Skip to main content
Top
Published in: Hepatology International 5/2023

Open Access 28-03-2023 | Hepatitis B | Original Article

Metabolic interventions improve HBV envelope-specific T-cell responses in patients with chronic hepatitis B

Authors: Yu-Long Fu, Shuang-Nan Zhou, Wei Hu, Jing Li, Ming-Ju Zhou, Xiao-Yu Li, You-Yuan Wang, Peng Zhang, Si-Yuan Chen, Xing Fan, Jin-Wen Song, Yan-Mei Jiao, Ruonan Xu, Ji-Yuan Zhang, Cheng Zhen, Chun-Bao Zhou, Jin-Hong Yuan, Ming Shi, Fu-Sheng Wang, Chao Zhang

Published in: Hepatology International | Issue 5/2023

Login to get access

Abstract

Background

Restoration of HBV-specific T cell immunity is a promising approach for the functional cure of chronic Hepatitis B (CHB), necessitating the development of valid assays to boost and monitor HBV-specific T cell responses in patients with CHB.

Methods

We analyzed hepatitis B virus (HBV) core- and envelope (env)-specific T cell responses using in vitro expanded peripheral blood mononuclear cells (PBMCs) from patients with CHB exhibiting different immunological phases, including immune tolerance (IT), immune activation (IA), inactive carrier (IC), and HBeAg-negative hepatitis (ENEG). Additionally, we evaluated the effects of metabolic interventions, including mitochondria-targeted antioxidants (MTA), polyphenolic compounds, and ACAT inhibitors (iACAT), on HBV-specific T-cell functionality.

Results

We found that HBV core- and env-specific T cell responses were finely coordinated and more profound in IC and ENEG than in the IT and IA stages. HBV env-specific T cells were more dysfunctional but prone to respond to metabolic interventions using MTA, iACAT, and polyphenolic compounds than HBV core-specific T-cells. The responsiveness of HBV env-specific T cells to metabolic interventions can be predicted by the eosinophil (EO) count and the coefficient of variation of red blood cell distribution width (RDW-CV).

Conclusion

These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB.

Graphical abstract

Appendix
Available only for authorised users
Literature
1.
go back to reference Organization WH. Global hepatitis report. Geneva, Switzerland: World Health Organization; 2017 Organization WH. Global hepatitis report. Geneva, Switzerland: World Health Organization; 2017
2.
go back to reference Fanning GC, Zoulim F, Hou J, Bertoletti A. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov. 2019;18:827–844PubMedCrossRef Fanning GC, Zoulim F, Hou J, Bertoletti A. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov. 2019;18:827–844PubMedCrossRef
3.
go back to reference Fung S, Choi HSJ, Gehring A, Janssen HLA. Getting to HBV cure: The promising paths forward. Hepatology. 2022;76:233–250PubMedCrossRef Fung S, Choi HSJ, Gehring A, Janssen HLA. Getting to HBV cure: The promising paths forward. Hepatology. 2022;76:233–250PubMedCrossRef
4.
go back to reference Naggie S, Lok AS. New therapeutics for hepatitis B: the road to cure. Annu Rev Med. 2021;72:93–105PubMedCrossRef Naggie S, Lok AS. New therapeutics for hepatitis B: the road to cure. Annu Rev Med. 2021;72:93–105PubMedCrossRef
5.
go back to reference Cox AL, El-Sayed MH, Kao J-H, Lazarus JV, Lemoine M, Lok AS, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol. 2020;17:533–542PubMedPubMedCentralCrossRef Cox AL, El-Sayed MH, Kao J-H, Lazarus JV, Lemoine M, Lok AS, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol. 2020;17:533–542PubMedPubMedCentralCrossRef
6.
go back to reference Revill PA, Chisari FV, Block JM, Dandri M, Gehring AJ, Guo H, et al. A global scientific strategy to cure hepatitis B. Lancet Gastroenterol Hepatol. 2019;4:545–558PubMedPubMedCentralCrossRef Revill PA, Chisari FV, Block JM, Dandri M, Gehring AJ, Guo H, et al. A global scientific strategy to cure hepatitis B. Lancet Gastroenterol Hepatol. 2019;4:545–558PubMedPubMedCentralCrossRef
7.
go back to reference Gehring AJ, Protzer U. Targeting innate and adaptive immune responses to cure chronic HBV infection. Gastroenterology. 2019;156:325–337PubMedCrossRef Gehring AJ, Protzer U. Targeting innate and adaptive immune responses to cure chronic HBV infection. Gastroenterology. 2019;156:325–337PubMedCrossRef
8.
go back to reference Lang J, Neumann-Haefelin C, Thimme R. Immunological cure of HBV infection. Hepatol Int. 2019;13:113–124PubMedCrossRef Lang J, Neumann-Haefelin C, Thimme R. Immunological cure of HBV infection. Hepatol Int. 2019;13:113–124PubMedCrossRef
9.
go back to reference Maini MK, Burton AR. Restoring, releasing or replacing adaptive immunity in chronic hepatitis B. Nat Rev Gastroenterol Hepatol. 2019;16:662–675PubMedCrossRef Maini MK, Burton AR. Restoring, releasing or replacing adaptive immunity in chronic hepatitis B. Nat Rev Gastroenterol Hepatol. 2019;16:662–675PubMedCrossRef
10.
go back to reference Iannacone M, Andreata F, Guidotti LG. Immunological insights in the treatment of chronic hepatitis B. Curr Opin Immunol. 2022;77: 102207PubMedCrossRef Iannacone M, Andreata F, Guidotti LG. Immunological insights in the treatment of chronic hepatitis B. Curr Opin Immunol. 2022;77: 102207PubMedCrossRef
11.
go back to reference Iannacone M, Guidotti LG. Immunobiology and pathogenesis of hepatitis B virus infection. Nat Rev Immunol. 2022;22:19–32PubMedCrossRef Iannacone M, Guidotti LG. Immunobiology and pathogenesis of hepatitis B virus infection. Nat Rev Immunol. 2022;22:19–32PubMedCrossRef
12.
go back to reference Zhang C, Li J, Cheng Y, Meng F, Song JW, Fan X, et al. Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients. Gut. 2023;72:153–167PubMedCrossRef Zhang C, Li J, Cheng Y, Meng F, Song JW, Fan X, et al. Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients. Gut. 2023;72:153–167PubMedCrossRef
13.
go back to reference Boni C, Laccabue D, Lampertico P, Giuberti T, Viganò M, Schivazappa S, et al. Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues. Gastroenterology. 2012;143:963-973.e969PubMedCrossRef Boni C, Laccabue D, Lampertico P, Giuberti T, Viganò M, Schivazappa S, et al. Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues. Gastroenterology. 2012;143:963-973.e969PubMedCrossRef
14.
go back to reference Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, et al. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013;58:225–233PubMedCrossRef Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, et al. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013;58:225–233PubMedCrossRef
15.
go back to reference Penna A, Laccabue D, Libri I, Giuberti T, Schivazappa S, Alfieri A, et al. Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis. J Hepatol. 2012;56:1239–1246PubMedCrossRef Penna A, Laccabue D, Libri I, Giuberti T, Schivazappa S, Alfieri A, et al. Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis. J Hepatol. 2012;56:1239–1246PubMedCrossRef
16.
go back to reference Rivino L, Le Bert N, Gill US, Kunasegaran K, Cheng Y, Tan DZ, et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J Clin Invest. 2018;128:668–681PubMedPubMedCentralCrossRef Rivino L, Le Bert N, Gill US, Kunasegaran K, Cheng Y, Tan DZ, et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J Clin Invest. 2018;128:668–681PubMedPubMedCentralCrossRef
17.
go back to reference Fisicaro P, Barili V, Rossi M, Montali I, Vecchi A, Acerbi G, et al. Pathogenetic mechanisms of T cell dysfunction in chronic HBV infection and related therapeutic approaches. Front Immunol. 2020;11:849PubMedPubMedCentralCrossRef Fisicaro P, Barili V, Rossi M, Montali I, Vecchi A, Acerbi G, et al. Pathogenetic mechanisms of T cell dysfunction in chronic HBV infection and related therapeutic approaches. Front Immunol. 2020;11:849PubMedPubMedCentralCrossRef
18.
go back to reference Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol. 2007;81:4215–4225PubMedPubMedCentralCrossRef Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol. 2007;81:4215–4225PubMedPubMedCentralCrossRef
19.
go back to reference Le Bert N, Gill US, Hong M, Kunasegaran K, Tan DZM, Ahmad R, et al. Effects of hepatitis B surface antigen on virus-specific and global T Cells in patients with chronic hepatitis B virus infection. Gastroenterology. 2020;159:652–664PubMedCrossRef Le Bert N, Gill US, Hong M, Kunasegaran K, Tan DZM, Ahmad R, et al. Effects of hepatitis B surface antigen on virus-specific and global T Cells in patients with chronic hepatitis B virus infection. Gastroenterology. 2020;159:652–664PubMedCrossRef
20.
go back to reference Kim JH, Ghosh A, Ayithan N, Romani S, Khanam A, Park JJ, et al. Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients. Sci Rep. 2020;10:1835PubMedPubMedCentralCrossRef Kim JH, Ghosh A, Ayithan N, Romani S, Khanam A, Park JJ, et al. Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients. Sci Rep. 2020;10:1835PubMedPubMedCentralCrossRef
21.
go back to reference Chen C, Jiang X, Liu X, Guo L, Wang W, Gu S, et al. Identification of the association between HBcAg-specific T cell and viral control in chronic HBV infection using a cultured ELISPOT assay. J Leukoc Biol. 2021;109:455–465PubMedCrossRef Chen C, Jiang X, Liu X, Guo L, Wang W, Gu S, et al. Identification of the association between HBcAg-specific T cell and viral control in chronic HBV infection using a cultured ELISPOT assay. J Leukoc Biol. 2021;109:455–465PubMedCrossRef
22.
go back to reference Hoogeveen RC, Robidoux MP, Schwarz T, Heydmann L, Cheney JA, Kvistad D, et al. Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection. Gut. 2019;68:893–904PubMedCrossRef Hoogeveen RC, Robidoux MP, Schwarz T, Heydmann L, Cheney JA, Kvistad D, et al. Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection. Gut. 2019;68:893–904PubMedCrossRef
23.
