Lu Jingming, Wang Fumin, Zhang Wei, Ren Yaoxing, Yang Tian, Ratti Francesca, Marques Hugo P, Silva Silvia, Soubrane Olivier, Lam Vincent, Poultsides George A, Popescu Irinel, Grigorie Razvan, Alexandrescu Sorin, Martel Guillaume, Workneh Aklile, Guglielmi Alfredo, Hugh Tom, Aldrighetti Luca, Endo Itaru, Lyu Yi, Zhang Xu-Feng, Pawlik Timothy M
Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
School of Future Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Ann Surg Oncol. 2025 Apr;32(4):2446-2455. doi: 10.1245/s10434-024-16705-8. Epub 2024 Dec 27.
We sought to define whether and how hepatic ischemia/reperfusion (I/R) as manifested by perioperative aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels impact long-term outcomes after curative-intent resection of hepatocellular carcinoma (HCC).
Intrasplenic injection of HCC cells was used to establish a murine model of HCC recurrence with versus without I/R injury. Patients who underwent curative resection for HCC were identified from a multi-institutional derivative cohort (DC) and separate external validation (VC) cohort. Perioperative changes of transaminase levels were examined relative to the recurrence-free (RFS) and overall survival (OS) among patients following HCC resection.
Mice exposed to hepatic I/R injury were more likely to experience tumor recurrence, as well as higher luminescence signal intensity (all p < 0.05) versus mice with no I/R injury. Relative changes between AST and ALT (sum of AST/ALT ratios, SAAR) on postoperative day (POD) 1 and POD 3 were calculated using the formula: via Fourier transform theory. Among 734 patients in DC, the median SAAR was 2.1. After adjusting for other competing risk factors, SAAR 2.0 remained strongly associated with risk of postoperative recurrence (ref. SAAR < 2.0, HR 1.32, p = 0.03), whereas SAAR 3.5 was associated with risk of postoperative mortality (ref. SAAR < 3.5, HR 1.86, p < 0.01). SAAR demonstrated good accuracy to predict postoperative recurrence (c-index 0.724, 0.731) and mortality (c-index 0.655, 0.765) in DC and VC, respectively.
Use of routine labs such as AST and ALT can help identify patients at high risk of recurrence and mortality following HCC resection.
我们试图确定围手术期天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平所表现出的肝脏缺血/再灌注（I/R）是否以及如何影响肝细胞癌（HCC）根治性切除术后的长期预后。
通过脾内注射肝癌细胞建立有或无I/R损伤的肝癌复发小鼠模型。从一个多机构衍生队列（DC）和单独的外部验证（VC）队列中识别接受肝癌根治性切除的患者。研究了肝癌切除术后患者转氨酶水平的围手术期变化与无复发生存期（RFS）和总生存期（OS）的关系。
与未发生I/R损伤的小鼠相比，遭受肝脏I/R损伤的小鼠更易发生肿瘤复发，且发光信号强度更高（所有p<0.05）。术后第1天（POD 1）和第3天（POD 3）AST与ALT的相对变化（AST/ALT比值之和，SAAR）采用公式：通过傅里叶变换理论计算得出。在DC队列的734例患者中，SAAR中位数为2.1。在调整其他竞争风险因素后，SAAR≥2.0仍与术后复发风险密切相关（参考SAAR<2.0，HR 1.32，p=0.03），而SAAR≥3.5与术后死亡风险相关（参考SAAR<3.5，HR 1.86，p<0.01）。SAAR在DC队列和VC队列中分别对术后复发（c指数0.724，0.731）和死亡（c指数0.655，0.765）具有良好的预测准确性。
使用AST和ALT等常规实验室检查有助于识别肝癌切除术后复发和死亡风险高的患者。
