Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

Table 3 Available studies describing the effects of rifaximin on endotoxemia in patients with advanced liver disease

Study	Study design	No. patients	Disease severity	Treatment schedule	Results	Safety
Vlachogiannakos et al[71] 2009	Prospective	30	welve patients (40%) were Child-Pugh B and 18 (60%) Child-Pugh C	Rifaximin 1200 mg/d for 28 d	Median (range) plasma endotoxin levels decreased significantly after rifaximin administration both in systemic [1.45 (0-3.1) vs 0.7 (0-2.7), P < 0.0001] and splanchnic circulation [1.8 (0-3.4) vs 0.8 (0-2.1), P < 0.0001]. Meanwhile, the difference seen in endotoxin levels between the splanchnic and systemic circulation at day 0 (P = 0.001) was not noted at day 29 (P = 0.137)	Abdominal pain: 3%
			CTP score: A: 0%, B: 40%, C: 60%			Self-limited diarrhea: 3%
			MELD score (mean, range): 17 (11-27)		Reduction in endotoxin levels in both systemic and splanchnic circulation compared to baseline (P < 0.0001)
			B: 40%, C: 60%		Reduction in HVPG compared to baseline (P < 0.0001)
					Reduction in HVPG correlated with hepatic vein endotoxin values (P = 0.023)
Kalambokis et al[73] 2012	Prospective	9	CTP score: B: 56%, C: 44%	8-wk course of rifaximin (1200 mg/d)	Rifaximin significantly reduced plasma endotoxin levels	Not reported
				Rifaximin 1200 mg/d for 8 wk	Reduction in plasma endotoxin levels compared to baseline (P < 0.01)
Vlachogiannakos et al[72] 2012	Prospective	69	welve patients (40%) were Child-Pugh B and 18 (60%) Child-Pugh C	23 pts who achieved a decrease in HVPG after 28-d rifaximin treatment[71]	Median (range) plasma endotoxin levels decreased significantly after rifaximin administration both in systemic [1.45 (0-3.1) vs 0.7 (0-2.7), P < 0.0001] and splanchnic circulation [1.8 (0-3.4) vs 0.8 (0-2.1), P < 0.0001]. Meanwhile, the difference seen in endotoxin levels between the splanchnic and systemic circulation at day 0 (P = 0.001) was not noted at day 29 (P = 0.137)	Nausea: 9%
						Self-limited rash in the extremities: 4%
						Persistent diarrhea: 4%
			CTP score	46 cirrhotic controls
			rifaximin		Reduction in plasma endotoxin levels in both systemic and splanchnic circulation compared to baseline (P < 0.0001)
			A: 0%, B: 48%, C: 52%
			controls:		Risk of developing variceal bleeding: 35% rifaximin vs 59.5% controls (P = 0.011)
			A: 0%, B: 48%, C: 52%		Incidence of HE: 31.5% rifaximin vs 47% controls (P = 0.034)
			MELD score (mean ± SD)		Incidence of SBP: 4.5% rifaximin vs 46% controls (P = 0.027)
			rifaximin: 17.2 ± 3.6		Incidence of HRS: 4.5% rifaximin vs 51% controls (P = 0.037)
			controls: 16.6 ± 3.5
Kalambokis et al[75] 2012	Prospective, randomized, placebo-controlled	23	CTP score	13 pts: rifaximin 1200 mg/d for 4 wk	Reduction in endotoxin levels compared to control group (P = 0.005)	Not reported
			rifaximin:		Increase in mean platelets count in rifaximin group compared to controls (P = 0.006)
			A: 0%, B: 46%, C: 54%
			placebo:	10 cirrhotic pts: placebo
			A: 0%, B: 40%, C: 60%
Bajaj et al[62] 2013	Prospective	20	MELD score (mean ± SD): 9.8 ± 3.3	Rifaximin 550 mg BID for 8 wk	Reduction in plasma endotoxin levels compared to baseline (P = 0.02)	Not reported

MELD: Model for end stage liver disease; CTP: Child turcotte pugh; HVPG: Hepatic venous pressure gradient.