Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis

doi:10.3748/wjg.v24.i13.1440

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Apr 7, 2018; 24(13): 1440-1450
Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1440

Table 1 Comparison of clinicopathological features at the time of biopsy between mild drinking and non-drinking groups

	Mild drinking group (n = 93)	Non-drinking group (n = 208)	P value
Age (yr)	55 (19-77)	56 (10-84)	0.50
Male	52 (56)	84 (40)	0.01
Body mass index (kg/m²)	26.5 (18.3-40.0)	26.2 (17.8-41.0)	0.53
Co-existing disease
Diabetes mellitus	32 (34)	78 (38)	0.57
Hypertension	41 (44)	81 (39)	0.44
Hyperlipidemia	55 (59)	135 (66)	0.29
Laboratory data
Albumin (mg/dL)	4.5 (3.2-5.4)	4.5 (3.0-5.2)	0.48
Total bilirubin (mg/dL)	0.91 (0.40-2.20)	0.86 (0.38-2.64)	0.12
Aspartate aminotransferase (IU/L)	44 (20-175)	47 (13-263)	0.80
Alanine aminotransferase (IU/L)	68 (22-237)	67 (13-522)	0.74
Gamma-glutamyl transpeptidase (IU/L)	69 (19-400)	54 (7-544)	0.02
Cholinesterase (IU/L)	363 (171-586)	384 (189-591)	0.05
Fasting blood sugar (mg/dL)	106 (84-215)	108 (77-221)	0.63
HOMA-IR	3.4 (1.0-42.6)	3.3 (0.3-24.5)	0.58
HbA1c (%)	5.9 (5.1-9.8)	6.0 (4.9-12.3)	0.21
Total cholesterol (mg/dL)	205 (138-336)	208 (70-295)	0.68
Triglyceride (mg/dL)	115 (42-404)	133 (32-801)	0.14
Platelet (×10⁴/μL)	21.1 (5.3-45.4)	22.1 (7.2-40.7)	0.04
Hyaluronic acid (ng/mL)	43 (12-320)	49 (9-1611)	0.57
Type IV collagen 7s (ng/mL)	4.3 (2-20)	4.5 (2-11)	0.93
Alpha-fetoprotein (ng/mL)	3.3 (0.7-13.5)	3.0 (0.7-20.3)	0.41
Pathology
Steatosis			0.86
1	33 (36)	64 (31)
2	36 (39)	90 (43)
3	24 (26)	54 (26)
Lobular inflammation			0.14
0	5 (5)	8 (4)
1	47 (51)	83 (40)
2	37 (40)	95 (46)
3	4 (4)	22 (11)
Ballooning			0.82
0	18 (19)	41 (20)
1	50 (54)	118 (57)
2	25 (27)	49 (24)
NAFLD activity score			0.79
1	4 (4)	5 (2)
2	8 (9)	16 (8)
3	16 (17)	34 (16)
4	17 (18)	32 (15)
5	25 (27)	62 (30)
6	14 (15)	36 (17)
7	9 (10)	18 (9)
8	0 (0)	5 (2)
Fibrosis			0.39
0	17 (18)	40 (19)
1	39 (42)	93 (45)
2	10 (11)	25 (12)
3	18 (19)	42 (20)
4	9 (10)	8 (4)
Fibrosis 3-4 (Advanced fibrosis)	27 (29)	50 (24)	0.36
Fibrosis 4 (Cirrhosis)	9 (10)	8 (4)	0.04

Data are expressed as median (range) or n (%). HbA1c: Hemoglobin A1c; HOMA-IR: Homeostasis model assessment for insulin resistance.

Table 2 Comparison of clinicopathological features at the time of biopsy between hepatocellular carcinoma and non- hepatocellular carcinoma groups

	HCC group (n = 9)	Non-HCC group (n = 292)	P value
Age (yr)	65 (56-84)	55 (10-81)	< 0.01
Male	3 (33)	133 (46)	0.52
Body mass index (kg/m²)	26.0 (18.3-28.7)	26.2 (17.8-41.0)	0.23
Drinking habit	6 (67)	87 (30)	0.02
Co-existing disease
Diabetes mellitus	8 (89)	102 (35)	< 0.01
Hypertension	9 (100)	113 (39)	< 0.01
Hyperlipidemia	3 (33)	187 (65)	0.06
Laboratory data
Albumin (mg/dL)	4.0 (3.7-4.6)	4.5 (3.0-5.4)	< 0.01
Total bilirubin (mg/dL)	0.91 (0.44-1.61)	0.88 (0.38-2.64)	0.75
Aspartate aminotransferase (IU/L)	52 (32-95)	46 (13-263)	0.71
Alanine aminotransferase (IU/L)	53 (16-132)	68 (13-522)	0.11
Gamma-glutamyl transpeptidase (IU/L)	65 (28-192)	56 (7-544)	0.48
Cholinesterase (IU/L)	249 (190-434)	380 (171-591)	< 0.01
Fasting blood sugar (mg/dL)	133 (84-172)	106 (77-221)	0.13
HOMA-IR	5.8 (1.2-9.8)	3.3 (0.3-42.6)	0.18
HbA1c (%)	6.6 (6.0-7.0)	5.9 (4.9-12.3)	0.01
Total cholesterol (mg/dL)	176 (153-264)	208 (70-336)	0.02
Triglyceride (mg/dL)	85 (64-140)	130 (32-801)	0.02
Platelet (×10⁴/μL)	11.0 (6.4-18.6)	22.0 (5.3-45.4)	< 0.01
Hyaluronic acid (ng/mL)	42 (17-263)	42 (9-1180)	0.96
Type IV collagen 7s (ng/mL)	5.6 (4.7-8.4)	4.4 (2.0-20.0)	0.03
Alpha-fetoprotein (ng/mL)	6.0 (3.7-20.3)	3.0 (0.7-13.2)	< 0.01
Pathology
Steatosis			0.01
1	7 (78)	90 (31)
2	2 (22)	124 (43)
3	0 (0)	78 (27)
Lobular inflammation			0.21
0	0 (0)	13 (4)
1	2 (22)	128 (44)
2	7 (78)	125 (43)
3	0 (0)	26 (9)
Ballooning			0.76
0	1 (11)	58 (20)
1	6 (67)	162 (56)
2	2 (22)	72 (25)
NAFLD activity score			0.53
1	0 (0)	9 (3)
2	0 (0)	24 (8)
3	3 (33)	47 (16)
4	2 (22)	47 (16)
5	4 (44)	83 (28)
6	0 (0)	50 (17)
7	0 (0)	27 (9)
8	0 (0)	5 (2)
Fibrosis			< 0.01
0	0 (0)	57 (20)
1	0 (0)	132 (45)
2	0 (0)	35 (12)
3	4 (44)	56 (19)
4	5 (56)	12 (4)

