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Current Hepatology Reports
Published in: Current Hepatology Reports 4/2016

01-12-2016 | Hepatitis B (JK Lim, Section Editor)

Current and Potential Future Chemopreventive Strategies Against Hepatitis B Virus Reinfection in Liver Transplant Recipients

Authors: Andres F. Carrion, Paul Martin

Published in: Current Hepatology Reports | Issue 4/2016

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Abstract

Although the availability of effective oral therapies for hepatitis B virus (HBV) infection has reduced the need for liver transplantation (LT) for decompensated cirrhosis due to chronic infection, HBV remains an important cause of hepatocellular carcinoma and acute liver failure. Recurrent HBV infection occurs almost invariably post-LT in the absence of prophylaxis if viremia was detectable pre-LT, so prophylaxis remains necessary to prevent graft reinfection. Current approaches include the use of nucleos(t)ide analogues pre- and post-LT and hepatitis B immune globulin, but several novel antiviral agents are currently under investigation in non-transplant populations and may potentially prove to be useful in the LT setting in the future.
Literature
1.
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55.CrossRefPubMed
2.
Ni YH, Huang LM, Chang MH, Yen CJ, Lu CY, You SL, et al. Two decades of universal hepatitis B vaccination in Taiwan: impact and implication for future strategies. Gastroenterology. 2007;132(4):1287–93.CrossRefPubMed
3.•
Lim YS, Han S, Heo NY, Shim JH, Lee HC, Suh DJ. Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine. Gastroenterology. 2014;147(1):152–61. Large retrospective analysis from Korea demonstrating improvement in patient important outcomes associated with entecavir therapy in individuals with chronic HBV infection.CrossRefPubMed
4.
Park YH, Kim BK, Kim JK, Kim HC, do Kim Y, Park JY, et al. Long-term outcomes of chronic hepatitis B virus infection in the era of antiviral therapy in Korea. J Gastroenterol Hepatol. 2014;29(5):1005–11.CrossRefPubMed
5.•
Jang JW, Choi JY, Kim YS, Woo HY, Choi SK, Lee CH, et al. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology. 2015;61(6):1809–20. Multicenter prospective cohort study demonstrating that antiviral therapy modifies the natural history of decompensated cirrhosis due to HBV infection.CrossRefPubMed
6.
Kim WR, Poterucha JJ, Kremers WK, Ishitani MB, Dickson ER. Outcome of liver transplantation for hepatitis B in the United States. Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2004;10(8):968–74.CrossRef
7.
O’Grady JG, Smith HM, Davies SE, Daniels HM, Donaldson PT, Tan KC, et al. Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications. J Hepatol. 1992;14(1):104–11.CrossRefPubMed
8.
Roche B, Samuel D. Prevention of hepatitis B virus reinfection in liver transplant recipients. Intervirology. 2014;57(3–4):196–201.CrossRefPubMed
9.
Harrison RF, Davies MH, Goldin RD, Hubscher SG. Recurrent hepatitis B in liver allografts: a distinctive form of rapidly developing cirrhosis. Histopathology. 1993;23(1):21–8.CrossRefPubMed
10.
Tur-Kaspa R, Shaul Y, Moore DD, Burk RD, Okret S, Poellinger L, et al. The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer. Virology. 1988;167(2):630–3.CrossRefPubMed
11.
Demetris AJ, Todo S, Van Thiel DH, Fung JJ, Iwaki Y, Sysyn G, et al. Evolution of hepatitis B virus liver disease after hepatic replacement. Practical and theoretical considerations. Am J Pathol. 1990;137(3):667–76.PubMedPubMedCentral
12.
Todo S, Demetris AJ, Van Thiel D, Teperman L, Fung JJ, Starzl TE. Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease. Hepatology. 1991;13(4):619–26.PubMedPubMedCentral
13.
Lau JY, Bain VG, Davies SE, O’Grady JG, Alberti A, Alexander GJ, et al. High-level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis. Gastroenterology. 1992;102(3):956–62.CrossRefPubMed
14.
Angus PW, Patterson SJ. Liver transplantation for hepatitis B: what is the best hepatitis B immune globulin/antiviral regimen? Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2008;14 Suppl 2:S15–22.CrossRef
15.
Rao W, Wu X, Xiu D. Lamivudine or lamivudine combined with hepatitis B immunoglobulin in prophylaxis of hepatitis B recurrence after liver transplantation: a meta-analysis. Transplant Int: Off J Eur Soc Organ Transplant. 2009;22(4):387–94.CrossRef
16.
Yahyazadeh A, Beckebaum S, Cicinnati V, Klein C, Paul A, Pascher A, et al. Efficacy and safety of subcutaneous human HBV-immunoglobulin (Zutectra) in liver transplantation: an open, prospective, single-arm phase III study. Transplant Int: Off J Eur Soc Organ Transplant. 2011;24(5):441–50.CrossRef
17.
Xie F, Yan L, Lu J, Zheng T, Shi C, Ying J, et al. Effects of nucleoside analogue on patients with chronic hepatitis B-associated liver failure: meta-analysis. PLoS One. 2013;8(1), e54773.CrossRefPubMedPubMedCentral
18.
Peng CY, Chien RN, Liaw YF. Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy. J Hepatol. 2012;57(2):442–50.CrossRefPubMed
19.
Kim WR, Terrault NA, Pedersen RA, Therneau TM, Edwards E, Hindman AA, et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology. 2009;137(5):1680–6.CrossRefPubMedPubMedCentral
20.
Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, Lee YS, et al. Efficacy of entecavir in treatment-naive patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol. 2010;52(2):176–82.CrossRefPubMed
21.
Marzano A, Marengo A, Marietti M, Rizzetto M. Lactic acidosis during entecavir treatment in decompensated hepatitis B virus-related cirrhosis. Dig Liver Dis: Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2011;43(12):1027–8.CrossRef
22.
Lange CM, Bojunga J, Hofmann WP, Wunder K, Mihm U, Zeuzem S, et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. Hepatology. 2009;50(6):2001–6.CrossRefPubMed
23.
Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F, et al. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology. 2011;53(1):62–72.CrossRefPubMed
24.
Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int. 2010;78(11):1171–7.CrossRefPubMed
25.
Fung J, Chan SC, Cheung C, Yuen MF, Chok KS, Sharr W, et al. Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B. Am J Gastroenterol. 2013;108(6):942–8.CrossRefPubMed
26.
Fung J, Cheung C, Chan SC, Yuen MF, Chok KS, Sharr W, et al. Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation. Gastroenterology. 2011;141(4):1212–9.CrossRefPubMed
27.
Wadhawan M, Gupta S, Goyal N, Taneja S, Kumar A. Living related liver transplantation for hepatitis B-related liver disease without hepatitis B immune globulin prophylaxis. Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2013;19(9):1030–5.CrossRef
28.
Katz LH, Paul M, Guy DG, Tur-Kaspa R. Prevention of recurrent hepatitis B virus infection after liver transplantation: hepatitis B immunoglobulin, antiviral drugs, or both? Systematic review and meta-analysis. Transplant Inf Dis: Off J Transplant Soc. 2010;12(4):292–308.CrossRef
29.
Loomba R, Rowley AK, Wesley R, Smith KG, Liang TJ, Pucino F, et al. Hepatitis B immunoglobulin and lamivudine improve hepatitis B-related outcomes after liver transplantation: meta-analysis. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2008;6(6):696–700.CrossRef
30.
Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125(6):1714–22.CrossRefPubMed
31.
Cholongitas E, Goulis J, Akriviadis E, Papatheodoridis GV. Hepatitis B immunoglobulin and/or nucleos(t)ide analogues for prophylaxis against hepatitis b virus recurrence after liver transplantation: a systematic review. Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2011;17(10):1176–90.CrossRef
32.
