Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence.
Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence.
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DOI：
10.1177/1756283x11401774
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发表时间：
2011-05-01
影响因子：
4.2
通讯作者：
Flamm, Steven L
中科院分区：
文献类型：
--
作者：
Flamm, Steven L
肝性脑病(HE)是慢性肝病患者的常见问题，以沉着减少和神经肌肉异常为特征。症状范围从微小的认知变化到昏迷和死亡。肠源性毒素，如氨，被认为在HE的发病机制中发挥核心作用。治疗策略针对的是增加肠源性氨的消除或减少，以及纠正引发HE发作的动态条件。治疗急性肝性脑病的标准是乳果糖，这是一种不可吸收的二糖，被认为可以增加氨的排出和减少吸收。虽然乳果糖似乎在急性发作时起作用，但维持乳果糖的HE复发率很高。人们一直在寻求降低HE高危患者的HE复发率的药物，但还没有发现任何药物。利福昔明是一种吸收不良的抗生素，被认为可以通过消除产氨的结肠细菌来减少氨的产生。许多小型研究表明，利福昔明治疗急性肝性脑病有效，且耐受性极好。这导致了一项随机、安慰剂对照的多中心试验，调查了利福昔明在6个月内降低基线水平、但在登记前6个月内至少有两次急性肝性脑病发作史的患者的复发风险的有效性。乳果糖可以由研究人员自行决定给药。共有299名患者随机接受利福昔明或安慰剂治疗；每组91%的患者接受乳果糖治疗。与安慰剂相比，服用利福昔明组的HE复发高危患者在6个月的时间里，急性HE发作次数(58%)和与HE相关的住院次数(50%)在统计学上显著减少。该药物耐受性良好，副作用与安慰剂相当。这导致利福昔明在2010年3月被美国食品和药物管理局批准用于降低HE复发的风险。建议有复发急性肝性脑病病史的患者服用利福昔明加或不加乳果糖，以降低复发肝性脑病和相关住院的风险。
Hepatic encephalopathy (HE) is a common problem in patients with chronic liver disease and is characterized by diminished mentation and neuromuscular abnormalities. Symptoms range from subtle cognitive changes to coma and death. Gut-derived toxins such as ammonia are thought to play a central role in the pathogenesis of HE. Treatment strategies are directed at increased elimination or reduction of gut-derived ammonia in addition to correction of dynamic conditions that provoke bouts of HE. The standard of care for treatment of acute HE is lactulose, a nonabsorbable disaccharide that is thought to increase elimination and reduce absorption of ammonia. Although lactulose seems to work in the acute setting, the rate of recurrent HE on maintenance lactulose is high. Medications have been sought that reduce the rate of recurrent HE in patients at high risk for HE but none have been identified. Rifaximin is a poorly absorbed antibiotic that is thought to reduce ammonia production by eliminating ammonia-producing colonic bacteria. Many small studies have suggested that rifaximin is effective in treating acute HE and is extremely well tolerated. This led to a randomized, placebo-controlled, multicenter, multinational trial investigating the efficacy of rifaximin over a 6-month period in reducing the risk of recurrent HE in patients at baseline, but with a history of at least two bouts of acute HE in the previous 6 months prior to enrollment. Lactulose could be administered at the discretion of the investigator. A total of 299 patients were randomized to receive rifaximin or placebo; 91% of patients in each group received lactulose. Compared with placebo, patients at high risk for recurrent HE in the rifaximin group had highly statistically significant reductions in bouts of acute HE (58%) and reductions in hospitalizations related to HE (50%) over a 6-month period. The medication was well tolerated with a side-effect profile comparable to placebo. This led to the approval of rifaximin for reduction of risk of recurrent HE by the US Food and Drug Administration in March 2010. It is recommended that patients with a history of recurrent acute HE should be maintained on rifaximin with or without lactulose to reduce the risk of recurrent HE and related hospitalization.