Noboru Shinkai1, Masanori Nojima2, Etsuko Iio3, Kayoko Matsunami3, Hidenori Toyoda4, Shuko Murakami1, Takako Inoue5, Shintaro Ogawa1, Takashi Kumada4, Yasuhito Tanaka6. 1. Departments of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 2. Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan. 3. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 4. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 5. Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan. 6. Departments of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ytanaka@med.nagoya-cu.ac.jp.
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.
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 Bpatients 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.
Entities:
Keywords:
Alpha-fetoprotein; Hepatocellular carcinoma; Mac-2-binding protein glycosylation isomer; Nucleot(s)ide analogue
Authors: H Nishikawa; H Enomoto; Y Iwata; K Kishino; Y Shimono; K Hasegawa; C Nakano; R Takata; T Nishimura; K Yoh; A Ishii; N Aizawa; Y Sakai; N Ikeda; T Takashima; H Iijima; S Nishiguchi Journal: J Viral Hepat Date: 2016-07-31 Impact factor: 3.728
Authors: Patrick Marcellin; Edward Gane; Maria Buti; Nezam Afdhal; William Sievert; Ira M Jacobson; Mary Kay Washington; George Germanidis; John F Flaherty; Raul Aguilar Schall; Jeffrey D Bornstein; Kathryn M Kitrinos; G Mani Subramanian; John G McHutchison; E Jenny Heathcote Journal: Lancet Date: 2012-12-10 Impact factor: 79.321