Abstract
Background
Nucleot(s)ide analogues (NA) can reduce the risk of hepatocellular carcinoma (HCC), but not completely prevent its development.
Methods
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.
Results
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.
Conclusions
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.
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Abbreviations
- HBV:
-
Hepatitis B virus
- HCC:
-
Hepatocellular carcinoma
- NA:
-
Nucleos(t)ide analogues
- CHB:
-
Chronic hepatitis B
- AFP:
-
Alpha-fetoprotein
- ETV:
-
Entecavir
- WFA+-M2BP:
-
Wisteria floribunda agglutinin-positive Mac-2-binding protein
- M2BPGi:
-
Mac-2-binding protein glycosylation isomer
- CHC:
-
Chronic hepatitis C
- NAFLD:
-
Non-alcoholic fatty liver disease
- TDF:
-
Tenofovir disoproxil fumarate
- ALT:
-
Alanine Aminotransferase
- COI:
-
Cut-off index
- AST:
-
Aspartate Aminotransferase
- Plt:
-
Platelet count
- T-Bil:
-
Total bilirubin
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Acknowledgements
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.].
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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.
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Shinkai, N., Nojima, M., Iio, E. et al. 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. J Gastroenterol 53, 883–889 (2018). https://doi.org/10.1007/s00535-017-1424-0
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DOI: https://doi.org/10.1007/s00535-017-1424-0