Diabetes Metab J.  2024 Jul;48(4):740-751. 10.4093/dmj.2023.0189.

A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease

• Choi SJ
• Yoon S
• Kim KK
• Kim D
• Lee HE
• Kim KG
• Shin SK
• Park IB
• Kim SM
• Lee DH

• KMID: 2558041
• DOI: http://doi.org/10.4093/dmj.2023.0189

Abstract

Background
We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis).
Methods
A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination.
Results
A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH.
Conclusion
Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.

Keyword

AKR1B10 protein, human; Biomarkers; Keratin-18; Magnetic resonance imaging; Non-alcoholic fatty liver disease

Figure

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  Fig. 1. Flow diagram of the inclusion of participants in the present study. NAFLD, nonalcoholic fatty liver disease; MR, magnetic resonance; MRI, magnetic resonance imaging; PDFF, proton density fat fraction.

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  Fig. 2. (A-F) Summary of the diagnostic performance of the blood composite biomarker and magnetic resonance (MR)-based composite marker for nonalcoholic steatohepatitis (NASH), advanced fibrosis, and high-risk NASH. For MR-based composite markers please see the details in the manuscript. AKR1B10, aldo-keto reductase family 1 member B10; CK-18, cytokeratin 18; AST, aspartate aminotransferase; ALT, alanine aminotransferase; AUROC, area under the receiver operating characteristic curve; CI, confidence interval; MRI, magnetic resonance imaging; PDFF, proton density fat fraction; MRE, magnetic resonance elastography; LSM, liver stiffness measurement; FIB-4, fibrosis-4 index; MAST, MRI-AST.

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