University of California, San Francisco, San Francisco, California, USA.
N Engl J Med. 2010 Mar 25;362(12):1071-81. doi: 10.1056/NEJMoa0907893.
Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established.
In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy.
Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events.
Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)
肝性脑病是肝硬化的一种慢性衰弱性并发症。利福昔明是一种吸收很少的抗生素，其治疗急性肝性脑病的疗效已有充分的文献记载，但尚未确定其对该病的预防作用。
在这项随机、双盲、安慰剂对照试验中，我们将 299 例因慢性肝病而缓解的复发性肝性脑病患者随机分为两组，分别接受利福昔明（剂量为每日 2 次，每次 550mg，共 140 例）或安慰剂（159 例）治疗 6 个月。主要疗效终点是首次肝性脑病突破发作的时间。主要次要终点是首次因肝性脑病住院的时间。
与安慰剂相比，利福昔明在 6 个月期间显著降低了肝性脑病发作的风险（利福昔明的危险比为 0.42；95%置信区间为 0.28 至 0.64；P<0.001）。利福昔明组中 22.1%的患者发生肝性脑病突破发作，而安慰剂组中则为 45.9%。利福昔明组中有 13.6%的患者因肝性脑病住院，而安慰剂组中则为 22.6%，其危险比为 0.50（95%置信区间为 0.29 至 0.87；P=0.01）。超过 90%的患者接受了乳果糖联合治疗。两组患者报告的不良事件发生率相似，严重不良事件发生率也相似。
在 6 个月的治疗期间，利福昔明维持肝性脑病缓解的效果优于安慰剂。利福昔明治疗还显著降低了因肝性脑病住院的风险。（临床试验.gov 编号，NCT00298038）。
