Andrew K. Burroughs: a research hepatologist extraordinaire.

Andrew K (Andy) Burroughs passed away in March 2014 at the early age of 60 years. Andy was one of the last of the great all round giants of hepatology. He was a consummate physician, clinical investigator and educator. Over a period of 35 years at the Royal Free Hospital Liver Unit he produced a prodigious quantity of original research and made major contributions in many areas of hepatology including portal hypertension, liver transplantation and chronic liver disease. His work on the methodology of clinical trials is carried on by the Baveno consensus meetings. From bedside clinical mastery to early molecular biology applications to diagnosis and pathology, his contributions left a mark in liver science and advanced medical science in general. He also was praised by his work in medical education particularly in post-graduate mentorship and, an admirable human touch with patients. We will not see his like again.

What's new in IBD therapy: An "omics network" approach.

The industrial revolution that began in the late 1800s has resulted in dramatic changes in the environment, human lifestyle, dietary habits, social structure, and so on. Almost certainly because this rapid evolution has outpaced the ability of the body to adapt to a number of environmental and behavioral changes, there has been a parallel emergence of several chronic inflammatory diseases, among which are inflammatory bowel diseases (IBD), primarily ulcerative colitis and Crohn's disease. The ability to treat these conditions has progressively improved in the last 50 years, particularly in the last couple of decades with the introduction of biological therapy targeting primarily soluble mediators produced by inflammatory cells. A large number of biologics are now available, but all of them induce similarly unsatisfactory (<50%) rates of clinical response and remission, and most of them lose efficacy over time, requiring dose escalation or switching from one biologic to another. So, treatment of IBD still needs improvement that will occur only if different approaches are taken. A reason why even the most recent forms of IBD therapy are unsatisfactory is because they target only selected components of an exceedingly complex pathophysiological process, a reality that must be honestly considered if better IBD therapies are to be achieved. Brand new approaches must integrate all relevant factors in their totality - the "omes" - and identify the key controllers of biological responses. This can be accomplished by using systems biology-based approaches and advanced bioinformatics tools, which together represent the essence of network medicine. This review looks at the past and the present of IBD pathogenesis and therapy, and discusses how to develop new therapies based on a network medicine approach.

Celebrating the career and contributions of Dr Henry T. Lynch (1928-2019).

This article celebrates the career of Dr Henry Lynch and his contributions to cancer genetics through his extensive research, clinical practice and his passion for personalising care by using a patient's genetic profile to determine management and treatment. Dr Lynch's contributions were momentous and continue to have relevance to medical practice, in particular in the fields of clinical genetics, medical oncology and gastroenterology.

50 years of Hepatology: The Royal Free Hospital School of Hepatology.

Writing about the history of Hepatology would necessarily imply writing about the history of the Liver Unit and the School of Hepatology created by Dr. Sheila Scherlock at the Royal Free Hospital (London). On the 70th anniversary of the creation of the first liver unit (Hammersmith Hospital) this article presents a brief account of the history, organization, structure, educational program and contributions of perhaps the first and the most influential medical research models created for the study of liver diseases: the Royal Free Hospital Liver Unit.

History of Nonalcoholic Fatty Liver Disease.

Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.

The hepatopathologist Hans Popper (1903-1988) : An early victim of National Socialism in Austria.

In 1988, the "father of modern hepatology" Hans Popper died. His medical merits are numerous and outstanding and have already been praised many times. In particular, his research on liver diseases has gained widespread recognition. Much less well known is the fact that Popper was dismissed from the University of Vienna due to his Jewish ancestry after the "Anschluss" ("annexation") of Austria to the Third Reich and subsequently emigrated to the USA.Popper's biographers, who primarily belonged to his close circle of friends and colleagues, were unquestionably aware of this central caesura in Popper's life. However, the scientific analysis and presentation of this very event has been incomplete and, moreover, feeds heavily from the personal memories of the authors, which are inevitably subjective. For precisely this reason, the present contribution focuses on Popper's role as a politically persecuted Jew and the resulting implications.The study comes to the conclusion that Popper shows all the characteristics of a Nazi victim, namely a Jewish background, the dismissal from university, the threat of persecution by the Gestapo, and the subsequent forced emigration. Popper decided against remigration after 1945 and instead earned professional recognition in the USA and later worldwide. In the 1980s, Popper was criticized for his permissive attitude towards his former academic teacher, the doctor and Nazi criminal Hans Eppinger. Even if he did not completely succeed in making his behavior in the "Eppinger Case" understandable and comprehensible, the events gradually fell into oblivion, as evidenced by several recent posthumous statements of honor in German-speaking countries.

ISDE Presidential Biography: David B. Skinner, MD.

