Review
Copyright ©The Author(s) 2023.
World J Hepatol. May 27, 2023; 15(5): 609-640
Published online May 27, 2023. doi: 10.4254/wjh.v15.i5.609
Table 3 Serological biomarkers and composite scores for the detection of nonalcoholic steatohepatitis
Ref.
Marker
Country
Categories Tested
Sample size (n)
Dx
Cutoff
AUROC (95%CI)
Sens (%)
Spec (%)
PPV (%)
NPV (%)
P value
Feldstein et al[66], 2013ALTItalyDiagnosing NASHNASH (n = 140), non-NASH (n = 61)Biopsy0.635 (0.556, 0.715)< 0.001
Walenbergh et al[70], 2015ALTItalyBorderline NASH vs definite NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.570.0011 (CatD vs ALT)
Walenbergh et al[70], 2015ALTItalySteatosis + Borderline NASH vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.53< 0.001 (CatD vs ALT)
Walenbergh et al[70], 2015ALTItalySteatosis vs borderline NASH + NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.660.103 (CatD vs ALT)
Walenbergh et al[70], 2015ALT [U/L]ItalySteatosis vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy> 64.50.5961.568.472.756.50.0004 (CatD vs ALT)
Manco et al[57], 2022Ang-2 [ng/mL]ItalyDiagnosing NASHNAFLD (n = 76), controls (n = 28, by ultrasound)Biopsy135.40.911 (0.844–0.979)85.785.38387.5< 0.001
Feldstein et al[66], 2013ASTItalyDiagnosing NASHNASH (n = 140), non-NASH (n = 61)Biopsy0.651 (0.573, 0.728)< 0.001
Walenbergh et al[70], 2015CatDItalyBorderline NASH vs definite NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.85
Walenbergh et al[70], 2015CatDItalySteatosis + Borderline NASH vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.88
Walenbergh et al[70], 2015CatDItalySteatosis vs borderline NASH + NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.81
Walenbergh et al[70], 2015CatD [pg/mL]ItalySteatosis vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy< 184450.9410089.592.9100
Vuppalanchi et al[68], 2014Change in ALTUnited StatesOverall histologic improvementNAFLD (n = 117)Biopsy0.79 (0.70-0.87)
Vuppalanchi et al[68], 2014Change in ALTUnited StatesResolution of NASHNAFLD (n = 117)Biopsy0.84 (0.76-0.93)
Vuppalanchi et al[68], 2014Change in ALT + CK18United StatesOverall histologic improvementNAFLD (n = 117)Biopsy0.79 (0.71-0.87)0.08 (CK18+ALT vs ALT)
Vuppalanchi et al[68], 2014Change in ALT + CK18United StatesResolution of NASHNAFLD (n = 117)Biopsy0.83 (0.75-0.92)0.92 (CK18+ALT vs ALT)
Vuppalanchi et al[68], 2014Change in CK18United States Overall histologic improvementNAFLD (n = 117)Biopsy0.72 (0.63-0.81)0.42 (CK18 vs ALT)
Vuppa-lanchi et al[68], 2014Change in CK18United StatesResolution of NASHNAFLD (n = 117)Biopsy0.69 (0.58-0.79)0.005 (CK18 vs ALT)
Walenbergh et al[70], 2015CK18ItalyBorderline NASH vs definite NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.570.0003 (CatD vs CK18)
Walenbergh et al[70], 2015CK18ItalySteatosis + Borderline NASH vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.52< 0.0001 (CatD vs CK18)
Walenbergh et al[70], 2015CK18ItalySteatosis vs borderline NASH + NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy0.740.4299 (CatD vs CK18)
Manco et al[57], 2022CK18 [U/L]ItalyDiagnosing NASHNAFLD (n = 76), controls (n = 28, by ultrasound)Biopsy3520.827 (0.735–0.919)77.173.27178.9< 0.001
Fitzpatrick et al[67], 2010CK18 [U/L]United KingdomPredicting NASHNAFLD (n = 45), controls (n = 13)Biopsy2070.85 (0.73–0.96)84889080
Feldstein et al[66], 2013CK18 [U/L]ItalyDiagnosing NASHNASH (n = 140), non-NASH (n = 61)Biopsy2330.93348586.993.771.6< 0.001
Walenbergh et al[70], 2015CK18 [U/L]ItalySteatosis vs NASHNASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)Biopsy> 327.50.727263.272.862.20.0225 (CatD vs CK18)
Feldstein et al[66], 2013GGTItalyDiagnosing NASHNASH (n = 140), non-NASH (n = 61)Biopsy0.672 (0.594-0.750)< 0.001
Manco et al[95], 2007Leptin [ng/mL]ItalyPredicting NAFLD Activity ScoreNAFLD (n = 72), F0 (n = 31), F1 (n = 41)Biopsy≤ 14.90.833936547
Manco et al[95], 2007Leptin [ng/mL]ItalyPredicting NAFLD Activity ScoreNAFLD (n = 72), F0 (n = 31), F1 (n = 41)Biopsy≥ 20.454765079
Mosca et al[101], 2019PIIINP [ng/mL]ItalyDefinite NASH vs No/Borderline NASHNo/borderline NASH (n = 115), definite NASH (n = 89)Biopsy> 7.600.737 (0.66-0.81)62918575
Manco et al[95], 2007TNF-α [pg/mL]ItalyPredicting NAFLD Activity ScoreNAFLD (n = 72), F0 (n = 31), F1 (n = 41)Biopsy≤ 5.90.9111836115
Manco et al[95], 2007TNF-α [pg/mL]ItalyPredicting NAFLD Activity ScoreNAFLD (n = 72), F0 (n = 31), F1 (n = 41)Biopsy≥ 7.982969096
AUROC: Area under the receiver operating characteristic curve; ALT: Alanine aminotransferase; Ang-2: Angiopoietin-2; AST: Aspartate aminotransferase; CatD: Cathepsin D; CK18: Cytokeratin 18; CI: Confidence interval; Dx: Diagnosis; GGT: Gamma-glutamyl transferase; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; NPV: Negative predictive value; PPV: Positive predictive value; Sens: Sensitivity; Spec: Specificity; TNF-a: Tumor necrosis factor alpha.