Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol 2013; 19(8): 1219-1229 [PMID: 23482703 DOI: 10.3748/wjg.v19.i8.1219]
Corresponding Author of This Article
Sombat Treeprasertsuk, MD, Associate Professor, Department of Medicine, Faculty of Medicine, Chulalongkorn University, 4 Rama Road, Pathumwan District, Bangkok 10330, Thailand. battan5410@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Original Article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Feb 28, 2013; 19(8): 1219-1229 Published online Feb 28, 2013. doi: 10.3748/wjg.v19.i8.1219
Table 1 Demographic data of 302 patients by nonalcoholic fatty liver disease fibrosis score at baseline n (%) (mean ± SD)
Variable at baseline
Total
Patients with a low probability ofadvanced liver fibrosis
Patients with an intermediate or highprobability of advanced liver fibrosis
P value
(n = 302)
(NFS < -1.5) (n = 181)
(NFS≥-1.5) (n = 121)
Age (yr)
47.3 ± 12.9
42.9 ± 11.1
53.8 ± 12.8
< 0.0001
Sex (% male)
132 (44)
92 (51)
40 (33)
0.002
Race, number (% White)
288 (95)
170 (94)
119 (97.5)
0.150
History of diabetes
48 (16)
5 (2.8)
43 (35.5)
< 0.0001
History of hypertension
125 (41)
55 (30.4)
70 (58)
< 0.0001
BMI (kg/m2)
33.6 ± 6.2
32.0 ± 5.2
36.0 ± 6.9
< 0.0001
Presence of obesity (BMI > 30 kg/m2)
221 (73)
121 (67)
100 (82.6)
0.002
Systolic blood pressure (mmHg)
136 ± 18
133 ± 17
139 ± 18
0.003
Diastolic blood pressure (mmHg)
83 ± 9
84 ± 8
81 ± 9
0.010
Cholesterol (mg/dL)
214 ± 48
215 ± 46
214 ± 50
0.780
Triglycerides (mg/dL)
221 ± 167
208 ± 123
242 ± 218
0.150
Glucose (mg/dL)
115 ± 41
103 ± 25
132 ± 54
< 0.0001
AST (U/L)
41.4 ± 21.9
40.8 ± 21.8
42.2 ± 28.9
0.620
ALT (U/L)
61.5 ± 43.3
69.7 ± 46
49.4 ± 35.7
< 0.0001
AST/ALT ratio
0.8 ± 0.4
0.7 ± 0.3
1.0 ± 0.6
< 0.0001
GGT (U/L)
131.9 ± 39.8
129.9 ± 32.9
134.2 ± 46.7
0.560
Platelets (× 109/L)
240 ± 62
259 ± 60
212 ± 53
< 0.0001
Albumin (g/dL)
4.3 ± 0.4
4.4 ± 0.3
4.1 ± 0.3
< 0.0001
Alkaline phosphatase (U/L)
196 ± 88
186 ± 68
211 ± 111
0.030
Framingham Risk Score
8.4 ± 6.2
6.9 ± 6.4
10.5 ± 5.2
< 0.0001
Calculated CHD risk (%)
16.2 ± 14.6
14.1 ± 13.8
19.3 ± 15.2
0.003
NFS
-1.7 ± 1.4
-2.6 ± 0.8
-0.4 ± 0.9
< 0.0001
Table 2 Clinical parameters, laboratory features and clinical outcomes at the end of follow-up by nonalcoholic fatty liver disease fibrosis score at baseline n (%) (mean ± SD)
Variable at the end of follow-up
Patients with a low probability ofadvanced liver fibrosis
Patients with an intermediate or high probability of advanced liver fibrosis
P value
(NFS < -1.5) (n = 181)
(NFS > -1.5) (n = 121)
Clinical findings
BMI (kg/m2)
32.9 ± 6.6
34.9 ± 7.6
0.02
Obesity (BMI > 30 kg/m2)
119 (65.8)
91 (75.2)
0.08
NFS
-1.4 ± 1.3
0.4 ± 1.4
< 0.0001
NFS of intermediate or high probability of advanced liver fibrosis
85 (47)
114 (94)
< 0.0001
History of diabetes
54 (29.8)
83 (68.6)
< 0.0001
Use of metformin
32 (17.7)
48 (39.7)
< 0.0001
Use of glitazones
10 (5.5)
19 (15.7)
0.003
Use of aspirin
84 (46)
83 (69)
0.0001
History of hypothyroidism
19 (10.5)
31 (25.6)
0.0005
History of cholecystectomy
27 (15)
33 (27.3)
0.008
History of obstructive sleep apnea
33 (18.2)
34 (28.1)
0.04
Laboratory findings
