Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers.
OBJECTIVE
The diagnosis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is limited by the need for liver biopsy. We aimed at testing the accuracy of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) for the diagnosis of NAFLD and NASH.


METHODS
146 patients with biopsy-proven NAFLD and 74 age- and gender-matched healthy controls were included. Serum CK-18, AFABP and FGF21 levels were determined by enzyme-linked immunosorbent assay.


RESULTS
Serum CK-18, AFABP, and FGF21 increased in a stepwise fashion in control subjects (median 103 U/L, 15.4 ng/ml, and 104 pg/ml), patients with non-NASH NAFLD (263 U/L, 18.9 ng/ml, and 249 pg/ml) and NASH (418 U/L, 19.4 ng/ml, and 354 pg/ml) (p<0.001, 0.060, and 0.016, respectively). The area under receiver-operating characteristics curve to diagnose NAFLD and NASH was 0.91 and 0.70 for CK-18, 0.66 and 0.59 for AFABP, and 0.84 and 0.62 for FGF21. At cut-offs of 203 and 670 U/L, CK-18 had 71% negative predictive value (NPV) and 77% positive predictive value (PPV) to exclude and diagnose NASH. A 2-step approach measuring CK-18 followed by FGF21 further improved the NPV to 74% and PPV to 82%. In a validation cohort of 51 patients with paired liver biopsies, the NPV and PPV of the 2-step approach were 67% and 78%, respectively.


CONCLUSIONS
CK-18 is the most accurate biomarker for NAFLD and NASH. A two-step approach using CK-18 and FGF21 further improves the accuracy in diagnosing NASH.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Jiayun
J
Shen
Henry Lik-Yuen
HL
Chan
Grace Lai-Hung
GL
Wong
Paul Cheung-Lung
PC
Choi
Anthony Wing-Hung
AW
Chan
Hoi-Yun
HY
Chan
Angel Mei-Ling
AM
Chim
David Ka-Wai
DK
Yeung
Francis Ka-Leung
FK
Chan
Jean
J
Woo
Jun
J
Yu
Winnie Chiu-Wing
WC
Chu
Vincent Wai-Sun
VW
Wong
D000328:Adult; D015415:Biomarkers / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease
D015415:Biomarkers; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D053538:Keratin-18; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors