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Corresponding author. Address: Institute for Liver and Digestive Health, Royal Free Hospital, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom.
Affiliations
Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, United Kingdom
For nearly 60 years, Prof. Williams has held centre stage in all aspects of clinical hepatology. He is undoubtedly among the most influential hepatologists that have ever walked this earth. Prof. Williams lives with his wife, Stephanie, a phenomenal lawyer. He had 8 children, but sadly one died aged 37. One daughter is a consultant physician in HIV and he also has a grandchild working in A&E. Tennis was his main sport as a junior and at university and while he still plays, in more recent years his sporting focus has primarily been on competitively sailing his 35 ft yacht. Last year he received The Satanita Trophy, which was presented to the best performing boat, namely his – Jos of Hamble, in the Members’ Regatta of the Royal Yacht Squadron. Sailing is his true passion and many of his fellows will tell you of a call to duty on his boat.
He has published over 2,500 papers, has an H-Index of over 150, cumulative citations of over 100K and has made many, many seminal observations. His greatest contributions have been in the field of liver transplantation, having been one of the key figures in its development. He also developed the King’s College criteria for prognosis in acute liver failure, the Pugh score in cirrhosis, and the use of advanced endoscopic therapy for oesophageal varices, as well being one of the people who recognised the existence of the newly defined syndrome, acute-on-chronic liver failure. Even today at the ripe old age of 88, he continues to lead one of the premier institutes of hepatology in the world and over the past 7 years he has masterminded the Lancet Commission into Liver Disease in the UK; the 6th Annual Report was launched only a couple of months back. Most importantly, he has provided the infrastructure for the training of over 600 clinical and basic scientists, many of whom have gone on to become leaders in various fields of hepatology.
Career, training and clinical contribution
Prof. Williams wanted to be a doctor since the age of 13 and studied medicine at what is now called the Royal London Hospital, graduating with a distinction in Medicine in 1953. After early clinical training and military service, his first exposure to hepatology was with Dame Sheila Sherlock in 1959. Inspired by her team at the Royal Free Hospital he became deeply immersed in research studies on bilirubin metabolism, inheritance of haemochromatosis and steroid therapy of jaundice. In 1961, he was awarded a Rockefeller Travelling Fellowship, to Columbia University, New York, to work with Dr Henry Wheeler, whose interest was in the quantitative assessment of liver function through measurements of bromsulphalein transport, and storage capacity. He also learnt to perform hepatic vein catheterisations with Stan Bradley. In 1963, he returned to the Royal Free where he focussed on more clinical research and published an important paper on blood flow and tropical splenomegaly, an interest which took him to Africa to study this syndrome further in 1965 following an award from the Wellcome Trust. This training set him up for a consultant post and subsequently an invitation to King’s College Hospital.
The critical events that led to the rapid growth of the liver unit he established and worked in over the next 30 years, were research grants, donations by Sheikh Zayed of the UAE and others, and the introduction of liver transplantation into clinical practice. Many of the innovations and seminal observations he made led to new standards for clinical hepatology, which are described briefly below. He established the perfect model of a ‘translational liver unit’ at a time when this concept hardly existed.
Prof William’s contributions are enormous. I list some of his most influential work below.
King’s College (1966-1996)
Liver transplantation
The critical event leading up to the development of liver transplantation was the building of a close partnership with Sir Roy Calne. In collaboration, they performed the first liver transplant in Europe, which was a dramatic success: on the 23rd September 1968. Unfortunately, this patient died from severe chronic rejection about 4 months later. However, this set the train moving and the Cambridge-King’s partnership established a programme that led to many novel and seminal observations including demonstration for the first time of the reversal of hepatic encephalopathy, recurrence of autoimmune diseases such as primary biliary cirrhosis and autoimmune hepatitis in the graft and the first experience of using tacrolimus to reverse chronic rejection. The introduction of the brain death law, discovery of the University of Wisconsin solution and cyclosporine changed liver transplantation from an experimental to a clinical procedure.
