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It is with great sadness that we record the passing of Professor Neil McIntyre on 19th July, aged 86. Neil was born on the 1st of May 1934 in Ferndale in the Rhondda Valley in Wales, and was educated at Rhondda County Grammar School for Boys. In 1951 he started his pre-clinical medical studies at King’s College, London, also achieving a 1st class BSc degree in Physiology in 1955. His clinical studies were at King’s College Hospital Medical School and he graduated MB BS in 1958 with distinctions in Pathology and Applied Pharmacology and Therapeutics. Thus he already had academic aspirations at that time, and indeed was co-author of publications in Nature and the British Journal of Experimental Pathology in 1955 and 1956. His early postgraduate training from 1959 to 1960 was at King’s College Hospital and the Hammersmith Hospital. In 1960 he was called up and was posted as a flight lieutenant in the Royal Air Force Medical Branch to what was then the State of Aden, where he spent three years.

On his return, he was appointed to the Royal Free Hospital and School of Medicine as a Medical Research Council Junior Research Fellow, and Registrar in Medicine to Professor Sheila Sherlock on the Academic Unit. His research led to his MD thesis (“Oral glucose tolerance; the physiological importance of the intestine and liver”)(1967). Meanwhile in 1966 he was awarded a two year Medical Research Council Travelling fellow at Harvard Medical School, working in the Gastrointestinal Unit, at the Massachusetts General Hospital with Professor Kurt Isselbacher.

After this in 1968 he returned to the UK and was appointed Senior Lecturer in the Department of Medicine (Liver Unit) at the Royal Free Hospital and School of Medicine, and was promoted through the years to Reader and then Professor. When Sheila Sherlock retired in October 1983, he was appointed to Chairman of the Department. With the joining of the Royal Free and University College Medical Schools he subsequently became Director of the Division of Hepatology at University College London Medical School and The Royal Free Hospital School of Medicine. He also served as Vice Dean and Clinical Sub-Dean until his retirement in 1999.

Neil enjoyed a long and productive academic career. Remarkably, as an undergraduate, he co-authored the two papers described above on the effects of denervation on the histochemical appearance of cholinesterase at the myoneural junction. Few could claim such a distinction. He and his team’s publications focussed on carbohydrate metabolism and insulin secretion, lipids, lipoproteins and cell membranes (particularly lecithin:cholesterol acyltransferase activity in liver disease), and the effect of lipoprotein changes on cell membranes composition and function. However he was the author of a myriad of clinical papers. His wide ranging interests in hepatology reflected the breadth and depth of his expertise, in a time when a narrow range of research topics was less required. Apart from the topics noted above, his publications ranged from haematological disorders in liver disease, portal hypertension, drug induced liver injury, alcoholic liver disease, genetic diseases, primary biliary cholangitis, computers in hospitals (in 1981), and computerised medical information (in 1974). A search of his seminal papers includes a classic description of haemolytic episodes in children and young people with Wilson's disease (New England Journal of Medicine, 1967).

He was the lead editor of the first edition of the Oxford Textbook of Clinical Hepatology in 1992, and co-editor of the second edition in 1999 with other renowned European hepatologists. This textbook presented a comprehensive account of clinical hepatology comprising more than 150 chapters by international experts in two volumes. Other books included 'Therapeutic Agents and the Liver', edited with Sheila Sherlock (1965); 'The Problem Orientated Medical Record: its Use in Hospital, General Practice, and Medical Education', edited with J.C. Petrie (1979); and
'Lipids and Lipoproteins in Clinical Practice' with David Harry in 1991.

Neil McIntyre had a particular lifelong interest in medical education and was instrumental in developing an up-to-date medical student curriculum at the Royal Free Hospital School of Medicine. He was always a stickler for the practice of clinical medicine and emphasized Oslerian traditions of history taking, and examination. He fostered, with considerable enthusiasm, Problem Orientated Medical Records (POMR), and audit. Amongst his more notable papers in these areas is one in the British Medical Journal which he co-authored with Sir Karl Popper, one of Britain’s foremost philosophers and social commentators, entitled “The critical attitude in medicine: the need for a new ethics”.

