Novel Biomarker Predicts Steatohepatitis Severity

The development and validation of a reproducible and noninvasive test that can accurately distinguish NASH from simple steatosis is urgently needed.

Scientists at Osaka University (Japan) enrolled 127 biopsy-proven NAFLD patients and 23 normal controls (NC) in a study to search for a suitable biomarker. For all patients, biochemical variables were measured using a conventional automated analyzer. The tests included were for platelet counts, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, albumin, total cholesterol, triglyceride, fasting blood glucose, immunoreactive insulin, ferritin, and hyaluronic acid.

The scientists developed their own enzyme-linked immunoassay (ELISA) to measure the levels human macrophage-associated lectin binding protein (Mac-2bp) in the blood of the enrollees. Mac-2bp is one of the major fucosylated glycoproteins, which were identified with glycol-proteomic analyses. The ELISA assay system was finally designed as a commercial kit and galectin-3 was also measured using Human Galectin-3 Assay kit from the same company (Immuno-Biological Laboratory; Fujioka, Japan). For the quantitative measurement of the caspase-generated neoepitope of cytokeratin 18 (CK-18), they used the M30-Apoptosense ELISA (Peviva AB; Bromma, Sweden).

Serum Mac-2bp levels were significantly increased in non-NASH patients to 1.103 ± 0.5 μg/mL compared with normal control at 0.675 ± 0.27 μg/mL. The serum Mac-2bp levels in NASH patients exhibited greater increases to 2.132 ± 1.24 μg/mL than did those in non-NASH patients. Serum M30 antigen levels were also significantly higher in NASH patients than in non-NASH patients. Multivariate logistic regression analyses showed Mac-2bp levels could predict the fibrosis stage and the presence of ballooning hepatocytes in NAFLD patients.

The authors concludes that despite some limitations, serum Mac-2bp levels could distinguish NASH from non-NASH patients and estimate the disease severity of NAFLD patients with accuracy superior to that of the M30 antigen in their patients. Further investigation is needed using a larger number and wider spectrum of NAFLD patients. The study was published online on September 17, 2013, in the journal Proteomics Clinical Applications.

Related Links:
Osaka University
Immuno-Biological Laboratory 
Peviva AB