{"id":5408,"date":"2019-09-11T16:19:55","date_gmt":"2019-09-11T14:19:55","guid":{"rendered":"https:\/\/www.resist-cluster.de\/?page_id=5408"},"modified":"2026-01-08T09:04:27","modified_gmt":"2026-01-08T08:04:27","slug":"project-b8","status":"publish","type":"page","link":"https:\/\/www.resist-cluster.de\/en\/research\/project-area-b\/project-b8\/","title":{"rendered":"Project B8"},"content":{"rendered":"

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Why do some people recover spontaneously after therapy disruption?<\/h1><\/div>

Prof. Cornberg\u00a0 |\u00a0 Prof. Prinz<\/a><\/p><\/h2><\/div>

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What is this research project about?<\/h1><\/div>
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Virus hepatitis: Model of a hepatitis B virus<\/p>\n<\/div>

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What is this research project about?<\/h1><\/div>

Hepatitis B virus (HBV) is a global clinical challenge. Worldwide more than 250 million people are chronically infected with HBV with 650.000 HBV-related deaths annually. Current treatment options for chronic hepatitis B in industrialized countries are PEG-IFN\u03b1 or nucleos(t)id-analoga (NA). The therapy with NA can suppress viral replication very efficiently. However, only in a small percentage of patients (less than 1% per year), loss of HBsAg (functional cure of HBV) occurs.<\/p>\n<\/div>

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What’s the current status?<\/h1><\/div>
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NA-treated patients are still at risk of developing liver cirrhosis, liver failure or hepatocellular carcinoma (HCC), since NA therapy only inhibits the generation of new hepatitis B virions, but does not affect the generation of HBsAg and subviral particles. Also, NA therapy does not affect the covalently closed circular HBV DNA (cccDNA), the template of HBV. Therefore, new strategies to induce HBsAg loss are needed.<\/p>\n

In previous clinical studies, Cornberg\/Kraft proposed a strategy to induce hepatic flares by stopping or interrupting NA therapy. They could show that stop of NA treatment in HBeAg- negative patients is safe and can result in decline of HBsAg levels or even in loss of HBsAg in up to 20 % of the patients. So far, it is still not completely clear, which mechanisms are involved in the increased functional cure in patients with NA treatment interruption. To this end, we have initiated a second prospective study (Terminator 2 study) in order to recruit more patients who will stop long-term NA therapy.<\/p>\n<\/div>

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Stages of chronic liver disease<\/p>\n<\/div>

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What are the project goals?<\/h1><\/div>

The aim of this project is to investigate T cell responses in detail before, during, and after NA treatment interruption. Besides \u03b1\u03b2 T cells we will also focus on \u03b3\u03b4 T cells. We also want to identify biomarkers to predict outcome of NA treatment termination. And we want to correlate HBV-specific T cell phenotype, function and TCR repertoire to outcome of NA therapy termination (endpoint HBsAg loss at 4 year after treatment termination).<\/p>\n<\/div><\/div><\/div>

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How do we get there?<\/h1><\/div>
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The project builds on collecting samples from patients enrolled in the the hepatitis B cohort<\/a> and in the Terminator 2 study. Preliminary results showed that \u03b3\u03b4 T cell numbers are elevated in HBV patients as compared to healthy controls. So far, nothing is known about the phenotype, TCR repertoire, and antiviral potential of \u03b3\u03b4 T cells in hepatitis B. While it is known that HBV- specific \u03b1\u03b2 T cell responses are important for control and clearance of HBV, we hypothesize that \u03b3\u03b4 T cell responses are also critical for patients which cleared the infection after stop of NA treatment. To monitor T cell responses in the course of infections, we have established NGS technologies that provide comprehensive access to complex antigen receptor repertoires.<\/p>\n

This project comprises phenotypical, functional and T cell receptor (TCR) analyses of blood-derived \u03b1\u03b2 and \u03b3\u03b4 T cells. Specifically, phenotypical and functional HBV-core specific CD4 and CD8 T cell responses will be analyzed in HLA-typed patients using 16 parameter flow cytometry (e.g. HLA-DRB1 for CD4 and HLA-A2+ for CD8). In parallel we will analyze the TCR repertoire of the dominant CD8 and CD4 T cell responses after FACS-sorting.<\/p>\n

To determine and investigate the role of \u03b3\u03b4 T cells in the Terminator 2 study patient cohort, we use multiplex NGS \u03b3\u03b4 TCR analyses. In particular, we have set up a pipeline to investigate \u03b3\u03b4 TCR repertoires by RNA-based multiplex PCR amplicon sequencing and \u03b1\u03b2 TCR repertoires by RNA-based 5\u2019-RACE PCR amplicon sequencing.<\/p>\n<\/div>

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Blood samples from hepatitis patients are scanned.<\/p>\n<\/div>

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Projectleaders<\/h1><\/div>

Project title: Receptor repertoire analysis of HBV-specific T cells and \u03b3\u03b4 T cells in HBeAg negative patients with chronic hepatitis B after stopping nucleos(t)ide analogue therapy<\/h4><\/div>
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Prof. Dr. Markus Cornberg<\/h3><\/div>

Projects: B8<\/a>, B9<\/a>, B10<\/a><\/h3><\/div>
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CV & VIDEO<\/span><\/a><\/div>
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Prof. Dr. Immo Prinz<\/h3><\/div>

Projects: B5<\/a>, B8<\/a>, B9<\/a><\/h3><\/div>
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CV & VIDEO<\/span><\/a><\/div>
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Project B8 Publications<\/h1><\/div>

Publications 2026<\/strong><\/p>\n

PEG is back: revisiting the role of pegylated interferon alfa and benchmarking its place in HBV cure strategies<\/strong><\/a>\u00a0M. Cornberg\u00a0Gut<\/strong>\u00a02026 Accession Number: 41494801 DOI: 10.1136\/gutjnl-2025-337336<\/p>\n

Publications 2025<\/strong><\/p>\n

Scientific and medical evidence informing expansion of hepatitis B treatment guidelines<\/strong> <\/a>P. T. Kennedy, L. Allweiss, A. Bertoletti, M. Cornberg, A. J. Gehring, L. G. Guidotti, et al. Lancet Gastroenterol Hepatol<\/strong> 2025 Accession Number: 40714040 DOI: 10.1016\/s2468-1253(25)00053-6<\/p>\n

Standardising HBV nomenclature: a call to action from the HBV Forum<\/strong><\/a> S. Wang, M. Leus, M. Cornberg, M. Ghany, C. Hwang, S. G. Lim, et al. Lancet Gastroenterol Hepatol<\/strong> 2025 Accession Number: 40451237 DOI: 10.1016\/s2468-1253(25)00158-x<\/p>\n

Origin of Hypofunctional CD103(+) NK Cells in Cirrhosis-Associated Ascites<\/strong><\/a> C. Niehaus, D. Geanon, A. Lietzau, M. Jankovic, C. Maucourant, B. Maasoumy, et al. Eur J Immunol<\/strong> 2025 Vol. 55 Issue 6 Pages e51311 Accession Number: 40498379 PMCID: PMC12154167 DOI: 10.1002\/eji.202451311<\/p>\n

Editorial: Stopping NUCs-When to Restart NUCs for the Best Outcome?<\/strong><\/a> M. Urbanek-Quaing and M. Cornberg Aliment Pharmacol Ther<\/strong> 2025 Vol. 61 Issue 1 Pages 204-205 Accession Number: 39499186 DOI: 10.1111\/apt.18370<\/p>\n

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative Hepatitis B Patients<\/strong><\/a> V. Ohlendorf, M. Wubbolding, C. Honer Zu Siederdissen, B. Bremer, K. Deterding, H. Wedemeyer, et al. J Viral Hepat<\/strong> 2024 Accession Number: 39425534 DOI: 10.1111\/jvh.14026<\/p>\n

Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation<\/strong><\/a> L. Buttler, D. A. Vel\u00e1zquez-Ram\u00edrez, A. Tiede, A. M. Conradi, S. Woltemate, R. Geffers, et al. Gut Microbes 2025<\/strong> Vol. 17 Issue 1 Pages 2487209 Accession Number: 40255076 DOI: 10.1080\/19490976.2025.2487209<\/p>\n

Reply: Refining epigenetic insights in HBV-Specific T Cell restoration<\/strong><\/a> Y. H. Chou and M. Cornberg Hepatology 2025 <\/strong>Accession Number: 40168461 DOI: 10.1097\/hep.0000000000001340<\/p>\n

\u00a0<\/strong>Enhancing HBV-specific T cell responses through a combination of epigenetic modulation and immune checkpoint inhibition.<\/strong><\/a> Urbanek-Quaing M, Chou YH, Gupta MK, Steppich K, Bremer B, Schmaus H, Deterding K, Maasoumy B, Wedemeyer H, Xu CJ, Kraft ARM, Cornberg M. Hepatology. 2024 Dec 19. Epub ahead of print.<\/p>\n

Publications 2024<\/strong><\/p>\n

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative Hepatitis B Patients<\/strong><\/a> V. Ohlendorf, M. Wubbolding, C. Honer Zu Siederdissen, B. Bremer, K. Deterding, H. Wedemeyer, et al. J Viral Hepat<\/strong> 2024 Accession Number: 39425534 DOI: 10.1111\/jvh.14026<\/p>\n

