Hideki Fujii 1 Shinya Fukumoto 1 Masaru Enomoto 2 Sawako UchidaKobayashi 2 Tatsuo Kimura 1 Akihiro Tamori 2 Yuji Nadatani 1 Shingo Takashima 1 Naoki Nishimoto 3 ID: 1033936
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1. BMC GastroenterologyValidation of a novel cutoff point for the Fibrosis-4 Index modified by age in patients with fatty liver diseases Hideki Fujii1, Shinya Fukumoto1, Masaru Enomoto2, Sawako Uchida-Kobayashi2, Tatsuo Kimura1, Akihiro Tamori2, Yuji Nadatani1, Shingo Takashima1, Naoki Nishimoto3, and Norifumi Kawada2Departments of 1Premier Preventive Medicine and 2Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan3Division of Data Management, Division of Biostatistics, Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan Address correspondence to: Hideki Fujii, M.D., Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno, Osaka 545-8585, JapanTel: +81-6-6645-3905Email: rolahdieki@med.osaka-cu.ac.jp
2. VariablesNumberAge (years)Sex (Female/Male)BMI (kg/m2)Waist circumference (cm) Smoking status(Never/Past/Current)Alcohol intake (g/day)Hypertension (Presence/Absence)DM (Presence/Absence)Dyslipidemia (Presence/Absence)Antihypertensive medication (+/-)Antidiabetic medication (+/-)Lipid-lowering medication (+/-)Systolic blood pressure (mmHg)TC (mg/dL)TG (mg/dL)HDL-C (mg/dL)LDL-C (mg/dL)Non-HDL-C (mg/dL)Uric acid (mg/dL)AST (U/L)ALT (U/L)g-glutamyltransferase (U/L)Total bilirubin (mg/dL)Albumin (g/dL)Platelet count (×109/L)Fasting plasma glucose (mg/dL)HbA1C (%)Creatinine (mg/dL)eGFR (ml/min/1.73 m2)FIB-4 indexAPRITotalClinical characteristic of patients21,80150.5 (12.0)11,821/9,98022.7 (3.5)82.6 (9.8)58.4%/28.8%/15.8%12,733/5,608/3,455 4.3 (0-50)21.2%/78.8%4,626/17,1757.3%/92.7%1,584/20,21739.8%/60.2%8,667/13,13412.4%/87.6%2,712/19,0863.3%/96.7%729/21,06710.1%/89.9%2,193/19,605118.7 (15.6)201 (34.4)97.3 (79.0)60.8 (15.8)115.8 (30.1)139.9 (34.1)5.2 (1.4)21.7 (9.4)21.3 (16.2)33.1 (44.8)0.81 (0.34)4.28 (0.25)234 (54.7)101 (17.2)5.7 (0.58)0.73 (0.22)80.2 (15.6)1.15 (0.59)0.33 (0.19)Non-MAFLDMAFLDP valueaNon-NAFLDNAFLDP valueb16,24249.5 (12.1)10,004/6,23821.5 (2.7)79.4 (8.0)62.6%/23.2%/14.2%10,170/3,762/2,308 10.9 (14.8)15.0%/85.0%2,438/13,8043.4%/96.6%551/15,69129.7%/70.3%4,816/11,4268.5%/91.5%1,386/14,8541.7%/98.3%271/15,9687.3%/92.7%1,189/15,052116.1 (15.0)199 (33.7)80.4 (54.7)64.3 (15.3)112.8 (29.1)134.9 (32.2)4.9 (1.3)20.3 (7.3)17.4 (9.8)27.2 (33.8)0.81 (0.34)4.26 (0.25)232 (54.6)98.3 (12.8)5.6 (0.42)0.71 (0.23)80.9 (15.5)1.15 (0.58)0.31 (0.16)5,55953.3 (10.9)1,817/3,74226.1 (3.4)92.0 (8.4)46.1%/33.2%/20.6%2,563/1,846/1,147 13.4 (16.4)39.4%/60.6%2,188/3,37118.6%/81.4%1,033/4,52669.3%/30.7%3,851/1,70823.9%/76.1%1,326/4,2328.2%/91.8%458/5,09918.1%/81.9%1,004/4,553126.4 (14.8)205 (35.8)147 (112)50.6 (12.5)124.6 (31.0)154.3 (35.2)6.0 (1.3)25.8 (13.0)32.7 (23.8)50.4 (64.1)0.80 (0.33)4.32 (0.25)238 (54.7)111 (23.7)6.0 (0.83)0.78 (0.17)78.1 (15.6)1.14 (0.60)0.39 (0.26)<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.00010.3436<0.0001<0.0001<0.0001<0.0001<0.0001<0.00010.1816<0.000117,33849.9 (12.1)10,114/7,22421.9 (3.1)80.4 (8.8)59.7%/24.8%/15.5%10,344/4,301/2,689 13.2 (16.4)17.9%/82.1%3,104/14,2344.7%/95.3%813/16,62532.6%/67.4%5,646/11,6928.5%/91.5%1,798/15,5372.2%/97.8%377/16,9568.1%/91.9%1,408/15,927117.1 (15.3)200 (33.8)87.0 (68.7)63.5 (15.5)113.2 (29.3)136.2 (32.8)5.0 (1.3)20.9 (8.8)18.6 (13.0)31.3 (47.0)0.81 (0.34)4.26 (0.25)232 (54.5)99.5 (14.5)5.6 (0.46)0.72 (0.23)80.6 (15.5)1.17 (0.60)0.32 (0.19)4,46352.8 (11.2)1,707/2,75625.8 (3.6)90.9 (8.9)53.5%/29.3%/17.2%2,389/1,307/766 4.8 (6.6)34.1%/65.9%1,522/2,94117.3%/82.7%771/3,69267.7%/32.3%3,021/1,44220.5%/79.5%914/3,5497.9%/92.1%352/4,11117.6%/82.4%785/3,678124.9 (15.2)204 (36.1)137 (100)50.2 (12.3)125.7 (30.9)154.1 (35.3)5.9 (1.3)24.6 (11.0)31.6 (22.0)40.1 (34.1)0.79 (0.33)4.32 (0.26)240 (54.9)109 (23.5)6.0 (0.84)0.77 (0.18)78.4 (15.7)1.09 (0.55)0.36 (0.21)<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001<0.0001Table Supplemental Information 1
3. Abbreviations: ALT: alanine aminotransferase; APRI: aspartate aminotransferase to platelet ratio index; AST: aspartate aminotransferase; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; FIB-4: Fibrosis-4 Index; HDL: high density lipoprotein; LDL: low density lipoprotein; MAFLD: Metabolic dysfunction-associated fatty liver disease; NAFLD: nonalcoholic fatty liver disease; total cholesterol: TC, triglycerides: TG. Mean (standard deviation) or number (%) . a compared with MAFLD group, b compared with NAFLD group.
4. Figure, Supplemental Information 2The number of patients with low, indeterminate, and high FIB-4 according to the two different cutoffs for FIB-4.0.000.250.500.751.00ShahLowIndeterminateHighIshibaLowIndeterminateHigh0.000.250.500.751.00ShahLowIndeterminateHighIshibaLowIndeterminateHighMAFLD without alcohol intake (N=4,118)B. MAFLD with alcohol intake (N=1,441)Abbreviations: FIB-4: Fibrosis-4 Index; MAFLD: Metabolic dysfunction-associated fatty liver disease; NAFLD: nonalcoholic fatty liver disease.
5. Figure, Supplemental Information 3Abbreviations: FIB-4, fibrosis-4; MAFLD, metabolic dysfunction-associated fatty liver disease; NAFLD, nonalcoholic fatty liver disease; yrs, years.Relationship between FIB-4 and age in patients with fatty liver