EASL Recognition Awardee for 2014
Authors: Heiner Wedemeyer
Journal: Journal of Hepatology (2014)

When Tillmann Sauerbruch introduced Didier Lebrec for the EASL Recognition Award 2013, he described a wonderful and truly European story. The Geoff-Dusheiko-Story is similar impressive, this time a global narrative! Born and trained in South Africa, two fellowships in the United States, Professor of Medicine at UCL in London, one of the world's most requested "KOL" in the development of new therapies for viral hepatitis B and C, teaching fellows from various countries, scientific collaborations with different groups around the world and serving EASL for many years as an Education Councillor – Geoff Dusheiko significantly contributed to the development of our discipline. Everyone I contacted in recent months – from Michael Kew (South Africa) to Jay Hoofnagle (NIH) and Neil McIntyre (London) – agreed that without any doubt Geoff Dusheiko very much deserved to receive the EASL Recognition Award! Geoffrey Dusheiko is Emeritus Professor of Medicine at the UCL Institute of Liver and Digestive Disease. He qualified in medicine in 1973, from the University of the Witwatersrand. Since he has worked and studied in South Africa, the United States and the United Kingdom, and benefited from this varied experience in developing and developed countries. He qualified as a specialist physician (Fellow of the College of Physicians of South Africa) in 1977. In 1979 he was awarded a South African Medical Research Council Fellowship which enabled him to work for two years as a visiting associate in the Liver Unit of the National Institutes of Health in Bethesda, USA with Dr Jay Hoofnagle and Dr E Anthony Jones. In 1987 he was awarded the Vice Chancellor's research fellowship and spent six months in the Department of Microbiology at the University of Minnesota, Minneapolis USA. In 1988 he was appointed Senior Lecturer in the Academic Department of Medicine, Royal Free Hospital and School of Medicine, and was appointed Reader in the same department in 1989 and subsequently Professor. Since his research fellowships he has established an international reputation in the field of viral hepatitis and antiviral therapy in the face of full-time clinical responsibilities. His very first publication was not addressing liver diseases but described two cases of Haemophilus endocarditis [[1]Dusheiko G.M. Cassel R. Haemophilus endocarditis. A report of two cases.S Afr Med J. 1978; 54: 245-247PubMed Google Scholar]. But soon after, he witnessed the indelible imprint of the morbidity and aftermath of chronic viral hepatitis in South Africa [[2]Kew M.C. Gear A.J. Baumgarten I. Dusheiko G.M. Maier G. Histocompatibility antigens in patients with hepatocellular carcinoma and their relationship to chronic hepatitis B virus infection in these patients.Gastroenterology. 1979; 77: 537-539Abstract Full Text PDF PubMed Scopus (20) Google Scholar] which has left him with a determination to see these collective diseases defeated. At the NIH (1979–1981), as a South African Medical Research Council Research Fellow, he worked under the tutelage of Dr Jay Hoofnagle, studying synthesis of neutralising antibodies in patients with chronic hepatitis B.Jay Hoofnagle: "Geoff deserves the Recognition Award. He would never ask for recognition himself. Geoff was my first fellow at the NIH (that is who came to work with me rather than being there when I arrived). He was a terrific worker and set up assays in the lab that we used for years". Jay Hoofnagle: "Geoff deserves the Recognition Award. He would never ask for recognition himself. Geoff was my first fellow at the NIH (that is who came to work with me rather than being there when I arrived). He was a terrific worker and set up assays in the lab that we used for years". The data suggested that patients with chronic hepatitis have an impairment in B cell production of neutralising antibodies, perhaps as a result of high dose immunological tolerance. This work was published in the Journal of Clinical Investigation [[3]Dusheiko G.M. Hoofnagle J.H. et al.Synthesis of antibodies to hepatitis-B virus by cultured lymphocytes from chronic hepatitis-B surface-antigen carriers.J Clin Invest. 1983; 71: 1104-1113Crossref PubMed Scopus (66) Google Scholar]. At the same time he was closely involved in some of the landmark studies of the time of the natural history, molecular virology, serology and potential antiviral treatment of chronic hepatitis. These studies documented the phenomena of spontaneous seroconversion to anti-HBe during the natural history of viral hepatitis, and are widely cited [[4]Hoofnagle J.H. Dusheiko G.M. et al.Seroconversion from hepatitis-B-E antigen to antibody in chronic type-B hepatitis.Ann Intern Med. 1981; 94: 744-748Crossref PubMed Scopus (586) Google Scholar]. Upon his return to South Africa, he initiated, and was the major architect of a series of studies elucidating the natural history and epidemiology of hepatitis B and hepatocellular carcinoma in an endemic area (with Michael Kew) [5Botha J.F. Dusheiko G.M. et al.Hepatitis-B virus carrier state in black-children in ovamboland – role of perinatal and horizontal infection.Lancet. 