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Table 1 Characteristics of the selected randomized controlled trials

From: Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis

Author, Year

Trial design

Country

N (M:F)

Agea (yrs)

Etiology of cirrhosis (V/A/other)

HE grade (MHE/I/II)

Serum zinc levelsa (ug/dL)

CP scorea,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

C: 12 (7:5)

C: 52.7 ± 13.4

C: 64.5 ± 21

C: A/B/C = 1/9/2

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

C: 44 (23:21)

C: 49 ± 9

C: 52 ± 5

C: A/B/C = 0/35/9

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/dc and BCAA granules

BCAA granules

150–180

C: 21 (13:8)

C: 65.1 ± 11.3

C: 60.2 ± 9

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/dd and standard therapye

Standard therapye 30–60 mL/d

180

C: 40 (23:17)

C: 66.5 ± 7.4

C: 51.6 ± 13.3

C: A/B/C = 7/26/7

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

C: 5 (4:1)

C: 73.6 ± 8.4

C: 51.8 ± 8.3

ND

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

C: 27 (15/12)

C: 55.8 ± 9.2

C: 46.9 ± 10.5

C: A/B/C = 4/20/3

  1. 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
  2. aData reported as the mean ± standard deviation
  3. bCirrhosis staging reported as A: < 7; B: 7–9; and C: > 9
  4. 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
  5. dPolaprezinc was composed of zinc 51 mg and L-carnosine 174 mg
  6. eStandard therapy contained BCAA granules and lactulose 30–60 mL/d