Professor Patrick Kennedy, MB BCh BAO BMedSci FRCP MD

Profile

Professor Kennedy is a leading liver specialist and his work in viral liver disease is known internationally. Trained in University College Dublin, he completed post-graduate training in London and was appointed as a Senior Lecturer at Barts and The London School of Medicine and Dentistry in 2009. He has produced novel work redefining disease phase in Chronic Hepatitis B (CHB).

His primary research interest is in Hepatitis B virus (HBV) within a translational platform. He has a special interest in liver disease in young people, specifically HBV; he set up and runs the dedicated young adult liver service at The Royal London Hospital. He is widely published in viral liver disease and has almost 100 peer reviewed publications in addition to multiple book chapters and he has also edited a textbook of Gastrohepatology. His work in HBV is known internationally. He has produced novel work redefining disease phase and described clonal hepatocyte expansion and HBV DNA integration in young patients with HBeAg positive chronic infection (formerly referred to as “immune tolerant” patients), the foundation for the re-evaluation of treatment candidacy in Chronic Hepatitis B (CHB). He is a passionate advocate for early treatment (and broadening treatment access) in CHB to prevent disease progression and liver cancer. Developing these themes, an important focus of his current work is individualized treatment strategies for CHB, namely the early initiation of antiviral therapy and then access to novel therapies as part of the HBV functional cure program. Professor Kennedy is the chief/principal investigator for a number of investigator-led and commercial phase 1, 2 and 3, clinical trials in CHB and hepatitis delta virus (HDV). This clinical trial portfolio dovetails his longstanding research interest and publication record, the ultimate goal of which is achieving HBV cure.

Professor Kennedy is the current Chair of the British Viral Hepatitis Group (BVHG) and former lead for the British Association for the Study of the Liver (BASL) special interest group in HBV. He is a member of the WHO guideline development group and the EASL CHB clinical practice guidelines. He provides expert opinion for the United Kingdom Advisory Panel on blood-borne viruses, in addition he is a key opinion leader in viral liver disease and a member of expert advisory panels for early drug development.

Summary

Professor Patrick Kennedy is a Clinical Professor of Translational Hepatology at the Faculty of Medicine and Dentistry (FMD), QMUL and Consultant Hepatologist at Barts Health NHS Trust.

His research focuses in translational aspects of Hepatitis B virus. He is also leads the Hepatitis B clinical service and runs the young adult Hepatology service at The Royal London Hospital.

Teaching

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Research

Research Interests:

Research themes

• Redefining disease phase in CHB virus infection
• Age-related immune responses in CHB (immune responses in children/young adults)
• Defining a threshold for age-dependent T cell exhaustion in CHB.
• Immune mediated mechanisms of liver injury in CHB
• Investigation of NK and T cell immune interactions in HBV therapies
• Determining treatment endpoints in CHB
• Analysis of NK and T cell receptor/ligand expression and interaction in CHB
• Expression and functional effect of immune regulatory receptors (IRR) in CHB
• Use of quantitative HBsAg in the disease phase & assessment of CHB
• Biomarkers to determine disease progression in CHB
• Novel tools for disease assessment in CHB

Publications

• Gish RG, Wong RJ, Di Tanna GL, Kaushik A, Kim C, Smith NJ, Kennedy PTF.
  Association between hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis. Hepatology. 2023 Oct 23
• Georgia Zeng, Apostolos Koffas, Lung-Yi Mak, Upkar S. Gill, Patrick TF Kennedy. Utility of novel viral and immune markers in predicting HBV treatment endpoints: A systematic review of treatment discontinuation studies. JHEP Reports. 2023.
• Svicher V*, Salpini R*, Piermatteo L, Carioti L, Battisti A, Colagrossi L, Scutari R, Surdo M, Cacciafesta V, Nuccitelli A, Hansi N, Ceccherini Silberstein F, Perno CF, Gill US, Kennedy PTF. Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B. Gut. 2020
• Le Bert N*, Gill US*, Hong M*, Kunasegaran K, Tan DZM, Ahmad R, Cheng Y, Dutertre CA, Heinecke A, Rivino L, Tan A, Hansi NK, Zhang M, Xi S, Chong Y, Pflanz S, Newell EW, Kennedy PTF*, Bertoletti A*. Effects of Hepatitis B Surface Antigen on Virus-specific and Global T Cells in Patients With Chronic HBV infection. Gastroenterology. 2020
• Mason WS, Gill US, Litwin S, Zhou Y, Peri S, Pop O, Hong ML, Naik S, Quaglia A, Bertoletti A, Kennedy PT. HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant. Gastroenterology. 2016

Gill US, Peppa D, Micco L, Singh HD, Carey I, Foster GR, Maini MK, Kennedy PT. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo. PLoS Pathog. 2016 Aug 3;12(8):e1005788. doi: 10.1371/journal.ppat.1005788. eCollection 2016 Aug.

