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2026年欧洲肝病学会年会（EASL 2026）于2025年5月27日-30日在西班牙•巴塞罗那召开。作为全球肝病学领域的学术盛会，本届大会汇聚国际顶尖专家学者，共同探讨肝病学、胃肠病学、移植外科及传染病学等领域的最新研究进展与临床实践突破。
大会设置前沿学术报告、高互动性研讨会及专题论坛，为与会者提供深度交流与专业提升的高端平台。为及时传递大会精华内容，肝胆相照平台全程跟踪报道。本篇精选肝癌(HCC)领域热点研究进行整理，以传递大会的最新动态和精彩看点。
研究一 OS-053
粪菌微生物移植联合阿替利珠单抗及贝伐珠单抗治疗对阿替利珠单抗/贝伐珠单抗耐药的肝细胞癌：开放标签、单臂 FAB-HCC 试点研究最终结果
Fecal microbiota transplantation combined with atezolizumab plus bevacizumab in hepatocellular carcinoma refractory to atezolizumab plus bevacizumab: final results of the open-label, single-arm, FAB-HCC pilot study
Authors：
Katharina Pomej, Adrian Frick, Bernhard Scheiner, Maximilian Baumgartner, Klaus Schmetterer, Lorenz Balcar, Larissa Pajancic, Abelina Kreuter, Petra Pjevac, Joana Silva, Bela Hausmann, Thomas Köcher, Carlos Reyna-Blanco, Katharina Lampichler, Nataliya Rohr-Udilova, Adrija Chakrabarty, Anton Klotz, Annika Lampl, Kerstin Zinober, Katharina Regnat, Michael Trauner, David Berry, Thomas Vogl, Dietmar Tamandl, Christoph Gasche, Matthias Pinter
▼ 背景与目的
近年来研究发现，调节肠道微生态（如粪菌微生物移植，FMT）可能有助于克服免疫检查点抑制剂耐药。本研究旨在评估：FMT 联合阿替利珠单抗（atezolizumab）及贝伐珠单抗（bevacizumab）治疗，对既往阿替利珠单抗/贝伐珠单抗治疗失败的晚期肝细胞癌（HCC）患者的安全性及疗效。
Modulation of the gut microbiome, such as fecal microbiota transplantation (FMT), may help overcome resistance to immune checkpoint inhibitors.
▼ 方法
本研究为单中心、开放标签、单臂试点研究（ClinicalTrials.gov：NCT05750030）。研究纳入既往接受阿替利珠单抗联合贝伐珠单抗治疗后进展的晚期 HCC 患者。所有患者通过结肠镜接受一次粪菌移植（FMT），供体来源包括对抗 PD-1 治疗有应答的 HCC 患者或健康供体，同时联合每 3 周一次的阿替利珠单抗/贝伐珠单抗治疗。主要终点为安全性，即治疗相关不良事件（TRAEs）的发生率及严重程度；主要次要终点为依据 mRECIST 与 RECIST v1.1 标准评估的最佳客观缓解率。
研究还进行了探索性分析，纵向采集患者血液及粪便样本。粪便样本接受 16S rRNA 测序及 HPLC-MS 代谢组学分析；扩增子测序变异采用 DESeq2 分析，代谢物及菌群丰度差异采用 Maaslin2 分析。外周血单个核细胞通过 CYTOFlex 流式细胞术分析。此外，研究采用噬菌体展示免疫共沉淀测序技术，对患者血浆中针对肠道菌群及环境抗原的系统性 IgG 表位谱进行分析，所用噬菌体文库包含 357,000 条多肽。
In this single-center, single-arm pilot study (ClinicalTrials.gov ID: NCT05750030), patients with advanced hepatocellular carcinoma (HCC) who had progressed on atezolizumab plus bevacizumab were enrolled. Patients received a single FMT via colonoscopy from either an anti-PD-1-responsive HCC donor or a healthy donor, combined with atezolizumab/bevacizumab every 3 weeks.
The primary endpoint was safety, assessed by the incidence and severity of treatment-related adverse events (TRAEs). The main secondary endpoint was best overall response according to mRECIST and RECIST v1.1.
For exploratory analyses, blood and stool samples were collected longitudinally. Stool samples underwent 16S rRNA sequencing and HPLC-MS metabolomics analysis. Amplicon-sequencing variants were analyzed using DESeq2, while differential abundance of metabolites and bacterial taxa was assessed using Maaslin2. Peripheral blood mononuclear cells were analyzed using CYTOFlex flow cytometry. Phage-display immunoprecipitation sequencing was performed on plasma samples to profile systemic IgG epitope repertoires against gut microbiota and environmental antigens using a phage library containing 357,000 peptides.
