PDF(Pubmed)
Abstract：
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.
摘要：
肝切除术后肝功能衰竭（PHLF）仍然是肝切除术后死亡的主要原因。氧化应激与术后并发症有关，但其对肝功能的影响尚不清楚。这是第一个在人类中，prospective,单中心,观察性试验研究根据ISGLS（国际肝脏外科研究小组）评估围手术期氧化应激和PHLF。血清8-异前列腺素，4-羟基壬烯醛（4-HNE），总抗氧化能力，维生素A和E,术中，顺序肝组织4-HNE和UCP2（解偶联蛋白2）免疫组织化学（IHC）进行评估。分析了与已知PHLF危险因素的相互作用以及氧化应激标志物的预测潜力。总的来说,包括52例患者（69.2％的主要肝切除）。13例患者（25%）经历过PHLF，90天死亡率的主要因素(23%vs.0%；p=0.013）。切除后,促氧化8-异前列腺素显著增加(p=0.038)，而4-HNE立即下降(p<0.001)。抗氧化标记物显示切除术后开始的消耗模式(p<0.001)。从剖腹手术后的活检到切除后的原位肝和切除标本，肝组织氧化应激逐步增加（所有p<0.001）。胆管癌患者在不同时间点表现出显著较高的血清和组织氧化应激水平，在晚期肿瘤阶段，术前值始终较高。结合术中，切除后4-HNE血清水平和原位IHC早期预测的PHLF，AUC为0.855（63.6％vs.0%；p<0.001)。这也与B/C级PHLF（36.4%与0%；p=0.021）和90天死亡率（18.2%vs.0%；p=0.036）。总之,肝功能障碍患者围手术期氧化应激水平的不同模式.结合术中血清和肝组织标志物可预测随后的PHLF。胆管癌患者表现出明显的全身和肝脏氧化应激，随着肿瘤晚期水平的增加，因此代表了未来探索性和治疗性研究的一个有价值的目标.
