Introduction The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab (A + B) is equally effective in viral and nonviral patients. Methods We retrospectively analyzed 885 HCC patients treated with the first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% nonviral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multivariate models to explore potential differences on overall survival (OS), time-to-progression (TTP), disease control rates (DCRs) based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to the second-line treatments and outcomes were also reported and compared between etiologies. Results Overall, no statistically significant differences were found in median OS (mOS: viral 15.9 months; nonviral 16.3 months), TTP (mTTP: viral 8.3 months; nonviral 7.2 months), and DCRs (viral 78.1%; nonviral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and nonviral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e., NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of the second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. Conclusion Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and nonviral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.

中文翻译：

---

疾病病因学对接受 Atezolizumab 加贝伐单抗治疗的肝细胞癌患者预后的影响：一项真实世界、多中心研究。


简介 病因学对晚期肝细胞癌 (HCC) 免疫治疗反应的影响正在争论中，IMbrave-150 的早期和近期事后分析与 PD-1/PD-L1 阻断剂临床试验的荟萃分析之间存在对比结果。因此，尚不清楚一线全身治疗阿特珠单抗加贝伐单抗（A + B）对病毒和非病毒患者是否同样有效。方法 我们回顾性分析了来自东西方多个中心的 885 例接受一线 A+B 治疗的 HCC 患者，其中 53.9% 为病毒性病因，46.1% 为非病毒性病因。使用单变量和多变量模型分析基线临床和实验室特征，以探讨基于病因的总生存期 (OS)、进展时间 (TTP)、疾病控制率 (DCR) 的潜在差异，并确定病因中的推定预后因素亚组。还报告了治疗毒性以及二线治疗的获得和结果，并在病因之间进行了比较。结果 总体而言，中位 OS（mOS：病毒性 15.9 个月；非病毒性 16.3 个月）、TTP（mTTP：病毒性 8.3 个月；非病毒性 7.2 个月）和 DCR（病毒性 78.1%；非病毒性 80.8%）没有发现统计学显着差异。病因学。生存和进展的预后因素主要是病毒性和非病毒性病因共有的，包括甲胎蛋白、天冬氨酸转氨酶、中性粒细胞与淋巴细胞比率（NLR）和 ALBI 评分。探索性分析强调了免疫因素（即 NLR 和嗜酸性粒细胞计数）与病毒患者的治疗结果可能存在更强的关联。 两个病因亚组的毒性特征、二线治疗的获得和类型及其 OS 结局几乎重叠。结论 在多中心、真实世界人群中，Atezolizumab 联合贝伐珠单抗的疗效不会根据 HCC 的潜在病因而变化，这与 IMbrave-150 试验的最新事后发现相匹配。初步分析表明，病毒性和非病毒性患者之间的一些预后因素存在差异，这可能是由于生物学和免疫学差异所致。有必要进行按病因分层的前瞻性和比较试验来验证这些发现并指导临床实践。