Dr. David Skinner, the 4th President of the ISDE, was a world-renowned surgeon, educator, scholar, and leader. He participated in the formation of the ISDE, hosted two international congresses in 1983 and 1989, and made important advances in the ISDE during his presidential tenure 1992-1995.

Chapter 2. ESPGHAN: 50 Years Memories-The Early Years.

Thirty-six founding members from Europe were present in 1968, when the European Society of Paediatric Gastroenterology (ESGA) had its first meeting in Paris. The aim was to create a forum for presentations and discussions of research activities in paediatric gastroenterology in Europe. At the second meeting of ESGA 1969 in Interlaken, an important landmark was set for all gastroenterologists in the world. In this conference, the first ever criteria for "the Diagnosis of Coeliac Disease" (CD) were established. In 1990, the revised criteria for the diagnosis of CD were published. After the introduction of new noninvasive techniques, like tissue transglutaminase 2-antibodies and the HLADQ2/HLADQ8 determinations in blood, "new" criteria for the diagnosis of CD were published in 2012 by the European society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Close collaboration of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition led to mutual meetings. The first combined meeting was 1978 in Paris, followed by meetings in New York, Amsterdam, Houston, and last in Toulouse. The first World Congress of Paediatric Gastroenterology took place in Boston 2000 followed by congresses in Paris, Iguazu, Taipeh, and Toronto. The creation of specialised committees (Nutrition Committees, GI-Committee, and Hepatology-Committee) enabled the society to elaborate numerous guidelines for standards in the diagnosis and treatment of diseases within the subspecialties. The Journal of Paediatric Gastroenterology and Nutrition, as organ of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition since 1991, serves as the voice for these worldwide accepted guidelines. Growing educational activities with summer schools, the Young Investigator Forum and the creation of working groups have distributed our current knowledge among the younger generation and led to fruitful reports, guidelines, and syllabus. In 1992, ESPGHAN was 1 of the founding 7 members of the United European Gastroenterology Federation (UEGF), which developed into a successful organisation for gastroenterology in Europe. This year we celebrate the 50th anniversary of ESPGHAN at our annual Meeting in Geneva.

Chapter 3. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition in Recent Years.

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition has experienced an amazing development in the 50 years of its existence. It grew from a small group of 36 friends who held an informal meeting with some 20 oral presentations to share and discuss their clinical and research work, to a large, multiprofessional society that sets widely recognized standards for clinical care and policy and hosts the world's largest congress of Paediatric Gastroenterology, Hepatology and Nutrition with more than 4500 delegates from 100 countries. However, the Society's mission has remained the same: to promote the health of children with special attention to the gastrointestinal tract, liver, and nutritional status, through knowledge creation, the dissemination of science based information, the promotion of best practice in the delivery of care and the provision of high-quality education. The European Society for Paediatric Gastroenterology Hepatology and Nutrition's success is based on the enthusiasm and engagement of its membership that contribute extensive volunteer work to support child health, while maintaining a positive spirit of collaboration and friendship, which characterises this Society. This article aims at describing recent developments and the current situation of the European Society for Paediatric Gastroenterology Hepatology and Nutrition.

Chapter 6.0. History of Paediatric Hepatology in ESPGHAN.

Hepatology played an important role in ESPGAN from the beginning. In 1989, the Hepatology Committee was started. In the early 1990s H for hepatology was included in ESPGHAN. Hepatology Summer schools were held from 1995 and later monothematic conferences met the needs of many young ESPGHAN members. The role of ESPGHAN members in the progress of diagnostic and therapeutic measures in hepatitis B and C will be elucidated (Chapter 6.1) as well as the role of other ESPGHAN members in the understanding of immunological hepatic disorders of childhood (Chapter 6.2). During childhood, many metabolic hepatic disorders threaten the life and health of children making orchestrated measures in diagnostic and therapeutic efforts necessary (Chapter 6.3). The pathophysiology of cholestasis was cleared by the detection of bile salt transporters, which were identified by ESPGHAN members in the Netherlands, France, United Kingdom and Germany (Chapter 6.4). Finally liver transplantation for acute fulminant and chronic end stage liver disease was established as a meanwhile standard treatment option (Chapter 6.5). Immunosupression in liver transplantation was improved and standardized through the cooperation of many ESPGHAN member driven studies (Chapter 6.6).

Chapter 7. The Contributions of the ESPGHAN Committees on Nutrition to Paediatric Nutrition.

