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Figure 1. Histological changes between the first and second biopsies. The horizontal axis
shows the percentage of progress, improve or no change. The striped bars denote progression
cases, the filled bars denote no change, and the diagonal bars denote improvement. (a)
Fibrosis, (b) NAFLD activity score
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Figure 2 Comparison of histological progression and non-progression cases (a) Body mass
index (BMI), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and
liver/spleen ratio (LS ratio) in computed tomography.
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Figure 2 Comparison of histological progression and non-progression cases (b) Aspartate
aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltranspeptidase (GGT),
uric acid (UA), LDL cholesterol, HbA1c, fasting blood sugar (FBS), and homeostasis model
assessment ratio (HOMA-IR). In each figure, the horizontal axis shows the first and second
biopsies and the longitudinal axis shows the means. The solid lines show progression cases
and the dotted line shows non-progression cases.
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Figure 3. Relationship between histological exacerbation and rs1799964 allele, ALT response,
and HbA1c elevation.
The horizontal axis shows HbA1c increase or non-increase and non-TT or TT in rs1799964.
The dark bars show ALT responders and the light bars show ALT non-responders. The
longitudinal axis shows percentage of patients who experienced histological exacerbation.
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Figure 4. Risk estimation of NAFLD using genetic variation and biochemical markers. The
receiver Operating Characteristic (ROC) curves shows the potential to predict histological
exacerbation based on ALT response, HbA1c levels, and allele type of rs1799964. The
probability for correct diagnosis rate is 90.0% with AUC=0.884. Using leave one out
cross-validation, we obtained a probability for correct diagnosis rate of 78.6% with
AUC=0.827.
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Table 1 Patient background
median
min
Age, years
61
Sex, (Male/Female)
(45/35)
observation period, days
931
NAS (first, 2/3/4/5/6/7/8)
(2/29/21/9/7/10/2)
Fibrosis stage(first, 1/2/3)
(17/37/26)
BMI, kg/m2
27.4
Platelet count, x104
21.9
AST, IU/L
32
( 328
max
90
2640
19.6
38.3
9.2
58.9
45.5
17
163
ALT, IU/L
79
23
324
γ-GTP, IU/L
61
18
481
Total cholesterol, mg/dL
222
139
372
Triglyceride, mg/dL
142.5
65
634
HDL cholesterol, mg/dL
49.5
29
100
LDL cholesterol, mg/dL
141.5
53
294
Fasting blood sugar, mg/dL
108
71
239
HbA1c, %
5.9
3.8
11.7
UA, mg/dL
5.8
2.9
8.9
Ferritin, ng/mL
179.4
8.2
1598.9 )
SAT
199.6
68.57 -
420.8
VAT
136.5
58.2
340.6
waist
96.59
79.27 -
124.20 )
CTLSratio
0.70
0.05
1.40
HOMA-IR
3.158
0.933 -
NGT/IGT/DM
14/27/39
Hyper tension
42/80
Dyslipidemia
71/80
Hyper uremia
23/80
12.039 )
Values are median( range )
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Table 2 (a) Comparison of histological progression cases and non-progression cases.
Progression
mean
Non-progression
sd
14.9
mean
60.06
sd
age
63.38
11.8
sex (M/F)
13/14
BMI
27.95
4.2
27.64
3.8
0.890
BMI (second)
26.05
6.8
25.66
5.2
0.339
SAT
219.58
98.9
208.65
95.4
0.662
SAT (second)
231.16
103.7 )
189.15
86.5
0.113
VAT
148.03
68.1
141.63
42.1
0.924
VAT (second)
130.35
53.1
113.58
48.3
0.193
LSratio
0.76
0.3
0.68
0.3
0.304
LSratio_ (second)
0.96
0.2
1.00
0.3
0.231
34/21
0.329
0.212
date are expressed as mean values and standard deviation.
p-values associated with continuous variables via a Mann-whitney U-test.
p-values associated with categorical values were caculated with t-test.
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Table 2 (b) Clinical parameters contribute to the histological progression.
Progression
Non--progression
mean
mean
sd
Mulltivariate analysis
sd
AST
50.4
( 28.0 )
57.7
35.9 )
0.538
AST (second)
41.0
( 23.8 )
30.1
21.5 )
0.031
AST_nonresponder 10/26
15/54
78.8
( 39.1 )
97.8
63.2 )
0.361
ALT_ (second)
57.3
( 40.9 )
45.6
63.7 )
0.041
12/54
3.3.E-04
rGTP
119.3
( 102.6 )
89.0
85.5 )
0.070
rGTP_ (second)
83.1
( 84.1 )
38.7
29.8 )
0.002
rGTP nonresponder 8/26
95%CI lo
95%CI hi
0.230
0.071
0.748
0.015
1.014
1.000
1.028
0.053
4.651
1.453
14.883
0.010
0.593
ALT
ALT_nonresponder 13/26
OR
10/54
0.010
LDL
134.5
( 34.9 )
146.0
42.7 )
0.423
LDL (second)
95.3
( 25.3 )
106.7
28.5 )
0.083
LDL increase
4/26
FBS
109.5
( 22.4 )
118.9
33.6 )
0.314
FBS_ (second)
115.1
( 26.4 )
110.9
33.0 )
0.700
HbA1c
6.31
( 1.4
6.37
1.2 )
0.382
HbA1c (second)
6.40
( 0.9
6.08
0.9 )
0.113
HbA1c increase
18/26
UA
5.95
( 1.5
5.89
1.3 )
0.933
UA_ (second)
5.39
( 1.4
5.47
1.2 )
0.890
UA increase
10 / 26
HOMA_IR
3.50
( 2.0
4.14
2.7 )
0.420
HOMA_IR_(second) 3.50
( 2.2
3.54
2.4 )
0.861
10/54
0.975
18/54
0.005
19 /54
0.970
responder ʂdecrease of more than 30% of the value, or decrease to the normal range
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Table 3 Risk factors contributing to the histological progression.
Univariate
analysis
Multivariate季 analysis季
OR
ALT_nonresponder
3.3.E-04
0.035
4.073
1.100
- 15.078
γ – GTP_nonresponder
0.010
HbA1c increase
0.005
0.003
11.902
2.264
- 62.555
rs1799964(CC vs nonCC)
0.006
0.009
9.558
1.755
- 52.045
95%CI lo
95%CI hi
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