1. IntroductionLiver transplantation is a life-saving procedure for patients with end-stage liver disease or acute liver failure. Despite advancements in surgical techniques and postoperative care, transplant recipients still face significant challenges, notably antibody-mediated rejection (AMR). AMR in liver transplantation poses a unique set of complexities and implications for patient management and graft survival. Estimates of its incidence vary, with reports indicating it to be between 0.3% to 2% [1]. This lower incidence is thought to be due to the liver’s unique anatomy and its characteristic as an ”immune-privileged” organ, which makes it less susceptible to AMR compared to organs like the heart (10–20% incidence) and kidney (20–50% incidence) [2].AMR occurs when the recipient’s immune system produces antibodies against the donor liver, specifically targeting human leukocyte antigens (HLAs) present on the donor organ. These antibodies, known as donor-specific antibodies (DSAs), are key players in the process of AMR, leading to graft injury and potentially graft loss if not promptly and effectively managed [3]. A previous study reported 13% of liver transplant recipients had DSAs at a median of 51 months post-transplant, and 9% developed de novo DSAs at a median of 36.5 months after the first screening [4]. Likewise, another study reported that preformed DSAs were found in 4.7% of patients, while 19.9% developed de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years) post-transplant [5]. The liver’s unique immunological environment often results in a more tolerogenic response compared to other organs, yet cases of severe AMR, particularly in the presence of high levels or specific subclasses of DSAs, have been documented [6].DSAs can either be preformed, existing in the recipient’s blood before transplantation, or de novo, developing after the transplant. Preformed DSAs are typically detected in patients who have been previously sensitized, such as through blood transfusions, previous transplants, or pregnancies. De novo DSAs, however, arise post-transplantation and are associated with various risk factors, including inadequate immunosuppression and immune system activation by infections or graft damage [7]. The development of de novo DSAs is particularly concerning as they have been linked to chronic rejection and long-term graft dysfunction. Diagnosing AMR in liver transplant recipients involves detecting DSAs in conjunction with histopathological examination of liver biopsy samples. Typical findings include C4d deposition, a complement degradation product, in the liver tissue, indicating antibody involvement in the graft injury. However, the diagnosis of AMR remains challenging due to the variable presentation and sometimes indistinct histological features, especially in chronic cases [2].The aim of this review is to synthesize current knowledge and recent advancements in the understanding of AMR in liver transplantation, with a particular focus on the role and impact of DSAs. We will examine the pathogenesis, clinical presentation, diagnostic criteria, and management strategies for AMR, as well as discuss the challenges and future directions in research and clinical practice. Understanding the intricacies of DSAs and their role in AMR is crucial for the development of targeted therapies and the improvement of graft survival and patient outcomes in liver transplantation.