▼ 结果
2023 年 8 月至 2024 年 11 月期间，共纳入 12 例患者，其中男性 10 例；Child-Pugh A 级 11 例；BCLC C 期 10 例。3–4 级治疗相关不良事件包括动脉高血压（n=5）和蛋白尿（n=3），均与贝伐珠单抗相关；另有 1 例腹泻与 FMT 相关。研究未观察到严重治疗相关不良事件。
依据 mRECIST 与 RECIST v1.1 标准评估，客观缓解率（ORR）分别达到 33% 与 25%。依据 mRECIST 标准，中位无进展生存期（PFS）为 6.9 个月（95%CI：3.0–10.8）；依据 RECIST v1.1 标准，中位 PFS 为 4.3 个月（95%CI：0.2–8.5）。
FMT 后，受体肠道菌群显著向供体菌群方向转变。与来源于抗 PD-1 应答患者的供体相比，健康供体来源的 FMT 具有更高的菌群植入效率，同时部分患者粪便及血浆中胆汁酸水平升高。
治疗应答患者在基线时具有更高比例的外周 naïve CD4+ CD45RA+ T 细胞；FMT 后，部分 T 细胞及单核细胞亚群也出现变化趋势。此外，应答患者在 FMT 后系统性 IgG 抗体反应谱变化更加明显，提示其体液免疫反应发生了更显著的早期重塑。
Between August 2023 and November 2024, 12 patients were enrolled (10 males; 11 Child-Pugh A; 10 BCLC stage C). Grade 3–4 TRAEs included arterial hypertension (n = 5) and proteinuria (n = 3), both related to bevacizumab, and diarrhea (n = 1), related to FMT. No serious TRAEs were observed.
The objective response rate according to mRECIST and RECIST v1.1 was 33% and 25%, respectively. Median progression-free survival was 6.9 months (95% CI, 3.0–10.8) according to mRECIST and 4.3 months (95% CI, 0.2–8.5) according to RECIST v1.1.
FMT resulted in a significant shift of the recipient microbiome toward the donor microbiome. Healthy-donor FMT was associated with higher engraftment compared with anti-PD-1-responder donor FMT, along with increased fecal and plasma concentrations of certain bile acids in recipients.
Responders had a higher proportion of peripheral naïve CD4+ CD45RA+ T cells at baseline, and trends were observed in specific T-cell and monocyte populations after FMT. Responders also demonstrated greater shifts in systemic IgG antibody reactivity after FMT, consistent with a more pronounced early remodeling of humoral immune responses.
▼ 结论
FMT 联合阿替利珠单抗及贝伐珠单抗治疗，在阿替利珠单抗/贝伐珠单抗耐药的肝细胞癌患者中表现出良好的安全性，并取得了较高的客观缓解率。这一结果提示，肠道微生态调控可能成为克服免疫治疗耐药的重要新策略。
FMT combined with atezolizumab plus bevacizumab was safe and achieved a high response rate in patients with atezolizumab/bevacizumab-refractory HCC.
研究二 FRI-221
阿替利珠单抗-贝伐珠单抗与度伐利尤单抗-替西木单抗治疗晚期肝细胞癌：总生存期相似，但疗效应答与安全性存在差异
Similar overall survival but distinct response and safety profiles with Atezolizumab-Bevacizumab versus Durvalumab-Tremelimumab in advanced HCC
Authors：
Claudia Campani¹, Victor Caudart², Lou-Devy Rouxel³, Yann Touchefeu⁴, Giuliana Amaddeo⁵, Chloe Metivier⁶, Leila Sadek⁷, Marie Lequoy⁸, Anna Pellat⁹, Apolline Commin⁶, Nathalie Ganne-Carrié¹, Clemence Hollande², Sarah Mouri³, Pierre Malherbe⁴, Hélene Regnault⁵, Jean Marie Peron⁷, Violaine Ozenne⁸, Lucia Parlati⁹, Sabrina Sidali¹, Paul Vigneron⁵, Cecile Cussac⁷, Romain Coriat⁴, Isabelle Ollivier-Hourmand⁶, Mathilde Wagner³, Jean-Charles Nault¹, Manon Allaire³, Mohamed Bouattour²
▼ 背景与目的
基于免疫治疗的联合方案已成为晚期肝细胞癌（HCC）的一线标准治疗，其中阿替利珠单抗联合贝伐珠单抗（AtezoBev）以及度伐利尤单抗联合替西木单抗（DurvaTreme）均为指南推荐方案。然而，目前关于两种方案之间真实世界比较数据仍较有限。本研究旨在比较 AtezoBev 与 DurvaTreme 在临床结局、肿瘤应答及安全性方面的差异。
Immunotherapy-based combinations are the standard first-line treatment for advanced hepatocellular carcinoma (HCC), with atezolizumab–bevacizumab (AtezoBev) and durvalumab–tremelimumab (DurvaTreme) recommended options. Comparative real-world data between these regimens remain limited. We compared clinical outcomes, tumor response, and safety of AtezoBev versus DurvaTreme.
