Table 1.

Published studies aimed to assess the role of treatment on quality of life of patients with minimal hepatic hencephalopathy

Author	Year	Study type	MHE/CHE diagnosis	Active treatment (s)	Patients treated	Weeks of treatment	Objectives	Main results
Prasad et al[10]	2007	Original, randomized	NCT A, NCT B, FCT A, FCT B, PC, BDT	Lactulose	45 (25)	12	Psychometry, QoL	Significant improvement in psychometry: P < 0001; and QoL: P < 0.002. Improvement in HRQoL was related to the improvement in psychometry.
Sidhu et al[43]	2011	Original, randomized	NCT A, FCT A, Digit Symbol test, BDT, PC	Rifaximin	94 (49)	8	MHE reversal, QoL	MHE reversal in 37/49 vs 9/45. Improvement in QoL. Improvement in HRQoL correlated with improvement in psychometry
Sidhu et al[65]	2016	Original, randomized	NCT A, FCT A, Digit Symbol test, BDT, PC	Lactulose vs Rifaximin	112 (55/57)	12	MHE reversal, QoL	MHE reversal in 38/55 and in 42/57; HRQoL was significantly improved in both groups
Mittal et al[68]	2011	Original, randomized	NCT A, NCT B, FCT A, FCT B, PC, BDT	Lactulose or Probiotics or LOLA	160 (40/40/40)	12	Psychometry, ammonia, QoL	MHE reversal in 19/40 vs 14/40 vs 14/40 vs 4/40. Improvement in QoL.
Bajaj et al[72]	2008	Original, randomized	NCT A, Digit Symbol Test, BDT	Probiotic yogurt	25 (17)	8	MHE reversal, OHE development, QoL, ammonia, cytokines	MHE reversal in 71% vs 0%; OHE development in 0% vs 25%; no differences in QoL and cytokine Levels. Excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence
Bajaj et al[81]	2011	Original, randomized	NCT A, NCT B, Digit Symbol test, BDT, ICT	Rifaximin	42 (21)	8	Psychometry, QoL, driving ability, anti-inflammatory interleukins	Improvement in psychometry, driving performance and QoL
Malaguarnera et al[76]	2018	Original, Observational	NCT-A, NCT-B, LTT, SDT, DST	Resveratrol	35 (35)	Variable	QoL, ammonia levels	Resveratrol showed efficacy in the treatment of depression, anxiety, and ammonia serum levels, and improved the quality of life Of MHE patients.
Malaguarnera et al[77]	2011	Randomized, double-blind, placebo-controlled study.	TMT-A, TMT-B	Acetyl-L-carnitine twice a day	33 (34)	13	Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis and QoL evaluations	treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression.
Zhang et al[82]	2015	Original	NCT A, NCT B, Digit Symbol test	Rifaximin	26 (26)	1	Psychometry, ammonia, SIBO	MHE reversal in 15/26; reduction in SIBO and ammonia levels
Bajaj et al[83]	2014	Original, randomized	NCT A NCT B, Digit Symbol test, BDT	Probiotics	30 (14)	8	Psychometry, ammonia, inflammatory markers, QoL	Reduction in endotoxin and TNF-α but not in cytokines. No effects on psychometric performance
Luo et al[84]	2011	Meta-analysis	Different diagnostic tools	Lactulose	434	Variable	Psychometry, ammonia levels, QoL, progression to OHE	Lactulose superior to placebo on all outcomes (psychometry: RR = 0.52, 95%CI: 0.44-0.62, P < 0.00001)

MHE: Minimal hepatic encephalopathy; OHE: Overt hepatic encephalopathy: HRQoL: Health related quality of life; NCT-A: Number connection test-A; NCT-B: Number connection test-B; BDT: Block design test; SDT: Serial dotting test; DST: Digit symbol test; LTT: Line tracing test; PHES: Psychometric hepatic encephalopathy score; ICT: Inhibitory control test; CFF: Critical flicker frequency; EEG: Electroencephalogram; ICT: Inhibitory control test; BCAA; Branched chain amino acids; SIBO: Small intestine bacterial overgrowt; CEP: Cognitive evoked potentials; TNF: Tumor necrosis factor.