Comparison 1.

Flumazenil versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality	11	842	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.48, 1.16]
1.1 Overt hepatic encephalopathy	10	822	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.48, 1.16]
1.2 Minimal hepatic encephalopathy	2	20	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 All‐cause mortality and bias control	12	844	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.48, 1.16]
2.1 Low risk of bias	1	527	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.37, 1.53]
2.2 High risk of bias	11	317	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.43, 1.31]
3 All‐cause mortality and trial design	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
3.1 Cross‐over	6	592	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.35, 1.34]
3.2 Parallel‐arm	6	252	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.45, 1.44]
4 All‐cause mortality and duration of follow‐up	11		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
4.1 ≤ 1 day	5	176	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.38, 1.87]
4.2 > 1 day	6	666	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.42, 1.21]
5 Hepatic encephalopathy	9	824	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.71, 0.80]
5.1 Overt hepatic encephalopathy	9	814	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.67, 0.80]
5.2 Minimal hepatic encephalopathy	1	10	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.41, 1.39]
6 Hepatic encephalopathy and bias control	9	824	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.71, 0.80]
6.1 Low risk of bias	1	527	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.72, 0.84]
6.2 High risk of bias	8	297	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.61, 0.78]
7 Hepatic encephalopathy and trial design	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
7.1 Cross‐over	4	584	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.72, 0.83]
7.2 Parallel‐arm	5	240	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.59, 0.79]
8 Hepatic encephalopathy and duration of follow‐up	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
8.1 ≤ 1 day	4	164	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.60, 0.83]
8.2 > 1 day	5	660	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.62, 0.84]
9 Hepatic encephalopathy and acute liver failure	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
9.1 Cirrhosis	7	734	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.71, 0.82]
9.2 Acute liver failure or cirrhosis	2	90	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.47, 0.80]
10 Number Connection Test	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11 All‐cause mortality and acute liver failure	11	842	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.48, 1.16]
11.1 Participants with cirrhosis	9	752	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.45, 1.14]
11.2 Participants with cirrhosis or acute liver failure	2	90	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.31, 3.62]