Summary of findings 1. Summary of findings table ‐ Rifaximin compared to placebo/no intervention for prevention and treatment of hepatic encephalopathy in people with cirrhosis.

Rifaximin compared to placebo/no intervention for prevention and treatment of hepatic encephalopathy in people with cirrhosis
Patient or population: prevention and treatment of hepatic encephalopathy in people with cirrhosis Setting: inpatient or outpatient Intervention: rifaximin Comparison: placebo/no intervention
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo/no intervention	Risk with rifaximin
Mortality ‐ total number Follow‐up: mean 85.7 days	58 per 1000	48 per 1000 (29 to 80)	RR 0.83 (0.50 to 1.38)	1007 (13 RCTs)	⊕⊕⊕⊝ Moderatea,b,c,d	Rifaximin likely results in little to no difference in mortality.
Serious adverse events ‐ total number of participants Follow‐up: mean 95.5 days	184 per 1000	194 per 1000 (153 to 243)	RR 1.05 (0.83 to 1.32)	801 (9 RCTs)	⊕⊕⊕⊝ Moderateb,c,d,e	Rifaximin likely results in little to no difference in serious adverse events.
Health‐related quality of life ‐ assessed using: SIP score (3 trials) or EQ‐5D‐3L score (1 trial) Follow‐up: mean 64.5 days	The mean health‐related quality of life ‐ total ranged from 0 to 12 in SIP score or EQ‐5D‐3L score	MD 1.43 lower in SIP score or EQ‐5D‐3L score (2.87 lower to 0.02 higher)	‐	214 (4 RCTs)	⊕⊕⊕⊝ Moderatec,e,f,g	Rifaximin likely results in little to no difference in health‐related quality of life overall, although there is a suggestion of benefit in minimal hepatic encephalopathy.
Hepatic encephalopathy ‐ total number Follow‐up: mean 86 days	479 per 1000	268 per 1000 (192 to 369)	RR 0.56 (0.42 to 0.77)	1009 (13 RCTs)	⊕⊕⊕⊝ Moderatec,e,h,i	Rifaximin likely improves hepatic encephalopathy overall and in minimal hepatic encephalopathy.
Non‐serious adverse events ‐ total number of particiapnts Follow‐up: mean 99.2 days	312 per 1000	871 per 1000 (137 to 1000)	RR 2.79 (0.44 to 17.78)	639 (6 RCTs)	⊕⊝⊝⊝ Very lowc,e,j,k	The evidence is very uncertain about the effect of rifaximin on non‐serious adverse events overall.
Blood ammonia measured in μmol/L, μg/dL or mmol/L at trial end Follow‐up: mean 105 days	The mean blood ammonia ranged from 46 to 126.4	MD 3.2 higher (7.74 lower to 14.14 higher)	‐	381 (6 RCTs)	⊕⊕⊝⊝ Lowc,e,g,h	Rifaximin may result in little to no difference in blood ammonia assessed at trial end.
Number Connection Test A assessed using: Z‐score (1 trial) or seconds (3 trials) assessed at trial end Follow‐up: mean 66.8 days	‐	SMD 0.31 SD lower (1.22 lower to 0.60 higher)	‐	203 (4 RCTs)	⊕⊕⊕⊝ Moderatec,e,l,m	Rifaximin likely results in little to no difference in Number Connection Test A performance at trial end.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomised clinical trial; RR: risk ratio; SIP: sickness impact profile; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
See interactive version of this table: https://gdt.gradepro.org/presentations/#/isof/isof_question_revman_web_429379845038926839.

^a Risk of bias: mortality outcomes unlikely to be affected by bias, not downgraded.
^b Inconsistency: I² = 0 and all studies consistently show no net effect; not downgraded.
^c Indirectness: populations, interventions, outcomes, and comparisons are appropriate; not downgraded.
^d Imprecision: optimal information size not met, downgraded by 1 level.
^e Risk of bias: although trials were at a high risk of bias, sensitivity analyses did not change our findings; not downgraded.
^f Although the overall I² statistic was 81, the inconsistencies could be explained by our subgroup analyses; not downgraded.
^g Imprecision: optimal information size met, but confidence interval includes both benefit and harm (overlaps 0); downgraded by 1 level.
^h Inconsistency: possible moderate heterogeneity within and between subgroups; downgraded by 1 level.
ⁱ Imprecision: optimal information size met; not downgraded.
^j Inconsistency: possible substantial heterogeneity within and between subgroups; downgraded by 1 level.
^k Imprecision: optimal information size met; there were few events and the confidence intervals were wide, including both appreciable benefit and appreciable harm; downgraded by 2 levels.
^l Inconsistency: although heterogeneity exists overall and in subgroup analysis, there are few trials, of which all show no benefit, so are consistent; not downgraded.
^m Imprecision: standardised mean difference limits assessment; however, the small sample size increases imprecision; downgraded by 1 level.