Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

Table 5 Published studies using antibiotics for minimal hepatic encephalopathy treatment

Ref.	Study type	Follow-up (wk)	MHE diagnosis	Active treatment (s)	Objectives	Patients (n)	Main results/impact measures
No history of OHE1
Ahluwalia et al[66], 2014	Quasi-experimental	8	NCT-A, NCT-B, DST, BDS, LTT, SDT, ICT	Rifaximin4	fMRI, ICT, MRS5	20	Changes in ICT, improvement of 12% respect to baseline, indicating a better cognition
Bajaj et al[61], 2013	Quasi-experimental	8	NCT-A, NCT-B, DST, BDT, LTT	Rifaximin4	Psychometry5	20	Improvement in NCT-A time (11.8%), NCT-B time (11.8%), DST raw score (9.1%), BDT raw score (0.0%), LTT time (20.7%), LTT errors (39.8%), SDT time (12.3%) from basal values
Bajaj et al[67], 2011	Randomized, single-blinded	8	NCT-A, DST, BDT, ICT	Rifaximin/placebo4	Driving performance, psychometry scores	21/21	Decrease of 46.6% of total errors respect to baseline in rifaximin group (P < 0.001)6. Improvement in NCT-A 91% vs 61% (NNT: 4); NCT-B: 81% vs 33% (NNT: 2); and ICT lures: 76% vs 43% (NNT: 3)7
Sidhu et al[59], 2015	Randomized, non-inferiority trial	12	NCT-A, FCT-A, DST, PCT, and BDT	Rifaximin/lactulose	Reversal of MHE	57/55	ITT analysis shows a reversal at 2 wk: lactulose 40.0% vs rifaximin 52.63% (NNT: 8). ITT analysis at 3 mo shows reversal in 69.1% and 73.7% of lactulose and rifaximin, (NNT: 22)
Goyal et al[62], 2017	Prospective cohort	24	NCT-A, FCT-A, DST, PCT, BDT	Previous intake of Rifaximin compared to lactulose3,4	Maintenance of remission for MHE	42/38	Still free of MHE: Rifaximin 42.8% vs lactulose 50.0% (NNT: 14)
Possible history of OHE1
Agrawal et al[24], 2011	Quasi-experimental	1	NCT, FTC, LTT.	Clarithromycin, lansoprazole, tinidazole3,4	Psychometric scores5	35	Improvement in 12.7%, 13.3%, and 18.7% respect to basal mean time in NCT, FCT and LTT, respectively
Zhang et al[27], 2015	Quasi-experimental	5	NCT-A, NCT-B, DST	Rifaximin 1 wk3,4	Reversal of MHE	26	After a week, reversal present in 11/26 (42.3%)
Sidhu et al[56], 2011	Double-blind, randomized	8	NCT-A/FCT-A, DST, PCT, BDT	Rifaximin/placebo	Reversal of MHE	49/45	Reversal at 2 wk: 57% vs 18% (NNT: 3)At 8 wk: Reversal of 75.5% vs 20% (NNT: 2)
Sharma et al[40], 2014	Randomized2	8	NCT-A/FCT-A, DST and/ or CFF	LOLA/rifaximin/Probiotics/Placebo4	Reversal of MHE5	31/31/32/30	ITT analysis: Improvement in CFF values (Hz) from baseline in 11.42%, 6.5%, 8.68%, and 2.28%

¹Studies in which the inclusion criteria comprise patient with clinical history to the overt hepatic encephalopathy events.

²Unblinded study.

³Compliance to treatment was not measured in one or the different treatment groups.

⁴Diet was not standardized according to the suggested treatment.

⁵Secondary objectives within the study.

⁶Analysis was performed within the same group (before–after treatment) despite the experimental design.

⁷Minimal hepatic encephalopathy reversion not measured. BDT: Block design test; CFF: Critical flicker frequency; DST: Digit symbol test; FCT: Figure connection test; FCT-A: Figure connection test A; ICT: Inhibitory Control Test; ITT: Intention to treat: LTT: Line tracing test; MHE: Minimal hepatic encephalopathy; NCT: Number connection test; NCT-A: Number connection test A; NCT-B: Number connection test B; NNT: Number Needed to Treat; OHE: Overt hepatic encephalopathy; PCT: Picture completion test; SDT: Serial dotting test.