Despite the advances in systemic therapy for unresectable hepatocellular carcinoma (HCC), patients with Child–Pugh class B (CP-B) liver function face a significant unmet need. This study evaluated the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) in patients with unresectable HCC and CP-B.
Methods
This retrospective study included 796 patients who received Atez/Bev between October 2020 and July 2024 from 10 institutions in Japan. The median observation period was 14.6 months. The liver function was assessed using the CP classification and modified ALBI (mALBI) grade. The progression-free survival (PFS), overall survival (OS) and median survival time (MST) were evaluated.
Results
Patients with CP-B had significantly shorter PFS and OS than those with CP-A (median PFS, 4.6 months vs. 7.0 months; MST, 10.3 months vs. 23.2 months) (PFS, p = 0.009; OS, p < 0.001). Although CP-B was associated with a higher incidence of bleeding-related events, the discontinuation rate due to adverse events did not differ from that of CP-A. As a factor for stratifying CP-B outcomes, significant differences in the PFS, OS and response rate were observed between mALBI grades ≤ 2b and 3 (PFS, p = 0.004; OS, p = 0.024; response rate, p = 0.001). In multivariate analysis, the mALBI grade (hazard ratio [95% CI]: 2.388 [1.186–4.810]; p = 0.014) was extracted as a factor contributing to OS in patients with CP-B.
Conclusion
Atez/Bev therapy demonstrated efficacy and safety in patients with CP-B, especially when hepatic reserve is maintained within mALBI grade 2b.
背景和目的尽管不可切除的肝细胞癌（HCC）的全身治疗取得了进展，但Child-Pugh B级（CP-B）肝功能患者仍面临着显著的未满足需求。本研究评估了atezolizumab联合贝伐单抗（Atez/Bev）在不可切除的HCC和CP-B患者中的疗效和安全性。方法本回顾性研究纳入了2020年10月至2024年7月来自日本10家机构的796例接受Atez/Bev治疗的患者。中位观察期14.6个月。采用CP分级和改良ALBI （mALBI）分级评估肝功能。评估无进展生存期（PFS）、总生存期（OS）和中位生存期（MST）。结果CP-B患者的PFS和OS均明显短于CP-A患者（中位PFS， 4.6个月vs 7.0个月；MST， 10.3个月vs 23.2个月）（PFS, p = 0.009； OS, p < 0.001）。虽然CP-B与较高的出血相关事件发生率相关，但因不良事件引起的停药率与CP-A没有差异。作为区分CP-B结局的一个因素，mALBI分级≤2b和3级之间的PFS、OS和有效率存在显著差异（PFS, p = 0.004； OS, p = 0.024；有效率，p = 0.001）。在多因素分析中，提取mALBI分级（风险比[95% CI]: 2.388 [1.186-4.810]; p = 0.014）作为CP-B患者OS的影响因素。结论Atez/Bev治疗在CP-B患者中显示出有效性和安全性，特别是当肝储备维持在mALBI 2b级时。
{"title":"Efficacy and Safety of Atezolizumab Plus Bevacizumab for Patients With Hepatocellular Carcinoma and Child–Pugh Class B","authors":"Ryu Sasaki, Shigeo Shimose, Issei Saeki, Takanori Ito, Yasuto Takeuchi, Joji Tani, Tetsu Tomonari, Kyo Sasaki, Satoru Kakizaki, Takeshi Hatanaka, Satoshi Miuma, Tomotake Shirono, Hideki Iwamoto, Norikazu Tanabe, Takafumi Yamamoto, Yuki Kanayama, Atsushi Naganuma, Sohji Nishina, Tetsuji Takayama, Hideki Kobara, Motoyuki Otsuka, Hiroki Kawashima, Taro Takami, Takumi Kawaguchi, Hisamitsu Miyaaki, Hepatology InVestigator Experts in Japan (HIVE-J) Study Group","doi":"10.1111/liv.70466","DOIUrl":"https://doi.org/10.1111/liv.70466","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Despite the advances in systemic therapy for unresectable hepatocellular carcinoma (HCC), patients with Child–Pugh class B (CP-B) liver function face a significant unmet need. This study evaluated the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) in patients with unresectable HCC and CP-B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 796 patients who received Atez/Bev between October 2020 and July 2024 from 10 institutions in Japan. The median observation period was 14.6 months. The liver function was assessed using the CP classification and modified ALBI (mALBI) grade. The progression-free survival (PFS), overall survival (OS) and median survival time (MST) were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with CP-B had significantly shorter PFS and OS than those with CP-A (median PFS, 4.6 months vs. 7.0 months; MST, 10.3 months vs. 23.2 months) (PFS, <i>p</i> = 0.009; OS, <i>p</i> < 0.001). Although CP-B was associated with a higher incidence of bleeding-related events, the discontinuation rate due to adverse events did not differ from that of CP-A. As a factor for stratifying CP-B outcomes, significant differences in the PFS, OS and response rate were observed between mALBI grades ≤ 2b and 3 (PFS, <i>p</i> = 0.004; OS, <i>p</i> = 0.024; response rate, <i>p</i> = 0.001). In multivariate analysis, the mALBI grade (hazard ratio [95% CI]: 2.388 [1.186–4.810]; <i>p</i> = 0.014) was extracted as a factor contributing to OS in patients with CP-B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Atez/Bev therapy demonstrated efficacy and safety in patients with CP-B, especially when hepatic reserve is maintained within mALBI grade 2b.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Sogbe, Brittany Bromfield, Roberto Tellez, Pamela M. Bloomer, Nelson Bennett, Christopher B. Hughes, Michael A. Dunn, Astrid Ruiz-Margáin, Andres Duarte-Rojo
Background and Aims
Hypogonadism is frequent in AdvCLD and associated with frailty and poor outcomes. This study aimed to evaluate the association between free testosterone (FT) levels and all-cause mortality in male patients with AdvCLD awaiting liver transplantation (LT), and to compare the prognostic value of FT with total testosterone (TT).