▼ 方法
本研究为一项多中心（9家中心）回顾性研究，纳入接受一线 AtezoBev 或 DurvaTreme 治疗的患者，并采用倾向评分进行 1:1 匹配。研究分析了总生存期（OS）、无进展生存期（PFS）、疾病控制率（DCR）、客观缓解率（ORR）以及不良事件。
This multicenter retrospective study (9 centers) included patients treated with first-line AtezoBev or DurvaTreme. Patients were matched 1:1 using propensity scores. Overall survival (OS), progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and adverse events were analyzed.
▼ 结果
共纳入 1053 例患者，其中 908 例接受阿替利珠单抗-贝伐珠单抗治疗，145 例接受度伐利尤单抗-替西木单抗治疗。经倾向评分匹配后，共有 280 例患者进入最终分析。两组基线特征较为平衡：约 60% 为 BCLC C 期，35% 存在血管侵犯，28% 存在肝外转移，60% 为 Child–Pugh A 级，24% 为 ALBI 1级。
中位随访时间为 20.1 个月时，AtezoBev 与 DurvaTreme 的总生存期（OS）相似（中位 OS：20.8个月 vs 未达到；p = 0.25）；但 AtezoBev 组的无进展生存期（PFS）更长（8.2个月 vs 4.7个月；p = 0.006）。
在首次影像学评估及最佳影像学评估时，AtezoBev 组的疾病控制率（DCR）均明显更高（首次评估：80.2% vs 52.4%；最佳评估：81.0% vs 54.1%；均 p < 0.001），而两组客观缓解率（ORR）无显著差异。
多因素分析显示，较高的基线白蛋白水平与更好的 OS 和 PFS 独立相关。治疗方案本身与 OS 无显著相关性，但 DurvaTreme 与疾病进展风险增加独立相关（HR 1.49，p = 0.006）。
此外，≥3个肿瘤结节与较低 ORR 独立相关（OR 0.51，p = 0.031），DurvaTreme 同样与 ORR 降低相关（OR 0.52，p = 0.038）。
分层分析显示，在 AtezoBev 队列中，≥3个肿瘤结节与 ORR 显著降低相关（OR 0.37，p = 0.017）；而在 DurvaTreme 队列中，MASLD 与 ORR 降低相关（OR 0.33，p = 0.033）。
Among 1053 patients (908 treated with atezolizumab–bevacizumab and 145 with durvalumab–tremelimumab), 280 patients were included after matching. Baseline characteristics were well balanced between groups: approximately 60% had BCLC stage C disease, 35% had vascular invasion, 28% had extrahepatic spread, 60% were Child–Pugh class A, and 24% were ALBI grade 1. After a median follow-up of 20.1 months, OS was similar between AtezoBev and DurvaTreme (median 20.8 months vs. not reached; p = 0.25), while PFS was longer with AtezoBev (8.2 vs. 4.7 months; p = 0.006). DCR was higher with AtezoBev at first (80.2% vs. 52.4%) and best imaging response (81.0% vs. 54.1%; both p < 0.001), whereas ORR did not differ. Higher baseline albumin was independently associated with improved OS and PFS. Treatment type was not associated with OS, but DurvaTreme was independently associated with increased risk of progression (HR 1.49, p = 0.006). The presence of ≥3 tumor nodules was independently associated with lower ORR (OR 0.51, p = 0.031), and DurvaTreme was also associated with reduced ORR (OR 0.52, p = 0.038). In treatment-stratified analyses, ≥3 tumor nodules were associated with a significantly lower ORR in the AtezoBev cohort (OR 0.37, p = 0.017), while MASLD was associated with reduced ORR in the DurvaTreme cohort (OR 0.33, p = 0.033).
▼ 结论
研究结果提示，晚期 HCC 一线免疫治疗方案的选择应结合肝功能、肿瘤负荷及患者个体特征进行精准化决策。未来仍需进一步研究预测疗效反应的相关因素，以优化晚期肝细胞癌患者的治疗选择。
These findings support a tailored selection of first-line immunotherapy in advanced HCC based on liver function, tumor burden, and patient-specific characteristics. Further studies are needed to identify predictive factors of response in order to optimize treatment selection.
