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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

Important update from the BSG VP Hepatology and the BASL and BSG Presidents

During the COVID-19 outbreak the NHS is doing everything it can to keep patients with liver disease safe. However, risks relate not just to the infection itself, but also to the significant disruption of routine care due to the pandemic. Information from China and Italy suggest that hospital admissions for non-COVID-19 illness can lead to further spread of infection. Changes in routine care are now required to keep vulnerable patients with liver disease out of hospital as much as possible. However, changes to the way care is delivered for patients with liver disease must be balanced against the risks of undertreating them.

‘Social distancing’ and ‘self-isolation’ are measures to reduce spread within a population and to protect high risk groups. The impact of immunosuppression on the severity of COVID-19 disease remains unclear. Factors associated with more severe disease are older age and presence of other medical conditions. These are also an understandable source of anxiety for patients with liver disease. Government guidance in this area is dynamic and all people in the UK should follow up to date recommendations from the government.

The government recommends social distancing for all in the UK, but this guidance defines a ‘high-risk’ group of patients with liver disease who are advised to take additional measures and go into self-isolation for 12 weeks.

Patients with liver disease in high risk group*:

`Shielded group` Advise mandatory self – isolation:

1) Patients having undergone liver transplantation and taking immunosuppression and

2) Patients with autoimmune hepatitis taking immunosuppression

The consensus view in our specialty acknowledges the higher risk for patients with decompensated cirrhosis, who are not included in the shielding cohort. We recommend that these patients with decompensated cirrhosis should be advised to adhere strictly to social distancing measures in order to protect themselves. Clinicians will not, however, have to identify this group to their GPs for coding as COVID at RISK.

*There may be others not in the above groups felt by the treating physician to also be at higher risk and these should be assessed on a case-case basis.

General Principles

• All healthcare professionals have a responsibility to safeguard patients, colleagues and themselves from the COVID 19 virus.
• We wish to emphasise the importance of following current guidance and advice from Public Health England, Health Protection Scotland, Public Health Wales and Public Health Agency Northern Ireland.
• You will find any updates to this document on the BSG website.

Potential Impact on Gastroenterology and Hepatology Services

• Based on developments over the last few days, it is likely that the NHS will have to manage increasing numbers of patients with COVID 19. There is a shared understanding that if COVID 19 becomes a significant epidemic in the UK, clinical services will be stretched and that this will be exacerbated by staff shortages due to sickness, imposed isolation and caring responsibilities.
• It is likely that there will be increasing requirements for healthcare professionals in gastroenterology and hepatology to support NHS Healthcare providers in managing the care of acutely ill patients. This will likely result in disruption or cancellation of clinics and endoscopy lists and other specialist activities.

Redeployment of Staff to Managing Acutely Unwell Patients

• In the event of a significant outbreak, healthcare professionals in gastroenterology and hepatology will be asked to support broader patient and population needs.
• It is important that these activities are considered in the context of patient safety. Healthcare professionals should not undertake any activity beyond their level of competence.
• Healthcare professionals should avail themselves of training opportunities to equip them to undertake specific tasks in looking after acutely unwell patients either with suspected or confirmed COVID 19 infection.

Advice for patients with Inflammatory Bowel Disease on immunosuppression

• The following advice is from Public Health England and is well summarised by Crohn’s and Colitis UK and the International Organisation for IBD (IOIBD).
• People taking immunosuppressants for their Crohn’s Disease or Ulcerative Colitis are not at increased risk of catching novel coronavirus, however they may be at extra risk of complications from the virus if they are infected.
• People on immunosuppressants should seek advice by telephone if they develop symptoms of either seasonal Influenza or novel coronavirus.
• For the majority of patients, it is advisable to continue with immunosuppressive treatment and other treatments for their inflammatory bowel disease.
• Patients are advised to take precautions to avoid infection through good personal hygiene and avoiding unnecessary close contact with people who are unwell.
• If patients stop taking immunosuppressive medicine, they may have a flare which will increase the risk of complications if infected with coronavirus.
• If patients still have concerns about continuing the medication, they should speak to the medical team.
• If patients are at an increased risk of infection, for example, if they have been in direct contact with an infected individual, have travelled to a high infectivity area, or have another serious comorbidity that increases the risk further, they should seek advice from their medical team by telephone before making any changes to their medication.