One of Prof William’s major contributions to hepatology is his seminal work on acute liver failure in close collaboration with John O’Grady and Jules Wendon. Taking advantage of the outbreaks of severe hepatitis in renal dialysis units in the UK, he was able to persuade the Department of Health to set up a dedicated unit for the treatment of acute liver failure, the first of its kind in the world. Their clinical and scientific observations led to an accurate characterisation of the syndrome, development of poor prognostic criteria that has stood the test of time for the past 30 years, characterisation of the mechanisms and management including the use of mannitol, N-acetylcysteine, renal replacement therapy and most importantly liver transplantation. His work with Nancy Rolando led to the first description of the role of systemic inflammation in the development of the hepatic encephalopathy in ALF.
Spectrum of some of the other pioneering research contributions
Together with Adrian Eddlestone, he developed novel techniques for investigating cellular and antibody-mediated immune reactions, which led to seminal studies in hepatitis B, autoimmune liver disorders and in the mechanisms underlying acute liver failure from halothane hypersensitivity. In collaboration with John Saunders, he defined the role of HLA type and gender in acceleration of liver damage in alcoholic liver disease. His group was the first to run multicentre controlled trials testing the use of azathioprine in autoimmune hepatitis, which remains the mainstay of treatment today. He also explored the role of cyclosporine in primary biliary cirrhosis in a large clinical trial, where a near-significant improvement in survival rate was obtained. The Pugh modification of the Child score for the staging of chronic liver disease was described by his group; perhaps one of the most highly cited papers in the hepatology literature. In collaboration with John Dawson, he was the first to use flexible endoscopy for injection sclerotherapy of varices and his work contributed immensely to the better understanding of liver blood flow in splenomegaly with or without existing cirrhosis. In haemochromatosis, he described new patterns of spinal and articular damage. Even in those days, he realised the importance of artificial intelligence as he was closely involved in designing a computer system for the diagnosis of difficult jaundice cases based on Bayesian probability. He was instrumental in the recruitment of Alex Mowat to King’s College in 1970, who went on to develop a paediatric liver unit of international repute.
University College London (1996-2010)
In 1996, forced into early retirement from King’s College on the grounds of age, a difficult point in his career, instead of giving up, he moved to University College London and built the Institute of Hepatology, which over the next 15 years became one of the most important units in the UK and internationally. Early on he recruited Nikolai Naoumov and Diego Vergani to help set up the clinical and research infrastructure. Among many translational areas of research was the description, with me, of the existence of acute-on-chronic liver failure for the first time in 2001. Innovation was at the heart of the institute and he was instrumental in building a platform of much activity in Europe around albumin dialysis (MARS® system) from which DIALIVE was developed. The drug ornithine phenylacetate for the treatment of hepatic encephalopathy, which is entering phase III studies was also discovered during this time. Maintaining an active interest in liver transplantation, Roger Williams started the first living donor programme in the UK for overseas patients with original observations on liver regeneration.
King’s College Hospital (2016-present)
In 2010, UCL decided to merge clinical and academic hepatology with the Royal Free which prompted him to form an independent research centre supported by his board of trustees and the liver charity known currently as ‘The Foundation for Liver Research’, which he set up in the early 1970s. In 2015 he received an invitation to return to King’s College Hospital where in close partnership with Shilpa Chokshi, he has rebuilt a fantastic basic science centre, which currently has 37 researchers, and high-quality research is already beginning to appear in collaboration with the clinical service at King’s and internationally with the EF-CLIF Consortium in Barcelona.
Personal perspective
Having known him at close quarters for about 12 years, I think his success is likely due to a combination of factors. In addition to his academic and clinical brilliance, his leadership skills, attention to detail and his amazing tenacity even in the face of greatest adversity and the ‘never-say-die’ attitude have been the cornerstone of his success. Unlike many senior hepatologists of his time and even of today, he understood very early that liver disease was a multisystem disease. Even in the 1970s, his first major grant from the Medical Research Council was to bring together basic scientists of differing disciplines – biochemists, physiologists, epidemiologists, and bioengineers to work alongside physicians, surgeons and pathologists specialising in hepatology. This perspective underpins the modern concepts around all aspects of liver disease and liver transplantation. It is increasingly clear that the widest of multisystem studies will be necessary if we are to reduce the mortality of patients with non-alcoholic fatty liver disease, the modern-day scourge of our specialty.
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