Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus
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ORIGINAL ARTICLE—LIVER, PANCREAS, AND BILIARY TRACT
Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs Mina Nakagawa1,2 • Nobutoshi Nawa2,6,7 • Eiko Takeichi1 • Taro Shimizu1 • Jun Tsuchiya1 • Ayako Sato1 • Masato Miyoshi1 • Fukiko Kawai-Kitahata1 • Miyako Murakawa1,5 • Sayuri Nitta1 • Yasuhiro Itsui1,4 • Seishin Azuma1 • Sei Kakinuma1,3 • Takeo Fujiwara7 • Mamoru Watanabe1,8 • Yujiro Tanaka6 • Yasuhiro Asahina1,3 • the Ochanomizu Liver Conference Study Group Received: 27 April 2020 / Accepted: 28 July 2020 Ó Japanese Society of Gastroenterology 2020
Abstract Background It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications. Methods This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients’ survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival. Results AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-
Mina Nakagawa and Nobutoshi Nawa contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00535-020-01715-6) contains supplementary material, which is available to authorized users. & Yasuhiro Asahina [email protected] 1
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
2
Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan
3
Department of Liver Disease Control, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
4
Department of General Medicine, Tokyo Medical and Dental University, Tokyo, Japan
2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases. Conclusion M2BPGi at SVR is a potential predictor for patients’ survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancerrelated and unrelated to HCV, as well as cardiovascular diseases, after viral eradication. Ke
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