1. The Impact of Biliary Injury on the Recurrence of Biliary Cancer and Benign Disease after Liver Transplantation: Risk Factors and Mechanisms.
- Author
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Wehrle, Chase J., Panconesi, Rebecca, Satish, Sangeeta, Maspero, Marianna, Jiao, Chunbao, Sun, Keyue, Karakaya, Omer, Allkushi, Erlind, Modaresi Esfeh, Jamak, Whitsett Linganna, Maureen, Ma, Wen Wee, Fujiki, Masato, Hashimoto, Koji, Miller, Charles, Kwon, David C. H., Aucejo, Federico, and Schlegel, Andrea
- Subjects
BILE duct tumors ,BILIOUS diseases & biliousness ,CANCER relapse ,REPERFUSION injury ,CHOLANGIOCARCINOMA ,IMMUNOCOMPROMISED patients ,BILE duct diseases ,CELLULAR signal transduction ,REACTIVE oxygen species ,CANCER chemotherapy ,INFLAMMATION ,LIVER transplantation ,DISEASE risk factors ,DISEASE complications - Abstract
Simple Summary: Ischemia-reperfusion injury (IRI) is the source of significant graft inflammation in liver transplantation. Such injuries can lead to increased recurrence of both benign and malignant diseases of the biliary tree after transplant. Herein, we review the mechanisms and risk factors for the link between IRI and biliary recurrence, as well as evidence for strategies to mitigate this damage. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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