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Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and the development of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapy

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Abstract

Aim

Wisteria floribunda agglutinin positive (WFA+) Mac-2-binding protein (M2BPGi) is a noninvasive glyco-marker for liver fibrosis. This study evaluated the utility of serial measurement of serum M2BPGi and total M2BP as a predictor of fibrosis and the development of hepatocellular carcinoma (HCC).

Methods

This study included 119 patients with chronic hepatitis C (CHC). Of these patients, 97 were treated with IFN-based therapy and 22 were treated with daclatasvir and asunaprevir. Serum M2BPGi values were measured prior to, at the end of, and at 24 weeks after the completion of treatment. As subanalysis, serum total M2BP levels were measured in patients treated with pegylated-interferon and ribavirin.

Results

In patients treated with IFN-based therapy, M2BPGi levels were elevated at the end of treatment but decreased afterwards. In contrast, M2BPGi levels in patients treated with IFN-free therapy decreased immediately after starting the treatment without transient elevation. Though pre-treatment M2BPGi levels significantly correlated with fibrosis in both patients with a sustained virological response (SVR) and non-SVR, post-treatment M2BPGi levels decreased regardless of the degree of fibrosis in patients with SVR. In multivariate analysis, non-SVR and HCC development were independent factors associated with M2BPGi level ≥2.2. In patients treated with pegylated-interferon and ribavirin, total M2BP levels were positively correlated with fibrosis and HCC development.

Conclusion

Real-time monitoring of the serum M2BPGi level after antiviral therapy for CHC patients could be a helpful screening tool for assessing the risk of HCC. M2BP and its glycan structure could be associated together with hepatocarcinogenesis.

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Abbreviations

HCV:

Hepatitis C virus

WFA:

Wisteria floribunda agglutinin

M2BP:

Mac-2-binding protein

M2BPGi:

Mac-2-binding protein glycosylation isomer

HCC:

Hepatocellular carcinoma

CHC:

Chronic hepatitis C

PEG-IFN:

Pegylated-interferon

RBV:

Ribavirin

SVR:

Sustained virological response

COI:

Cut off index

DAA:

Direct-acting antiviral agent

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AFP:

α-Fetoprotein

US:

Ultrasonography

CT:

Computed tomography

MRI:

Magnetic resonance imaging

PC:

Positive control

NC:

Negative control

PPV:

Positive predictive value

NPV:

Negative predictive value

SMV:

Simeprevir

TVR:

Telaprevir

ASV:

Asunaprevir

DCV:

Daclatasvir

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Acknowledgements

This study is based on the participation of six multicenter hospitals (Tokyo Medical and Dental University Hospital, Kashiwa City Hospital, Showa General Hospital, Toride Kyodo General Hospital, Mishima General Hospital).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Hiroko Nagata, Mina Nakagawa, Yuki Nishimura-Sakurai, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Shun Kaneko, Fumio Goto, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Yasuhiro Asahina & Mamoru Watanabe

  2. Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan

    Mina Nakagawa & Shuji Tohda

  3. Department of Clinical Laboratory, Tokyo Medical and Dental University, Tokyo, Japan

    Miyako Murakawa

  4. Department of General Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Yasuhiro Itsui

  5. Department of Liver Disease Control, Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan

    Sei Kakinuma & Yasuhiro Asahina

  6. Department of Clinical Laboratory, Sanraku Hospital, Tokyo, Japan

    Naoko Tojo

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  1. Hiroko Nagata
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  2. Mina Nakagawa
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  18. Yasuhiro Asahina
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  19. Mamoru Watanabe
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Consortia

The Ochanomizu Liver Conference Study Group

Corresponding author

Correspondence to Yasuhiro Asahina.

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Conflict of interest

Dr. Asahina and Dr. Kakinuma belong to donation-funded department funded by Chugai Pharmaceutical Co. Ltd., Toray Industries Inc., Bristol-Myers Squibb, Dainippon Sumitomo Pharma Co. Ltd., and Merck Sharp & Dohme.

Financial support

This study was supported by grants for research received from Sysmex Corporation, grants from the Ministry of Education, Culture, Sports, Science and Technology-Japan, the Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development, the Japan Health Sciences Foundation, the Miyakawa Memorial Research Foundation, and the National Institute of Biomedical Innovation.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all patients. The Ethical Committee of Tokyo Medical and Dental University approved this study, which was conducted in accordance with the Declaration of Helsinki (Confirmation No. 1863).

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Nagata, H., Nakagawa, M., Nishimura-Sakurai, Y. et al. Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and the development of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapy. Hepatol Int 10, 956–964 (2016). https://doi.org/10.1007/s12072-016-9754-1

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  • DOI: https://doi.org/10.1007/s12072-016-9754-1

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