Moneim 2021.

Study characteristics
Methods	Randomised, open‐label clinical trial
Participants	The trial assessed the effects of rifaximin plus lactulose versus lactulose alone in preventing the development of hepatic encephalopathy in 100 people with hepatitis C‐related liver cirrhosis and a history of at least one previous episode of overt hepatic encephalopathy. All participants were classified as Grade I or less on the West‐Haven (Conn's) criteria at inclusion. There were 50 participants in the rifaximin plus lactulose group, and 50 in the lactulose alone group. Age (mean ± SD) years Rifaximin plus lactulose 58.5 ± 7.8 Lactulose only 60.5 ± 7.7 Proportion of men (%) Rifaximin plus lactulose 60 Lactulose only 58 Aetiology of cirrhosis: all participants had hepatitis C‐related liver cirrhosis.
Interventions	Intervention: rifaximin 400 mg thrice daily plus lactulose 30 to 45 ml thrice daily to produce 2 to 3 soft stools per day Control intervention: lactulose 30 to 45 ml thrice daily to produce 2 to 3 soft stools per day. Co‐interventions: none Duration of treatment: 6 months
Outcomes	Neuropsychiatric assessment Mental status: West Haven criteria
Inclusion period	January 2015 to December 2018
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, adverse events
Country of origin	Single centre in Egypt
Notes	Publication status: full paper Vested interests bias: none reported Additional information: overall, 22% of participants in the intervention group and 20% in the control group had grade I hepatic encephalopathy at baseline. Recurrence defined as the development of grade II change or more.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random assignment using a computer random sequence generator in a 1:1 allocation ratio.
Allocation concealment (selection bias)	Low risk	Sequentially numbered, opaque, sealed, envelopes were used and kept by the hospital pharmacist. These were opened only once participant details were written on the envelope.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants who received treatment were included in the safety and efficacy analyses. Microbial resistance data was missing for 56 of the 100 participants due to technical problems; this was analysed using intention‐to‐treat analysis.
Selective reporting (reporting bias)	Low risk	All clinically relevant outcomes reported in the full‐text when compared to the trial registry.
Other bias	Low risk	No other bias detected
Overall bias assessment (mortality)	Low risk	Low risk of bias in all domains except for performance and detection bias ‐ unlikely to influence mortality
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of bias in performance and detection domains