Association between endotoxemia and histological features of nonalcoholic fatty liver disease

Table 1 Clinicopathological features of nonalcoholic fatty liver disease patients n (%)

Parameter	All (n = 126)	NAFL (n = 26)	NASH (n = 100)	P value
Clinical findings
Age (yr)	56 (44-65)	52 (42-58)	58 (45-65)	0.17
Male	54 (43)	14 (54)	40 (40)	0.20
BMI ≥ 25 kg/m2	76 (60)	12 (46)	64 (64)	0.10
Diabetes	43 (34)	5 (19)	38 (38)	0.07
Hypertension	49 (39)	8 (31)	41 (41)	0.34
Hyperlipidemia	82 (65)	19 (73)	63 (63)	0.34
BMI (kg/m2)	25.8 (23.6-29.4)	24.6 (22.6-28.5)	26.4 (23.9-29.5)	< 0.05
Ethanol (g/d)	0 (0-5)	0 (0-2.8)	0 (0-5)	0.26
Leukocytes (× 103/μL)	5.57 (4.73-6.82)	5.07 (4.76-5.75)	5.72 (4.72-6.86)	0.24
Erythrocytes (× 104/μL)	490 (453-515)	490 (474-512)	489 (452-515)	0.36
Hemoglobin (g/dL)	14.9 (14.0-15.8)	15.1 (14.6-15.9)	14.8 (13.9-15.8)	0.14
Hematocrit (%)	44.2 (41.6-46.6)	45.3 (43.3-46.9)	43.9 (41.5-46.6)	0.31
MCV (fl)	91.2 (88.5-93.7)	91.5 (89.1-93.0)	91.1 (88.4-94.1)	0.81
MCH (pg)	30.7 (29.6-31.7)	31 (30.2-31.6)	30.5 (29.6-31.7)	0.42
MCHC (%)	33.6 (33.0-34.3)	33.9 (33.5-34.4)	33.4 (32.9-34.2)	0.08
Platelets (× 104/μL)	23.8 (17.9-26.8)	23.3 (19.1-26.7)	23.8 (17.8-26.9)	0.88
PT-INR	1.00 (0.98-1.05)	1.00 (0.98-1.03)	1.01 (0.97-1.05)	0.40
APTT (s)	28.6 (26.6-31.2)	28.6 (27.5-30.1)	28.6 (26.3-31.3)	0.84
FIBG (mg/dL)	287 (243-314)	284 (247-321)	287 (242-313)	0.73
Total protein (g/dL)	7.6 (7.3-7.9)	7.6 (7.3-7.9)	7.6 (7.3-7.8)	0.97
Albumin (g/dL)	4.5 (4.3-4.7)	4.6 (4.5-4.7)	4.5 (4.3-4.7)	0.14
Bilirubin (mg/dL)	0.9 (0.7-1.1)	0.8 (0.7-1.1)	0.9 (0.7-1.1)	0.30
AST (U/L)	40 (29-63)	27 (23-33)	47 (33-70)	< 0.00001
ALT (U/L)	61 (36-92)	39 (30-56)	69 (42-104)	0.0002
LDH (U/L)	214 (186-240)	189 (165-231)	219 (191-249)	0.02
ALP (U/L)	254 (214-323)	246 (218-312)	258 (214-323)	0.86
γGT (U/L)	53 (35-82)	44 (26-70)	54 (37-87)	0.21
ChE (U/L)	384 (342-429)	399 (369-445)	376 (340-427)	0.12
Urea nitrogen (mg/dL)	13 (11-15)	13.2 (12-14.5)	13 (11-15)	0.65
Creatinine (mg/dL)	0.70 (0.58-0.82)	0.79 (0.62-0.84)	0.66 (0.57-0.82)	0.17
Uric acid (mg/dL)	5.6 (4.8-6.8)	6.0 (5.2-7.5)	5.6 (4.8-6.6)	0.26
eGFR (mL/min/1.73 m2)	79 (69-89)	77 (59-88)	79 (70-89)	0.53
Total cholesterol (mg/dL)	209 (181-233)	218 (175-247)	206 (182-230)	0.41
Triglycerides (mg/dL)	119 (91-156)	122 (88-165)	119 (93-156)	0.95
LDL-cholesterol (mg/dL)	134 (109-152)	136 (103-155)	131 (113-147)	0.80
HDL-cholesterol (mg/dL)	52 (45-59)	53 (45-61)	52 (45-57)	0.59
Glucose (mg/dL)	106 (97-120)	99 (92-112)	107 (98-122)	0.02
Insulin (μU/mL)	12 (7.3-17.6)	7.5 (5.1-11.5)	13.1 (8.2-17.9)	0.002
HbA1c (%)	5.8 (5.6-6.4)	5.8 (5.4-6.0)	5.9 (5.6-6.6)	0.02
HOMA-IR	3.2 (1.9-4.8)	2.0 (1.2-3.2)	3.5 (2.2-4.9)	0.001
IgG (mg/dL)	1261 (1089-1535)	1264 (1118-1524)	1261 (1086-1541)	0.77
IgM (mg/dL)	94 (65-126)	83 (54-113)	97 (72-129)	0.18
IgA (mg/dL)	269 (180-333)	252 (185-293)	272 (180-349)	0.56
CRP (mg/dL)	0.10 (0.04-0.17)	0.05 (0.03-0.16)	0.08 (0.05-0.17)	0.13
Hyaluronic acid (mg/dL)	40 (24-74)	29 (23-52)	47 (25-88)	0.08
Type 4 collagen 7S (mg/dL)	4.5 (3.7-5.5)	3.7 (3.6-4.5)	4.5 (3.8-6.3)	0.003
CK18 fragment (U/L)	298 (155-561)	164 (121-293)	351 (178-645)1	0.0003
Histological findings
Steatosis 1/2/3	43/57/26	15/9/2	28/48/24	0.004
Ballooning 0/1/2	26/68/32	26/0/0	0/68/32	< 0.00001
Lobular inflammation 0/1/2/3	7/61/53/5	3/19/4/0	4/42/49/5	0.0003
Fibrosis 0/1/2/3/4	27/56/14/22/7	16/10/0/0/0	11/46/14/22/7	< 0.00001

