Rifaximin vs conventional oral therapy for hepatic encephalopathy: A meta-analysis

Table 1 Characteristics of included studies

Authors	Country	Rifaximin (n)	Control (n)	Rifaximin dose(mg/d)	Comparative agent	Duration of treatment	Outcomes
Bucci et al[35]	Italy	30	28	1200	Lactulose 45 mL/d	15 d	Mental status, asterixis, cancellation test, reitan test, EEG, serum ammonia, degree and severity of HE
Di Piazza et al[33]	Italy	8	6	1200	Neomycin 4500 mg/d	21 d	Bradylalia, flapping tremor, performance, visual evoked potentials and the trial making test
Fera et al[37]	Italy	20	20	1200	Lactulose 120 mL/d	90 d	Mental status, asterixis, cancellation test, reitan test, EEG, PSE severity
Festi et al[17]	Italy	20	15	1200	Neomycin 3000 mg/d	21 d	Asterixis, EEG, blood ammonia
Festi et al[17]	Italy	9	12	1200	Lactulose 60 mL/d	21 d	Asterixis, EEG, blood ammonia
Loguercio et al[39]	Italy	14	13	1200	Lactulose 90 mL/d	3 mo	Mental status, asterixis, NCT, blood ammonia
Mas et al[36]	Spain	50	53	1200	Lactitol 60 g/d	5-10 d	HE grade, mental status, asterixis, NCT, EEG, PSE index, blood ammonia
Massa et al[18]	Italy	20	20	1200	Lactulose 90 mL/d	15 d	Mental status, asterixis, cancellation test, EEG, trail making test, PSE index, blood ammonia
Miglio et al[38]	Italy	25	24	1200	Neomycin 3000 mg/d	6 mo	HE grade, blood ammonia, neuropsychiatric signs
Paik et al[21]	South Korea	32	22	1200	Lactulose 90 mL/d	7 d	Mental status, flapping tremors, NCT, blood ammonia, HE index
Parini et al[34]	Italy	15	15	1200	Paromomycin 1500 mg/d	10 d	Blood ammonia, state of consciousness, behavior, intellectual functions, neurologic symptoms
Pedretti et al[25]	Italy	15	15	1200	Neomycin 3000 mg/d	21 d	PSE index, blood ammonia, EEG, NCT, asterixis, trail making test, mental status
Song et al[32]	South Korea	39	25	1200	Lactulose 90 mL/d	7 d	Blood ammonia, mental status, flapping tremors, NCT, HE index

EEG: Electroencephalogram; HE: Hepatic encephalopathy; PSE: Portosystemic encephalopathy; NCT: Number connection test.

Table 2 Risk of bias in the published controlled trials

Author	Allocation system described	Allocation concealment	Blinding			Handling of missing data	Power calculation for number of patients to be treated
			Patient	Personnel	Assessor
Bucci et al[35]	Yes	Yes	Yes	Yes	NA	Unclear	No
Di Piazza et al[33]	No	No	Yes	Yes	NA	Unclear	No
Fera et al[37]	No	Yes	Yes	No	NA	Unclear	No
Festi et al[17]	No	No	No	No	NA	Unclear	No
Loguercio et al[39]	No	No	Yes	No	NA	Unclear	No
Mas et al[36]	Yes	Yes	Yes	Yes	NA	Unclear	No
Massa et al[18]	No	Yes	Yes	Yes	NA	Unclear	No
Miglio et al[38]	No	Yes	Yes	Yes	NA	Unclear	No
Paik et al[21]	Yes	Yes	Yes	No	NA	Unclear	No
Parini et al[34]	Yes	Yes	Yes	No	No	Unclear	No
Pedretti et al[25]	Yes	Yes	Yes	Yes	NA	Unclear	No
Song et al[32]	NA	NA	NA	NA	NA	NA	NA

NA: Not available.

Table 3 Summary of the meta-analysis on psychometric outcomes measured at the end of each randomized controlled trial

Variable	Rifaximin			Control			Mean difference
	Mean	SD	Total	Mean	SD	Total	IV, random, 95% CI
Mental status
Bucci et al[35]	0.8	0.5	30	1.2	0.3	28	-0.40 [-0.61, -0.19]
Loguercio et al[39]	0.42	0.67	14	0.9	0.74	13	-0.48 [-1.01, 0.05]
Massa et al[18]	0.6	0.2	20	1.2	0.3	20	-0.60 [-0.76, -0.44]
Paik et al[21]	0.5	0.7	32	0.3	0.4	22	0.20 [-0.09, 0.49]
Parini et al[34]	0.22	0.39	15	0.16	0.34	15	0.06 [-0.20, 0.32]
Subtotal (95% CI)			111			98	-0.24 [-0.57, 0.08]
Heterogeneity: Tau² = 0.11; χ² = 32.85, df = 4 (P < 0.00001); I² = 88%
Test for overall effect: Z = 1.45 (P = 0.15)
Asterixis
Bucci et al[35]	0.5	0.3	30	0.9	0.5	28	-0.40 [-0.61, -0.19]
Mas et al[36]	0	0.5	50	0	0.5	53	0.00 [-0.19, 0.19]
Massa et al[18]	0.1	0.2	20	0.1	0.2	20	0.00 [-0.12, 0.12]
Paik et al[21]	0.3	0.7	32	0.4	0.6	22	-0.10 [-0.45, 0.25]
Parini et al[34]	0.28	0.5	15	0.16	0.04	15	0.12 [-0.13, 0.37]
Pedretti et al[25]	1.6	0.7	15	2	0.8	15	-0.40 [-0.94, 0.14]
Subtotal (95% CI)			162			153	-0.10 [-0.26, 0.07]
Heterogeneity: Tau² = 0.02; χ² = 14.47, df = 5 (P = 0.01); I² = 65%
Test for overall effect: Z = 1.15 (P = 0.25)
EEG
Bucci et al[35]	0.4	0.2	30	0.6	0.3	28	-0.20 [-0.33, -0.07]
Mas et al[36]	0.6	0.9	50	0.9	0.9	53	-0.30 [-0.65, 0.05]
Pedretti et al[25]	0.4	0.5	15	0.6	0.6	15	-0.20 [-0.60, 0.20]
Subtotal (95% CI)			95			96	-0.21 [-0.33, -0.09]
Heterogeneity: Tau² = 0.00; χ² = 0.28, df = 2 (P = 0.87); I² = 0%
Test for overall effect: Z = 3.52 (P = 0.0004)
PSE sum
Mas et al[36]	4	0.1	50	6	2	53	-2.00 [-2.54, -1.46]
Massa et al[18]	3	0.5	20	5.5	0.5	20	-2.50 [-2.81, -2.19]
Pedretti et al[25]	7.1	2.4	15	9.3	2.7	15	-2.20 [-4.03, -0.37]
Subtotal (95% CI)			85			88	-2.33 [-2.68, -1.98]
Heterogeneity: Tau² = 0.02; χ² = 2.52, df = 2 (P = 0.28); I² = 21%
Test for overall effect: Z = 13.11 (P < 0.00001)

IV: Inverse variance; EEG: Electroencephalogram; PSE: Portosystemic encephalopathy.