Neil also contributed to many learned Societies, including as secretary to the Medical Research Society (1972-1977) and the nascent European Association for the Study of the Liver (EASL)(1975-1977), as well as being a Council Member for Europe of the International Association for the Study of the Liver (IASL)(1978-1982). He was also a member of the Committee for the British Association for the Study of the Liver (1976-1978), as well as a member of Council of the British Society of Gastroenterology and of the Association for the Study of Medical Education. Between 1976 and 1978 he was also President of the Osler club of London. In 2006-2007 he was President of the History of Medicine Society of Wales. Neil was a member of Council and a member of the research committee of the Royal College of Physicians of London. He served as an associate editor of the Journal of Hepatology and on the editorial board of Gut

Neil was renowned for his eclectic interests and chose his subjects with considerable perspicacity. A keen medical historian from his student days, he spent much of his time in retirement working on his treatise “How British Women Became Doctors: The Story of the Royal Free Hospital and its Medical School” and on other historical topics. “I was concerned that the school’s remarkable past might be airbrushed from history and that the hospital might also fail to get the attention it deserved,” he said. In this book he described how a group of young female students formed the London School of Medicine for Women in 1874. They had been blocked from qualifying as doctors through any of the British universities, so took matters into their own hands. The Royal Free, then based at Gray’s Inn Road, stepped up to train the 14 students, admitting the women for clinical studies. This initiative “laid the ‘foundation stone’” for the medical education, qualification and licensing of women in Britain and many other countries.

He wrote of his interest in medical statues: “My interest in medical statues began as a student at King’s in the late 1950s when I wrote a short biography of its founder Robert Bentley Todd for the King’s College Hospital Gazette.” This led (as described in the publication of his lecture at the RCP of London) to his novel ‘hobby’: Neil identified more than 300 statues worldwide, and many busts and other monuments to doctors.

However, clinical medicine, basic science, medical education and medical history were not his only enthusiasms. He was a born and bred Welshman who espoused this part of his being enthusiastically throughout his life. He enjoyed rugby, which he played as a student, and cricket, and continued to play golf for as long as he was able. We remember him practicing his putting across his spacious office in the Academic Unit. Through this and the clinical and academic work Neil encouraged the Royal Free “international family” to continue their strong ties as first engendered by Sheila Sherlock. He will be remembered with respect and affection by numerous colleagues nationally and internationally and by a generation of Royal Free graduates.

Neil married Wendy Anne Kelsey in 1966, the year that she qualified from the Royal Free School of Medicine, and she became a highly respected general practitioner and trainer. They had one son, and one daughter and three grandchildren. His daughter also studied medicine at the Royal Free, continuing its proud tradition of women students.

We send our heartfelt condolences to Wendy, and all his family

Geoff Dusheiko and James Dooley
August 2020

I recall my first conversation with Dr Williams, nearly forty years ago in November 1980. Adrian Eddleston had accepted my application to join him as a research fellow in immunology on the Liver Unit pending an interview with the head of department. Laura, my first daughter, decided to make an entry on the morning of the interview, not unexpectedly since childbirth after a certain point never is, but certainly not on any planned schedule. I rang the Liver Unit very early that morning to apologise for my failure to attend the interview and to my surprise went straight through to Dr Williams. I had expected some warm words of congratulation, but the message was very short and simple. If I really wanted to work on the unit I must visit as soon as possible. I took that advice and attended for an interview the following week (we only discussed sailing) and as with so many people who preceded or followed me with “Roger” as our mentor it was the point in a career when Hepatology became the only option. That first conversation made me realise the professional commitment that he expected of himself and his colleagues. That conversation also instilled a feeling that persisted over 40 years in all my contacts with Roger that I had never quite worked hard enough. I have never met anyone with such a strong work ethic, nor anyone so driven to continue to research into liver disease. Often a difficult character, with views he held strongly, he earned the respect of all of us in the field and I will remember him with both respect and affection that only increased over 40 years. One word sums him up: unique.

