NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients

doi:10.3748/wjg.v19.i8.1219

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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. 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
Variable at baseline	(n = 302)	(NFS < -1.5) (n = 181)	(NFS≥-1.5) (n = 121)	P value
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

NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Glutamyltransferase; CHD: Coronary heart disease; NFS: NAFLD fibrosis score.

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)	P value
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

NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NFS: NAFLD fibrosis score; LDL: Low-density lipoprotein.

Table 3 Causes of mortality in 39 patients with nonalcoholic fatty liver disease

Causes of death	All causes mortality n (% of death)	All causes mortality (% of 302 patients)
Non-liver cancer	13 (33.3)	4.3%
Coronary heart disease	8 (20.5)	2.6%
Liver-related mortality (inclu- ding hepatocellular carcinoma)	5 (12.8)	1.7%
Infection (including sepsis)	4 (10.3)	1.3%
Stroke	3 (7.7)	1.0%
Cardiac arrhythmia	2 (5.1)	0.7%
COPD and/or respiratory failure	2 (5.1)	0.7%
Other causes of death (GI bleeding, renal failure)	2 (5.1)	0.7%
Total	39 (100)	12.9%

COPD: Chronic obstructive lung disease; GI: Gastrointestinal.

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

NAFLD: Nonalcoholic fatty liver disease.

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

To avoid overestimation of the model, we excluded those variables used as a part of NAFLD fibrosis score calculation (age, history of diabetes, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, albumin, body mass index and Framingham risk score). NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FRS: Framingham risk score; CHD: Coronary heart disease; NFS: NAFLD fibrosis score.

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

Model 1 without interaction among 9 included variables: gender, systolic blood pressure, diastolic blood pressure, nonalcoholic fatty liver disease (NAFLD) fibrosis score at baseline, use of metformin, use of simvastatin, use of aspirin, presence of new-onset of coronary heart disease (CHD) and new onset of liver complications; Model 2 without interaction among 10 included variables: gender, systolic blood pressure, diastolic blood pressure, NAFLD fibrosis score (NFS) at baseline, NFS changes per year, use of metformin, use of simvastatin, use of aspirin, presence of new-onset coronary heart disease (CHD) and new onset of liver complications; Model 3 added variables of interaction between NFS at baseline and NFS changes per year, interaction among use of aspirin, metformin, aspirin and simvastatin into model 2.

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

In order to avoid overestimation of the model, we excluded those variables used as a part of nonalcoholic fatty liver disease fibrosis score calculation (age, history of diabetes, aspartate aminotransferase/alanine aminotransferase ratio, platelet counts, albumin, body mass index and Framingham risk score). NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FRS: Framingham risk score; CHD: Coronary heart disease; NFS: NAFLD fibrosis score; ALP: Alkaline phosphatase; GGT: Glutamyltransferase; HDL: High-density lipoprotein.

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

Model without interaction among 8 included variables; gender, nonalcoholic fatty liver disease fibrosis score at baseline, use of metformin, use of simvastatin, use of aspirin, history of hypercholesterolemia, alanine aminotransferase and alkaline phosphatase. NAFLD: Nonalcoholic fatty liver disease.

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

NAFLD: Nonalcoholic fatty liver disease.

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
URL: https://www.wjgnet.com/1007-9327/full/v19/i8/1219.htm
DOI: https://dx.doi.org/10.3748/wjg.v19.i8.1219