Zeng 2021.

Study characteristics
Methods	Randomised, open‐label clinical trial
Participants	This trial assessed the effects of long‐term administration of low‐dose rifaximin versus 'conventional therapy' in preventing complications and prolonging survival in 195 people with decompensated cirrhosis. All participants were free of hepatic encephalopathy at baseline; the effects of rifaximin versus standard treatment for preventing the development of overt hepatic encephalopathy were assessed for this review. There were 97 participants in the rifaximin group and 98 in the standard of care group. Age (mean ± SD) years Rifaximin 56.01 ± 9.34 Control 55.47 ± 9.96 Proportion of men (n: %) Rifaximin 64/97 (66.0) Control 61/98 (62.2) Aetiology of cirrhosis (n: %) Rifaximin Hepatitis C 4 (4.1) Hepatitis B 50 (51.5) Alcohol 16 (16.5) Standard care Hepatitis C 1 (1.0) Hepatitis B 47 (48.0) Alcohol 16 (16.3)
Interventions	Intervention: rifaximin 400 mg twice daily Control intervention: standard care Co‐interventions: none Duration of treatment: 6 months treatment, with 6 months follow‐up
Outcomes	Neuropsychiatric assessment Mental status ‐ presumably West Haven criteria
Inclusion period	September 2014 to November 2017
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, adverse events, blood ammonia
Country of origin	A total of 8 investigatory centres in China
Notes	Publication status: full paper Vested interests bias: none Additional information: there was a significant imbalance in the proportion of participants in the rifaximin and control groups who had a history of hepatic encephalopathy at baseline (20.6 vs 4.1%; P < 0.001). Hence, the comparison of the number of episodes of overt hepatic encephalopathy during the follow‐up period between the two groups was analysed by adjusted logistic regression. The authors were contacted on 11 April 2021 for further information on co‐interventions given, quality of life outcomes, and hospital length of stay: response still awaited. Trial identifier: NCT: clinicaltrials.gov/ct2/show/NCT02190357
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible individuals were randomly allocated into a rifaximin group and a control group with a randomised block digital table in a ratio of 1:1.
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label trial
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outlined number of participants screened (n = 265), the number subsequently enrolled (n = 200) and the remaining participants after exclusion or withdrawal. All participants who discontinued the study drug were accounted for (intention‐to‐treat).
Selective reporting (reporting bias)	Low risk	All outcomes were reported.
Other bias	Low risk	No other bias detected.
Overall bias assessment (mortality)	Low risk	Low risk of bias for mortality outcomes
Overall bias assessment (non‐mortality outcomes)	High risk	Blinding and allocation concealment have a high risk of bias.

EEG: electroencephalogram; NAFLD/NASH: non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis; NCT‐A: Number Connection Test A; PHES: portosystemic hepatic encephalopathy score; PSE: portosystemic encephalopathy; SD: standard deviation; SEM: standard error of the mean; TIPS: transhepatic portalsystemic shunt