研究三 FRI-225
度伐利尤单抗–替西木单抗治疗晚期肝细胞癌：来自 LOR-HCC（意大利伦巴第真实世界 HCC 研究组）的真实世界数据
Durvalumab–Tremelimumab in advanced hepatocellular carcinoma: real-world data from the LOR-HCC (Lombardy, Italy real-world HCC group)
Authors：
Andrea Casadei Gardini¹, Lorenzo Canova², Chiara Mazzarelli³, Silvia Camera¹, Elisa Bocchero⁴˒⁵, Pietro Pozzoni⁶, Sara Vavassori⁷, Salvatore Corallo⁸, Massimo De Giorgio⁹, Anna Maria Stagno¹⁰, Giulia Grizzi¹¹, Rita Cengarle¹², Gianluca Tomasello¹³, Mariangela Bruccoleri¹⁴, Katia Bencardino¹⁵, Mara Persano¹, Martina Pino⁴˒⁵, Alessia Riva⁶, Martina Torchio¹⁶, Elena Rota Caremoli¹⁷, Lorenzo Argiento¹⁴, Federica Tosi¹⁵, Margherita Rimini¹, Tiziana Pressiani⁵, Lorenza Rimassa⁴˒⁵, Massimo Iavarone¹⁴˒¹⁸
▼ 背景与目的
替西木单抗联合度伐利尤单抗（STRIDE 方案）的双免疫检查点阻断治疗已成为不可切除肝细胞癌（uHCC）的一线标准治疗方案。然而，目前关于其安全性、毒性发生时间特征以及肝功能动态变化的真实世界数据仍较有限。本研究旨在评估 STRIDE 方案在日常临床实践中的耐受性、治疗期间肝功能变化及临床疗效。
Dual immune checkpoint blockade with tremelimumab plus durvalumab (STRIDE) is an established first-line therapy for unresectable hepatocellular carcinoma (uHCC), but real-world evidence on safety, toxicity kinetics, and liver function dynamics remains limited. We aimed to evaluate tolerability, on-treatment changes in hepatic function, and effectiveness in a multicenter cohort of patients treated with STRIDE in routine clinical practice.
▼ 方法
本研究为一项回顾性分析，纳入意大利伦巴第地区 12 家中心连续收治的 115 例接受 STRIDE 治疗的 uHCC 患者，相关数据为前瞻性收集。研究记录了患者基线及治疗期间的临床、生化及影像学指标。不良事件依据 CTCAE v5.0 标准进行分级，并采用 Child–Pugh 分级评估肝功能变化。毒性发生的时间模式采用平滑风险函数进行分析。同时评估无进展生存期（PFS）、总生存期（OS）以及疾病进展与死亡的竞争风险累积发生率。
We conducted a retrospective analysis of prospectively collected data from 115 consecutive patients with uHCC treated with STRIDE across 12 centers in Lombardy, Italy. Clinical, biochemical, and radiological variables were recorded at baseline and throughout therapy. Adverse events were graded according to CTCAE v5.0, and Child–Pugh classification was used to assess hepatic functional evolution. Temporal toxicity patterns were evaluated using smoothed hazard functions. Progression-free survival (PFS), overall survival (OS), and competing-risk cumulative incidence of progression and death were analyzed.
▼ 结果
中位随访时间为 8.9 个月。超过 80% 的不良事件发生于治疗最初 2 个月内，而严重毒性事件较少见。从基线至第 28 天，7.8% 的患者 Child–Pugh 分级由 A 级进展为 B 级；至第 56 天时，该比例增加至 12.1%。
中位无进展生存期（PFS）为 5.7 个月。中位总生存期（OS）尚未达到，6 个月 OS 率为 78.2%，18 个月 OS 率为 53.3%。
疾病进展是最主要的早期事件，6 个月时疾病进展的累积发生率为 49.2%。
Median follow-up was 8.9 months. More than 80% of adverse events occurred within the first 2 months, while severe toxicities were infrequent. Child–Pugh deterioration from class A to B occurred in 7.8% of patients from baseline to day 28, increasing to 12.1% by day 56. Median PFS was 5.7 months. Median OS was not reached, with OS rates of 78.2% at 6 months and 53.3% at 18 months. Disease progression was the predominant early event, with a cumulative incidence of 49.2% at 6 months.
▼ 结论
在真实世界临床实践中，STRIDE 方案展现出可重复验证的疗效及可控的安全性特征。不良事件主要集中于治疗早期发生，随后趋于稳定。动态肝功能评估显示，部分患者在治疗过程中出现轻度但具有临床意义的肝功能下降。
In routine clinical practice, STRIDE demonstrated reproducible effectiveness and a manageable safety profile, with adverse events clustering early during treatment and stabilizing thereafter. Dynamic assessment of liver function showed that hepatic function declined modestly overall, but this deterioration remained clinically meaningful in affected patients.