The first Committee on Nutrition (CoN) was founded in 1974. Two years later nutrition (N) was added to the society's name, which then became ESPGAN. The Committee systematised compositional and quality criteria for breast milk substitutes and food for special medical purposes, the first of many examples on how recommendations and comments published by the Committees on Nutrition (CsoN) were adopted by the European Economic Community, later the European Union and also influenced the World Health Organization/Food and Agriculture Organization of the United Nations Codex standards. A second CoN focusing on preterm infants was established in 1979 and its recommendations on nutrition of these infants were widely implemented. The third and standing CoN, established 1986, started to organise high-quality symposia at the annual meetings appreciating the need to enhance the expertise in nutritional research. From 1991 the CoN has organised Summer Schools in paediatric nutrition for young colleagues further emphasising its educational interest and more recently an annual, more specialised Nutrition Masterclass. Successively the interest of the CoN has expanded to other areas, such as highlighting dilemmas and uncertainties in the field of nutrition including the design, choice of outcomes and statistical analysis of trials in infant nutrition. The work of the CsoN have had great impact on paediatric nutrition and the committee will continue its important role by writing commentaries and systematic reviews and revising guidelines when required to inform and stimulate discussion among colleagues as well as stimulate training in paediatric nutrition by organising workshops and scientific meetings, training courses, and other approaches, and by interaction with other expert groups.

Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): Captivating Witness Reports of a Success Story.

Since the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan-European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.

Chapter 9. Words From Partner Societies.

On the occasion of the 50th anniversary of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner associations submitted comments and felicitations which are presented here. These include words from the Latin American (LASPGHAN), North American (NASPGHAN) and Panarabian Societies (PASPGHAN) and the Commonwealth Association (CAPGHAN) of Paediatric Gastroenterology, Hepatology and Nutrition, the Federation of International Societies of Paediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN), the European Academy of Pediatrics (EAP), the European Pediatric Association/Union of National Pediatric Societies (EPA-UNEPSA), the International Pediatric Association (IPA), the European Crohn's and Colitis Organisation (ECCO), European Society for Clinical Nutrition and Metabolism (ESPEN) , the Federation of European Nutrition Societies (FENS), and United European Gastroenterology (UEG).

Chapter 1. The Historical Roots of Paediatric Gastroenterology, Hepatology, and Nutrition.

The last 50 years have seen the establishment of paediatric gastroenterology, hepatology, and nutrition (PGHAN) as a well-recognised and thriving clinical specialty throughout most of Europe, and further afield. This has happened, in part, through the existence of the European Society for Paediatric Gastroenterology and Nutrition (ESPGHAN) as a forum for those interested in this branch of children's medicine. To illustrate the pan-European roots of PGHAN, some key scientific and medical events, discoveries, and inventions relevant to 3 common clinical problems-diarrhoea, jaundice, and infant-feeding-have been chosen to survey the historical development of the ways in which each was understood and treated within the changing thinking and practice of past times. Together they are used to trace the prehistory of ESPGHAN and provide a background against which to explain the genesis of the Society and how its spheres of clinical and scientific interest came to be defined.

Chapter 4. The Relationship Between the European and North American Societies for Pediatric Gastroenterology, Hepatology and Nutrition.

This chapter is based on the memories of those who shaped the relationship between the European and the North American Societies for Pediatric Gastroenterology, Hepatology and Nutrition. The first joint meeting of the 2 Societies took place in Paris in 1978, followed by 1 in New York in 1985, 1 in Amsterdam in 1990, 1 in Houston in 1994, and the last one in Toulouse in 1998. The formation of the Federation of the International Societies for Pediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN) preceded the First World Congress of all Societies, which took place in Boston in 2000. The success of this meeting was followed by world congresses in Paris in 2004, Iguassu in 2008, Taiwan in 2012, and Montreal in 2016. NASPGHAN and ESPGHAN jointly took on the direction of the Journal of Pediatric Gastroenterology and Nutrition in 1991. Communication between the 2 Societies is extremely active, with members participating in many joint projects.

Chapter 6.1. Pediatric Chronic Hepatitis B and C: 30 Years of ESPGHAN Clinical Research and Recommendations.

The expression of hepatitis B and C virus infections in children differs from that in adults and requires specific paediatric expertise. The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has been a pioneer in this field, having stressed the need for straightforward recommendations since the mid-1980s. Following much observation, surveillance, and research, a panel of ESPGHAN experts was able to develop such recommendations on hepatitis B infection in children in 2009, which was then followed in June 2013 by proper guidelines. In the field of Chronic Hepatitis C, in 2011 ESPGHAN experts published also the Guidance for Clinical Trials for Children and Adolescents, and approved in 2012 the NASPGHAN guidelines for treatment. The ESPGHAN Society is to be commended for its pioneering work in furthering our understanding of chronic hepatitis B and C disease presentations in infants, children, and adolescents.

Present, Past,and Future of the Latin American Association for the Study of the Liver- Asociación Latinoamericana para el Estudio del Higado (ALEH).

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