1984; 1: 1210-1212Abstract PubMed Scopus (161) Google Scholar, 6Dusheiko G.M. Bowyer S.M. et al.Replication of hepatitis-B virus in adult carriers in an endemic area.J Infect Dis. 1985; 152: 566-571Crossref PubMed Scopus (23) Google Scholar, 7Dusheiko G.M. Conradie J.C. et al.Small and asymptomatic hepatocellular-carcinoma detected by alpha-fetoprotein screening in black hepatitis-B carriers – a report of 2 cases.S Afr Med J. 1986; 69: 129-132PubMed Google Scholar, 8Dusheiko G.M. Dibisceglie A. et al.Prolonged recombinant leukocyte alpha-interferon treatment of chronic hepatitis-B.Hepatology. 1984; 4 (789–789)PubMed Google Scholar]. These studies documented, for example, the importance of horizontal spread of hepatitis B in African children, and contrasted this epidemiology with that in Chinese [[5]Botha J.F. Dusheiko G.M. et al.Hepatitis-B virus carrier state in black-children in ovamboland – role of perinatal and horizontal infection.Lancet. 1984; 1: 1210-1212Abstract PubMed Scopus (161) Google Scholar]. They documented the molecular changes in hepatitis B viral replication in patients with advanced liver disease, and demonstrated a changing epidemiology in patients migrating from rural to urban areas. He directed studies examining the effect of gene methylation on hepatitis B replication on the expression of hepatitis B virus in carriers with replicative and non-replicative infection. Together with Ann Bowcock, he documented the chromosomal integration sites of hepatitis B virus in PLC/PRF/5 (Alexander) HCC cells [[9]Bowcock A.M. Pinto M.R. et al.The Plc/Prf/5 human hepatoma-cell line 2. Chromosomal assignment of hepatitis-B virus integration sites.Cancer Genet Cytogenet. 1985; 18: 19-26Abstract Full Text PDF PubMed Scopus (29) Google Scholar]. While at the University of Minnesota (1986–87), he studied alpha fetoprotein messenger RNA expression by in situ hybridisation in patients with hepatocellular carcinoma. These findings suggest that steady-state quantities of alpha fetoprotein RNA are increased in malignant hepatocytes, perhaps because there is an anomalous reversion increasing gene transcription [10Varagona G. Brown D. et al.Increased steady-state levels of alpha-fetoprotein messenger-RNA in hepatocellular-carcinoma – an analysis by in situ hybridization.Liver. 1992; 12: 62-68Crossref PubMed Scopus (6) Google Scholar, 11Varagona G. Dusheiko G.M. et al.Increased alpha-fetoprotein in hepatocellular-carcinoma – hypothesis on the underlying molecular mechanism.Clin Sci. 1990; 78 (P22–P22)Crossref Google Scholar]. In 1982 he realised the possible antiviral potential of recombinant interferon alpha, devised a treatment strategy, and in a landmark study, documented that a proportion of patients with replicative chronic hepatitis B responded to interferon alpha [[12]Dusheiko G. Dibisceglie A. et al.Recombinant leukocyte interferon treatment of chronic hepatitis-B.Hepatology. 1985; 5: 556-560Crossref PubMed Scopus (155) Google Scholar]. The first experiences of interferon for hepatitis B were summarised in the first article Geoff published in the EASL journal – the Journal of Hepatology [[13]Dusheiko G.M. Paterson A.C. Pitcher L. Kassianides C. DiBisceglie A.M. Song E. Kew M.C. Recombinant leukocyte interferon treatment of chronic hepatitis B. An analysis of two therapeutic trials.J Hepatol. 1986; 3: S199-S207Abstract Full Text PDF PubMed Scopus (34) Google Scholar]. This study also, however, showed that the efficacy of interferon alpha was restricted, and he catalogued the exacerbation of hepatitis required for efficacy, the criteria favouring a response, and documented the loss of both HBeAg and HBsAg in patients with a response. The events accompanying the response pointed to the role of the immune response in reducing hepatitis B replication. These studies were followed by further controlled trials, which have stood the test of time. These early studies, were (with human insulin), the first therapeutic use of a recombinant human protein.Adrian di Bisceglie (AASLD president): "Geoff had just returned from time at the NIH with Jay Hoofnagle and he had somehow arranged to be one of the first sites to use Roche recombinant interferon (Roferon-A). I remember Geoff took me into the cold room in the research area and showed me a pile of white boxes on the floor and told me "that is interferon".I had little or no idea of the implications of what we were about to do, but Geoff had an approved protocol to administer recombinant interferon to patients with hepatitis B. I believe his team was the first to administer recombinant interferon to a patient with hepatitis B anywhere in the world – and remember, this occurred in South Africa!We gave 50 million units three times a week and made patients terribly ill – but that very first patient was a young woman who was an intern who wanted to be a surgeon, so she volunteered. Interestingly enough she not only cleared HBeAg and developed anti-HBe but went on to clear HBsAg. Of course this story is testimony to Geoff's innovation and determination – to get this done in South Africa at that time was near miraculous!" Adrian di Bisceglie (AASLD