Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis

利福昔明 肝性脑病 医学 肝硬化 胃肠病学 内科学 脑病 重症监护医学 抗生素 化学 生物化学
作者
Harry D Zacharias,Fady Kamel,Jaclyn Tan,Nina Kimer,Lise Lotte Gluud,Marsha Y. Morgan
出处
期刊:The Cochrane library [Elsevier]
卷期号:2023 (7) 被引量:17
标识
DOI:10.1002/14651858.cd011585.pub2
摘要

Background Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non‐absorbable antibiotic that inhibits urease‐producing bacteria and reduces absorption of dietary and bacterial ammonia. Objectives To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non‐absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non‐absorbable disaccharide. Search methods We searched the Cochrane Hepato‐Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023. Selection criteria We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non‐absorbable disaccharide, versus placebo/no intervention, or a non‐absorbable disaccharide alone. Data collection and analysis Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health‐related quality of life, hepatic encephalopathy, non‐serious adverse events, blood ammonia, Number Connection Test‐A, and length of hospital stay. Main results We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non‐absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non‐absorbable disaccharide versus a non‐absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non‐mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I2 = 0%; 13 trials, 1007 participants; moderate‐certainty evidence), and there may be no overall effect when compared to non‐absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I2 = 0%; 10 trials, 786 participants; low‐certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non‐absorbable disaccharide to a non‐absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I2 = 0%; 14 trials, 1946 participants; moderate‐certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I2 = 0%; 9 trials, 801 participants; moderate‐certainty evidence) and there may be no overall effect when compared to non‐absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I2 = 0%; 8 trials, 681 participants; low‐certainty evidence). However, there was very low‐certainty evidence that use of rifaximin plus a non‐absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non‐absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I2 = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health‐related quality of life when compared to placebo/no intervention (mean difference (MD) ‐1.43, 95% CI ‐2.87 to 0.02; P = 0.05, I2 = 81%; 4 trials, 214 participants; moderate‐certainty evidence), and may benefit health‐related quality of life in people with minimal hepatic encephalopathy (MD ‐2.07, 95% CI ‐2.79 to ‐1.35; P < 0.001, I2 = 0%; 3 trials, 176 participants). The overall effect on health‐related quality of life when comparing rifaximin to non‐absorbable disaccharides is very uncertain (MD ‐0.33, 95% CI ‐1.65 to 0.98; P = 0.62, I2 = 0%; 2 trials, 249 participants; very low‐certainty evidence). None of the combined rifaximin/non‐absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I2 = 68%; 13 trials, 1009 participants; moderate‐certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I2 = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I2 = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non‐absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I2 = 0%; 13 trials, 921 participants; low‐certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non‐absorbable disaccharide to a non‐absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I2 = 62%; 17 trials, 2332 participants; low‐certainty evidence). Authors' conclusions Compared to placebo/no intervention, rifaximin likely improves health‐related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health‐related quality of life, or hepatic encephalopathy compared to non‐absorbable disaccharides. However, when used in combination with a non‐absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high‐quality trials are needed.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
荒谬发布了新的文献求助10
1秒前
Tristan发布了新的文献求助10
1秒前
wyg1994发布了新的文献求助30
2秒前
2秒前
万能图书馆应助歪比八不采纳,获得10
3秒前
阿晓晓发布了新的文献求助10
4秒前
进取拼搏发布了新的文献求助10
4秒前
4秒前
淡然冬灵发布了新的文献求助10
5秒前
Owen应助poggio采纳,获得10
5秒前
李健应助dmsoli采纳,获得10
9秒前
王小磊完成签到,获得积分10
9秒前
刘晓倩发布了新的文献求助10
10秒前
合适夜绿完成签到,获得积分10
11秒前
ptyss发布了新的文献求助10
12秒前
13秒前
Rw完成签到 ,获得积分10
13秒前
科研通AI2S应助Tristan采纳,获得10
14秒前
香蕉如音完成签到,获得积分10
16秒前
隐形曼青应助哈呼呼采纳,获得10
21秒前
邓希静完成签到 ,获得积分10
21秒前
21秒前
星辰大海应助ptyss采纳,获得10
22秒前
搜集达人应助ptyss采纳,获得10
22秒前
鲤鱼绿旋完成签到,获得积分10
23秒前
土豆完成签到,获得积分10
24秒前
笑一个吧发布了新的文献求助10
24秒前
合适夜绿发布了新的文献求助10
24秒前
25秒前
hbgcld发布了新的文献求助10
29秒前
可爱奇异果完成签到 ,获得积分10
29秒前
31秒前
forgive完成签到,获得积分10
35秒前
查查完成签到,获得积分10
35秒前
歪比八不发布了新的文献求助10
36秒前
nmamtf发布了新的文献求助10
36秒前
打打应助荒谬采纳,获得10
36秒前
37秒前
小高宽度发布了新的文献求助10
38秒前
38秒前
高分求助中
BIOLOGY OF NON-CHORDATES 1000
进口的时尚——14世纪东方丝绸与意大利艺术 Imported Fashion:Oriental Silks and Italian Arts in the 14th Century 800
Autoregulatory progressive resistance exercise: linear versus a velocity-based flexible model 550
Zeitschrift für Orient-Archäologie 500
The Collected Works of Jeremy Bentham: Rights, Representation, and Reform: Nonsense upon Stilts and Other Writings on the French Revolution 320
Play from birth to twelve: Contexts, perspectives, and meanings – 3rd Edition 300
Equality: What It Means and Why It Matters 300
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3349431
求助须知:如何正确求助?哪些是违规求助? 2975524
关于积分的说明 8669583
捐赠科研通 2656310
什么是DOI,文献DOI怎么找? 1454531
科研通“疑难数据库(出版商)”最低求助积分说明 673370
邀请新用户注册赠送积分活动 663821