Wadhawan Manav, Gupta Charu
Institute of Digestive & Liver Diseases, BLK Superspeciality Hospital Delhi, India.
J Clin Exp Hepatol. 2023 Jul-Aug;13(4):691-697. doi: 10.1016/j.jceh.2023.01.003. Epub 2023 Jan 9.
The liver is well known for its immunotolerance, but rejection without immunosuppression is frequently encountered post liver transplantation, especially in humans. Indeed, the amount of immunosuppression required post liver transplant is less compared to other organ transplants like kidney, heart, and intestine. Reports of successful weaning of immunosuppression have been reported but are not practiced for fear of unwanted alloimmune response leading to rejection. Life-long immunosuppression is needed in most patients for graft survival but is associated with side effects like renal dysfunction, metabolic abnormalities, or risk of malignancies. Also, the appropriate dose of immunosuppression to achieve adequate graft function and prevention of toxicities is very important. One shoe does not fit all. There are significant individual variations in response and side effect profile. Also, the level of immunosuppression varies with the underlying liver disease like autoimmune disease requires higher immunosuppression. Thus, monitoring the adequate immunosuppression with the minimization of drug toxicity is imperative post-transplant. Unfortunately, the current methods for immunosuppression monitoring rely on testing the immunosuppressive drug levels rather than the immune system activity. We have discussed the concept of alloreactivity, available methods of immunosuppression and drug monitoring and investigational methods in this review.
肝脏以其免疫耐受性而闻名，但肝移植后尤其是在人类中经常会遇到无免疫抑制情况下的排斥反应。事实上，与肾、心脏和肠道等其他器官移植相比，肝移植后所需的免疫抑制量较少。已有免疫抑制成功撤减的报道，但由于担心不必要的同种异体免疫反应导致排斥反应，这些方法并未得到实际应用。大多数患者为了移植物存活需要终身免疫抑制，但这会带来诸如肾功能障碍、代谢异常或恶性肿瘤风险等副作用。此外，为实现足够的移植物功能并预防毒性而使用合适剂量的免疫抑制非常重要。并非一种方法适用于所有人。在反应和副作用方面存在显著的个体差异。而且，免疫抑制水平会因潜在的肝脏疾病而有所不同，例如自身免疫性疾病需要更高的免疫抑制。因此，移植后监测足够的免疫抑制并将药物毒性降至最低至关重要。不幸的是，目前免疫抑制监测方法依赖于检测免疫抑制药物水平而非免疫系统活性。在本综述中，我们讨论了同种异体反应性的概念、可用的免疫抑制和药物监测方法以及研究方法。
