Retrospective Cohort Study
Copyright ©The Author(s) 2022.
World J Gastroenterol. Apr 21, 2022; 28(15): 1563-1573
Published online Apr 21, 2022. doi: 10.3748/wjg.v28.i15.1563
Table 1 Details of the three noninvasive methods used in this study
Index
Number of parameters and variables
Formula
Ref.
FIB-8 index8; age, AST, ALT, platelets, BMI, albumin/globulin, GGT, diabetesFIB4 + 0.025 × BMI (kg/m2) - 0.702 × (albumin/globulin ratio) + 0.004 × GGT (U/L) + 0.858 × diabetes (yes = 1, no = 0)1Sripongpun et al[11], 2019
FIB-4 index4; age, AST, ALT, plateletsAge (years) × AST (U/L)/[platelet count (109/L) × √ALT (U/L)]Sterling et al[15], 2006
NFS6; age, BMI, diabetes, AST/ALT, platelets, albumin-1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet count (× 109/L) - 0.66 × albumin (g/dL)Angulo et al[16], 2007
1The FIB-8 score in the abstract was calculated by 1.3 × FIB-4 + 0.03 × BMI - 0.93 × (albumin/globulin ratio) + 0.005 × GGT (U/L) + 1.1 × diabetes (yes = 1, no = 0), which is slightly different from the actual formula presented at the liver meeting congress (the score in the table). We have contacted the authors of the abstract and were informed that the actual formula to use is the one shown in the table.
NAFLD: Nonalcoholic fatty liver disease; FIB-8: Fibrosis-8 score; FIB-4: Fibrosis-4 score; NFS: NAFLD fibrosis score; AUROC: Areas under the receiver operating characteristic curves; GGT: Gamma-glutamyl transferase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; BMI: Body mass index.
Table 2 Characteristics of patients with F0-1 fibrosis compared to those with F ≥ 2 fibrosis stage (n = 511)
Variables
Total (n = 511)
Fibrosis stage F0-1 (n = 354)
Fibrosis stage ≥ F2 (n = 157)
P value
Age (yr), median (IQR)51 (41, 58)49.5 (39, 57)55 (48, 61)< 0.001
Sex0.138
Male, n (%)240 (47.0)174 (49.2)66 (42.0)
Female, n (%)271 (53.0)180 (50.8)91 (58.0)
BMI (kg/m2), median (IQR)29.0 (26.3, 32.6)28.8 (26.2, 31.9)29.5 (26.3, 33.8)0.099
Diabetes, n (%)268 (52.4)156 (44.0)112 (71.3)< 0.001
Albumin (g/dL), median (IQR)4.4 (4.1, 4.6)4.4 (4.2, 4.6)4.30 (4.0, 4.6)0.053
Globulin (g/dL), median (IQR)3.4 (3.0, 3.8)3.4 (3.0, 3.8)3.5 (3.1, 3.8)0.21
AST (U/L), median (IQR)39 (28, 60)35 (26, 52)53.5 (36, 75)<0.001
ALT (U/L), median (IQR)65 (42, 101)59.5 (40, 98)75 (50, 111)< 0.001
GGT (U/L), median (IQR)63 (37, 108)56.5 (35, 92)81 (48, 151)< 0.001
Platelet (× 109/μL), median (IQR)254 (213, 297)266 (226.8, 302)230 (189, 277)< 0.001
Hemoglobin (g/dL), median (IQR)14.2 (13.3, 15.2)14.2 (13.4, 15.2)14.1 (13.3, 15.2)0.393
White blood cells (cells/μL), median (IQR)7430 (6060, 8700)7400 (6100, 8725)7500 (5950, 8695)0.768
INR, median (IQR)1.01 (0.96, 1.06)1.00 (0.95, 1.07)1.01 (0.97, 10.6)0.625
Total cholesterol (mg/dL), median (IQR)189.5 (166, 217)193 (170, 220)182 (159, 209)0.004
LDL-cholesterol (mg/dL), median (IQR)115 (92, 139)116 (96, 143)107 (85, 132)0.003
HDL-cholesterol (mg/dL), median (IQR)46 (39, 52)46 (39, 53)44 (38, 50)0.168
