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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.”

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Contact:
Roy Probert, Senior Communications Manager
Tel: 01865 223070
Mobile: 07747 456443
roy.probert@ouh.nhs.uk

On Friday 24th April Dr John Walshe celebrates his 100th birthday, and I am sure that we would all wish to send him our best wishes and heartfelt congratulations on this auspicious day. Reaching this age is a tremendous achievement, but his historic contributions to Medicine, and in particular to our current knowledge of Wilson’s disease, its diagnosis and treatment, are unique, and generations of patients with this condition owe their lives and health to him.

So John, we revere you beyond words, and send our best wishes and thoughts to you on this special day.

Dr John Walshe was born on the 24th April 1920 in Kensington, London, to Francis and Bertha Marie (née Dennehy) Walshe. His father was a Consultant Neurologist at the National Hospital for Nervous Diseases, Queen Square; knighted in 1953, Sir Francis was a distinguished, internationally known neurologist. He was elected FRS in 1946.

John Walshe’s first association with Cambridge University was when, as a schoolboy in 1938, he went there to sit his First MB examination. He was accepted at Trinity Hall, Cambridge to study medicine and qualified BA in 1942. He then did his clinical studies at University College Hospital in London (UCH), qualifying MA, MB BChir (Cantab) in 1945. He served with the Royal Army Medical Corps in the Middle East Command between 1946 and 1948, spending time also in Greece and Cyprus. After this he returned to UCH.

His journey towards Wilson’s disease started in the early 1950s at UCH. He was working under Professor Charles Dent, a pioneer in metabolic diseases, and studying changes in amino acid metabolism in liver disease, and in particular in urine using paper chromatography. In one study he found an additional band in the urine, and thought that he might have discovered a new amino acid. However, the patient involved was on penicillin and it transpired that this was ‘penicillamine’, a metabolic product of penicillin. This work was published in the Quarterly Journal of Medicine in 1953. He moved on.

The next event, central to Wilson’s disease and involving his extraordinary mind and insight – an exceptional example of ‘translational medicine’ – occurred in the USA. During his year as a Fulbright Scholar on the Liver Unit at Boston City Hospital (Harvard Medical Unit) in 1955, the hepatology team were approached by the neurological team for advice on the management of a patient with Wilson’s Disease who was not improving as they had hoped on the treatment then available (parenteral British Anti-Lewisite). John Walshe’s scientific insight, knowing the chemical structure of penicillamine, led him to suggest (while crossing a walkway on the way back to their laboratory) that penicillamine might bind copper and lead to its excretion. A small amount of penicillamine was procured. He took some himself (remembering one of Professor Dent’s sayings: ‘You must never give an unknown compound to a patient if you are not prepared to take it yourself’) (see Walshe, 2019), and having no untoward effects, some was then given to the patient. Urine analysis showed an increase in copper excretion.

When he returned to England, he continued to study penicillamine in patients with Wilson’s disease and published the first pivotal papers on a group of patients in 1956. The place of D-penicillamine as an oral treatment for Wilson’s disease has remained ever since, has saved lives and improved the lives of innumerable patients in the ensuing 60 plus years. Many patients have remained in touch with him from those early and subsequent years.

Penicillamine may be associated with adverse effects, and it was because of a patient’s inability to continue with treatment that John Walshe (on the advice of Dr HBF [Hal] Dixon, in the Department of Biochemistry at Cambridge University) chose triethylenetetramine (trientine) dihydrochloride as an alternative copper chelator, and this has also become one of the mainstays of the treatment of Wilson’s disease. Dr Walshe also published early observations on zinc treatment (developed by others in Holland and the USA) and on ammonium tetrathiomolybdate.

In his long career he has published more than 150 papers and book chapters on Wilson’s disease and its link with copper metabolism, both from his own unit and with collaborators abroad. Many deserve mention, but space does not allow. I would, however, like to make note of his invaluable research assistant Kay Gibbs, and his collaboration with Professor Diane Wilson Cox in Canada, a pioneer in molecular genetics of Wilson’s disease.

Most of his career was spent in Cambridge, as Reader in Metabolic Disease and Director of Research in the Department of Medicine between 1957 and 1987. He was also an Honorary Consultant Physician at Addenbrooke’s Hospital, Cambridge, during this period.

