis, ≥50% liver involvement and prior immune-checkpoint inhibitor exposure independently predicted shorter PFS and OS.</p><p><strong>Conclusion: </strong>Extensive liver involvement emerged as the key predictor of poor prognosis, whereas Vp4 PVTT and bile duct invasion were not associated with significantly worse outcomes.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitor Rechallenge in Unresectable Hepatocellular Carcinoma: A Multicenter Efficacy and Safety Study.","authors":"Jing-Kun Chen, Jia-Liang Wei, Zhen-Dong Yang, Shao-Ping Liu, Zhi-Cheng Li, Kang Chen, Chuang Qin, Ze Su, Lin Ye, Shu-Qun Li, Guo-Xing Liu, Jian-Yuan Meng, Ying-Hui Wu, Ting Quan, Jian Li, Zhu-Jian Deng, Da-Long Yang, Jia-Yong Su, Guan-Lin Chen, Cai-Yi Dong, Bin-Yan Gu, Wen-Yang Li, Xiao-Shan Qin, Xiu-Qiong Long, Liang Ma, Jian-Hong Zhong","doi":"10.1159/000551629","DOIUrl":"10.1159/000551629","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) are a standard treatment for unresectable hepatocellular carcinoma, but sometimes they must be discontinued because of resistance or immune-related adverse events. The present study explored whether later resuming ICI therapy in such patients (\"rechallenge\") can improve their prognosis.</p><p><strong>Methods: </strong>Data were retrospectively analyzed for patients treated between March 2019 and May 2024 at 12 medical centers in China. Patients had unresectable hepatocellular carcinoma and were initially treated with ICIs, which were discontinued due to resistance or severe immune-related adverse events and then later resumed. Event-free survival, objective response, and disease control based on RECIST 1.1 criteria, as well as incidence and severity of immune-related adverse events, were assessed separately during first-line ICI (ICI-1) and second-line ICI (ICI-2) therapy.</p><p><strong>Results: </strong>The final analysis included 272 patients (247 men) with a median age of 50 (IQR 43-58) years old at enrollment; ICI-1 was discontinued in 253 patients (93.0%) because of tumor progression. Both ICI-1 and ICI-2 therapies lasted a median of 3.0 months and, for approximately 80% of patients, involved the combination of ICIs and targeted agents rather than ICI monotherapy. During ICI-1 or ICI-2 therapy, respective median event-free survival times were 5.3 (95% CI 4.7-5.9) months and 4.4 (95% CI 3.8-5.0) months, objective response rates were 23.2% and 18.4%, disease control rates were 69.9% and 48.2%, and rates of immune-related adverse events of grades 3-4 were 18.4% and 19.9%. Objective response was observed in 26 patients (9.6%) during both therapy lines, while 10 (12.2%) suffered disease progression during ICI-1 therapy yet achieved partial response during ICI-2 treatment. No deaths due to immune-related adverse events occurred during the study.</p><p><strong>Conclusion: </strong>ICI rechallenge following tumor progression or severe immune-related adverse events can benefit some patients with unresectable hepatocellular carcinoma without posing additional safety risks.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Clinic Approach Improves Immunotherapy Treatment Outcomes in Unresectable Hepatocellular Carcinoma: A Multicentre Retrospective Study.","authors":"Andrea Dalbeni, Alessandra Auriemma, Marco Vicardi, Filippo Cattazzo, Maria Elena Bellucco, Chiara Mazzarelli, Federica Villa, Giulia Dispinzieri, Leonardo Antonio Natola, Caterina Soldà, Sara Lonardi, Luisa Foltran, Sara Torresan, Simone Rota, Tiziana Pressiani, Lorenza Rimassa, David Sacerdoti, Michele Milella","doi":"10.1159/000549738","DOIUrl":"10.1159/000549738","url":null,"abstract":"<p><strong>Introduction: </strong>Given the complexity of managing unresectable hepatocellular carcinoma (HCC), few Italian centres have implemented integrated multidisciplinary clinics (MDTc), where hepatologists and oncologists jointly assess patients. This study aimed to evaluate whether this model improves survival outcomes in patients treated with atezolizumab and bevacizumab (A+B).</p><p><strong>Methods: </strong>In this multicentre retrospective study, 146 patients with cirrhosis and unresectable HCC treated with A+B were included. Based on the outpatient care model, centres were categorized into two groups: those with MDTc and those with standard oncology clinics, where hepatologists were consulted on demand. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included disease control rate (DCR) and objective response rate (ORR). An inverse probability weighting (IPW) analysis was performed to adjust for baseline imbalances between groups.</p><p><strong>Results: </strong>Seventy-seven (53%) patients were managed in MDTc settings, and 69 (47%) in oncology clinics. Median treatment duration was 6.0 months (IQR 2.0-11.0). Median OS did not significantly differ between groups [19.7 months (95% confidence intervals [CI]: 16.6-23.1) vs. 13.4 months (95% CI: 10.7-19.5); <i>p</i> = 0.07], whereas median PFS was significantly longer in the MDTc group (13.6 months [95% CI: 8.9-NA] vs. 7.7 months [95% CI: 4.9-13.0]; <i>p</i> = 0.02). While ORR was similar, DCR was higher in the MDTc group (70.1% vs. 60.3%; <i>p</i> = 0.05). Patients followed in MDTc remained on first-line therapy significantly longer (8 months [IQR 3-12] vs. 4 months [IQR 1-8]; <i>p</i> = 0.009). Although the overall treatment discontinuation rate did not differ between the two groups, liver-related events were more frequent and accounted for a greater proportion of discontinuations in oncology clinics (40.6% vs. 10.4%; <i>p</i> = 0.04). Furthermore, treatment duration was shorter in patients discontinuing A+B due to liver-related events than other causes (2.5 months [IQR 1.8-6.3] vs. 7.1 months [IQR 3.9-11.2]; <i>p</i> < 0.001). However, in the IPW analysis, the association between MDTc management and clinical outcomes was no longer significant.</p><p><strong>Conclusions: </strong>In patients with unresectable HCC treated with A+B, MDTc management did not significantly improved OS but was associated with better PFS and DCR. These benefits were likely driven by longer treatment duration and lower rates of liver-related decompensation, underscoring the value of integrated hepatologic-oncologic management in this complex population.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}