Summary of findings 3. Summary of findings table ‐ Rifaximin plus non‐absorbable disaccharides compared to non‐absorbable disaccharides alone for prevention and treatment of hepatic encephalopathy in people with cirrhosis.

Rifaximin plus non‐absorbable disaccharides compared to non‐absorbable disaccharides alone 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 plus non‐absorbable disaccharides Comparison: non‐absorbable disaccharides alone
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with non‐absorbable disaccharides alone	Risk with rifaximin plus non‐absorbable disaccharides
Mortality ‐ total number Follow‐up: mean 93 days	148 per 1000	102 per 1000 (81 to 127)	RR 0.69 (0.55 to 0.86)	1946 (14 RCTs)	⊕⊕⊕⊝ Moderatea,b,c,d	Rifaximin plus non‐absorbable disaccharides likely reduces mortality slightly overall.
Serious adverse events ‐ total number of participants Follow‐up: mean 107.8 days	256 per 1000	169 per 1000 (115 to 251)	RR 0.66 (0.45 to 0.98)	1076 (7 RCTs)	⊕⊝⊝⊝ Very lowc,d,e,f	The evidence is very uncertain about the effect of rifaximin plus non‐absorbable disaccharides on serious adverse events.
Hepatic encephalopathy ‐ total number Follow‐up: mean 82 days	465 per 1000	270 per 1000 (223 to 330)	RR 0.58 (0.48 to 0.71)	2332 (17 RCTs)	⊕⊕⊝⊝ Lowc,g,h,i	Rifaximin plus non‐absorbable disaccharides may reduce hepatic encephalopathy overall.
Non‐serious adverse events ‐ total number of participants Follow‐up: mean 163.4 days	592 per 1000	521 per 1000 (509 to 680)	RR 0.99 (0.86 to 1.15)	384 (4 RCTs)	⊕⊝⊝⊝ Very lowc,j,k,l	The evidence is very uncertain about the effect of rifaximin plus non‐absorbable disaccharides on non‐serious adverse events.
Blood ammonia measured in μg/mL at trial end Follow‐up: mean 143 days	The mean blood ammonia ranged from 88.6 to 109	MD 6.88 lower (14.78 lower to 1.02 higher)	‐	325 (2 RCTs)	⊕⊝⊝⊝ Very lowc,m,n,o	The evidence is very uncertain about the effect of rifaximin plus non‐absorbable disaccharides on blood ammonia at trial end.
Number Connection Test A, assessed using: seconds (1 trial) or Z‐score (1 trial) at trial end Follow‐up: mean 68 days	‐	SMD 0.05 SD lower (1.28 lower to 1.17 higher)	‐	76 (2 RCTs)	⊕⊝⊝⊝ Very lowc,p,q,r	The evidence is very uncertain about the effect of rifaximin plus non‐absorbable disaccharides on Number Connection Test A 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_429381317235175431.

^a Risk of bias: mortality outcome is unlikely to be affected by bias and sensitivity analysis did not change our findings; not downgraded.
^b Inconsistency: most studies showed no difference and I² = 0% overall and for 2 subgroups, and 37% for acute hepatic encephalopathy; 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: with removal of high‐risk trials, sensitivity analysis leaves only 2 remaining studies with a new subgroup‐level benefit, limiting our certainty of the findings; downgraded by 2 levels.
^f Inconsistency: I² = 71% in acute hepatic encephalopathy and 67% overall. Most trials show no difference but 3 favour rifaximin; downgraded by 1 level.
^g Risk of bias: only 2 trials remained in our sensitivity analysis from 17 trials. Although no change was observed, our certainty is therefore limited. Low‐risk trials did show similar direction of effect to high‐risk trials; downgraded by 1 level.
^h Inconsistency: I² = 69% and 61% in 2 subgroup analyses, and 62% overall. Most trials show benefit, although there are some subgroup‐level outliers; downgraded by 1 level.
ⁱ Imprecision: optimal information size met, with most studies showing a benefit; not downgraded.
^j Risk of bias: only 2 trials from 8 in total remained in our sensitivity analysis, which changed our findings, and therefore our certainty is very limited; downgraded by 2 levels.
^k Inconsistency: most trials show no difference, I² = 0% in all analyses; not downgraded.
^l Some subgroups have few participants, causing wide confidence intervals; downgraded by 1 level.
^m Risk of bias: one of the two trials is at a high risk of bias. Although the sensitivity analysis does not change our findings, our certainty is therefore limited; downgraded by 1 level.
ⁿ Inconsistency: both trials showed no effect, I² = 0%; not downgraded.
^o Imprecision: optimal information size not met; there were few events and the confidence intervals were wide, including both appreciable benefit and appreciable harm; downgraded by 2 levels.
^p Risk of bias: only two trials were analysed, which are both at high risk. It is unclear whether low‐risk trials would show different findings and so our certainty is very limited; downgraded by 2 levels.
^q Inconsistency: despite the overall I² = 84%, both trials showed no benefit; not downgraded.
^r Imprecision: only 72 participants in 2 trials were included, with the effect including both benefit and harm, severely limiting our certainty; downgraded by 2 levels.