He established the Liver Unit at King’s College Hospital in 1966, leading it for 30 years, by which time the unit was recognised internationally as one of the foremost liver centres for both clinical practice and clinical research. The early work in Acute Liver Failure in particular, was ground-breaking and established a clinical model that has since been copied everywhere. His contribution to clinical practice in Liver Transplantation was a first both in Europe and the UK and several years passed before other UK centres followed his example. Undoubtedly, physicians trained in his unit (or their trainees) comprise a majority of leading Hepatologists now practising in the UK, with many others trained on the Liver Unit leading similar units across the world. Perhaps only two UK physicians are recognised universally as giants in our field with professional lifespans exceeding many decades, namely the late Professor Dame Sheila Sherlock and Professor Roger Williams. He was awarded the order of CBE in the Queen’s Birthday Honours list of 1993, recognition of his outstanding contribution to medicine in the UK and in particular to Hepatology. In 2006 he was further honoured by the Queen, when included in a celebration for those who had continued to contribute to public service beyond the age of 65 years.

On his “retirement” from King’s College Hospital in 1996 Professor Williams continued his career in Hepatology as Professor of Hepatology and Director of the newly established Institute of Hepatology at University College London and also held an appointment as an Honorary Consultant Physician at UCLH NHS Foundation Trust; then in 2010 he established and became Director of the Institute of Hepatology and Foundation for Liver Research, where he remained at work 60 years from the start of his career in liver disease.

He was hyperactive in research (more than 2,500 original peer reviewed papers in a 60-year career with 340 published in the past 10 years); he continued to present keynote and ‘state of the art lectures’ (over 60 in his career with 25 since “retirement” in 1996); he continued to receive recognition from colleagues across the globe and received multiple awards for his contribution to Hepatology including highpoints such as the Hans Popper Life Achievement Award of the International Liver Congress in 2008, the Distinguished Service Award of the International Liver Transplantation Society in 2011 and most notably the Distinguished Achievement Award of the American Association for the Study of Liver Disease (AASLD) in 2013, the first and only time this award had been made to a UK Hepatologist. Similar career recognition by the European Association for the Study of the Liver had been planned for the annual meeting this year.

A major contribution to our field in the past decade was the Lancet Commission on Liver Disease in the UK alongside The Lancet’s Dr Richard Horton. This multi-disciplinary group, both created and held together by the force of Professor William’s character, has now published six annual reports with a seventh under review. Each of these highlights the worrisome prevalence of liver disease and liver cancer in the UK population, problems that increase year on year, are linked clearly to poverty and compounded by inequity of access to adequate liver services. He has illustrated the clinical problem for the next generation to resolve.

Professor Williams spent his life in Hepatology and BASL will undoubtedly celebrate the life of our own pioneer when large gatherings become possible once more. But for now, our thoughts are with his wife Stephanie, his family and his colleagues at the Institute of Liver Studies.

Graeme Alexander
July 2020

This guidance represents the professional advice from the British Association for the Study of the Liver, British Society of Gastroenterology, British Transplantation Society, NHS Blood & Transplant and input from the British Liver Trust.

The patients in the groups below are advised to shield and should consult the government web-site for advice on what that entails:

1. Patients with chronic liver disease who are on immunosuppressants

Data: There are as yet no large enough datasets to support/refute this approach and thus this is based on clinical judgement. 

2. Any patient with liver cirrhosis and decompensation or complication as defined by presence/recent history (within 12 months) of ascites, hepatic encephalopathy, hepatocellular carcinoma, variceal bleed or synthetic liver dysfunction.

Data: This is supported by data from the COVID-HEP registry that indicates that patients with decompensated liver cirrhosis have an unadjusted mortality rate 5-28 times higher than patients with liver disease without cirrhosis.

3. Patients who are actively on the liver transplant waiting list or who have received a liver transplant

Data: This is supported by data from NHSBT that indicates that patients who have had liver transplant have an unadjusted mortality rate of 25%.

Shielding is for a patient’s protection rather than a legal obligation. The need for shielding can be flexed further on a case by case basis in consultation with your healthcare team.