go back to reference Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, et al. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut. 2019;68:905–915PubMedCrossRef Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, et al. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut. 2019;68:905–915PubMedCrossRef
24.
go back to reference Cheng Y, Zhu O, Becht E, Aw P, Chen J, Poidinger M, et al. Multifactorial heterogeneity of virus-specific T cells and association with the progression of human chronic hepatitis B infection. Sci Immunol. 2019;4:eaau6905PubMedCrossRef Cheng Y, Zhu O, Becht E, Aw P, Chen J, Poidinger M, et al. Multifactorial heterogeneity of virus-specific T cells and association with the progression of human chronic hepatitis B infection. Sci Immunol. 2019;4:eaau6905PubMedCrossRef
25.
go back to reference Ferrando-Martinez S, Snell Bennett A, Lino E, Gehring AJ, Feld J, Janssen HLA, et al. Functional exhaustion of HBV-specific CD8 T cells impedes PD-L1 blockade efficacy in chronic HBV infection. Front Immunol. 2021;12: 648420PubMedPubMedCentralCrossRef Ferrando-Martinez S, Snell Bennett A, Lino E, Gehring AJ, Feld J, Janssen HLA, et al. Functional exhaustion of HBV-specific CD8 T cells impedes PD-L1 blockade efficacy in chronic HBV infection. Front Immunol. 2021;12: 648420PubMedPubMedCentralCrossRef
26.
go back to reference Fisicaro P, Valdatta C, Massari M, Loggi E, Biasini E, Sacchelli L, et al. Antiviral intrahepatic T-cell responses can be restored by blocking programmed death-1 pathway in chronic hepatitis B. Gastroenterology. 2010;138(682–693):693.e681–684 Fisicaro P, Valdatta C, Massari M, Loggi E, Biasini E, Sacchelli L, et al. Antiviral intrahepatic T-cell responses can be restored by blocking programmed death-1 pathway in chronic hepatitis B. Gastroenterology. 2010;138(682–693):693.e681–684
27.
go back to reference Fisicaro P, Valdatta C, Massari M, Loggi E, Ravanetti L, Urbani S, et al. Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV. Gastroenterology. 2012;143:1576-1585.e1574PubMedCrossRef Fisicaro P, Valdatta C, Massari M, Loggi E, Ravanetti L, Urbani S, et al. Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV. Gastroenterology. 2012;143:1576-1585.e1574PubMedCrossRef
28.
go back to reference Bengsch B, Martin B, Thimme R. Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol. 2014;61:1212–1219PubMedCrossRef Bengsch B, Martin B, Thimme R. Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol. 2014;61:1212–1219PubMedCrossRef
29.
go back to reference Ferrando-Martinez S, Huang K, Bennett AS, Sterba P, Yu L, Suzich JA, et al. HBeAg seroconversion is associated with a more effective PD-L1 blockade during chronic hepatitis B infection. JHEP Rep. 2019;1:170–178PubMedPubMedCentralCrossRef Ferrando-Martinez S, Huang K, Bennett AS, Sterba P, Yu L, Suzich JA, et al. HBeAg seroconversion is associated with a more effective PD-L1 blockade during chronic hepatitis B infection. JHEP Rep. 2019;1:170–178PubMedPubMedCentralCrossRef
30.
go back to reference Fisicaro P, Boni C, Barili V, Laccabue D, Ferrari C. Strategies to overcome HBV-specific T cell exhaustion: checkpoint inhibitors and metabolic re-programming. Curr Opin Virol. 2018;30:1–8PubMedCrossRef Fisicaro P, Boni C, Barili V, Laccabue D, Ferrari C. Strategies to overcome HBV-specific T cell exhaustion: checkpoint inhibitors and metabolic re-programming. Curr Opin Virol. 2018;30:1–8PubMedCrossRef
31.
go back to reference Barili V, Boni C, Rossi M, Vecchi A, Zecca A, Penna A, et al. Metabolic regulation of the HBV-specific T cell function. Antiviral Res. 2021;185: 104989PubMedCrossRef Barili V, Boni C, Rossi M, Vecchi A, Zecca A, Penna A, et al. Metabolic regulation of the HBV-specific T cell function. Antiviral Res. 2021;185: 104989PubMedCrossRef
32.
go back to reference Fisicaro P, Barili V, Montanini B, Acerbi G, Ferracin M, Guerrieri F, et al. Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B. Nat Med. 2017;23:327–336PubMedCrossRef Fisicaro P, Barili V, Montanini B, Acerbi G, Ferracin M, Guerrieri F, et al. Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B. Nat Med. 2017;23:327–336PubMedCrossRef
