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Virologica Sinica

, Volume 33, Issue 5, pp 459–461 | Cite as

Targeting cIAPs, a New Option for Functional Cure of Chronic Hepatitis B Infection?

  • Hongyan Liu
  • Jinlin Hou
  • Xiaoyong Zhang
PERSPECTIVE

Hepatitis B virus (HBV) infection causes a wide spectrum of liver diseases in more than 240 million people worldwide (Ott et al.2012). Patients with chronic hepatitis B (CHB) may progress to HBV-related end-stage liver diseases, such as hepatic failure, cirrhosis or hepatocellular carcinoma (HCC) (Tang et al.2018). Many international clinical practice guidelines for CHB treatment have suggested the functional cure as an ideal goal for antiviral therapy (Sarin et al.2016; European Association for the Study of the Liver 2017; Terrault et al.2018). Functional cure means sustained, undetectable HBV surface antigen (HBsAg) and HBV DNA in serum with or without seroconversion to hepatitis B surface antibody following a finite or indefinite course of treatment, which implies no virological relapse or progression of liver disease after treatment cessation (Lok et al.2017). Generally, HBsAg loss is considered as a satisfactory biomarker for functional cure. However, approved antiviral agents...

Notes

Acknowledgements

This work was partly supported by Grants from the National Natural Science Foundation of China (81641173) and the Collaboration and Innovation Health Care Major Project of Guangzhou (201604020010).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The authors declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

References

  1. Beug ST, Cheung HH, LaCasse EC, Korneluk RG (2012) Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol 33:535–545CrossRefGoogle Scholar
  2. Block TM, Alter H, Brown N, Brownstein A, Brosgart C, Chang KM, Chen PJ, Cohen C, El-Serag H, Feld J, Gish R, Glenn J, Greten TF, Guo JT, Hoshida Y, Kowdley KV, Li W, Lok AS, McMahon B, Mehta A, Perrillo R, Rice CM, Rinaudo J, Schinazi RF, Shetty K (2018) Research priorities for the discovery of a cure for chronic hepatitis B: report of a workshop. Antivir Res 150:93–100CrossRefGoogle Scholar
  3. Chesi M, Mirza NN, Garbitt VM, Sharik ME, Dueck AC, Asmann YW, Akhmetzyanova I, Kosiorek HE, Calcinotto A, Riggs DL, Keane N, Ahmann GJ, Morrison KM, Fonseca R, Lacy MQ, Dingli D, Kumar SK, Ailawadhi S, Dispenzieri A, Buadi F, Gertz MA, Reeder CB, Lin Y, Chanan-Khan AA, Stewart AK, Fooksman D, Bergsagel PL (2016) IAP antagonists induce anti-tumor immunity in multiple myeloma. Nat Med 22:1411–1420CrossRefGoogle Scholar
  4. Ebert G, Allison C, Preston S, Cooney J, Toe JG, Stutz MD, Ojaimi S, Baschuk N, Nachbur U, Torresi J, Silke J, Begley CG, Pellegrini M (2015a) Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci USA 112:5803–5808CrossRefGoogle Scholar
  5. Ebert G, Preston S, Allison C, Cooney J, Toe JG, Stutz MD, Ojaimi S, Scott HW, Baschuk N, Nachbur U, Torresi J, Chin R, Colledge D, Li X, Warner N, Revill P, Bowden S, Silke J, Begley CG, Pellegrini M (2015b) Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus. Proc Natl Acad Sci USA 112:5797–5802CrossRefGoogle Scholar
  6. Estornes Y, Bertrand MJ (2015) IAPs, regulators of innate immunity and inflammation. Semin Cell Dev Biol 39:106–114CrossRefGoogle Scholar
  7. European Association for the Study of the Liver (2017) EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 67:370–398CrossRefGoogle Scholar
  8. Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez-Aseguinolaza G, Protzer U, Ruggeri ZM, Chisari FV, Isogawa M, Sitia G, Iannacone M (2015) Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell 161:486–500CrossRefGoogle Scholar
  9. Li N, Feng L, Han HQ, Yuan J, Qi XK, Lian YF, Kuang BH, Zhang YC, Deng CC, Zhang HJ, Yao YY, Xu M, He GP, Zhao BC, Gao L, Feng QS, Chen LZ, Yang L, Yang D, Zeng YX (2016) A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis. Cancer Lett 381:14–22CrossRefGoogle Scholar
  10. Li BX, Wang HB, Qiu MZ, Luo QY, Yi HJ, Yan XL, Pan WT, Yuan LP, Zhang YX, Xu JH, Zhang L, Yang DJ (2018) Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway. J Exp Clin Cancer Res 37:53CrossRefGoogle Scholar
  11. Lok AS, Zoulim F, Dusheiko G, Ghany MG (2017) Hepatitis B cure: from discovery to regulatory approval. Hepatology 66:1296–1313CrossRefGoogle Scholar
  12. Ott JJ, Stevens GA, Groeger J, Wiersma ST (2012) Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 30:2212–2219CrossRefGoogle Scholar
  13. Pan W, Luo Q, Yan X, Yuan L, Yi H, Zhang L, Li B, Zhang Y, Sun J, Qiu MZ, Yang DJ (2018) A novel SMAC mimetic APG-1387 exhibits dual antitumor effect on HBV-positive hepatocellular carcinoma with high expression of cIAP2 by inducing apoptosis and enhancing innate anti-tumor immunity. Biochem Pharmacol 154:127–135CrossRefGoogle Scholar
  14. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH (2016) Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 10:1–98CrossRefGoogle Scholar
  15. Tang LSY, Covert E, Wilson E, Kottilil S (2018) Chronic hepatitis B infection: a review. JAMA 319:1802–1813CrossRefGoogle Scholar
  16. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB (2018) Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67:1560–1599CrossRefGoogle Scholar
  17. Wang Z, Ni J, Li J, Shi B, Xu Y, Yuan Z (2011) Inhibition of hepatitis B virus replication by cIAP2 involves accelerating the ubiquitin–proteasome-mediated destruction of polymerase. J Virol 85:11457–11467CrossRefGoogle Scholar
  18. Xu R, Li Y, Ji J, Qiu M, Zhang Y, Liu W, Tian X, Li S, Wang H, Wang F, Zhang D, Wang F, Wang Z, Luo H, Zou B, Wang D, Ren C, Jin Y, Zhai Y, Yang D (2018) A phase I study of a novel IAP inhibitor APG-1387 in patients with advanced solid tumors. J Clin Oncol 36:15_suppl, 2593CrossRefGoogle Scholar
  19. Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, Peters MG, Lai CL (2018) Hepatitis B virus infection. Nat Rev Dis Primers 4:18035CrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang HospitalSouthern Medical UniversityGuangzhouChina

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