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 12, Number 8, August 2020, pages 472-482

Non-Alcoholic Fatty Liver Disease Modifies Serum Gamma-Glutamyl Transferase in Cigarette Smokers

Figure 1. Box plot of GGT levels by the combination of smoking status and presence of HS. GGT: gamma-glutamyl transferase; HS: hepatic steatosis.

Figure 2. Distribution of GGT quartiles by smoking status and presence of NAFLD. GGT: gamma-glutamyl transferase; NAFLD: non-alcoholic fatty liver disease.

Figure 3. Distribution of GGT quartiles by smoking status and presence of metabolic syndrome. GGT: gamma-glutamyl transferase.

Figure 4. β-coefficient of the linear regression of smoking and GGT level stratified by gender. GGT: gamma-glutamyl transferase.

**Table 1.** Baseline Characteristics of Study Population
Clinical, anthropometric and biochemical characteristics	Smokers (-) and NAFLD (-) (N = 3,731)	Smokers (-) and NAFLD (+) (N = 2,060)	Smokers (+) and NAFLD (-) (N = 324)	Smokers (+) and NAFLD (+) (N = 239)	P-value
NAFLD: non-alcoholic fatty liver disease; BMI: body mass index; SD: standard deviation; SBP: systolic blood pressure; DBP: diastolic blood pressure; HTN: hypertension; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; HDL-C: high-density lipoprotein cholesterol; LDL: low-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high-sensitivity C-reactive protein; TG: triglycerides.
Male (%)	71	94	70	95	< 0.001
Mean age, years (± SD)	42 (9)	46 (9)	42 (10)	47 (9)	< 0.001
Mean BMI, kg/m² (± SD)	25 (3)	29 (4)	25 (3)	29 (3)	< 0.001
Mean waist circumference, cm (± SD)	87 (10)	100 (10)	87 (11)	100 (9)	< 0.001
Obesity, BMI ≥ 30 kg/m² (%)	9	46	12	45	< 0.001
Mean SBP, mm Hg (± SD)	116 (12)	124 (12)	116 (12)	124 (12)	< 0.001
Mean DBP, mm Hg (± SD)	75 (8)	80 (7)	75 (8)	80 (8)	< 0.001
HTN present (%)	8	22	8	21	< 0.001
Median AST, IU/L (interquartile range)	27 (24 - 32)	32 (28 - 39)	26 (23 - 31)	30 (26 - 37)	< 0.001
Median ALT, IU/L (interquartile range)	29 (23 - 37)	43 (33 - 56)	28 (21 - 36)	39 (31 - 53)	< 0.001
Median GGT, IU/L (interquartile range)	26 (19 - 36)	40 (30 - 56)	28 (21 - 43)	42 (33 - 62)	< 0.001
Median TG, mg/dL (interquartile range)	99 (74 - 136)	149 (109 - 208)	113 (84 - 163)	179 (124 - 240)	< 0.001
Mean HDL, mg/dL (± SD)	52 (14)	43 (10)	49 (13)	42 (10)	< 0.001
Mean LDL, mg/dL (± SD)	128 (32)	136 (34)	129 (35)	135 (34)	< 0.001
Mean FBG, mg/dL (± SD)	87 (9)	93 (12)	87 (9)	93 (12)	< 0.001
Median hs-CRP, mg/L (interquartile range)	1 (0.5 - 0.9)	1.7 (0.9 - 3)	1.2 (0.5 - 2.6)	1.8 (1 - 3.5)	< 0.001
High hs-CRP (≥ 3 mg/L) (%)	28	36	32	41	< 0.001
Mean uric acid, mg/dL (± SD)	5.4 (4.4 - 6.3)	6.4 (5.7 - 7.2)	5.4 (4.6 - 6.4)	6.3 (5.6 - 7)	< 0.001
Antihypertensive (%)	8	21	7	21	< 0.001
Lipid lowering medication (%)	7	12	7	14	< 0.001
Subjects with metabolic syndrome (%)	8	41	11	46	< 0.001
Median TG/HDL-C (interquartile range)	1.9 (1.3 - 3)	3.5 (2.4 - 5.4)	2.4 (1.5 - 3.8)	4.4 (2.8 - 6.5)	< 0.001