Telephone and Virtual Clinics

• In order to maintain social distancing and reduce the risk of transmission of COVID-19, we encourage telephone consultations with patients or virtual clinics to avoid patients having to attend the clinic in person.
• We suggest that in such circumstances, a clause is added to the clinics letter that the patient has not been examined and that part of the assessment is therefore limited but has been only omitted due to exceptional circumstances.
• Good IT support is necessary to support telephone or virtual clinics, for example use of Skype.

Hepatology Patients

• Acute services can be helped by reducing acute admissions where possible by setting up alternative routes of care as in the case of day-case unit paracenteses services to prevent emergency admissions for paracentesis (these can be about 100/100,000 population).
• Patients suitable for telephone and virtual clinics include those with stable cirrhosis and those long-term after transplant.
• Patients post-transplant, those with AIH on second line immunosuppression, and those with decompensated cirrhosis and/or alcoholic hepatitis patients are considered high risk for COVID 19.
• Patients with compensated cirrhosis are considered to be in the intermediate risk group for COVID 19.

Advice for Patients with Liver, or Small Bowel Transplants

• We recommend that healthcare professionals looking after such patients refer to the guidance from the British Transplantation Society.

Endoscopy and COVID19

• Endoscopy Teams are advised to follow both national guidance for reducing transmission of infection with COVID19 (websites above) but also agree their own local protocols and policies in collaboration with senior management, Infectious Disease or Infection Control teams. There are both general measure that should be followed and specific measures around personal protective equipment (PPE).
• General measures include checking patient’s travel history at admission, providing a COVID19 information sheet about symptoms to report and checking patients temperatures upon arrival. Where there is concern, elective procedures should be postponed and rebooked as soon as possible once the patient no longer poses a risk. Units should develop standard operating procedures (SOP) for COVID19 control measures and share these widely among staff groups.
• PPE for endoscopy procedures – advice is that standard infection control measures should be followed except for aerosol generating procedures (AGP) in patients at high risk of or with confirmed COVID19 infection. AGP in this context means upper GI procedures and for patients who fall into this category, enhanced PPE is recommended including FFP3 masks. Endoscopy teams should also consider enhanced PPE for emergency and out-of-hours procedures and also consider arrangements for the most appropriate location to perform these within their hospital. Units are encouraged to ensure staff know how to be fitted for the appropriate size of FFP3 mask and how to put on PPE correctly.
• Official advice is that enhanced PPE is not currently felt to be necessary for upper endoscopy in patients at low risk or for lower GI procedures. Concerns have been raised that the virus may be faecally transmitted but there is presently insufficient evidence to recommend the use of enhanced PPE measures for lower GI procedures. Stocks of FFP3 masks are also limited and their use needs to be carefully prioritised. This is, however, a rapidly changing situation and teams should check regularly for updates to both local and national guidance
• Units should discuss locally and consider whether or not to suspend some endoscopic activity e.g. low-risk surveillance scopes (non-dysplastic Barrett’s, polyp follow-up, IBD etc) for a period to help reduce or delay virus spread but also as it is likely there will be staff shortages through illness, absence to care for others or redeployment.

Summary

Individual hospital trusts and health boards will be looking to implement local guidance based on national and international best practice. For reasons mentioned above, we encourage telephone or virtual clinics. This guidance aligns with the current data available but as the situation changes further guidance may be required. Individual treatment decisions about patient care will be between the patient and the treating physician.

Dr Tony Tham
Clinical Services & Standards Committee Chair
BSG

These guidelines on Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association for the Study of the Liver (BASL). The guidelines development group (GDG) comprises elected members of the BSG Liver Section, representation from British Association for the Study of the Liver (BASL), a nursing representative, and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system.

These guidelines are aimed at health care professionals considering referring a patient for a TIPSS. They comprise the following subheadings: (1) indications; (2) patient selection; (3) procedural details; (4) complications; and (5) research agenda. They are not designed to address: (1) the management of the underlying liver disease; (2) the role of TIPSS in children; or (3) complex technical and procedural aspects of TIPSS.

Download TIPSS guidelines_gutjnl-2019-320221.full.pdf