Poudyal 2019.

Study characteristics
Methods	Randomised, three‐armed, open‐label clinical trial
Participants	This trial assessed the effects of lactulose, lactulose plus L‐ornithine L‐aspartate and lactulose plus rifaximin in 132 people with cirrhosis and an acute episode of hepatic encephalopathy, grade I‐IV. Comparisons between the lactulose plus rifaximin versus lactulose alone arms were included in the analyses. There were 44 participants in both included groups. Age (mean ± SD) years Lactulose plus rifaximin 48.2 ± 10.7 Lactulose alone 48.7 ± 9.0 Proportion of men (n: %) Lactulose plus rifaximin 37 (84) Lactulose alone 29 (66) Aetiology of cirrhosis (n: %) Lactulose plus rifaximin Alcohol 36 (81.8) Hepatitis B 3 (6.8) Hepatitis C 3 (6.8) Other 2 (4.6) Lactulose alone Alcohol 39 (88.6) Hepatitis B 3 (6.8) Hepatitis C 1 (2.3) Other 1 (2.3)
Interventions	Group 1: rifaximin 550 mg capsule twice daily plus lactulose 30 to 60 ml, thrice daily, to ensure passage of 2 to 3 semi‐soft stools a day Group 2: lactulose 30 to 60 ml, thrice daily, to ensure passage of 2 to 3 semi‐soft stools in a day Co‐intervention: other standard treatments according to need, including antibiotics Duration of treatment: until discharge from hospital or death
Outcomes	Neuropsychiatric assessment Mental status: West Haven criteria The criteria used to determine outcome were not detailed but were classified as complete reversal or treatment failure.
Inclusion period	February 2017 to January 2018
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, length of hospital stay
Country of origin	Single centre in Nepal
Notes	Publication status: full paper Vested interests bias: none Additional information: authors contacted on 13 April 2021 for further information on treatment duration, randomisation methods, allocation concealment, blinding methods, handling of incomplete data, trial registration status, serious adverse events, and data on our secondary outcomes. Response received on 16 April 2021.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The authors did not report the methods of random sequence generation, although the trial was reported as randomised. Author's response: "randomisation was simple randomisation".
Allocation concealment (selection bias)	Unclear risk	There was no information on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Author's response: "It was single blinded. Patient was blinded" However, one group received an IV preparation of LOLA while the other group received oral rifaximin.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Author's response: "It was single blinded. Patient was blinded" However, one group received an IV preparation while the other comparison group received tablets.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were accounted for.
Selective reporting (reporting bias)	Low risk	All predefined outcomes accounted for in the results
Other bias	Low risk	No other bias identified
Overall bias assessment (mortality)	Low risk	Deaths are reported.
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of detection bias