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

Table 4 Published studies using non-absorbable disaccharides 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
Prasad et al[47], 2007	Randomized2	12	NCT-A/FCT-A, NCT-B/FCT-B, PCT, BDT	Lactulose vs no treatment	Psychometry	31/30	ITT analysis: Improvement in 20/31 (64.5%) vs 2/30 (6.7%); NNT:2
Horsmans et al[55], 1997	Randomized, double-blind	2	NCT, RTT.	Lactulose vs lactose as placebo4,5	Psychometry	7/7	Improvement in time on Psychometric test on lactulose group respect to basal values.7 Rate of improvement NCT: 5/7 (71.42%) vs 1/7 (14.28%); NNT:2
Sharma et al[50], 2008	Randomized2	4	NCT-A/FCT-A, NCT-B/FCT-B, P300ERP	Lactulose, probiotics, and lactulose + probiotics5	Psychometry, P300ERP6	35/35/35	Normalization in 17/31 (54.8%), 16/31 (51.6%), and 17/30 (56.6%) of MHE patients
Morgan et al[60], 1989	Cross-over, randomized	83	EEG, NCT, DST, DCT	Lactulose vs lactitol4	Psychometry	14/14	No differences between treatments in median change in psychometric time or scores
Possible history of OHE1
Dhiman et al[51], 2000	Randomized2	12	NCT-A/FCT-A, NCT-B /FCT-B, PCT, BDT.	Lactulose vs no lactulose4	MHE improvement	14/12	Improvement in 8/10 (80.0%) vs 0/8 (0.0%), P < 0.001)8
Wang et al[49], 2019	Randomized2	8	NCT-A, DST	Lactulose vs no lactulose	MHE reversal	67/31	ITT analysis: 43/67 (64.2%) vs 7/31 (22.6%); NNT: 3PPS: 41/59 (69.5%) vs 6/28 (21.4%); NNT: 2

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

²Unblinded study.

³Washout period of 4-6 wk between treatments.

⁴Compliance to treatment was not measured in one or the different treatment groups.

⁵Diet was not standardized according to the suggested treatment.

⁶Secondary objectives within the study.

⁷Analysis was performed within the same group (before–after treatment) despite the experimental design.

⁸Minimal hepatic encephalopathy reversion not measured. BDT: Block design test; DCT: Digit copying test; DST: Digit symbol test; EEG: Electroencephalogram; FCT-A: Figure connection test A; FCT-B: Figure connection test B; ITT: Intention to treat; 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; PPS: Per protocol analysis set; RTT: Race track test.