PMID: 27487232.

 

Mason WS, Gill US, Litwin S, Zhou Y, Peri S, Pop O, Hong ML, Naik S, Quaglia A, Bertoletti A, Kennedy PT. HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant. Gastroenterology. 2016 Jul 21. pii: S0016-5085(16)34808-9. doi: 10.1053/j.gastro.2016.07.012. PMID: 27453547

 

Schurich A, Pallett LJ, Jajbhay D, Wijngaarden J, Otano I, Gill US, Hansi N, Kennedy PT, Nastouli E, Gilson R, Frezza C, Henson SM, Maini MK. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host. Cell Rep. 2016 Aug 2;16(5):1243-52. doi: 10.1016/j.celrep.2016.06.078. Epub 2016 Jul 21. PMID: 27452473

 

Stegmann KA, Robertson F, Hansi N, Gill US, Pallant C, Christophides T, Pallett LJ, Peppa D, Dunn C, Fusai G, Male V, Davidson BR, Kennedy PT, Maini MK. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver. Sci Rep. 2016 May 23;6:26157. doi: 10.1038/srep26157. PMID: 27210614

 

Bermingham SL, Hughes R, Fenu E, Sawyer LM, Boxall E, Kennedy PT, Dusheiko G, Hill-Cawthorne G, Thomas H. Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.  Value Health. 2015 Sep;18(6):800-9. PMID: 27210614

 

Pallett LJ, Gill US, Quaglia A, Sinclair LV, Jover-Cobos M, Schurich A, Singh KP, Thomas N, Das A, Chen A, Fusai G, Bertoletti A, Cantrell DA, Kennedy PT, Davies NA, Haniffa M, Maini MK. Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells. Nat Med. 2015 Jun;21(6):591-600. PMID: 26409607

 

Bertoletti A, Kennedy PT. The immune tolerant phase of chronic HBV infection: new perspectives on an old concept. Cell Mol Immunol. 2015 May;12(3):258-63. doi: 10.1038/cmi.2014.79. Epub 2014 Sep 1. Review. PMID: 25176526

 

Gill US, Zissimopoulos A, Al-Shamma S, Burke K, McPhail MJ, Barr DA, Kallis YN, Marley RT, Kooner P, Foster GR, Kennedy PT. Assessment of Bone Mineral Density in Tenofovir treated Chronic Hepatitis B patients: Can FRAX identify those at greatest risk? J Infect Dis. 2015 Feb;211(3):374-82. PMID: 25156561

 

Gill US, Kennedy PT. Chronic hepatitis B virus in young adults: the need for new approaches to management. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1045-53. doi: 10.1586/14787210.2014.940899. Epub 2014 Jul 23. Review. PMID: 25052517

 

Gehring AJ, Haniffa M, Kennedy PT, Ho ZZ, Boni C, Shin A, Banu N, Chia A, Lim SG, Ferrari C, Ginhoux F, Bertoletti A. Mobilizing monocytes to cross-present circulating viral antigen in chronic infection. J Clin Invest. 2013 Sep;123(9):3766-76. doi: 10.1172/JCI66043. Epub 2013 Aug 1.

PMID: 23908113

 

Peppa D, Gill US, Reynolds G, Easom NJ, Pallett LJ, Schurich A, Micco L, Nebbia G, Singh HD, Adams DH, Kennedy PT, Maini MK. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med. 2013 Jan 14;210(1):99-114. doi: 10.1084/jem.20121172. Epub 2012 Dec 17. PMID: 23254287

 

Kennedy PT, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, Naik S, Foster GR, Bertoletti A. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):637-45. doi: 10.1053/j.gastro.2012.06.009. Epub 2012 Jun 15.

PMID: 22710188

 

View all Patrick Kennedy's Research Publications at: http://www.researchpublications.qmul.ac.uk

COLLABORATIONS

 

Dr Kennedy has a number of longstanding and highly successful collaborations, notably with Mala Maini and Antonio Bertoletti, in addition to multiple collaborations with investigators (and clinicians) from national and international research institutes. These include:

 

National collaborators

Professor Mala Maini                          Division of Infection & Immunity, UCL

Dr Alberto Quaglia                              Histopathology, King's College Hospital NHS Foundation Trust

Dr Harry Antoniades                           Department of Medicine, Imperial College London & The Liver Intensive Care Unit, Kings College Hospital.

