Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue’s ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.
肝移植已知会基于代谢谱及组织从缺血再灌注损伤中恢复的能力，在整个器官中引发显著炎症。这一级联反应导致移植后并发症，影响肝脏合成功能（即时）及胆道树瘢痕形成。新发胆道狭窄以及恶性与良性肝病（如胆管癌和原发性硬化性胆管炎）的复发，均与此炎症直接相关。琥珀酸等毒性代谢物的积累导致电子无序流动，引发功能严重失调的线粒体复合体I释放活性氧。这启动了炎症性缺血再灌注损伤级联反应，继而引发缺血性胆道狭窄及促肿瘤信号通路上调。此类炎症兼具局部性与全身性，可促进免疫抑制状态，导致潜在恶性或良性肝病复发。胆管癌的传统治疗方式在可行时首选切除术，随后进行细胞毒性化疗。肝移植肿瘤学日益被视为肝内胆管癌和肝门部胆管癌患者的潜在根治性疗法。在肝细胞癌的移植肿瘤学中，缺血再灌注损伤与疾病复发之间的关联已得到日益广泛的认识。然而，由于病例数量较少，针对胆管癌的类似分析尚未充分开展。该机制关联在此疾病中可能更为关键，因为缺血再灌注损伤对肝内胆管造成的损害最为严重。本文综述了肝移植后胆道炎症与胆道病理的相关机制，重点关注移植相关缺血再灌注损伤炎症与胆管癌及胆道树良性肝病复发之间的关联，并对风险因素与保护策略进行重点探讨。
肿瘤(癌症)患者之家