Hudson Mark, Schuchmann Marcus
Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Eur J Gastroenterol Hepatol. 2019 Apr;31(4):434-450. doi: 10.1097/MEG.0000000000001311.
A consolidated overview of evidence for the effectiveness and safety/tolerability of hepatic encephalopathy (HE) treatment over the long term is currently lacking. We identified and assessed published evidence for the long-term (≥6 months) pharmacological management of HE with lactulose and/or rifaximin. A literature search was conducted in PubMed (cutoff date 05 March 2018) using the search terms 'hepatic encephalopathy+rifaximin' and 'hepatic encephalopathy+lactulose'. All articles containing primary clinical data were manually assessed to identify studies in which long-term (≥6 months) effectiveness and/or safety/tolerability end points were reported for lactulose and/or rifaximin. Long-term effectiveness outcomes were reported in eight articles for treatment with lactulose alone and 19 articles for treatment with rifaximin, alone or in combination with lactulose. Long-term safety/tolerability outcomes were reported in six articles for treatment with lactulose alone and nine articles for treatment with rifaximin, alone or in combination with lactulose. These studies showed that lactulose is effective for the prevention of overt HE recurrence over the long term and that the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability. Current evidence therefore supports recommendations for the use of lactulose therapy for the prevention of overt HE recurrence over the long term, and for the additional benefit of adding rifaximin to lactulose therapy. Addition of rifaximin to standard lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization.
目前缺乏关于肝性脑病（HE）长期治疗有效性及安全性/耐受性证据的综合概述。我们识别并评估了已发表的关于使用乳果糖和/或利福昔明对HE进行长期（≥6个月）药物治疗的证据。在PubMed（截止日期为2018年3月5日）中进行文献检索，使用检索词“肝性脑病+利福昔明”和“肝性脑病+乳果糖”。对所有包含原始临床数据的文章进行人工评估，以识别报告了乳果糖和/或利福昔明长期（≥6个月）有效性和/或安全性/耐受性终点的研究。有8篇文章报告了单独使用乳果糖治疗的长期有效性结果，19篇文章报告了单独使用利福昔明或联合乳果糖治疗的长期有效性结果。有6篇文章报告了单独使用乳果糖治疗的长期安全性/耐受性结果，9篇文章报告了单独使用利福昔明或联合乳果糖治疗的长期安全性/耐受性结果。这些研究表明，乳果糖对长期预防显性HE复发有效，与单独使用乳果糖治疗相比，在乳果糖中添加利福昔明可显著降低显性HE复发和与HE相关的住院风险，且不影响耐受性。因此，目前的证据支持长期使用乳果糖治疗预防显性HE复发的建议，以及在乳果糖治疗中添加利福昔明的额外益处。在标准乳果糖治疗中添加利福昔明可能会通过减少显性HE复发和相关再住院，在长期内大幅降低医疗资源的使用。