Methods
In this prospective cohort study, 191 male patients with AdvCLD awaiting LT underwent FT and TT evaluation. The primary outcome was all-cause mortality, assessed using a competing-risk model with LT as the competing event.
Results
Among the 191 patients, 41 (21.5%) had low FT levels. This group was more likely to have a higher Child-Turcotte-Pugh class and MELD-Na score, as well as higher proportion of individuals with a history of hepatic encephalopathy (HE) compared to those with normal FT levels (p < 0.05). Patients with low FT also exhibited greater frailty (liver frailty index: 4.2 ± 0.8 vs. 3.6 ± 0.9, p < 0.001, respectively). After adjustment for MELD-Na, low FT was significantly associated with increased mortality risk (adjusted subdistribution hazard ratio [aSHR] 1.97; 95% CI: 1.07–3.61). Additionally, patients with low FT had a lower cumulative probability of undergoing LT compared to those with normal FT levels (43.4% vs. 74.3%). In contrast, low TT was not associated with mortality (aSHR: 1.65; 95% CI: 0.90–3.02).
Conclusion
Low FT levels are independently associated with higher mortality and lower LT probability in men with AdvCLD and outperform TT as a prognostic marker. These findings support FT as a valuable biomarker to identify high-risk patients and guide future interventional strategies.
{"title":"Free Testosterone Is Associated With Worse Survival in Patients With Advanced Chronic Liver Disease Awaiting Liver Transplantation","authors":"Miguel Sogbe, Brittany Bromfield, Roberto Tellez, Pamela M. Bloomer, Nelson Bennett, Christopher B. Hughes, Michael A. Dunn, Astrid Ruiz-Margáin, Andres Duarte-Rojo","doi":"10.1111/liv.70393","DOIUrl":"10.1111/liv.70393","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hypogonadism is frequent in AdvCLD and associated with frailty and poor outcomes. This study aimed to evaluate the association between free testosterone (FT) levels and all-cause mortality in male patients with AdvCLD awaiting liver transplantation (LT), and to compare the prognostic value of FT with total testosterone (TT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective cohort study, 191 male patients with AdvCLD awaiting LT underwent FT and TT evaluation. The primary outcome was all-cause mortality, assessed using a competing-risk model with LT as the competing event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 191 patients, 41 (21.5%) had low FT levels. This group was more likely to have a higher Child-Turcotte-Pugh class and MELD-Na score, as well as higher proportion of individuals with a history of hepatic encephalopathy (HE) compared to those with normal FT levels (<i>p</i> < 0.05). Patients with low FT also exhibited greater frailty (liver frailty index: 4.2 ± 0.8 vs. 3.6 ± 0.9, <i>p</i> < 0.001, respectively). After adjustment for MELD-Na, low FT was significantly associated with increased mortality risk (adjusted subdistribution hazard ratio [aSHR] 1.97; 95% CI: 1.07–3.61). Additionally, patients with low FT had a lower cumulative probability of undergoing LT compared to those with normal FT levels (43.4% vs. 74.3%). In contrast, low TT was not associated with mortality (aSHR: 1.65; 95% CI: 0.90–3.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low FT levels are independently associated with higher mortality and lower LT probability in men with AdvCLD and outperform TT as a prognostic marker. These findings support FT as a valuable biomarker to identify high-risk patients and guide future interventional strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interpreting the Clinical Significance of Spleen Stiffness in Baveno VII Risk Stratification","authors":"Yuanyuan Yang","doi":"10.1111/liv.70457","DOIUrl":"10.1111/liv.70457","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng-Yeh Yang, Chun-Yen Lin, Rong-Nan Chien, Sheng-Nan Lu
{"title":"Response to Letter to the Editor ‘Key Considerations to Broaden the Validity of HCV-Related LC/CLD Mortality Research in Taiwan’","authors":"Cheng-Yeh Yang, Chun-Yen Lin, Rong-Nan Chien, Sheng-Nan Lu","doi":"10.1111/liv.70455","DOIUrl":"10.1111/liv.70455","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellina Lytvyak, Gideon Hirschfield, Devika Shreekumar, Yu Jun Wong, Aldo J. Montano-Loza