Triglyceride (mg/dL), median (IQR)120 (77, 157)120 (77, 155)119 (80, 159)0.483
HbA1C (%), median (IQR)6.1 (5.6, 7.2)5.9 (5.5, 6.8)6.8 (5.8, 7.6)< 0.001
Fibrosis stage, n (%)< 0.001
0151 (29.5)151 (42.7)0 (0)
1203 (39.7)203 (57.3)0 (0)
269 (13.5)0 (0)69 (43.9)
372 (14.1)0 (0)72 (45.9)
416 (3.1)0 (0)16 (10.2)
Median CAP (dB/m), median (IQR)308.5 (230, 342)299 (211, 339)324 (294, 347)< 0.001
Median TE (kPa), median (IQR)7.6 (5.6, 10.9)6.6 (5.1, 8.8)11.1 (8.6, 15.5)< 0.001
FIB-8, median (IQR)2.0 (1.2, 2.9)1.8 (1.1, 2.4)3.0 (2.2, 4.0)< 0.001
FIB-4, median (IQR)1.0 (0.7, 1.5)0.8 (0.6, 1.2)1.5 (1.0, 2.1)< 0.001
NFS, mean ± SD-1.8 ± 1.5-2.0 ± 1.4-1.2 ± 1.3< 0.001
NAFLD: Nonalcoholic fatty liver disease; FIB-8: Fibrosis-8 score; FIB-4: Fibrosis-4 score; NFS: NAFLD fibrosis score; AUROC: Areas under the receiver operating characteristic curves; GGT: Gamma-glutamyl transferase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; BMI: Body mass index; CAP: Controlled Attenuation Parameter.
Table 3 Performance of fibrosis-8, fibrosis-4, and nonalcoholic fatty liver disease fibrosis score for predicting significant fibrosis (F ≥ 2) in the Asian population (n = 511)
FIB-8 score
FIB-4 score
NFS
AUC for predicting ≥ F2 fibrosis0.77a,b0.740.68
95% confidence interval0.73-0.820.70-0.790.63-0.73
Low and high cutoffs for ≥ F2 fibrosis0.88 and 1.770.81 and 1.81 (17)-2.45 and 0.03 (17)
Sensitivity (according to the low cutoff)92.36%80.25%80.89%
Specificity (according to the high cutoff)67.51%93.50%93.20%
Proportion of patients in low/indeterminate/high group18.8/35.4/45.8%38.2/47.1/14.7%31.9/58.1/10%
aP = 0.001 compared with NFS.
bP = 0.073 compared with FIB-4.
NAFLD: Nonalcoholic fatty liver disease; FIB-8: Fibrosis-8 score; FIB-4: Fibrosis-4 score; NFS: NAFLD fibrosis score; AUROC: Areas under the receiver operating characteristic curves.
Table 4 Comparison of study population using the fibrosis-8 score for predicting significant fibrosis (F ≥ 2)
Variable
Data from AASLD 2019, n = 522
FIB-8 score validation (EASL 2020), n = 130
FIB-8 score validation (Our cohort), n = 511
PopulationMean age: 49 ± 12. Female: 62.5%; BMI: 34 ± 7 kg/m2; DM: 30%; ≥ F2: 52.5%Mean age: 52.4; Female: 53.1%; BMI: 31.5 kg/m2; DM: 34%; ≥ F2: 35.4%Mean age: 49.3 ± 11.9; Female: 53.0%; BMI: 30.4 ± 7.1 kg/m2; DM: 52.4%; ≥ F2: 30.7%
Sensitivity and specificity %86.7% and 82.7%, respectively, Validation set> 90%, 80.6%92.3%, 67.5%
AUC for predicting > F2 fibrosis0.78, Validation set0.840.77
Performance superior to> FIB-4 score; P < 0.001; > NFS; P = 0.005> FIB-4 score (AUC 0.80); > NFS (AUC 0.77)> FIB-4 score; P = 0.073; > NFS; P = 0.001
NAFLD: Nonalcoholic fatty liver disease; FIB-8: Fibrosis-8 score; FIB-4: Fibrosis-4 score; NFS: NAFLD fibrosis score; AASLD: American Association for the Study of Liver Diseases; EASL: European Association for the Study of the Liver; AUROC: Areas under the receiver operating characteristic curves; BMI: Body mass index; DM: diabetes mellitus.