Application of this guidance

There are 3 elements:
1. Categorisation as high vulnerability – the guidance above should clarify that. This should be notified to employers etc.

2. Recommended response to that categorisation – This is nationally set, under review and changing with updated guidance from PHE and the CMO. Recommendations are based on complex factors including the current national categorisation of the pandemic, geography, occupation, local and national disease prevalence, R rates, risk factors for exposure etc.

3. Patient choice – Based on the above, patients, with support from clinical teams, are equipped to make personal decisions about what they will then do. Issues to weigh up will include home and family circumstances including age range of those at home and nature of accommodation, the person’s mental health, overall wellbeing, employment status and financial position.

Each year BASL presents the Dame Sheila Sherlock research prize, one of the highlights of the annual meeting. This prize is awarded annually to recognise the enormous contribution of Dame Sheila Sherlock to the development of Hepatology as a discipline in its own right.

Dame Sheila was involved in the foundation of the British Liver Club in 1961, which subsequently evolved into The British Association for the Study of the Liver (BASL). She was one of our past presidents and the first recipient of The BASL Distinguished Service Award. In keeping with Dame Sheila’s enthusiasm for fostering young researchers, this eponymous research prize is awarded to young investigators without substantive posts in either medicine or science for their research contributions in the field of Hepatology.

The winner will receive free registration to the meeting, an award and a prize of £1,000 and an invite to deliver the prize lecture at the BASL Virtual Annual Meeting on 21st - 23rd September 2020.

To apply, please send one A4 sheet outlining your research and another A4 sheet listing up to 5 related publications.

Please send submissions to steve@basl.org.uk before the deadline of 09:00hrs on Monday 3rd August 2020.

A new international study has found high mortality rates from COVID-19 among people with chronic liver disease and cirrhosis.

The researchers, led by teams at Oxford University Hospitals NHS Foundation Trust and the University of North Carolina, set up an international registry to collect clinical details of patients with chronic liver disease and cirrhosis who develop COVID-19.

Between 25 March 2020 and 20 April 2020, 152 cases were submitted to the registry, over 95 percent of which were hospitalised. Patients with cirrhosis had poor outcomes with an overall death rate of 40 percent. Those with advanced disease called ‘decompensated cirrhosis’ had the highest rate of death (between 43 and 63 percent), compared with 12 percent for patients with liver disease but without cirrhosis.

The paper has been published online by the Journal of Hepatology.

Dr Thomas Marjot, who leads the project alongside Dr Gwilym Webb and Professor Ellie Barnes at the Translational Gastroenterology Unit at Oxford’s John Radcliffe Hospital, said: “Until now, very little was known about the impact of COVID-19 on patients with pre-existing liver disease.

“Our data, which were gathered from 21 countries, show that people with liver disease, and especially those with decompensated cirrhosis, have particularly poor outcomes once they develop COVID-19.

“Even when other risk factors for poor outcomes - such as age, obesity, diabetes and high blood pressure - were taken into account, the severity of baseline liver disease was still associated with increased mortality,” he explained.

The study also showed that many patients with cirrhosis and COVID-19 developed features of worsening liver function (encephalopathy, ascites, bleeding), and in 24 percent of cases this occurred even without any chest symptoms or breathing difficulties.

However, Dr Marjot explained, these preliminary findings should be interpreted with caution: “our study is limited by selection bias; this is when doctors tend to report more severe cases with the worst outcomes. Many patients with cirrhosis and COVID-19 who have good outcomes will therefore not be included in the registry.”

“Nonetheless, these findings do suggest high death rates with COVID-19 in patients with cirrhosis and that contracting the virus may lead to a deterioration in liver function. Therefore, anyone coming into hospital with worsening symptoms of liver disease should be considered for coronavirus testing”.

Pamela Healy, Chief Executive of the British Liver Trust said: “This important study demonstrates the devastating impact of coronavirus on liver patients. We are asking the Government to quickly review the shielding guidance and ensure that those with the most severe forms of liver disease have clear advice and support. Whilst lockdown may be easing for many of us, these patients often have multiple complex problems and urgently need clarity and to remain protected.”

Ends

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