{"title":"Author Response to Letter to the Editor: Tofacitinib as a Steroid-Free Induction in Autoimmune Hepatitis: An Initial Experience","authors":"Ellina Lytvyak, Gideon Hirschfield, Devika Shreekumar, Yu Jun Wong, Aldo J. Montano-Loza","doi":"10.1111/liv.70446","DOIUrl":"10.1111/liv.70446","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From Creatinine Cut-Offs to Bedside Precision: A Road-Map for Safer Terlipressin in Early Hepatorenal Syndrome","authors":"Zuomin Wang, Qinwei Liu, Wangdong Deng","doi":"10.1111/liv.70453","DOIUrl":"10.1111/liv.70453","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the Editor: Rethinking Myeloperoxidase Inhibition in MASH—Lessons From the COSMOS Trial","authors":"Weixiong Zhu, Wancheng Li, Yuanhui Su, Wence Zhou","doi":"10.1111/liv.70432","DOIUrl":"https://doi.org/10.1111/liv.70432","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steatotic liver disease (SLD) affects more than 30% of the global population; however, trends in its prevalence remain poorly understood. This study aimed to elucidate prevalence trends of metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with moderate alcohol intake (MetALD), and alcohol-associated liver disease (ALD) in the Japanese general population.
Methods
This retrospective study included participants who underwent health checkups between 2004 and 2022 in Gifu, Japan. SLD was defined by liver ultrasonography and categorised as either MASLD, MetALD, or ALD in the total population, as well as in non-obese (body mass index [BMI] ≤ 25 kg/m2), and lean (BMI ≤ 23 kg/m2) subgroups. Annual percent change (APC) in the prevalence of each SLD subtype was analysed using the Joinpoint regression model.
Results
Among 184 463 participants, 49 651 (26.9%) were diagnosed with SLD, including 41 819 (22.7%) with MASLD, 3792 (2.1%) with MetALD, and 2037 (1.1%) with ALD. Over the study period, APC in the total population revealed significant increases in MASLD (APC, 2.02%; 95% confidence interval [CI], 1.46–2.66; p < 0.001) and MetALD (APC, 1.14%; 95% CI, 0.17–2.19; p = 0.026), with similar trends observed in the non-obese and lean subgroups. ALD prevalence increased only in the lean population (APC, 2.87%; 95% CI, 0.33–5.94; p = 0.031).
Conclusions
MASLD and MetALD increased significantly irrespective of body composition, whereas ALD increased in the lean population over the past two decades. These findings highlight a silent rise of SLD in the Japanese general population.
{"title":"Increasing Prevalence of Steatotic Liver Disease in a Japanese Health Checkup Population, 2004–2022","authors":"Yuki Nakahata, Takao Miwa, Akihiro Obora, Takao Kojima, Nobuaki Yagi, Masahito Shimizu","doi":"10.1111/liv.70454","DOIUrl":"10.1111/liv.70454","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Steatotic liver disease (SLD) affects more than 30% of the global population; however, trends in its prevalence remain poorly understood. This study aimed to elucidate prevalence trends of metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with moderate alcohol intake (MetALD), and alcohol-associated liver disease (ALD) in the Japanese general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included participants who underwent health checkups between 2004 and 2022 in Gifu, Japan. SLD was defined by liver ultrasonography and categorised as either MASLD, MetALD, or ALD in the total population, as well as in non-obese (body mass index [BMI] ≤ 25 kg/m<sup>2</sup>), and lean (BMI ≤ 23 kg/m<sup>2</sup>) subgroups. Annual percent change (APC) in the prevalence of each SLD subtype was analysed using the Joinpoint regression model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 184 463 participants, 49 651 (26.9%) were diagnosed with SLD, including 41 819 (22.7%) with MASLD, 3792 (2.1%) with MetALD, and 2037 (1.1%) with ALD. Over the study period, APC in the total population revealed significant increases in MASLD (APC, 2.02%; 95% confidence interval [CI], 1.46–2.66; <i>p</i> < 0.001) and MetALD (APC, 1.14%; 95% CI, 0.17–2.19; <i>p</i> = 0.026), with similar trends observed in the non-obese and lean subgroups. ALD prevalence increased only in the lean population (APC, 2.87%; 95% CI, 0.33–5.94; <i>p</i> = 0.031).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MASLD and MetALD increased significantly irrespective of body composition, whereas ALD increased in the lean population over the past two decades. These findings highlight a silent rise of SLD in the Japanese general population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Post Hoc and Precarious: A Cautionary Note on Terlipressin in Early-Stage ACLF","authors":"Zhihao Lei","doi":"10.1111/liv.70456","DOIUrl":"10.1111/liv.70456","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jue Wang, Jiale Qiu, Kin Ching Tsang, Zezhuo Su, Chenzi Zhang, Jun Tang, Yaofeng Wang, Chenqing Zhang, Chi-Kong Li, Guangjin Pan, Bo Feng