Limited stability of Hepatitis B virus RNA in plasma and serum <\/strong><\/a>V. Ohlendorf, B. Bremer, L. Sandmann, C. Mix, T. Tergast, M. Cornberg, et al. Sci Rep<\/strong> 2024 Vol. 14 Issue 1 Pages 27128 Accession Number: 39511219 PMCID: PMC11543676 DOI: 10.1038\/s41598-024-77329-2<\/p>\n

Attenuated effector T cells are linked to control of chronic HBV infection<\/strong><\/a> K. Heim, Sagar, O. Sogukpinar, S. Llewellyn-Lacey, D. A. Price, F. Emmerich, et al. Nat Immunol<\/strong> 2024 Vol. 25 Issue 9 Pages 1650-1662 Accession Number: 39198634 PMCID: PMC11362014 DOI: 10.1038\/s41590-024-01928-4<\/p>\n<\/div>

Publications 2025<\/strong><\/p>\n

Standardising HBV nomenclature: a call to action from the HBV Forum<\/strong><\/a> S. Wang, M. Leus, M. Cornberg, M. Ghany, C. Hwang, S. G. Lim, et al. Lancet Gastroenterol Hepatol<\/strong> 2025 Accession Number: 40451237 DOI: 10.1016\/s2468-1253(25)00158-x<\/p>\n

Origin of Hypofunctional CD103(+) NK Cells in Cirrhosis-Associated Ascites<\/strong><\/a> C. Niehaus, D. Geanon, A. Lietzau, M. Jankovic, C. Maucourant, B. Maasoumy, et al. Eur J Immunol<\/strong> 2025 Vol. 55 Issue 6 Pages e51311 Accession Number: 40498379 PMCID: PMC12154167 DOI: 10.1002\/eji.202451311<\/p>\n

Editorial: Stopping NUCs-When to Restart NUCs for the Best Outcome?<\/strong><\/a> M. Urbanek-Quaing and M. Cornberg Aliment Pharmacol Ther<\/strong> 2025 Vol. 61 Issue 1 Pages 204-205 Accession Number: 39499186 DOI: 10.1111\/apt.18370<\/p>\n

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative Hepatitis B Patients<\/strong><\/a> V. Ohlendorf, M. Wubbolding, C. Honer Zu Siederdissen, B. Bremer, K. Deterding, H. Wedemeyer, et al. J Viral Hepat<\/strong> 2024 Accession Number: 39425534 DOI: 10.1111\/jvh.14026<\/p>\n

Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation<\/strong><\/a> L. Buttler, D. A. Vel\u00e1zquez-Ram\u00edrez, A. Tiede, A. M. Conradi, S. Woltemate, R. Geffers, et al. Gut Microbes 2025<\/strong> Vol. 17 Issue 1 Pages 2487209 Accession Number: 40255076 DOI: 10.1080\/19490976.2025.2487209<\/p>\n

Reply: Refining epigenetic insights in HBV-Specific T Cell restoration<\/strong><\/a> Y. H. Chou and M. Cornberg Hepatology 2025 <\/strong>Accession Number: 40168461 DOI: 10.1097\/hep.0000000000001340<\/p>\n

Publications 2024<\/strong><\/p>\n

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative Hepatitis B Patients<\/strong><\/a> V. Ohlendorf, M. Wubbolding, C. Honer Zu Siederdissen, B. Bremer, K. Deterding, H. Wedemeyer, et al. J Viral Hepat<\/strong> 2024 Accession Number: 39425534 DOI: 10.1111\/jvh.14026<\/p>\n

\u00a0<\/strong>Enhancing HBV-specific T cell responses through a combination of epigenetic modulation and immune checkpoint inhibition.<\/strong><\/a> Urbanek-Quaing M, Chou YH, Gupta MK, Steppich K, Bremer B, Schmaus H, Deterding K, Maasoumy B, Wedemeyer H, Xu CJ, Kraft ARM, Cornberg M. Hepatology. 2024 Dec 19. Epub ahead of print.<\/p>\n

Limited stability of Hepatitis B virus RNA in plasma and serum <\/strong><\/a>V. Ohlendorf, B. Bremer, L. Sandmann, C. Mix, T. Tergast, M. Cornberg, et al. Sci Rep<\/strong> 2024 Vol. 14 Issue 1 Pages 27128 Accession Number: 39511219 PMCID: PMC11543676 DOI: 10.1038\/s41598-024-77329-2<\/p>\n

Attenuated effector T cells are linked to control of chronic HBV infection<\/strong><\/a> K. Heim, Sagar, O. Sogukpinar, S. Llewellyn-Lacey, D. A. Price, F. Emmerich, et al. Nat Immunol<\/strong> 2024 Vol. 25 Issue 9 Pages 1650-1662 Accession Number: 39198634 PMCID: PMC11362014 DOI: 10.1038\/s41590-024-01928-4<\/p>\n<\/div>

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Publications of the Project B8<\/h1><\/div>
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