J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 10, Number 5, May 2018, pages 437-444

The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease

Figure 1. Correlations between blood zinc concentrations (vertical axis) and blood test results (absolute r ≥ 2.0). (a) Albumin. (b) Aspartate aminotransferase (AST). (c) Ammonia. (d) Prothrombin time. (e) Total bilirubin. (f) Total cholesterol. (g) BCAA-to-tyrosine ratio (BTR).

Figure 2. Blood albumin concentrations and the probability of zinc deficiency (blood zinc concentrations < 70 μg/dL).

Figure 3. Hypotheses of causal relationships between zinc deficiency and pathological conditions of liver cirrhosis. The solid arrow indicates the presence of a causal relationship; dashed arrows indicate the causal relationship is unknown.

**Table 1.** Patients’ Characteristics
Values are expressed as mean ± SD. y/o: years old; HCV: hepatitis C virus; HBV: hepatitis B virus; NASH: non-alcoholic steatohepatitis; BMI: body mass index; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BUN: blood urea nitrogen; BCAA: branched-chain amino acid; HOMA-IR: homeostasis model assessment-insulin resistance; AFP: alpha-fetoprotein; DM: diabetes mellitus.
N	235
Age (y/o)	67.4 ± 11.1
Gender (male/female)	109/126
Etiology (HCV/HBV/alcohol/NASH/others)	148/27/25/15/20
BMI (kg/m²)	23.8 ± 4.1
Daily alcohol intake (none/< 60 g/≥ 60 g)	179/25/23
Platelets count (× 10³/mm³)	102.9 ± 64.4
AST (IU/L)	52.0 ± 32.1
ALT (IU/L)	41.8 ± 29.4
Albumin (g/dL)	3.67 ± 0.53
Total bilirubin (mg/dL)	1.10 ± 0.53
Prothrombin time (international normalized ratio)	1.13 ± 0.18
Creatinine (mg/dL)	0.90 ± 1.30
BUN (mg/dL)	16.4 ± 10.8
BCAA-to-tyrosine ratio (BTR)	3.97 ± 1.77
Child-Pugh score	6.03 ± 1.15
Ammonia (µg/dL)	48.7 ± 33.5
Total cholesterol (mg/dL)	157.9 ± 33.5
Triglycerides (mg/dL)	93.4 ± 49.6
Fasting blood glucose (mg/dL)	114.8 ± 31.7
HbA1c (%)	5.50 ± 1.03
HOMA-IR	5.71 ± 8.86
Zinc (µg/dL)	64.1 ± 15.8
Ferritin (ng/mL)	168.2 ± 522.0
AFP (ng/mL)	18.1 ± 37.4
Edema, ascites (+/-)	46/187
Administration of diuretics (+/-)	78/157
Administration of BCAA (+/-)	78/157
Administration of oral DM agents (+/-)	56/179
Administration of insulin (+/-)	22/213

Table 1. Patients’ Characteristics

Values are expressed as mean ± SD. y/o: years old; HCV: hepatitis C virus; HBV: hepatitis B virus; NASH: non-alcoholic steatohepatitis; BMI: body mass index; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BUN: blood urea nitrogen; BCAA: branched-chain amino acid; HOMA-IR: homeostasis model assessment-insulin resistance; AFP: alpha-fetoprotein; DM: diabetes mellitus.

235

Age (y/o)

67.4 ± 11.1

Gender (male/female)

109/126

Etiology (HCV/HBV/alcohol/NASH/others)

148/27/25/15/20

BMI (kg/m²)

23.8 ± 4.1

Daily alcohol intake (none/< 60 g/≥ 60 g)

179/25/23

Platelets count (× 10³/mm³)

102.9 ± 64.4

AST (IU/L)

52.0 ± 32.1

ALT (IU/L)

41.8 ± 29.4

Albumin (g/dL)

3.67 ± 0.53

Total bilirubin (mg/dL)

1.10 ± 0.53

Prothrombin time (international normalized ratio)

1.13 ± 0.18

Creatinine (mg/dL)

0.90 ± 1.30

BUN (mg/dL)

16.4 ± 10.8

BCAA-to-tyrosine ratio (BTR)

3.97 ± 1.77

Child-Pugh score

6.03 ± 1.15

Ammonia (µg/dL)

48.7 ± 33.5

Total cholesterol (mg/dL)

157.9 ± 33.5

Triglycerides (mg/dL)

93.4 ± 49.6

Fasting blood glucose (mg/dL)

114.8 ± 31.7

HbA1c (%)

5.50 ± 1.03

HOMA-IR

5.71 ± 8.86

Zinc (µg/dL)

64.1 ± 15.8

Ferritin (ng/mL)

168.2 ± 522.0

AFP (ng/mL)

18.1 ± 37.4

Edema, ascites (+/-)

46/187

Administration of diuretics (+/-)

78/157

Administration of BCAA (+/-)

78/157

Administration of oral DM agents (+/-)

56/179

Administration of insulin (+/-)