AST (U/L)
38.9 ± 30.6
33.2 ± 17.8
0.04
ALT (U/L)
53.9 ± 49.7
38.9 ± 21
0.0004
AST/ALT ratio
0.8 ± 0.5
1.0 ± 0.8
0.03
Hematocrit (%)
40.4 ± 4.4
38.6 ± 5.3
0.003
Platelets (× 109/L)
259 ± 67
217 ± 74
< 0.0001
Albumin (g/dL)
4.1 ± 0.4
3.9 ± 0.6
< 0.0001
Cholesterol (mg/dL)
193 ± 40
178 ± 43
0.005
LDL-cholesterol (mg/dL)
109 ± 34
92 ± 30
< 0.0001
Glucose (mg/dL)
119 ± 42
131 ± 42
0.02
Clinical outcomes at the end of follow-up
Lost to follow up
27 (15)
8 (7)
Alive with continued follow-up
131 (72)
81 (67)
Presence of primary endpoints
23 (13)
32 (26)
0.002
All-cause death
12 (6.6)
27 (22.3)
< 0.0001
New events of coronary heart disease
15 (8.3)
15 (12.4)
0.24
Liver complications
1 (0.6)
5 (4.1)
0.03
Table 3 Causes of mortality in 39 patients with nonalcoholic fatty liver disease
Other causes of death (GI bleeding, renal failure)
2 (5.1)
0.7%
Total
39 (100)
12.9%
Table 4 Association between the primary endpoint and the grading of the nonalcoholic fatty liver disease fibrosis score, classified into 3 subgroups (n = 302) n (%)
Grading of the NAFLD fibrosis score(n = 302)
Low prob. of advanced liverfibrosis (n = 181)
Intermediate prob. of advanced liverfibrosis (n = 108)
High prob. of advancedliver fibrosis (n = 13)
P value
Presence of primary endpoint (n = 55, 18.2%)
23/181 (12.7)
24/108 (22.2)
8/13 (61.5)
< 0.0001
All-cause death (n = 39, 12.9%)
12/181 (6.6)
21/108 (19.4)
6/13 (46.2)
< 0.0001
Table 5 Comparison of nonalcoholic fatty liver disease patients alive vs deceased n (%) (mean ± SD)
Variables
NAFLD patients alive (n = 263)
NAFLD patients deceased (n = 39)
P value
At baseline
Age (yr)
45.2 ± 11.5
61.1 ± 13.8
< 0.0001
Sex (% male)
120 (45.6)
12 (30.8)
0.08
History of diabetes
37 (14.1)
11 (28.2)
0.02
Systolic blood pressure (mmHg)
134 ± 17
143 ± 21
0.02
Diastolic blood pressure (mmHg)
83 ± 8
79 ± 10
0.03
Glucose (mg/dL)
112 ± 38.6
132.7 ± 54.3
0.03
AST (U/L)
42.2 ± 25.5
35.5 ± 20.0
0.06
ALT (U/L)
64.2 ± 44.6
43.6 ± 27.4
0.000
AST/ALT ratio
0.8 ± 0.4
1.0 ± 0.7
0.06
Albumin (g/dL)
4.3 ± 0.3
4.0 ± 0.4
< 0.0001
FRS
7.9 ± 6.2
11.4 ± 5.2
0.000
Calculated CHD risk (%)
15.3 ± 14.0
22.2 ± 17.1
0.02
NFS
-1.9 ± 1.3
-0.8 ± 1.7
0.0004
NFS of intermediate or high probability of advanced liver fibrosis (%)
94 (35.7)
27 (69.2)
< 0.0001
Presence of histologically advanced liver fibrosis
7/35 (20.0)
5/11 (45.5)
0.09
During the follow-up period
77 (29.3)
3 (7.7)
0.004
Use of metformin
Use of aspirin
151 (57.4)
16 (41.0)
0.05
Use of simvastatin
107 (40.7)
3 (7.9)
< 0.0001
New events of coronary heart disease
16 (6.1)
14 (35.9)
< 0.0001
Liver complications
1 (0.4)
5 (12.8)
< 0.0001
At the end of follow-up
BMI (kg/m2)
33.9 ± 6.9
31.8 ± 8.2
0.1
Hematocrit (%)
40.4 ± 4.1
34.5 ± 6.3
< 0.0001
Glucose (mg/dL)
122.0 ± 38.6
139.0 ± 62.3
0.12
AST/ALT ratio
0.9 ± 0.5
1.3 ± 1.0
0.01
Albumin (g/dL)
4.1 ± 0.3
3.3 ± 0.7
< 0.0001
Creatinine (mg/dL)
1.0 ± 0.5
1.7 ± 1.3
0.004
NFS
-0.9 ± 1.4
0.7 ± 2.3
< 0.0001
NFS change per year (Median; IQR)
0.07 (0.02, 0.12)
0.14 (0.01, 0.31)
0.03
NFS of intermediate to high probability of advanced liver fibrosis (%)
168 (63.9)
31 (79.5)
0.05
