Background&aims: Unlike other malignancies, hepatic functional reserve competes with tumour progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumour progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients. Approach&Results: From the AB-real observational study(n=898), we accrued 571 patients with advanced/unresectable HCC, Child-Pugh A class treated with frontline atezolizumab+bevacizumab(AB). Hepatic decompensation and tumour progression during follow-up were studied in relationship to patients’ OS using time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95%CI 5.1-19.7), 293 patients(51.3%) developed tumour progression without decompensation and 94(16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation(hazard ratio[HR] 19.04, 95%CI 9.75-37.19), HCC progression(HR 9.91, 95%CI 5.85-16.78), albumin-bilirubin(ALBI) grade 2/3(HR 2.16, 95%CI 1.69-2.77) and number of nodules>3(HR 1.63, 95%CI 1.28-2.08) were independently associated with OS. Pre-treatment ALBI grade 2/3(subdistribution HR [sHR] 3.35, 95%CI 1.98-5.67) was independently associated with decompensation, whereas viral aetiology was protective(sHR 0.55, 95%CI 0.34-0.87). Among patients with viral aetiology, effective antiviral treatment was significantly associated with lower risk of decompensation (sHR 0.48, 95%CI 0.25-0.93). Conclusions: Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI>1 and non-viral aetiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with non-viral aetiologies and the importance of multi-disciplinary management to maximise OS.

中文翻译：

---

肝代偿失调是接受阿特珠单抗联合贝伐珠单抗治疗的肝细胞癌患者死亡的主要原因：成功抗病毒治疗的影响


背景与目的：与其他恶性肿瘤不同，肝功能储备与肿瘤进展竞争决定肝细胞癌（HCC）的死亡风险。然而，尚未在联合免疫治疗接受者中评估肝代偿失调对肿瘤进展在影响总生存期（OS）方面的相对贡献。方法和结果：从 AB 真实观察性研究（n=898）中，我们收集了 571 例接受一线阿替利珠单抗+贝伐单抗（AB）治疗的 Child-Pugh A 级晚期/不可切除 HCC 患者。使用时间依赖性 Cox 模型研究了随访期间的肝代偿失调和肿瘤进展与患者 OS 的关系。在竞争风险分析中评估基线特征作为失代偿的预测因子。在中位随访时间为 11.0 个月 (95%CI 5.1-19.7) 期间，293 名患者 (51.3%) 出现肿瘤进展但没有失代偿，94 名患者 (16.5%) 出现失代偿。在多变量时间依赖性分析中，失代偿（风险比[HR] 19.04，95%CI 9.75-37.19），HCC进展（HR 9.91，95%CI 5.85-16.78），白蛋白-胆红素（ALBI）2/3级（HR 2.16，95%CI 1.69-2.77）和结节数量>3（HR 1.63，95%CI 1.28-2.08）与 OS 独立相关。治疗前 ALBI 2/3 级（亚分布 HR [sHR] 3.35，95%CI 1.98-5.67）与失代偿独立相关，而病毒病因具有保护性（sHR 0.55，95%CI 0.34-0.87）。在病毒病因患者中，有效的抗病毒治疗与较低的失代偿风险显着相关（sHR 0.48，95%CI 0.25-0.93）。结论：肝代偿失调是 AB 后预后最差的患者，并且在基线 ALBI > 1 和非病毒病因的患者中更为常见。 有效的抗病毒治疗可以防止失代偿，突显非病毒病因患者的预后劣势以及多学科管理对最大化 OS 的重要性。