Gordon R D, Starzl T E
Department of Surgery, University of Pittsburgh, PA.
Clin Transpl. 1988:5-27.
After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.
对于癌症患者进行肝移植后,大多数肿瘤在18至36个月内疾病复发率很高,尽管有少数长期存活者。在匹兹堡,对于仅通过肝移植未能成功治疗的病变,正在尝试进行上腹部内脏的扩大切除并用人造肝胰联合移植替代。尽管乙肝病毒(HBV)相关疾病肝移植后移植物再感染发生率很高,但仍有相当比例的患者获得长期存活。高效价免疫球蛋白和干扰素在预防再感染方面作用甚微。针对乙肝表面抗原(HBsAg)的人单克隆抗体的临床试验正在进行。酒精性肝病的肝移植一直存在争议。然而,Laennec肝硬化肝移植后的存活率与其他慢性、良性且非HBV相关肝病肝移植后的存活率相当。硬化疗法后进行肝移植是食管静脉曲张急性出血和终末期肝病患者的首选治疗方法。对于肝功能储备良好的患者,单独硬化疗法或硬化疗法后进行选择性分流是合适的替代方法。仅有25%的胆道闭锁婴儿能从肝门肠吻合术中获益。为满足等待移植的小婴儿的需求,几个移植项目已成功加大力度使用部分(减体积)肝移植物。环孢素和小剂量泼尼松仍是肝移植后免疫抑制的基础用药。然而,肾毒性和高血压是环孢素常见且棘手的副作用。三联和四联药物方案越来越普遍,旨在尽量减少环孢素的毒性。一种新药FK506的一期临床试验最近在匹兹堡启动。肝的超急性排斥反应已在动物模型中得到证实,并且在最近关于肝移植后急性出血性坏死的临床描述中也受到强烈怀疑。到目前为止,仅发现ABO血型不相容的移植是超急性排斥反应的一个危险因素。威斯康星大学的Belzer及其同事研发的新型保存液显著延长了肝移植物的保存时间,并提高了肝保存质量。