. 2019 Jul 6;18:34. doi: 10.1186/s12937-019-0461-3

Table 1.

Characteristics of the selected randomized controlled trials

Author, Year	Trial design	Country	N (M:F)	Age^a (yrs)	Etiology of cirrhosis (V/A/other)	HE grade (MHE/I/II)	Serum zinc levels^a (ug/dL)	CP score^a,b/ classification	Intervention	Comparison	Treatment duration (days)
Reding, 1984 [14]	Randomized, double-blind, placebo-controlled	Belgium	Z: 10 (8:2)	Z: 52.1 ± 9.9	0/22/0	0/22/0	Z: 60.3 ± 17.9	Z: A/B/C = 1/8/1	Zinc acetate 600 mg/d	Placebo	7
Reding, 1984 [14]	Randomized, double-blind, placebo-controlled	Belgium	C: 12 (7:5)	C: 52.7 ± 13.4	0/22/0	0/22/0	C: 64.5 ± 21	C: A/B/C = 1/9/2	Zinc acetate 600 mg/d	Placebo	7
Riggio, 1991 [15]	Double-blind crossover trial	Italy	10:5	47–71	6/5/4	3/10/2	29.9 ± 8.4	ND	Zinc sulfate 600 mg/d	Placebo	10
Bresci, 1993 [13]	Randomized, double-blind, placebo-controlled	Italy	Z: 46 (33:13)	Z: 51 ± 9	50/30/10	≤ grade I	Z: 50 ± 6	Z: A/B/C = 0/30/16	Zinc acetate 600 mg/d and lactulose	Lactulose 90 g/d	180
Bresci, 1993 [13]	Randomized, double-blind, placebo-controlled	Italy	C: 44 (23:21)	C: 49 ± 9	50/30/10	≤ grade I	C: 52 ± 5	C: A/B/C = 0/35/9	Zinc acetate 600 mg/d and lactulose	Lactulose 90 g/d	180
Hayashi, 2007 [26]	Randomized, double-blind, placebo-controlled	Japan	Z: 19 (10:9)	Z: 66.0 ± 9.9	38/0/2	ND	Z: 58.4 ± 9.2	ND	Zinc sulfate 200 or 600 mg/d^c and BCAA granules	BCAA granules	150–180
Hayashi, 2007 [26]	Randomized, double-blind, placebo-controlled	Japan	C: 21 (13:8)	C: 65.1 ± 11.3	38/0/2	ND	C: 60.2 ± 9	ND	Zinc sulfate 200 or 600 mg/d^c and BCAA granules	BCAA granules	150–180
Takuma, 2010 [28]	Randomized, unblinded, placebo-controlled	Japan	Z: 39 (17:22)	Z: 66.5 ± 5.7	58/13/8	0/49/30	Z: 48.9 ± 9.3	Z: A/B/C = 8/23/8	Polaprezinc 225 mg/d^d and standard therapy^e	Standard therapy^e 30–60 mL/d	180
Takuma, 2010 [28]	Randomized, unblinded, placebo-controlled	Japan	C: 40 (23:17)	C: 66.5 ± 7.4	58/13/8	0/49/30	C: 51.6 ± 13.3	C: A/B/C = 7/26/7	Polaprezinc 225 mg/d^d and standard therapy^e	Standard therapy^e 30–60 mL/d	180
Katayama, 2014 [27]	Randomized, double-blind, placebo-controlled	Japan	Z: 7 (3:4)	Z: 64.3 ± 7.1	ND	≤ grade 1	Z: 55.1 ± 8.1	ND	Zinc acetate 150 mg/d	Placebo	90
Katayama, 2014 [27]	Randomized, double-blind, placebo-controlled	Japan	C: 5 (4:1)	C: 73.6 ± 8.4	ND	≤ grade 1	C: 51.8 ± 8.3	ND	Zinc acetate 150 mg/d	Placebo	90
Mousa, 2016 [17]	Randomized, double-blind, placebo-controlled	Egypt	Z: 31 (16/14)	Z: 54.5 ± 9.6	57/0/3	58/0/0	Z: 49.6 ± 11.2	Z: A/B/C = 6/22/3	Zinc gluconate 175 mg/d, Vit. A 50,000 IU, Vit. C 500 mg, Vit. E 100 mg, and lactulose	Lactulose 30–60 ml twice to three times a day	90
Mousa, 2016 [17]	Randomized, double-blind, placebo-controlled	Egypt	C: 27 (15/12)	C: 55.8 ± 9.2	57/0/3	58/0/0	C: 46.9 ± 10.5	C: A/B/C = 4/20/3		Lactulose 30–60 ml twice to three times a day	90

M male, F female, N number, CP Child-Pugh, Z zinc supplementation, d day, C control, ND no data, HE hepatic encephalopathy, MHE minimal hepatic encephalopathy, V viral, A alcoholic, BZL blood zinc level, BCAA Branched-chain amino acids

^aData reported as the mean ± standard deviation

^bCirrhosis staging reported as A: < 7; B: 7–9; and C: > 9

^cThe zinc sulfate dose was 600 mg/d when serum zinc levels of < 50 μg/dL and was 200 mg/d when zinc levels of 50–70 μg/dL

^dPolaprezinc was composed of zinc 51 mg and L-carnosine 174 mg

^eStandard therapy contained BCAA granules and lactulose 30–60 mL/d