33.
go back to reference Acerbi G, Montali I, Ferrigno GD, Barili V, Schivazappa S, Alfieri A, et al. Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B. J Hepatol. 2021;74:783–793PubMedCrossRef Acerbi G, Montali I, Ferrigno GD, Barili V, Schivazappa S, Alfieri A, et al. Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B. J Hepatol. 2021;74:783–793PubMedCrossRef
34.
go back to reference Schmidt NM, Wing PAC, Diniz MO, Pallett LJ, Swadling L, Harris JM, et al. Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint. Nat Commun. 2021;12:2814PubMedPubMedCentralCrossRef Schmidt NM, Wing PAC, Diniz MO, Pallett LJ, Swadling L, Harris JM, et al. Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint. Nat Commun. 2021;12:2814PubMedPubMedCentralCrossRef
35.
go back to reference EASL. Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;2017(67):370–398 EASL. Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;2017(67):370–398
36.
go back to reference Berg T, Simon KG, Mauss S, Schott E, Heyne R, Klass DM, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol. 2017;67:918–924PubMedCrossRef Berg T, Simon KG, Mauss S, Schott E, Heyne R, Klass DM, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol. 2017;67:918–924PubMedCrossRef
37.
go back to reference Yang S, Zeng W, Zhang J, Lu F, Chang J, Guo JT. Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary? Emerg Microbes Infect. 2021;10:1545–1554PubMedPubMedCentralCrossRef Yang S, Zeng W, Zhang J, Lu F, Chang J, Guo JT. Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary? Emerg Microbes Infect. 2021;10:1545–1554PubMedPubMedCentralCrossRef
38.
go back to reference Aliabadi E, Urbanek-Quaing M, Maasoumy B, Bremer B, Grasshoff M, Li Y, et al. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut. 2022;71:2300PubMedCrossRef Aliabadi E, Urbanek-Quaing M, Maasoumy B, Bremer B, Grasshoff M, Li Y, et al. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut. 2022;71:2300PubMedCrossRef
39.
go back to reference Xiong S, Zhu D, Liang B, Li M, Pan W, He J, et al. Longitudinal characterization of phenotypic profile of T cells in chronic hepatitis B identifies immune markers associated with HBsAg loss. EBioMedicine. 2021;69: 103464PubMedPubMedCentralCrossRef Xiong S, Zhu D, Liang B, Li M, Pan W, He J, et al. Longitudinal characterization of phenotypic profile of T cells in chronic hepatitis B identifies immune markers associated with HBsAg loss. EBioMedicine. 2021;69: 103464PubMedPubMedCentralCrossRef
40.
go back to reference Bertoletti A, Kennedy PTF. HBV antiviral immunity: not all CD8 T cells are born equal. Gut. 2019;68:770–773PubMedCrossRef Bertoletti A, Kennedy PTF. HBV antiviral immunity: not all CD8 T cells are born equal. Gut. 2019;68:770–773PubMedCrossRef
41.
go back to reference Cheng Y, Zhu YO, Becht E, Aw P, Chen J, Poidinger M, et al. Multifactorial heterogeneity of virus-specific T cells and association with the progression of human chronic hepatitis B infection. Sci Immunol. 2019;4:eaau6905CrossRefPubMedPubMedCentral Cheng Y, Zhu YO, Becht E, Aw P, Chen J, Poidinger M, et al. Multifactorial heterogeneity of virus-specific T cells and association with the progression of human chronic hepatitis B infection. Sci Immunol. 2019;4:eaau6905CrossRefPubMedPubMedCentral
42.
go back to reference Aliabadi E, Urbanek-Quaing M, Maasoumy B, Bremer B, Grasshoff M, Li Y, et al. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut. 2021;4:eaau6905 Aliabadi E, Urbanek-Quaing M, Maasoumy B, Bremer B, Grasshoff M, Li Y, et al. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut. 2021;4:eaau6905
43.
