High levels of serum Mac-2-binding protein glycosylation isomer (M2BPGi) predict the development of hepatocellular carcinoma in hepatitis B patients treated with nucleot(s)ide analogues
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Nucleot(s)ide analogues (NA) can reduce the risk of hepatocellular carcinoma (HCC), but not completely prevent its development.
Two hundred and thirty-four chronic hepatitis B patients virologically well controlled with entecavir or tenofovir disoproxil fumarate for more than 1 year were enrolled in this study. Over the median observation period of 51 (12–142) months, 24 of 234 patients developed HCC. We quantified HBV markers, alpha-fetoprotein (AFP) and Mac-2-binding protein glycosylation isomer (M2BPGi) at baseline and 48 weeks after therapy.
Serum AFP and M2BPGi tended to decline from baseline to 48 weeks after treatment both in patients who did and those who did not develop HCC. Univariate Cox regression analysis indicated that serum M2BPGi levels ≥ 1.215 COI at 48 weeks were associated with HCC development [hazard ratio (HR) 5.73; p ≤ 0.001]. Multivariate analysis showed that male sex (HR 5.6; p = 0.01), AFP ≥ 9.65 ng/ml (HR 22.01; p ≤ 0.001), M2BPGi ≥ 1.215 (HR 5.07; p = 0.004) at 48 weeks were significant independent predictive factors for HCC development. Based on a scoring system consisting of three factors above described, Kaplan–Meier analysis for four groups (score 0, 1, 2, ≥ 3), revealed significant differences in cumulative HCC occurrence for each group within 2 years. The rate of incidence of HCC was 0, 5.4, 23.4, and 75% in each group, respectively.
In patients receiving NA therapy, higher M2BPGi at 48 weeks, as well as male sex and higher AFP at 48 weeks were independent risk factors for HCC development.
KeywordsMac-2-binding protein glycosylation isomer Hepatocellular carcinoma Nucleot(s)ide analogue Alpha-fetoprotein
Hepatitis B virus
Chronic hepatitis B
Wisteria floribunda agglutinin-positive Mac-2-binding protein
Mac-2-binding protein glycosylation isomer
Chronic hepatitis C
Non-alcoholic fatty liver disease
Tenofovir disoproxil fumarate
This work was supported in part by a grant-in-aid from the Research Program on Hepatitis from Japan Agency for Medical Research and Development (AMED) and a Grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology [Scientific Research (B) No.16H05288 to Y.T.].
Compliance with ethical standards
Conflict of interest
Yasuhito Tanaka received lecture fees from Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline plc, Bristol–Myers Squibb, Fujirebio Inc., and Gilead Sciences, Inc.
Yasuhito Tanaka received research fees from Bristol–Myers Squibb, Chugai Pharmaceutical Co., Ltd., and Fujifilm Corporation.
- 13.Fujiyoshi M, Kuno A, Gotoh M, et al. Clinicopathological characteristics and diagnostic performance of Wisteria floribunda agglutinin positive Mac-2-binding protein as a preoperative serum marker of liver fibrosis in hepatocellular carcinoma. J Gastroenterol. 2015;50(11):1134–44.CrossRefPubMedGoogle Scholar
- 20.Kuno A, Sato T, Shimazaki H, et al. Reconstruction of a robust glycodiagnostic agent supported by multiple lectin-assisted glycan profiling. Proteom Clin Appl. 2013;7(9–10):642–7.Google Scholar