Celsa Ciro, Cabibbo Giuseppe, Fulgenzi Claudia Angela Maria, Battaglia Salvatore, Enea Marco, Scheiner Bernhard, D'Alessio Antonio, Manfredi Giulia F, Stefanini Bernardo, Nishida Naoshi, Galle Peter R, Schulze Kornelius, Wege Henning, Ciccia Roberta, Hsu Wei-Fan, Vivaldi Caterina, Wietharn Brooke, Lin Ryan Po-Ting, Pirozzi Angelo, Pressiani Tiziana, Dalbeni Andrea, Natola Leonardo A, Auriemma Alessandra, Rigamonti Cristina, Burlone Michela, Parisi Alessandro, Huang Yi-Hsiang, Lee Pei-Chang, Ang Celina, Marron Thomas U, Pinter Matthias, Cheon Jaekyung, Phen Samuel, Singal Amit G, Gampa Anuhya, Pillai Anjana, Roehlen Natascha, Thimme Robert, Vogel Arndt, Soror Noha, Ulahannan Susanna, Sharma Rohini, Sacerdoti David, Pirisi Mario, Rimassa Lorenza, Lin Chun-Yen, Saeed Anwaar, Masi Gianluca, Schönlein Martin, von Felden Johann, Kudo Masatoshi, Cortellini Alessio, Chon Hong Jae, Cammà Calogero, Pinato David James
Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy.
Hepatology. 2025 Mar 1;81(3):837-852. doi: 10.1097/HEP.0000000000001026. Epub 2024 Jul 19.
Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients.
From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a 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 tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma 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. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93).
Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.
与其他恶性肿瘤不同，在决定肝细胞癌（HCC）患者的死亡风险时，肝脏功能储备与肿瘤进展相互竞争。然而，在接受联合免疫治疗的患者中，尚未评估肝失代偿与肿瘤进展对总生存期（OS）影响的相对贡献。
从AB真实世界观察性研究（n = 898）中，我们纳入了571例接受一线阿替利珠单抗+贝伐珠单抗（AB）治疗的Child-Pugh A级晚期/不可切除肝细胞癌患者。使用时间依赖性Cox模型研究随访期间的肝失代偿和肿瘤进展与患者OS的关系。在竞争风险分析中，将基线特征评估为失代偿的预测因素。在中位随访11.0个月（95%CI：5.1 - 19.7）期间，293例患者（51.3%）出现无失代偿的肿瘤进展，94例（16.5%）出现失代偿。在多变量时间依赖性分析中，失代偿（HR：19.04，95%CI：9.75 - 37.19）、肝细胞癌进展（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>3个（HR：1.63，95%CI：1.28 - 2.08）与OS独立相关。治疗前ALBI 2/3级（亚分布风险比[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作用（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著相关（sHR：0.48，95%CI：0.25 - 0.93）。
肝失代偿可识别出接受AB治疗后预后最差的患者，在基线ALBI>1且病因非病毒的患者中更常见。有效的抗病毒治疗可能预防失代偿，凸显了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。
