Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy

Figures & data

Table 1 Overview of the literature

Study	Number of patients	Primary outcomes	Significant trial results
Randomized trials
Eftimiadi et al^Citation23	20	Gut flora	No statistical comparison reported
De Marco et al^Citation17	32	HE grade, s-ammonia, and blood biochemistry	No significant difference among treatment groups
Testa et al^Citation26	20	s-ammonia, NCT, and gut flora	No significant difference among treatment groups
Riggio et al^Citation24	75	Breakthrough of HE; s-ammonia	No significant difference among treatment groups
Song et al^Citation25,a	64	Mental status and s-ammonia	No significant difference among treatment groups
Williams et al^Citation28,b	54	PSE index, EEG, and s-ammonia	No significant difference among treatment groups
Di Piazza et al^Citation22	14	Asterixis; trail-making test	No significant difference among treatment groups
Venturini et al^Citation27	18	Benzodiazepine-like compounds	Benzidiazepine-like compounds lowered in rifaximin group
Festi et al^Citation31	59	Asterixis, s-ammonia, and EEG	No significant difference among treatment groups
Miglio et al^Citation34	60	s-ammonia, trans-aminases, and trail-making test	Improved trail-making test in rifaximin group
Parini et al^Citation19	30	HE grade and s-ammonia	No significant difference among treatment groups
Pedretti et al^Citation36	30	Neuropsychometric tests, EEG, PSE index, and s-ammonia	Lower s-ammonia in the rifaximin group
Fera et al^Citation30	40	Mental state, A-cancellation-test (neuropsychometric test), trail-making test, EEG irregularities, and s-ammonia	Mental state improved in rifaximin group, trail-making test improved in lactulose group
Paik et al^Citation35	54	HE index, s-ammonia, and NCT	No significant difference among treatment groups
Massa et al^Citation33	40	Mental state, a-cancellation test, trail-making test, and s-ammonia	Improvement in mental status and trail-making test in the rifaximin group
Bucci and Palmieri^Citation16	58	Mental state, a-cancellation test, EEG, and PSE index	Improvement in EEG irregularities and a-cancellation test in rifaximin group.
Loguercio et al^Citation32	26	Mental state, asterixis, NCT, s-ammonia	Decrease in s-ammonia level in the rifaximin+lactitol group
Mas et al^Citation18	103	s-ammonia, NCT, EEG, and PSE index	No significant difference among treatment groups
Bass et al^Citation29,a	93	s-ammonia, NCT, mental state, PSE index, and asterixis	Improvement in asterixis in rifaximin group
Bass et al^Citation15	299	HE episodes and hospitalizations	Decreased number of recurrent episodes of HE and hospitalization rates in rifaximin group
Sidhu et al^Citation38	94	HRQL, SIP score, and NCT	Decrease in SIP score in rifaximin group
Bajaj et al^Citation14	42	Biochemistry, neuropsychometric testing, driving capacity, and sickness impact profile	Improvement in sickness impact profile and fewer driving errors in rifaximin group
Sharma et al^Citation37	120	Mortality, recovery of HE, and hospitalization	Lower mortality and hospitalization duration in rifaximin group
Prospective trials
Vlachogiannakos et al^Citation42	69	Prevention of HE, portal hypertension, and complications to cirrhosis	Lower risk of developing HE and complications to cirrhosis in rifaximin group
Irima et al^Citation40,c	78	Prevention of recurrent HE; hospitalizations	No significant difference among treatment groups
Tandon et al^Citation41	115	Antibiotic resistant infections and antibiotic exposure	No data on rifaximin treatment alone
Sanyal et al^Citation45,‡,a	392	Infection rates and antibiotic use	No statistical comparison reported
Bajaj et al^Citation43,‡,a	82	Incidence of breakthrough HE	No statistical comparison reported
O’Leary et al^Citation44	175	Recurrent infections and use of antibiotics	Higher rates of rifaximin use in patients with recurrent infections
Retrospective analyses
Leevy and Phillips^Citation2	145#	Hospitalization rates, HE grade, asterixis, and adverse events	Decreased hospitalization rates, decreased asterixis, and fewer patients with HE grade 3–4 during rifaximin treatment
Neff et al^Citation49	39	Hospitalization rates, economic data, and MELD score	No statistical comparison between groups reported
Mantry and Munsaf^Citation46	65	Hospitalizations	Reduced risk of hospitalization during rifaximin treatment
Neff et al^Citation47	203	Prevention of HE; MELD score	No comparison between groups performed
Neff^Citation50	45,480	Treatment patterns and use of rifaximin	No statistical comparison between groups reported
Neff et al^Citation48	211	Development of Clostridium difficile infections	No control group; no Clostridium difficile infections

Notes:

‡ Reports on the same prospective trial, a follow-up of the randomized trial by Bass et al;¹⁵

# roll-over analysis where patients are initially treated with lactulose for 6 months followed by rifaximin for 6 months

a published as abstracts

b dose-finding trial, no control group

c only abstract in English.

Abbreviations: EEG, electroencephalography; HE, hepatic encephalopathy; HRQL, health-related quality of life; MELD, Model of End Stage Liver Disease; NCT, number connection test; PSE, portal systemic encephalopathy; SIP, sickness impact profile.

Table 2 Safety assessment of rifaximin

Study	Adverse events – rifaximin			Adverse events – control
	Number of patients	Mild	Severe	Number of patients	Mild	Severe
Randomized trials
Bucci and Palmieri^Citation16	30	9	0	28	65	0
Loguercio et al^Citation32	27	0	0	13	0	0
Massa et al^Citation33	20	0	0	20	28	0
Mas et al^Citation18	50	3	3	53	2	3
Paik et al^Citation35	32	1	0	22	1	0
De Marco et al^Citation17	18	0	0	14	0	0
Parini et al^Citation19	15	0	0	15	0	0
Pedretti et al^Citation36	15	0	0	15	9	0
Bajaj et al^Citation14	21	20	0	21	29	0
Bass et al^Citation29	48	NA	6	45	NA	6
Bass et al^Citation15	140	406	44	159	417	44
Sidhu et al^Citation38	49	12	0	45	0	0
Sharma et al^Citation37	63	2	8	57	10	11
Total	528	453	61	507	561	64
Prospective studies
Vlachogiannakos et al^Citation42	23	NA	12	46	NA	58
Irimia et al^Citation40	66	NA	17	12	NA	4
Total	89	NA	29	58	NA	62
Retrospective studies
Mantry and Munsaf^Citation46	65*	1	1	65*	102	9
Leevy and Phillips^Citation2	145*	569	10	145*	472	107
Total	210	570	11	210	574	116

Note:

* Retrospective design (patients received both treatments consecutively).

Abbreviation: NA, not assessed.

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