Dr William Tong                                 Virology, Barts Health NHS Trust

Dr Sandhia Naik                                  Paediatric Hepatology, Barts Health NHS Trust

Dr Ivana Carey                                    Institute of Liver Studies, Kings College London  

Dr Ashley Brown                                Department of Medicine, Imperial College London

Dr Dan Forton                                     Gastroenterology & Hepatology, St Georges Healthcare

Professor Deirdre Kelly                      Paediatric Hepatology, Birmingham Childrens Hospital

Professor William Rosenberg             Institute of Immunity & Transplantation

Dr Salma Ayis                                    Medicine Clinical Academic Group, Kings College London

Professor Martin Pitt                          University of Exeter Medical School

Professor William Irving                    Faculty of Medicine & Health Sciences, University of Nottingham

Professor John McLauchlan               Centre for Virus Research, University of Glasgow

Professor Mark Thursz                       Department of Medicine, Imperial College London

Dr Mark McPhail                               Department of Medicine, Imperial College London

 

 

International collaborators

Professor Antonio Bertoletti              Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore

Professor William Mason                  Fox Chase Cancer Centre, Philadelphia, USA 

Dr Valentina Svicher                         Department of Experimental Medicine & Surgery, University of Rome Tor Vergata,

Professor Carlos F. Perno                  Department of Experimental Medicine & Surgery, University of Rome Tor Vergata,

Dr Adam Gehring                              Centre for Liver Disease, Toronto General Research Institute

Professor Serag Zakaria                     Faculty of Medicine, Cairo University, Egypt.

 

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View all Patrick Kennedy's Research Publications at: http://www.researchpublications.qmul.ac.uk

Supervision

Professor Kennedy supervises doctoral MD and PhD students along with BSc and MSc students as the per the Institutional programs at the Blizard Institute

Doctoral students

Dr Upkar Gill (Uppy) is a Wellcome Trust funded Clinical Research Training fellow and Honorary Registrar in Gastroenterology/Hepatology. His PhD research is co-supervised with Professor Mala Maini in collaboration with Professor Antonio Bertoletti, both of whom Dr Kennedy has a long-standing successful research partnership with. He originally started working with Dr Kennedy as an NIHR funded Academic Clinical Fellow before successfully securing his own funding with a WT fellowship. He has been involved with a number of projects spanning Dr Kennedy’s research themes but his primary research focus is investigating methods of harnessing the immune response in CHB to optimize current treatment strategies by probing NK and T cells interaction in vivo, in order to delineate optimal treatment regimes and end-points. He is an honorary research fellow at Duke-NUS Graduate Medical School, Singapore, where he has been working in Professor Antonio Bertoletti’s lab. He has published and presented work, obtaining prizes, at a number of national and international meetings.

 

Dr Navjot Hansi (Jyoti) is a Clinical Research fellow and Honorary Registrar in Gastroenterology/Hepatology. Her doctoral research is also co-supervised with Professor Mala Maini. She has been investigating the expression of inhibitory receptors on NK cells in CHB infection. The main focus being on the inhibitory receptor, LAIR, in conjunction with its ligand, collagen to determine whether the expression is involved in constraining liver fibrosis. In addition she is involved in projects to determine the role of quantitative HBsAg in non-inflammatory phases of CHB, to further delineate the use of the marker in disease progression. She has also been leading an industry sponsored project to determine management strategies in UK Hepatology centres following recent NICE guidance.

 

Dr Grace Dolman is a post-doctoral research fellow and Honorary Registrar in Gastroenterology/Hepatology. She undertook her doctoral PhD training at the NIHR Nottingham Digestive Diseases Biomedical Research Unit (www.nddcbru.org.uk), supervised by Dr Neil Guha. Her research focused on identifying tissue biomarkers to predict progression to clinical outcomes in patients with advanced fibrosis secondary to chronic hepatitis C infection. She has presented her work at international conferences and undertaken the Nottingham translational postgraduate research training programme. She is now working on Dr Kennedy’s NIHR RfPB programme, with his dedicated research nurse, Louise Payaniandy. This national research programme is centred on the use of quantitative HBsAg in disease assessment.

 

Professor Kennedy also successfully supervises BSc and MSc students on an annual basis. These students undertake small projects in relation to Dr Kennedy’s outlined research themes.