Cai CJ, Lu MQ, Chen YH, Zhao H, Li MR, Chen GH. Clinical study on prevention of HBV re-infection by entecavir after liver transplantation. Clin Transpl. 2012;26(2):208–15.CrossRef
33.
Xi ZF, Xia Q, Zhang JJ, Chen XS, Han LZ, Wang X, et al. The role of entecavir in preventing hepatitis B recurrence after liver transplantation. J Dig Dis. 2009;10(4):321–7.CrossRefPubMed
34.
Saab S, Desai S, Tsaoi D, Durazo F, Han S, McClune A, et al. Posttransplantation hepatitis B prophylaxis with combination oral nucleoside and nucleotide analog therapy. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2011;11(3):511–7.CrossRef
35.
Agarwal K, Fung SK, Nguyen TT, Cheng W, Sicard E, Ryder SD, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol. 2015;62(3):533–40.CrossRefPubMed
36.
Lai CL, Ahn SH, Lee KS, Um SH, Cho M, Yoon SK, et al. Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. Gut. 2014;63(6):996–1004.CrossRefPubMed
37.
Yuen MF, Ahn SH, Lee KS, Um SH, Cho M, Yoon SK, et al. Two-year treatment outcome of chronic hepatitis B infection treated with besifovir vs. entecavir: results from a multicentre study. J Hepatol. 2015;62(3):526–32.CrossRefPubMed
38.
Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48–64.CrossRefPubMed
39.
Volz T, Allweiss L, Ben MM, Warlich M, Lohse AW, Pollok JM, et al. The entry inhibitor myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol. 2013;58(5):861–7.CrossRefPubMed
40.••
Brahmania M, Feld J, Arif A, Janssen HL. New therapeutic agents for chronic hepatitis B. Lancet Infect Dis. 2016;16(2):e10–21. Extensive review on emerging therapies for HBV under different phases of investigation.CrossRefPubMed
41.
Zimmerman KA, Fischer KP, Joyce MA, Tyrrell DL. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virol. 2008;82(16):8013–21.CrossRefPubMedPubMedCentral
42.
Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014;343(6176):1221–8.CrossRefPubMed
43.
Kennedy EM, Bassit LC, Mueller H, Kornepati AV, Bogerd HP, Nie T, et al. Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. Virology. 2015;476:196–205.CrossRefPubMed
44.
Gish RG, Yuen MF, Chan HL, Given BD, Lai CL, Locarnini SA, et al. Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent. Antivir Res. 2015;121:97–108.CrossRefPubMed
45.
Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science. 2003;299(5608):893–6.CrossRefPubMed
46.
Wu GY, Zheng XJ, Yin CC, Jiang D, Zhu L, Liu Y, et al. Inhibition of hepatitis B virus replication by Bay 41–4109 and its association with nucleocapsid disassembly. J Chemother. 2008;20(4):458–67.CrossRefPubMed
47.
Feld JJ, Colledge D, Sozzi V, Edwards R, Littlejohn M, Locarnini SA. The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging. Antivir Res. 2007;76(2):168–77.CrossRefPubMed
48.
Phillips S, Chokshi S, Chatterji U, Riva A, Bobardt M, Williams R, et al. Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production. Gastroenterology. 2015;148(2):403–14.e7.CrossRefPubMed
49.
Gaggar A, Coeshott C, Apelian D, Rodell T, Armstrong BR, Shen G, et al. Safety, tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific therapeutic vaccine, in healthy subjects: a randomized study. Vaccine. 2014;32(39):4925–31.CrossRefPubMed
50.
Lobaina Y, Hardtke S, Wedemeyer H, Aguilar JC, Schlaphoff V. In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors. Mol Immunol. 2015;63(2):320–7.CrossRefPubMed
51.
European Association For The Study Of The L. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167–85.CrossRef
52.
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.CrossRefPubMed
Metadata
Title
Current and Potential Future Chemopreventive Strategies Against Hepatitis B Virus Reinfection in Liver Transplant Recipients
Authors
Andres F. Carrion
Paul Martin
Publication date
01-12-2016
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 4/2016
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-016-0314-x

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