Table 1. Baseline Characteristics of Study Population

Clinical, anthropometric and biochemical characteristics

Smokers (-) and NAFLD (-) (N = 3,731)

Smokers (-) and NAFLD (+) (N = 2,060)

Smokers (+) and NAFLD (-) (N = 324)

Smokers (+) and NAFLD (+) (N = 239)

P-value

NAFLD: non-alcoholic fatty liver disease; BMI: body mass index; SD: standard deviation; SBP: systolic blood pressure; DBP: diastolic blood pressure; HTN: hypertension; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; HDL-C: high-density lipoprotein cholesterol; LDL: low-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high-sensitivity C-reactive protein; TG: triglycerides.

Male (%)

< 0.001

Mean age, years (± SD)

42 (9)

46 (9)

42 (10)

47 (9)

< 0.001

Mean BMI, kg/m² (± SD)

25 (3)

29 (4)

25 (3)

29 (3)

< 0.001

Mean waist circumference, cm (± SD)

87 (10)

100 (10)

87 (11)

100 (9)

< 0.001

Obesity, BMI ≥ 30 kg/m² (%)

< 0.001

Mean SBP, mm Hg (± SD)

116 (12)

124 (12)

116 (12)

124 (12)

< 0.001

Mean DBP, mm Hg (± SD)

75 (8)

80 (7)

75 (8)

80 (8)

< 0.001

HTN present (%)

< 0.001

Median AST, IU/L (interquartile range)

27 (24 - 32)

32 (28 - 39)

26 (23 - 31)

30 (26 - 37)

< 0.001

Median ALT, IU/L (interquartile range)

29 (23 - 37)

43 (33 - 56)

28 (21 - 36)

39 (31 - 53)

< 0.001

Median GGT, IU/L (interquartile range)

26 (19 - 36)

40 (30 - 56)

28 (21 - 43)

42 (33 - 62)

< 0.001

Median TG, mg/dL (interquartile range)

99 (74 - 136)

149 (109 - 208)

113 (84 - 163)

179 (124 - 240)

< 0.001

Mean HDL, mg/dL (± SD)

52 (14)

43 (10)

49 (13)

42 (10)

< 0.001

Mean LDL, mg/dL (± SD)

128 (32)

136 (34)

129 (35)

135 (34)

< 0.001

Mean FBG, mg/dL (± SD)

87 (9)

93 (12)

87 (9)

93 (12)

< 0.001

Median hs-CRP, mg/L (interquartile range)

1 (0.5 - 0.9)

1.7 (0.9 - 3)

1.2 (0.5 - 2.6)

1.8 (1 - 3.5)

< 0.001

High hs-CRP (≥ 3 mg/L) (%)

< 0.001

Mean uric acid, mg/dL (± SD)

5.4 (4.4 - 6.3)

6.4 (5.7 - 7.2)

5.4 (4.6 - 6.4)

6.3 (5.6 - 7)

< 0.001

Antihypertensive (%)

< 0.001

Lipid lowering medication (%)

< 0.001

Subjects with metabolic syndrome (%)

< 0.001

Median TG/HDL-C (interquartile range)

1.9 (1.3 - 3)

3.5 (2.4 - 5.4)

2.4 (1.5 - 3.8)

4.4 (2.8 - 6.5)