Data are expressed as median (range) or n (%). HCC: Hepatocellular carcinoma; HOMA-IR: Homeostasis model assessment for insulin resistance; HbA1c: Hemoglobin A1c; NAFLD: Non-alcoholic fatty liver disease.

Table 3 Factors related to hepatic carcinogenesis by multivariate survival analysis using Cox's regression model for all patients

	P value	Relative risk	95%CI
Fibrosis	< 0.01	11.6	2.36-56.9
Diabetes mellitus	< 0.01	89.5	6.01-1331.2
Triglyceride	0.04	0.98	0.95-0.99
Drinking habit	0.07	4.43	0.88-22.4

Table 4 Comparison of clinicopathological features at the time of biopsy between hepatocellular carcinoma and non- hepatocellular carcinoma groups in non-alcoholic fatty liver disease patients with advanced fibrosis (F3-4)

	HCC group (n = 9)	Non-HCC group (n = 68)	P value
Age (yr)	65 (56-84)	64 (30-81)	0.32
Male	3 (33)	14 (21)	0.39
Body mass index (kg/m²)	26.0 (18.3-28.7)	27.7 (20.1-41.0)	0.05
Drinking habit	6 (67)	21 (31)	0.03
Co-existing disease
Diabetes mellitus	8 (89)	32 (47)	0.02
Hypertension	9 (100)	38 (56)	0.01
Hyperlipidemia	3 (33)	35 (52)	0.31
Laboratory data
Albumin (mg/dL)	4.0 (3.7-4.6)	4.3 (3.2-5.0)	0.07
Total bilirubin (mg/dL)	0.91 (0.44-1.61)	0.91 (0.48-2.15)	0.99
Aspartate aminotransferase (IU/L)	52 (32-95)	63 (20-200)	0.13
Alanine aminotransferase (IU/L)	53 (16-132)	71 (19-298)	0.09
Gamma-glutamyl transpeptidase (IU/L)	65 (28-192)	65 (25-205)	0.75
Cholinesterase (IU/L)	249 (190-434)	345 (171-467)	0.02
Fasting blood sugar (mg/dL)	133 (84-172)	110 (82-215)	0.30
HOMA-IR	5.8 (1.2-9.8)	4.3 (1.1-15.6)	0.54
HbA1c (%)	6.6 (6.0-7.0)	6.1 (5.0-10.9)	0.14
Total cholesterol (mg/dL)	176 (153-264)	201 (131-294)	0.10
Triglyceride (mg/dL)	85 (64-140)	119 (42-351)	0.03
Platelet (×10⁴/μL)	11.0 (6.4-18.6)	16.6 (5.3-32.6)	< 0.01
Hyaluronic acid (ng/mL)	42 (17-263)	59 (11-1180)	0.45
Type IV collagen 7s (ng/mL)	5.6 (4.7-8.4)	6.8 (3.5-20.0)	0.61
Alpha-fetoprotein (ng/mL)	6.0 (3.7-20.3)	5.0 (1.1-11.3)	0.04
Pathology
Steatosis			0.07
1	7 (78)	26 (38)
2	2 (22)	32 (47)
3	0 (0)	10 (15)
Lobular inflammation			0.45
0	0 (0)	1 (2)
1	2 (22)	17 (25)
2	7 (78)	37 (54)
3	0 (0)	13 (19)
Ballooning			0.76
0	1 (11)	1 (2)
1	6 (67)	34 (50)
2	2 (22)	33 (49)
NAFLD activity score			0.25
1	0 (0)	1 (2)
2	0 (0)	1 (2)
3	3 (33)	5 (7)
4	2 (22)	10 (15)
5	4 (44)	26 (38)
6	0 (0)	16 (24)
7	0 (0)	8 (12)
8	0 (0)	1 (2)

Table 5 Factors related to hepatic carcinogenesis by multivariate survival analysis using Cox's regression model for patients with advanced fibrosis (F3-4)

	P value	Relative risk	95%CI
Drinking habit	0.04	4.83	1.01-23.00
Alpha-fetoprotein	0.01	1.23	1.04-1.44
Diabetes mellitus	0.03	12.00	1.20-119.66

Citation: Kimura T, Tanaka N, Fujimori N, Sugiura A, Yamazaki T, Joshita S, Komatsu M, Umemura T, Matsumoto A, Tanaka E. Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis. World J Gastroenterol 2018; 24(13): 1440-1450
URL: https://www.wjgnet.com/1007-9327/full/v24/i13/1440.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i13.1440