Table 6 Multivariate logistic regression model showing OR (95%CI) for predictors for death in 302 patients with nonalcoholic fatty liver disease
Multivariate analysis
P value
OR
95%CI
Model 1
Presence of new-onset CHD
< 0.0001
9.0
2.9-28.4
NFS at baseline
< 0.0001
1.9
1.4-2.6
Use of metformin
0.02
0.2
0.04-0.8
Use of simvastatin
0.001
0.05
0.01-0.3
Model 2
NFS changes per year
0.04
14.9
1.1-206.4
Presence of new onset of CHD
0.001
8.0
2.4-26.1
NFS at baseline
< 0.0001
2.1
1.5-2.9
Use of metformin
0.02
0.2
0.04-0.7
Use of simvastatin
0.001
0.06
0.01-0.3
Model 3
Presence of new onset of CHD
< 0.0001
9.2
2.6-32.2
NFS at baseline
< 0.0001
2.6
1.7-3.9
Use of metformin
0.03
0.2
0.04-0.8
Use of simvastatin
0.001
0.03
0.003-0.2
Interaction between NFS
0.004
0.06
0.008-0.4
at baseline and NFS
change per year
NFS changes per year
0.6
2.2
0.07-67.8
Table 7 Comparison of nonalcoholic fatty liver disease patients with and without death after excluding those with established type 2 diabetes at baseline (n = 254) n (%) (mean ± SD)
Variables
NAFLD patients without death (n = 226)
NAFLD patients with death (n = 28)
P value
Age (yr)
44.5 ± 11.5
59.2 ± 14.3
< 0.0001
Sex (% male)
113 (50)
10 (35.7)
0.11
History of hypercholesterolemia
56 (24.8)
9 (32.1)
< 0.0001
Obesity
164 (72.6)
22 (78.6)
0.34
BMI (kg/m2)
33.5 ± 6.2
35.0 ± 6.6
0.25
Platelet count (× 109/mm3)
241 ± 58
242 ± 87
0.98
Glucose (mg/dL)
215.7 ± 46.6
215.7 ± 46.6
Cholesterol (mg/dL)
215 ± 48
219 ± 56
0.72
HDL-cholesterol (mg/dL)
42 ± 12
43 ± 20
0.76
AST (U/L)
42.0 ± 23.0
39.7 ± 21.0
0.62
ALT (U/L)
65.7 ± 45.0
50 ± 29
0.02
AST/ALT ratio
0.76 ± 0.38
0.93 ± 0.57
0.14
ALP(U/L)
184 ± 66
246 ± 179
0.09
GGT (U/L)
132 ± 41
142 ± 36
0.32
Albumin (g/dL)
4.3 ± 0.3
4.2 ± 0.4
< 0.0001
FRS
7.6 ± 6.2
10.5 ± 5.6
0.02
Calculated CHD risk (%)
15.3 ± 14.4
22.0 ± 18.8
0.076
NFS
-2.11 ± 1.15
-1.09 ± 1.61
0.003
NFS of intermediate or high probability of advanced liver fibrosis (%)
59 (26.1)
19 (67.9)
< 0.0001
B. During the follow-up periods
Use of metformin
52 (23.0)
1 (3.6)
0.009
Use of aspirin
119 (52.7)
9 (32.1)
0.03
Use of simvastatin
90 (39.8)
3 (10.7)
< 0.0001
NFS change per year (median; IQR)
0.08 ± 0.08
0.12 ± 0.36
0.61
Table 8 Multivariate logistic regression model showing OR (95%CI) of predictors for death in 254 patients with nonalcoholic fatty liver disease after excluding those with established type 2 diabetes at baseline
Multivariate analysis
P value
OR
95%CI
NAFLD fibrosis score at baseline
< 0.0001
1.92
1.4-2.7
Alkaline phosphatase
0.012
1.006
1.001-1.010
Table 9 The association between the primary end point and the grading of the nonalcoholic fatty liver disease fibrosis score, classified into 2 subgroups, after excluding those with established type 2 diabetes at baseline n (%)
Grading of the NAFLD fibrosis score (n = 254)
Low prob. of advanced liver fibrosis(n = 176)
Intermediate prob. or High prob. of advanced liverfibrosis (n = 78)
P value
Presence of primary end point (n = 43; 17%)
20/176 (11.4)
23/78 (29.5)
< 0.0001
All-cause death (n = 28; 11%)
9/176 (5.1)
19/78 (24.4)
< 0.0001
Citation: Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol 2013; 19(8): 1219-1229