< 0.001

**Table 2.** Linear Regression of the Association Between Smoking and GGT Level Stratified by NAFLD
	Total (standardized coefficient)	HS+ (standardized coefficient)	HS- (standardized coefficient)	Interaction (HS-smoking)
P < 0.05, P < 0.005, **P < 0.001. Model 1: unadjusted. Model 2: adjusted for age, gender. Model 3: model 2 + SBP, waist circumference, fasting glucose, lipid lowering medications, hypertension meds, LDL-C, AST, alcohol consumption and C-reactive protein. GGT: gamma-glutamyl transferase; NAFLD: non-alcoholic fatty liver disease; HS: hepatic steatosis; SBP: systolic blood pressure; LDL-C: low-density lipoprotein cholesterol; AST: aspartate aminotransferase.
Model 1	6.83 (3.69 - 9.96)***	10.31 (4.68 - 15.95)***	2.36 (-1.14 - 5.85)	P = 0.012
Model 2	6.51 (3.46 - 9.56)***	10.19 (4.57 - 15.81)***	2.57 (-0.83 - 5.9)	P = 0.015
Model 3	4.65 (1.61 - 7.69)**	11.12 (5.76 - 16.48)***	-0.02 (-3.59 - 3.56)	P < 0.001

Table 2. Linear Regression of the Association Between Smoking and GGT Level Stratified by NAFLD

Total (standardized coefficient)

HS+ (standardized coefficient)

HS- (standardized coefficient)

Interaction (HS-smoking)

*P < 0.05, **P < 0.005, ***P < 0.001. Model 1: unadjusted. Model 2: adjusted for age, gender. Model 3: model 2 + SBP, waist circumference, fasting glucose, lipid lowering medications, hypertension meds, LDL-C, AST, alcohol consumption and C-reactive protein. GGT: gamma-glutamyl transferase; NAFLD: non-alcoholic fatty liver disease; HS: hepatic steatosis; SBP: systolic blood pressure; LDL-C: low-density lipoprotein cholesterol; AST: aspartate aminotransferase.

Model 1

6.83 (3.69 - 9.96)***

10.31 (4.68 - 15.95)***

2.36 (-1.14 - 5.85)

P = 0.012

Model 2

6.51 (3.46 - 9.56)***

10.19 (4.57 - 15.81)***

2.57 (-0.83 - 5.9)

P = 0.015

Model 3

4.65 (1.61 - 7.69)**

11.12 (5.76 - 16.48)***

-0.02 (-3.59 - 3.56)

P < 0.001

**Table 3.** Linear Regression of the Association Between Smoking and GGT Level Stratified by Obesity
	Obesity+ (standardized coefficient)	Obesity- (standardized coefficient)	Interaction (obesity-smoking)
P < 0.05, P < 0.005, **P < 0.001. Model 1: unadjusted. Model 2: adjusted for age, gender. Model 3: model 2 + SBP, fasting glucose, lipid lowering medications, hypertension meds, LDL-C, AST, alcohol consumption and C-reactive protein. GGT: gamma-glutamyl transferase; SBP: systolic blood pressure; LDL-C: low-density lipoprotein cholesterol; AST: aspartate aminotransferase.
Model 1	11.14 (3.24 - 19.03)*	4.65 (1.43 - 7.87)*	P = 0.072
Model 2	10.46 (2.64 - 18.27)*	4.60 (1.48 - 7.73)**	P = 0.096
Model 3	12.73 (5.5 - 19.96)**	1.74 (-1.45 - 4.94)	P < 0.001

Table 3. Linear Regression of the Association Between Smoking and GGT Level Stratified by Obesity

Obesity+ (standardized coefficient)

Obesity- (standardized coefficient)

Interaction (obesity-smoking)

*P < 0.05, **P < 0.005, ***P < 0.001. Model 1: unadjusted. Model 2: adjusted for age, gender. Model 3: model 2 + SBP, fasting glucose, lipid lowering medications, hypertension meds, LDL-C, AST, alcohol consumption and C-reactive protein. GGT: gamma-glutamyl transferase; SBP: systolic blood pressure; LDL-C: low-density lipoprotein cholesterol; AST: aspartate aminotransferase.

Model 1

11.14 (3.24 - 19.03)*

4.65 (1.43 - 7.87)*

P = 0.072

Model 2

10.46 (2.64 - 18.27)*

4.60 (1.48 - 7.73)**

P = 0.096

Model 3

12.73 (5.5 - 19.96)**

1.74 (-1.45 - 4.94)

P < 0.001