22/213

**Table 2.** Relationship Between Serum Zinc and Patients’ Characteristics (Continuous Variables)
	│r│	P value
y/o: years old; BMI: body mass index; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BUN: blood urea nitrogen; BCAA: branched-chain amino acid; HOMA-IR: homeostasis model assessment-insulin resistance; AFP: alpha-fetoprotein; DM: diabetes mellitus.
Age (y/o)	0.253	0.0014
BMI (kg/m²)	0.158	0.067
Platelets count (× 10³/mm³)	0.189	0.0177
AST (IU/L)	0.245	0.002
ALT (IU/L)	0.077	0.3384
Albumin (g/dL)	0.587	< 0.0001
Total bilirubin (mg/dL)	0.222	0.0053
Prothrombin time (international normalized ratio)	0.255	0.0029
Creatinine (mg/dL)	0.149	0.0688
BUN (mg/dL)	0.128	0.1231
BCAA-to-tyrosine ratio (BTR)	0.357	< 0.0001
Child-Pugh score	0.469	< 0.0001
Ammonia (µg/dL)	0.246	0.0028
Total cholesterol (mg/dL)	0.314	< 0.0001
Triglycerides (mg/dL)	0.079	0.3493
Fasting blood glucose (mg/dL)	0.076	0.3527
HbA1c (%)	0.115	0.1623
HOMA-IR	0.072	0.4165
Ferritin (ng/mL)	0.069	0.4146
AFP (ng/mL)	0.17	0.0344

Table 2. Relationship Between Serum Zinc and Patients’ Characteristics (Continuous Variables)

│r│

P value

y/o: years old; BMI: body mass index; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BUN: blood urea nitrogen; BCAA: branched-chain amino acid; HOMA-IR: homeostasis model assessment-insulin resistance; AFP: alpha-fetoprotein; DM: diabetes mellitus.

Age (y/o)

0.253

0.0014

BMI (kg/m²)

0.158

0.067

Platelets count (× 10³/mm³)

0.189

0.0177

AST (IU/L)

0.245

0.002

ALT (IU/L)

0.077

0.3384

Albumin (g/dL)

0.587

< 0.0001

Total bilirubin (mg/dL)

0.222

0.0053

Prothrombin time (international normalized ratio)

0.255

0.0029

Creatinine (mg/dL)

0.149

0.0688

BUN (mg/dL)

0.128

0.1231

BCAA-to-tyrosine ratio (BTR)

0.357

< 0.0001

Child-Pugh score

0.469

< 0.0001

Ammonia (µg/dL)

0.246

0.0028

Total cholesterol (mg/dL)

0.314

< 0.0001

Triglycerides (mg/dL)

0.079

0.3493

Fasting blood glucose (mg/dL)

0.076

0.3527

HbA1c (%)

0.115

0.1623

HOMA-IR

0.072

0.4165

Ferritin (ng/mL)

0.069

0.4146

AFP (ng/mL)

0.17

0.0344

**Table 3.** Relationship Between Serum Zinc and Patients' Characteristics (Categorized Variables)
	Serum level of zinc (µg/dL)	P value
Values are expressed as mean ± SD. C: hepatitis C virus; B: hepatitis B virus; Al: alcohol; N: non-alcoholic steatohepatitis; O: others; BCAA: branched-chain amino acid; DM: diabetes mellitus.
Gender (male/female)	65.7 ± 16.3/62.6 ± 15.3	0.2423
Etiology (C/B/Al/N/O)	62.2 ± 14.9/72.9 ± 14.3/66.1 ± 20.5/60.8 ± 13.7/60.9 ± 14.8	0.04
Daily alcohol intake (none/< 60g/≥ 60 g)	62.3 ± 15.0/73.0 ± 19.3/63.4±16.1	0.1132
Edema or ascites (+/-)	56.0 ± 19.6/65.9 ± 14.3	< 0.0001
Hepatic encephalopathy(+/-)	51.3 ± 18.3/64.8 ± 15.4	0.0215
Administration of diuretics (+/-)	58.6 ± 18.9/65.6 ± 14.6	0.0045
Administration of BCAA (+/-)	55.0 ± 13.1/70.5 ± 14.4	< 0.0001
Administration of oral DM agents (+/-)	65.0 ± 16.4/63.8 ± 15.7	0.7637
Administration of insulin (+/-)	61.9 ± 19.3/64.3 ± 15.5	0.347

Table 3. Relationship Between Serum Zinc and Patients' Characteristics (Categorized Variables)

Serum level of zinc (µg/dL)

P value

Values are expressed as mean ± SD. C: hepatitis C virus; B: hepatitis B virus; Al: alcohol; N: non-alcoholic steatohepatitis; O: others; BCAA: branched-chain amino acid; DM: diabetes mellitus.

Gender (male/female)

65.7 ± 16.3/62.6 ± 15.3

0.2423

Etiology (C/B/Al/N/O)

62.2 ± 14.9/72.9 ± 14.3/66.1 ± 20.5/60.8 ± 13.7/60.9 ± 14.8

0.04

Daily alcohol intake (none/< 60g/≥ 60 g)

62.3 ± 15.0/73.0 ± 19.3/63.4±16.1

0.1132

Edema or ascites (+/-)

56.0 ± 19.6/65.9 ± 14.3

< 0.0001

Hepatic encephalopathy(+/-)

51.3 ± 18.3/64.8 ± 15.4

0.0215

Administration of diuretics (+/-)

58.6 ± 18.9/65.6 ± 14.6

0.0045

Administration of BCAA (+/-)

55.0 ± 13.1/70.5 ± 14.4

< 0.0001

Administration of oral DM agents (+/-)

65.0 ± 16.4/63.8 ± 15.7

0.7637

Administration of insulin (+/-)

61.9 ± 19.3/64.3 ± 15.5

0.347