Background: Atezolizumab plus bevacizumab is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). Immune-related liver injury (IrLI) is common; however, the association between IrLI severity and patient outcomes remains unknown. This study aimed to investigate the prognostic value of irLI in such patients. Methods: One hundred and sixteen patients who fulfilled the IMBrave150 inclusion criteria were enrolled. IrLI was defined as an increase in serum ALT and/or AST levels attributed to treatment and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 61 patients (52.6%) developed any grade of irLI, with a median onset time of 1.7 months. Multivariate analysis revealed that grade II ALBI (hazard ratio [HR] = 2.003,p= 0.028) and BCLC stage C (HR = 3.876,p= 0.016) were associated with worse OS and PFS (HR = 1.327,p= 0.044 and HR = 1.790,p= 0.039, respectively), whereas grade 2 irLI was associated with better OS (HR = 0.223,p= 0.046) and PFS (HR = 0.244,p= 0.011). Patients with grade 2 irLI showed better median OS (not reached) than those without irLI (16.7 months), those with grade 1 (17.5 months), and those with grade ≥ 3 (7.3 months) (overall log-rankp= 0.037). Furthermore, patients with grade 2 irLI demonstrated significantly enhanced PFS (not reached) compared to those without irLI (5.7 months), grade 1 (4.6 months), or grade ≥ 3 (2.3 months), with an overall log-rankp= 0.010. In addition, patients with grade 2 irLI had the highest disease control rate (overallp= 0.053). Conclusion: In patients with uHCC treated with Ate/Bev, moderate elevation of liver enzymes (grade 2 irLI) was associated with significantly improved survival and tumor control.
背景：阿替利珠单抗联合贝伐珠单抗是不可切除肝细胞癌（uHCC）的标准一线治疗方案。免疫相关肝损伤（IrLI）较为常见，但其严重程度与患者预后的关系尚不明确。本研究旨在探讨IrLI对此类患者的预后价值。 方法：纳入符合IMBrave150研究入组标准的116例患者。IrLI定义为治疗引起的血清ALT和/或AST水平升高，并根据美国国家癌症研究所不良事件通用术语标准5.0版进行分级。 结果：共有61例患者（52.6%）发生任何级别的IrLI，中位发生时间为1.7个月。多因素分析显示，ALBI 2级（风险比[HR]=2.003，p=0.028）和BCLC C期（HR=3.876，p=0.016）与较差的总生存期（OS）和无进展生存期（PFS）相关（分别为HR=1.327，p=0.044和HR=1.790，p=0.039），而2级IrLI与更好的OS（HR=0.223，p=0.046）和PFS（HR=0.244，p=0.011）相关。与未发生IrLI（16.7个月）、1级IrLI（17.5个月）及≥3级IrLI（7.3个月）的患者相比，2级IrLI患者的中位OS（未达到）更优（总对数秩p=0.037）。此外，2级IrLI患者的PFS（未达到）显著优于未发生IrLI（5.7个月）、1级（4.6个月）或≥3级（2.3个月）患者，总对数秩p=0.010。同时，2级IrLI患者的疾病控制率最高（总p=0.053）。 结论：在接受阿替利珠单抗联合贝伐珠单抗治疗的uHCC患者中，中度肝酶升高（2级IrLI）与显著改善的生存期和肿瘤控制相关。
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