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Table 3 Predictors of development of hepatocellular carcinoma in patients with NAFLD

From: Hepatocellular carcinoma is the most common liver-related complication in patients with histopathologically-confirmed NAFLD in Japan

Factor Category Univariate (95% CI) P value* Multivariate (95% CI) P value*
Hazard ratio Hazard ratio
Demographic data
 Gender Male 1      
Female 0.24 (0.03–1.97) 0.186    
 Age < 70 y 1    1   
≥70 y 18.6 (3.74–92.6) < 0.001 9.54 (1.63–55.9) 0.012
 Body mass index < 25.0 kg/m2 1      
≥25.0 kg/m2 0.46 (0.11–1.88) 0.276    
 Type 2 diabetes mellitus Absence 1      
Presence 3.64 (0.95–14.0) 0.060    
 Hypertension Absence 1      
Presence 1.06 (0.28–3.95) 0.932    
 Hyperlipidemia Absence 1      
Presence 0.36 (0.05–2.91) 0.339    
Histological findings
 Steatosis 5–33% 1      
> 33% 0.40 (0.10–1.63) 0.201    
 Lobular inflammation < 2 foci per 200× field 1      
≥2 foci per 200× field 0.31 (0.04–2.50) 0.272    
 Ballooning None / Few cells 1      
Many cells 0.47 (0.05–3.84) 0.482    
 Stage 0–3 1    1   
4 33.9 (7.14–161) < 0.001 7.14 (1.29–39.5) 0.024
 NAFLD activity score < 5 1      
≥5 0.19 (0.02–1.50) 0.114    
 Diagnosis according to FLIP algorithm non-NASH 1      
NASH 1.34 (0.17–10.8) 0.784    
Laboratory data
 Serum aspartate aminotransferase < 2 × ULN IU/l 1      
≥2 × ULN IU/l 2.74 (0.73–10.2) 0.134    
 Serum alanine aminotransferase < 2 × ULN IU/l 1      
≥2 × ULN IU/l 0.85 (0.22–3.22) 0.810    
 Gamma-glutamyl transpeptidase < 110 IU/l 1      
≥110 IU/l 1.29 (0.34–4.86) 0.706    
 Platelet count < 200 × 103/mm3 1    1   
≥200 × 103/mm3 0.06 (0.01–0.50) 0.009 0.14 (0.01–1.33) 0.086
 Fasting plasma glucose < 110 mg/dl 1      
≥110 mg/dl 3.61 (0.85–15.3) 0.081    
 HbA1c < 5.8% 1      
≥5.8% 56.2 (0.01–634,349) 0.397    
 Uric acid < 7.1 mg/dl 1      
≥7.1 mg/dl 0.03 (0.00–21.0) 0.298    
 Total cholesterol < 200 mg/dl 1      
≥200 mg/dl 0.18 (0.04–0.87) 0.033    
 Triglycerides < 150 mg/dl 1      
≥150 mg/dl 0.46 (0.09–2.28) 0.342    
 High-density lipoprotein cholesterol < 41 mg/dl 1      
≥41 mg/dl 0.58 (0.15–2.25) 0.428    
 Low-density lipoprotein cholesterol < 136 mg/dl 1      
≥136 mg/dl 0.24 (0.03–2.06) 0.191    
 Serum ferritin < 81 μg/l 1      
≥81 μg/l 0.71 (0.14–3.61) 0.674    
 High sensitive C-reactive protein < 0.2 mg/dl 1      
≥0.2 mg/dl 1.02 (0.11–10.0) 0.984    
 Alpha-fetoprotein < 5 μg/l 1    1   
≥5 μg/l 7.15 (1.44–35.6) 0.016 4.44 (0.84–23.4) 0.079
 PIVKA-II < 21 AU/l 1      
≥21 AU/l 0.47 (0.06–4.05) 0.495    
  1. *Significance was determined using a Cox proportional hazard model. CI confidence interval, ULN upper limit of normal