go back to reference Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV. Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections. J Virol. 2002;76:8609–8620PubMedPubMedCentralCrossRef Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV. Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections. J Virol. 2002;76:8609–8620PubMedPubMedCentralCrossRef
44.
go back to reference Wong GLH, Gane E, Lok ASF. How to achieve functional cure of HBV: stopping NUCs, adding interferon or new drug development? J Hepatol. 2022;76:1249–1262PubMedCrossRef Wong GLH, Gane E, Lok ASF. How to achieve functional cure of HBV: stopping NUCs, adding interferon or new drug development? J Hepatol. 2022;76:1249–1262PubMedCrossRef
45.
go back to reference Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143:629-636.e621PubMedCrossRef Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143:629-636.e621PubMedCrossRef
46.
go back to reference Peña-Asensio J, Calvo H, Miquel J, Sanz-de-Villalobos E, González-Praetorius A, Torralba M, et al. Model to predict on-treatment restoration of functional HBV-specific CD8(+) cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B. Aliment Pharmacol Ther. 2022;55:1545–1559PubMedPubMedCentralCrossRef Peña-Asensio J, Calvo H, Miquel J, Sanz-de-Villalobos E, González-Praetorius A, Torralba M, et al. Model to predict on-treatment restoration of functional HBV-specific CD8(+) cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B. Aliment Pharmacol Ther. 2022;55:1545–1559PubMedPubMedCentralCrossRef
47.
go back to reference Rinker F, Zimmer CL, Höner Zu SC, Manns MP, Kraft ARM, Wedemeyer H, et al. Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B. J Hepatol. 2018;69:584–593PubMedCrossRef Rinker F, Zimmer CL, Höner Zu SC, Manns MP, Kraft ARM, Wedemeyer H, et al. Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B. J Hepatol. 2018;69:584–593PubMedCrossRef
48.
go back to reference García-López M, Lens S, Pallett LJ, Testoni B, Rodríguez-Tajes S, Mariño Z, et al. Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients. J Hepatol. 2021;74:1064–1074PubMedPubMedCentralCrossRef García-López M, Lens S, Pallett LJ, Testoni B, Rodríguez-Tajes S, Mariño Z, et al. Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients. J Hepatol. 2021;74:1064–1074PubMedPubMedCentralCrossRef
49.
go back to reference Gill US, Pallett LJ, Kennedy PTF, Maini MK. Liver sampling: a vital window into HBV pathogenesis on the path to functional cure. Gut. 2018;67:767–775PubMed Gill US, Pallett LJ, Kennedy PTF, Maini MK. Liver sampling: a vital window into HBV pathogenesis on the path to functional cure. Gut. 2018;67:767–775PubMed
50.
go back to reference van Buuren N, Ramirez R, Turner S, Chen D, Suri V, Aggarwal A, et al. Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection. JHEP Rep. 2021;4:100388PubMedCrossRef van Buuren N, Ramirez R, Turner S, Chen D, Suri V, Aggarwal A, et al. Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection. JHEP Rep. 2021;4:100388PubMedCrossRef
51.
go back to reference Boettler T, Gill US, Allweiss L, Pollicino T, Tavis JE, Zoulim F. Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection. JHEP Rep. 2022;4: 100480PubMedPubMedCentralCrossRef Boettler T, Gill US, Allweiss L, Pollicino T, Tavis JE, Zoulim F. Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection. JHEP Rep. 2022;4: 100480PubMedPubMedCentralCrossRef
Metadata
Title
Metabolic interventions improve HBV envelope-specific T-cell responses in patients with chronic hepatitis B
Authors
Yu-Long Fu
Shuang-Nan Zhou
Wei Hu
Jing Li
Ming-Ju Zhou
Xiao-Yu Li
You-Yuan Wang
Peng Zhang
Si-Yuan Chen
Xing Fan
Jin-Wen Song
Yan-Mei Jiao
Ruonan Xu
Ji-Yuan Zhang
Cheng Zhen
Chun-Bao Zhou
Jin-Hong Yuan
Ming Shi
Fu-Sheng Wang
Chao Zhang
Publication date
28-03-2023
Publisher
Springer India
Keyword
Hepatitis B
Published in
Hepatology International / Issue 5/2023
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-023-10490-4

Other articles of this Issue 5/2023

Hepatology International 5/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine