Table 3.
Published Studies on Treatment of Minimal Hepatic Encephalopathy.
| First author | Year | Study type | MHE/CHE diagnosis | Active treatment (s) | Patients treated | Weeks of treatment | Objectives | Main results |
|---|---|---|---|---|---|---|---|---|
| Watanabe18 | 1997 | Original, randomized | NCT A, symbol digit test, BDT | Lactulose | 22 out of 36 | 8 | Psychometry | MHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. |
| Horsmans19 | 1997 | Original, randomized | NCT, RTT, sinusoid test, psychomotor performance tests | Lactulose | 7 out of 14 | 2 | Psychometry, ammonia | NCT improved respectively in 5/7 vs. 1/7; RRT in 6/7 vs. 4/7 and ammonia levels in 5/7 vs. 1/7. |
| Dhiman20 | 2000 | Original, randomized | NCT A, NCT B, FCT A, FCT B, PC, BDT | Lactulose | 10 out of 18 | 12 | Psychometry | Psychometry improvement in 8/10 vs. 0/8. |
| Prasad21 | 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. |
| Sharma22 | 2008 | Original, randomized controlled trial | NCT A, NCT B or FCT A and FCT B, CEP | Lactulose or probiotic or lactulose + probiotic | 92 (31/31) | 4 | Psychometry, CEP, ammonia | Normalization of all parameters in half of treated patients (17/31, 16/31 and 17/30 respectively). |
| Mittal23 | 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. |
| Sharma24 | 2012 | Original, randomized | NCT A, NCT B, FCT A, FCT B, digit symbol test, serial dotting test, LTT, CFF | Lactulose | 105 (55) | 12 | Psychometry; OHE development | Improvement of MHE in 21/32 (66%) vs. 9/36 (25%). |
| Sidhu25 | 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. |
| Pratap26 | 2015 | Original, randomized | NCT A, FCT B (or FCT A, FCT B), CEP | Lactulose or probiotic | 73 (40/33) | 8 | MHE measures, ammonia | Psychometric improvement in 23/33 and in 25/40. Improvement in MHE correlated with reduction of ammonia levels. |
| Sidhu27 | 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. |
| Bajaj28 | 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. |
| Liu29 | 2004 | Original, randomized | NCT, brainstem evoked potentials | Synbiotics or fiber | 55 (20/20) | 4 | Psychometry, ammonia psychometry | Modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child–Turcotte–Pugh functional class improved in nearly 50% of cases. |
| Malaguarnera30 | 2007 | Original, randomized | TMT A, TMT B, symbol digit test, BD, MMSE, EEG | Probiotic + prebiotic | 60 (30) | 12 | Psychometry, ammonia, EEG | Improvement in psychometry and ammonia; no EEG modifications. |
| Bajaj31 | 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. |
| Bajaj32 | 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. |
| Burkard33 | 2013 | Original, randomized | PHES battery | Potassium–iron–phosphate–citrate | 51 (25) | 4 | Psychometry | Normalization of psychometry in 72% vs. 26.9%. QoL improvement. |
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 overgrowth; CEP, cognitive evoked potentials.