Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem around the world. Among NAFLD patients, those with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and hepatocellular carcinoma (HCC). To distinguish NASH from simple steatosis and to estimate its disease severity would be of great clinical significance. It is because NASH would become a more important liver disease developing HCC after viral hepatitis is overcome. Mac-2 binding protein (Mac-2bp) is one of the major fucosylated glycoproteins, which we identified with glyco-proteomic analyses. In this study, we investigated the availability of Mac-2bp for differential diagnosis of NASH from NAFLD as a biomarker.

Methods: Our cohort of 127 patients had biopsy-proven NAFLD. Serum Mac-2bp levels were determined with our developed ELISA kit. For the quantitative measurement of the caspase-generated neoepitope of CK-18, we used the M30-Apoptosense ELISA (Peviva, Bromma, Sweden). Then, we compared the usefulness of serum Mac-2bp levels with the M30 antigen for the prediction of NASH diagnosis and disease severity. The normal controls (NC) were sera from 23 healthy subjects. Statistical analysis was performed with JMP 10 software.

Results: In our cohort, Mac-2bp levels were significantly increased in nonNASH patients compared with NC (1.103 ± 0.500 vs 0.675 ± 0.271 μg/mL, P<0.01). More importantly, the Mac-2bp levels in NASH patients exhibited greater increases than did those in nonNASH patients (2.132 ± 1.237 μg/mL, P<0.01). We also compared the sensitivity and specificity of Mac-2bp with those of the M30 antigen for the discrimination of NASH using the ROC curve. The sensitivity of Mac-2bp was almost the same as that of the M30 antigen for the differentiation of NASH and nonNASH (74.3 vs 78.9 %). The specificity of Mac-2bp was higher than that of the M30 antigen (77.8 vs 61.1 %). The area under the receiver operating characteristic (AUROC) curve of Mac-2bp for predicting NASH was higher than that of the M30 antigen (0.816 vs 0.725). There was no correlation between Mac-2bp and the M30 antigen levels in NAFLD patients. Moreover, Mac-2bp levels could predict the fibrosis stage of NAFLD patients. Multivariate logistic regression analysis showed Mac-2bp levels were significant determinants for NASH diagnosis and monitoring of liver fibrosis staging in NAFLD, but M30 antigen levels were not.

Conclusions: Measurement of serum Mac-2bp can distinguish NASH from nonNASH patients, and predict liver disease severity including the incidence of HCC in patients with NAFLD.

Citation Format: Yoshihiro Kamada, Kayo Mizutani, Hironobu Fujii, Maaya Akita, Yuka Ohara, Shinji Takamatsu, Eiji Miyoshi. Serum Mac-2 binding protein levels as a novel diagnostic biomarker for prediction of disease severity and nonalcoholic steatohepatitis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 886. doi:10.1158/1538-7445.AM2014-886