Table 5.
Published studies using antibiotics for minimal hepatic encephalopathy treatment
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Ref.
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Study type
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Follow-up (wk)
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MHE diagnosis
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Active treatment (s)
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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% |
Studies in which the inclusion criteria comprise patient with clinical history to the overt hepatic encephalopathy events.
Unblinded study.
Compliance to treatment was not measured in one or the different treatment groups.
Diet was not standardized according to the suggested treatment.
Secondary objectives within the study.
Analysis was performed within the same group (before–after treatment) despite the experimental design.
Minimal 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.