He obtained his MRCP in 1952/3, and was awarded his FRCP in 1964, and Doctor of Science (ScD, University of Cambridge) in 1965. He was honoured with an MD (honoris causa) by the University of Uppsala in 1994. He was the Bertram Louis Abrahams lecturer at the Royal College of Physicians of London (‘The Biochemical Lesion in Wilson’s Disease’) in 1966. He has also given the Hudson Memorial Lecture in 1983, and the Worshipful Company of Pewterers’ Lecture at the National Hospital of Nervous Diseases, Queen Square, in 1995. In 1977, he was awarded the gold medal in therapeutics of the Worshipful Company of Apothecaries.

After his retirement from the University of Cambridge and Addenbrooke’s Hospital in 1987, he was given an honorary senior lectureship at UCL and became an Honorary Physician at UCH, allowing him to continue Wilson’s disease clinics at UCH and then the Middlesex Hospital, until finally ‘retiring’ in 2000. Dr Godfrey Gillett, a Consultant in Metabolic Medicine from Sheffield, joined Dr Walshe in these specialist clinics, and continues with them today.

Since this final retirement, Dr Walshe has continued to take an interest in his former patients from his home in Cambridgeshire and regularly attends the annual meeting of the Wilson’s Disease Support Group – UK (a support group for patients, their friends and families, founded in 2000) of which he is Honorary President.

In 1958 he and his wife Ann, who sadly died in 2011 after 55 years of marriage, settled in a wonderful 17th Century Grade II listed house in Hemingford Grey, north of Cambridge. He still lives there cared for by his daughter Susan and son-in-law Philip. His other daughter Clare lives near Oxford.

Throughout his life John Walshe has had a wealth of interests in many areas, but was a very keen photographer particularly of churches and stained glass windows. In his early years at Cambridge he took a particular interest in brass rubbings, making a record of those at Ely Cathedral which he later gave to the Dean of Ely, and which he believes are now stored at the University Library. His house is packed with historic artefacts from around the world, including model elephants – a connection with Wilson’s disease, since patients were asked to draw an elephant to give an assessment of the neurological features of their condition. This appealed to both children and adults.

John Walshe is a polymath, a translational scientist and expert clinician who has changed the lives of patients with Wilson’s disease worldwide. He has remained focussed on this often neglected, challenging and rare disease for much of his professional life. His latest paper on Wilson’s disease (published in the Quarterly Journal of Medicine) was in 2016 when he was 96 years old: incredible – and rarely matched by any other clinician scientist.

John – we are honoured to have benefitted from knowing you, to have enjoyed your encyclopaedic knowledge and to have been able to apply your lifetime’s work to the benefit of our patients.

Many, many congratulations on this very, very, special birthday.

Dr James Dooley
Emeritus Reader in Medicine
UCL Institute of Liver and Digestive Health
(Royal Free Campus)
Hampstead, London NW3

I would like to acknowledge the help of Professor Graeme Alexander, Dr Godfrey Gillett, Dr Bill Griffiths and Dr Rupert Purchase, and the following sources, in writing this account:

JM Walshe. Copper: Quest for a Cure. Bentham Books, eBook, 2009

JM Walshe. Wilson Disease: My Involvement – A Brief Reminiscence. In: Clinical and Translational Perspectives on Wilson Disease. Ed Kerkar N, Roberts EA. Academic Press, 2019.

Dr John Walshe. Biography on the Hemingford Grey Parish Council Website. By Esther Harrod

Rupert Purchase. Dr John Walshe and the treatment of Wilson’s disease (prepared for the Wilson’s Centenary Meeting in 2012).

Rupert Purchase. An Archive of Dr John Walshe’s Publications

Shorvon S, Compston A. Queen Square. A History of the National Hospital and its Institute of Neurology. Cambridge University Press, 2019.

The government previously had asked patients receiving immunosuppression for a liver transplant or autoimmune hepatitis to be shielded. As no central register exists for patients with autoimmune hepatitis on immunosuppressive medications, individual hospitals with the help of specialists have been identifying these patients for shielding.

NHS England is asking that both lists of these patients should be passed onto the COVID19 lead within their hospital by Monday 13th April. They will then pass this information onto NHSE.

Can you please ensure this information is passed onto the relevant person within your Trust?

Professor Guruprasad Aithal
President, BASL