Gerth Hans Ulrich, Pohlen Michele, Pavenstädt Hermann, Schmidt Hartmut
Department of Medicine A, University Hospital Muenster, Muenster Germany.
Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Muenster, Muenster Germany.
Z Gastroenterol. 2017 Apr;55(4):383-393. doi: 10.1055/s-0043-100020. Epub 2017 Mar 14.
Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups. There are no prospective randomized studies on the treatment of liver failure by intoxication. However, several case series report positive treatment effects using the MARS system, particularly in mushroom poisoning or acetaminophen intoxication. In acute liver failure (ALF) studies, the usage of BLS showed no survival advantage. Using ALS systems, a positive effect on mortality could be demonstrated in patient subgroups after several consecutive MARS therapies. The first randomized controlled trial demonstrating a survival benefit used large-volume plasmapheresis. Apparently, immunomodulatory and hemodynamic effects of the treatment play a crucial role in this context. In patients with acute-on-chronic liver failure (ACLF) accompanied by hyperbilirubinemia without any further organ failure (singular hepatic dysfunction), prognostic favorable effects by using a BLS system have been shown. However, once other extrahepatic organ systems are affected, indicating a progressive transition to multi-organ failure, a survival advantage could be achieved with the MARS and Prometheus system. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for each liver support.
体外肝脏支持可分为无细胞的人工方法(人工肝支持,ALS)和基于细胞的生物人工方法(生物人工肝支持,BLS)。ALS通过同时清除蛋白结合物质和水溶性物质来改善肝衰竭的生化参数。在此,MARS疗法属于研究最多的方法,已被证明对肝性脑病(HE)、肝肾综合征(HRS)或高胆红素血症有有益作用。然而,尚未显示任何肝脏支持对肝衰竭有总体生存优势,且仅限于荟萃分析或患者亚组。目前尚无关于中毒性肝衰竭治疗的前瞻性随机研究。然而,几个病例系列报告了使用MARS系统的积极治疗效果,特别是在蘑菇中毒或对乙酰氨基酚中毒方面。在急性肝衰竭(ALF)研究中,使用BLS未显示出生存优势。使用ALS系统,在连续多次进行MARS治疗后的患者亚组中可证明对死亡率有积极影响。第一项证明有生存益处的随机对照试验使用了大容量血浆置换。显然,该治疗的免疫调节和血流动力学效应在这方面起着关键作用。在伴有高胆红素血症且无任何其他器官衰竭(单纯肝功能障碍)的慢加急性肝衰竭(ACLF)患者中,已显示使用BLS系统有预后良好的效果。然而,一旦其他肝外器官系统受到影响,表明已逐渐过渡到多器官衰竭,使用MARS和Prometheus系统可实现生存优势。对于这种非常异质性的疾病,成功治疗的关键在于为各自的肝透析程序准确指明适应证。未来需要开展研究以确定每种肝脏支持更准确的患者选择标准。