¹n = 96. Data are expressed as number (percentage) or median (25^th, 75^th percentiles). Histological findings were scored according to the criteria proposed by Kleiner et al[22] Comparisons between NAFL and NASH groups were carried out using the χ² test or Mann-Whitney U test. BMI: Body mass index; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; PT-INR: International ratio of prothrombin time; APTT: Activated partial thromboplastin test; FIBG: Fibrinogen; AST: Aspartate aminotransferase; NAFL: Nonalcoholic fatty liver; NASH: Nonalcoholic steatohepatitis; ALT: Alanine aminotransferase; LDH: Lactate dehydrogenase; eGFR: Estimated glomerular filtration rate; ALP: Alkaline phosphatase; γGT: γ-glutamyltransferase; ChE: Cholinesterase; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; HbA1c: Hemoglobin A1c; HOMA-IR: Homeostasis model assessment for insulin resistance; CRP: C-reactive protein; CK18: Cytokeratin 18.

Table 2 Correlations between lipopolysaccharide-binding protein/EndoCab IgG and individual pathological features

	LBP		EndoCab IgG
	r	P value	r	P value
Steatosis	0.38	< 0.0001	-0.10	0.25
Ballooning	0.23	0.01	0.11	0.22
Lobular inflammation	0.13	0.14	0.05	0.94
Fibrosis	0.03	0.74	0.13	0.13

Histological findings were scored according to the criteria proposed by Kleiner et al[22] Correlation coefficients (r) and P values were calculated by Spearman’s test. LBP: Lipopolysaccharide-binding protein.

Table 3 Correlations between lipopolysaccharide-binding protein/EndoCab IgG and routine clinical data

	LBP		EndoCab IgG
	r	P value	r	P value
Age	-0.10	0.25	0.341	0.00011
BMI	0.11	0.23	-0.02	0.86
Leukocyte	0.311	0.00051	-0.07	0.44
Erythrocyte	0.11	0.23	-0.23	0.01
Hemoglobin	0.02	0.87	-0.20	0.024
Hematocrit	0.05	0.55	-0.22	0.013
MCV	-0.15	0.10	0.08	0.37
MCH	-0.15	0.92	0.10	0.25
MCHC	-0.15	0.11	0.02	0.81
Platelet	0.22	0.015	-0.29	0.001
PT-INR	-0.13	0.15	0.12	0.18
APTT	0.06	0.51	0.08	0.37
FIBG	0.301	0.00091	-0.05	0.59
Total protein	-0.01	0.91	0.12	0.18
Albumin	-0.02	0.84	-0.17	0.06
Bilirubin	-0.23	0.01	-0.03	0.73
AST	0.381	< 0.00011	0.07	0.44
ALT	0.351	< 0.00011	-0.09	0.31
LDH	0.24	0.006	0.13	0.16
ALP	0.16	0.07	0.08	0.39
γGT	0.21	0.02	-0.06	0.53
ChE	-0.04	0.69	-0.21	0.02
Urea nitrogen	-0.24	0.007	-0.08	0.35
Creatinine	-0.05	0.60	-0.26	0.004
Uric acid	0.07	0.47	-0.21	0.02
eGFR	0.15	0.12	-0.02	0.85
Total cholesterol	0.09	0.31	0.02	0.86
Triglycerides	0.07	0.46	0.11	0.22
LDL-cholesterol	0.08	0.37	0.001	0.99
HDL-cholesterol	-0.06	0.54	-0.001	0.99
Glucose	-0.08	0.35	0.19	0.04
Insulin	0.17	0.07	0.01	0.96
HbA1c	0.05	0.59	0.27	0.002
HOMA-IR	0.14	0.14	0.04	0.65
IgG	-0.09	0.33	0.301	0.00091
IgM	0.12	0.19	-0.02	0.80
IgA	-0.10	0.28	0.25	0.006
CRP	0.471	< 0.00011	0.05	0.61
Hyaluronic acid	-0.08	0.42	0.361	0.00021
Type 4 collagen 7S	-0.04	0.65	0.17	0.08
CK18 fragment	0.28	0.002	0.002	0.98

¹Items with r≥ 0.3 and P < 0.05. Correlation coefficients (r) and P values were calculated by Spearman’s test. BMI: Body mass index; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; PT-INR: International ratio of prothrombin time; APTT: Activated partial thromboplastin test; FIBG: Fibrinogen; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; LDH: Lactate dehydrogenase; eGFR: Estimated glomerular filtration rate; ALP: Alkaline phosphatase; γGT: γ-glutamyltransferase; ChE: Cholinesterase; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; HbA1c: Hemoglobin A1c; HOMA-IR: Homeostasis model assessment for insulin resistance; CRP: C-reactive protein; CK18: Cytokeratin 18.