Background & Aims
The prognosis for patients with hepatocellular carcinoma (HCC) remains suboptimal, despite the rapid advancement of anti-cancer immunotherapy. Chimeric antigen receptor (CAR) T cell therapy targeting glypican-3 (GPC3) has been developed for HCC; however, clinical trials have demonstrated heterogeneous responses among patients and limited CAR-T cell infiltration. Locoregional administration has emerged as a promising strategy for CAR-T therapy against solid tumours, yet its potential for HCC treatment has not been thoroughly explored.
Methods
In this study, we constructed anti-GPC3 CAR-T cells and examined their therapeutic efficacy through locoregional and systemic administration using multiple HCC xenograft mouse models.
Results
Comparison of CAR-T cell injections via portal vein and tail vein in mice with orthotopic HepG2 tumours demonstrated significantly enhanced tumour growth inhibition with locoregional CAR-T therapy. Consistently, tumour infiltration of CAR-T cells was significantly enhanced by portal vein injection and correlated with increased cytotoxicity, enhanced chemotaxis and reduced exhaustion of the tumour-infiltrating CAR-T cells compared to the tail vein injection group. Treatment with escalating CAR-T cell dosages resulted in further improved functionality of CAR-T cells and treatment efficacy, alongside improved liver function. Furthermore, portal vein injection exhibited superior tumour inhibition compared to tail vein injection in a metastatic model concurrently bearing orthotopic and extrahepatic tumour lesions.
Conclusion
Collectively, our study demonstrates that locoregional CAR-T therapy through the portal vein is associated with increased CAR-T cell infiltration and improved therapeutic efficacy, offering promise for the treatment of both early- and late-stage patients.
{"title":"Enhanced Functionality of Anti-GPC3 CAR-T Cells Against Hepatocellular Carcinoma Through Locoregional Administration","authors":"Jue Wang, Jiale Qiu, Kin Ching Tsang, Zezhuo Su, Chenzi Zhang, Jun Tang, Yaofeng Wang, Chenqing Zhang, Chi-Kong Li, Guangjin Pan, Bo Feng","doi":"10.1111/liv.70450","DOIUrl":"10.1111/liv.70450","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>The prognosis for patients with hepatocellular carcinoma (HCC) remains suboptimal, despite the rapid advancement of anti-cancer immunotherapy. Chimeric antigen receptor (CAR) T cell therapy targeting glypican-3 (GPC3) has been developed for HCC; however, clinical trials have demonstrated heterogeneous responses among patients and limited CAR-T cell infiltration. Locoregional administration has emerged as a promising strategy for CAR-T therapy against solid tumours, yet its potential for HCC treatment has not been thoroughly explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we constructed anti-GPC3 CAR-T cells and examined their therapeutic efficacy through locoregional and systemic administration using multiple HCC xenograft mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Comparison of CAR-T cell injections via portal vein and tail vein in mice with orthotopic HepG2 tumours demonstrated significantly enhanced tumour growth inhibition with locoregional CAR-T therapy. Consistently, tumour infiltration of CAR-T cells was significantly enhanced by portal vein injection and correlated with increased cytotoxicity, enhanced chemotaxis and reduced exhaustion of the tumour-infiltrating CAR-T cells compared to the tail vein injection group. Treatment with escalating CAR-T cell dosages resulted in further improved functionality of CAR-T cells and treatment efficacy, alongside improved liver function. Furthermore, portal vein injection exhibited superior tumour inhibition compared to tail vein injection in a metastatic model concurrently bearing orthotopic and extrahepatic tumour lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, our study demonstrates that locoregional CAR-T therapy through the portal vein is associated with increased CAR-T cell infiltration and improved therapeutic efficacy, offering promise for the treatment of both early- and late-stage patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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