president): "Geoff had just returned from time at the NIH with Jay Hoofnagle and he had somehow arranged to be one of the first sites to use Roche recombinant interferon (Roferon-A). I remember Geoff took me into the cold room in the research area and showed me a pile of white boxes on the floor and told me "that is interferon". I had little or no idea of the implications of what we were about to do, but Geoff had an approved protocol to administer recombinant interferon to patients with hepatitis B. I believe his team was the first to administer recombinant interferon to a patient with hepatitis B anywhere in the world – and remember, this occurred in South Africa! We gave 50 million units three times a week and made patients terribly ill – but that very first patient was a young woman who was an intern who wanted to be a surgeon, so she volunteered. Interestingly enough she not only cleared HBeAg and developed anti-HBe but went on to clear HBsAg. Of course this story is testimony to Geoff's innovation and determination – to get this done in South Africa at that time was near miraculous!" Geoff Dusheiko was recruited to the Royal Free Hospital of Medicine in London by Neil McIntyre in 1988 and became Professor of Medicine at the University College in 1996. During the last 25 years, he was without any doubt one of the most requested experts in the field of viral hepatitis and significantly contributed to the development of the field. He has continued to pursue his interests in the complex nature of chronic viral hepatitis, since joining the Royal Free Hospital. After the discovery of hepatitis C virus, he studied the epidemiology and expression of this important disease in at–risk patients. He has had pointed out the regional prevalences of the disease, the association of hepatitis C and interferon with thyroid disease, and has put into perspective the clinical features of the disease and the sustained response rates of anti-HCV positive patients treated with interferon alpha. With Peter Scheuer, Geoff documented the histological characteristic morphology of chronic hepatitis C infection [[14]Scheuer P.J. Ashrafzadeh P. et al.The pathology of hepatitis-C.Hepatology. 1992; 15: 567-571Crossref PubMed Scopus (532) Google Scholar]. He also enjoyed a productive collaboration with Peter Simmonds, University of Edinburgh and who documented the occurrence of a new and different genotype of hepatitis C in Middle Eastern and African patients, and pointed out the geographical distribution of HCV types, and the clinical, epidemiological, and therapeutic significance of the diversity of hepatitis C virus [[15]Dusheiko G. Schmilovitzweiss H. et al.Hepatitis-C virus genotypes – an investigation of type-specific differences in geographic origin and disease.Hepatology. 1994; 19: 13-18Crossref PubMed Scopus (498) Google Scholar]. Geoff Dusheiko was member of the very first NIH consensus on hepatitis C and contributed a very frequently quoted review article on the management of side effects of interferon therapies [[16]Dusheiko G. Side effects of alpha interferon in chronic hepatitis C.Hepatology. 1997; 26: S112-S121Crossref PubMed Google Scholar]. All of these studies on hepatitis C have been validated, and have had important therapeutic implications for patients. In recent years, he has continued to play a pivotal role in developing new antiviral compounds for hepatitis C and is an acknowledged expert in this complex and rapidly developing field. Not to a surprise, he was principal investigator in various pivotal trials exploring the efficacy of new direct antivirals against hepatitis C and is co-authoring many NEJM and other publications of treatment trials published during the last years [e.g., [17Zeuzem S. Dusheiko G.M. Salupere R. Mangia A. Flisiak R. Hyland R.H. et al.VALENCE investigators. Sofosbuvir and ribavirin in HCV genotypes 2 and 3.N Engl J Med. 2014; 370: 1993-2001Crossref PubMed Scopus (701) Google Scholar, 18Afdhal N.H. Dusheiko G.M. Giannini E.G. Chen P.J. Han K.H. Mohsin A. et al.Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.Gastroenterology. 2014; 146 (e1): 442-452Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar]]. For practicing physicians it is now absolutely crucial to get balanced judgement of all the emerging data. Geoff Dusheiko is well respected in this context for his neutral and practical recommendations how to implement novel therapeutic achievements in clinical practice [19Dusheiko G. Burney T. Hepatitis C treatment: interferon free or interferon freer.Lancet. 2013; 381: 5Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 20Dusheiko G. Wedemeyer H. W protease inhibitors and direct-acting antivirals for hepatitis C: interferon's long goodbye.Gut. 2012; 61: 1647-1652Crossref PubMed Scopus (23) Google Scholar]. Geoff Dusheiko was also instrumental together with colleagues at the University of Birmingham in showing that recurrent hepatitis B could be prevented after liver transplantation using new nucleoside analogues. Together with Dr Tim Harrison (UCL) he was one of the first describing a mutation in YMDD motif in the polymerase region of hepatitis B in nucleoside analogue treated patients [[21]Ling R. Mutimer D. et al.Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine.Hepatology. 1996; 24: 711-713Crossref PubMed Google Scholar] – a finding that later on gained enormous importance for clinical practice in the treatment of hepatitis B in general. Overall, Geoff Dusheiko has published widely in the field and has published ∼330 peer manuscripts. His Hirsch index score is 57. His publications include various papers in the New England Journal of Medicine, The Lancet, Hepatology, Journal of Hepatology and Gastroenterology and Nature reviews. While still a resident in 1979 he documented the occurrence of a previously un-described inherited metabolic disorder (glutaric aciduria type II) causing steatosis and hypoglycemia in an adult, and published a description in the New England Journal of Medicine [[22]Dusheiko G. Kew M.C. et al.Recurrent hypoglycemia associated with glutaric aciduria type-I in an adult.N Engl J Med. 1979; 301: 1405-1409Crossref PubMed Scopus (100) Google Scholar]. His expertise means that he continues to be utilised as a faculty speaker for all the major associations for the study of the liver, and he has played a major role in postgraduate education at a national and international level. He has supervised several PhD and MD students, some of whom have gone on to be the most heavily funded researchers in the field. He remains interested in broad fields of research, including studies of the natural history, pathology, viral genotyping, applied molecular virology, antiviral therapies, immunological responsiveness and pathogenesis, and pharmacoeconomics of viral hepatitis. He has particularly enjoyed collaborations with Prof Mala Maini and Antonio Bertoletti – together they contributed ground breaking and very frequently quoted studies on the immunopathogenesis of viral hepatitis [23Das A. Ellis G. Pallant C. Lopes A.R. Khanna P. Peppa D. et al.IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.J Immunol. 2012; 189: 3925-3935Crossref PubMed Scopus (275) Google Scholar, 24Dunn C. Peppa D. Khanna P. Nebbia G. Jones M. Brendish N. et al.Temporal analysis of early immune responses in patients with acute hepatitis B virus infection.Gastroenterology. 2009; 137: 1289-1300Abstract Full Text Full Text PDF PubMed Scopus (291) Google Scholar, 25Reignat S. Webster G.J. Brown D. Ogg G.S. King A. Seneviratne S.L. et al.Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.J Exp Med. 2002; 195: 1089-1101Crossref PubMed Scopus (206) Google Scholar]. At a National level, he has served on the UK Haemophilia Directors Working party on chronic liver disease and haemophilia, the British Liver Trust Medical Advisory Board, and is on the governing board for the British Association for the Study of the Liver. He is a member of the National Institute for Clinical Excellence (NICE) guidelines committee on the management of hepatitis B. He has served as the Royal College of Physicians representative for NICE to advise on the introduction and cost effectiveness of most newly introduced antiviral therapies in the UK over the past decade. Internationally, he has been instrumental in drawing up guidelines for the management of chronic hepatitis B and C for EASL. He has served on the European Working party on treatment of chronic viral hepatitis, working parties for the World Congress of Surgery on the Diagnosis and Management Small Hepatocellular Carcinoma, National Institutes of Health Consensus Conferences on Management of Hepatitis C, Planning strategies for the EASL: Management of hepatitis C, and World Health Organisation Technical Consultations on Hepatitis C. He has served on working parties for the American Association for the Study of Liver Diseases, the Asian Pacific Association for the Study of the Liver, the African Association for the Study of the Liver, the International Association for the Study of the Liver, and the European Hepatitis Group (Eurohep). He has also been invited to advise the European Medicines Agency. I really appreciate to have had the chance to work together with Geoff Dusheiko in the EASL Governing Board. Geoff was a member of the Governing Board as an Educational Councillor for four years. The members of our society may not even imagine how much time and work Geoff donated to our society. In times of change with many challenging strategic decisions to be made, it was very important to have Geoff Dusheiko in Board. His experience, clear and straight forward way of thinking and strong character was vital for the committee during these years. Lastly, it is most important to acknowledge Geoff Dusheiko as a friend and colleague. There is really not a single person I know who ever mentioned a bad word about Geoff. He is a very nice man who has the – unfortunately these days rather rare – strength to listen and to give honest advice. When running EASL as Secretary General until 2011, it was very important for me to ask Geoff Dusheiko for advice and for help to solve challenging conflicts. EASL can be proud that Geoff Dusheiko accepted to receive the 2014 Recognition Award and will certainly benefit from his experience and energy also during the exciting times ahead!