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The Legacy of Sheila Sherlock in Hepatology

Interviews with Prof Massimo Pinzani and Dr Douglas Thorburn, Royal Free Hospital

Written by James Coker  Reporter, European Medical Journal  @EMJJamesCoker

Sheila Sherlock’s impact on the field of hepatology is felt throughout the world, as she has been at the heart of pioneering research discoveries and the adoption of innovative treatment techniques. As this took place during a time when understanding of the liver was in its infancy, her work has been the bedrock for many ground-breaking advances in the field. Her achievements are of even greater magnitude considering she was one of the few females in an industry dominated at the time by men, and has therefore inspired a new generation of women to become leaders in healthcare.

Her impact is perhaps felt most at the Royal Free Hospital, which she first joined 60 years ago this year. And in 2008, the liver treatment service at the hospital was renamed The Sheila Sherlock Liver Centre in her honour. To commemorate the 60-year anniversary of her joining this institution, we spoke to two leading hepatologists from the Royal Free Hospital to discuss her legacy there and work and trends in the future in liver disease. These were Prof Massimo Pinzani, Sheila Sherlock Chair of Hepatology, Royal Free Hospital and Director, UCL Institute for Liver and Digestive Health, and Dr Douglas Thorburn, Consultant Hepatologist and Clinical Director for Liver Transplantation, Hepatology and HPB, Royal Free Hospital.

International Legacy

Prof Pinzani joined the Royal Free in 2012, 11 years after the passing of Sheila Sherlock. Nevertheless, she has still had a major influence on his career. “I knew about Sheila Sherlock, I had all the editions of her book and although I never had her as a teacher or a mentor, and most of the professors in Italy of the generation of my mentor were very much influenced by her. They all came once a year to a meeting she was organising like a small school for a few days at the Royal Free and so she had a huge overall impact on hepatology all over the world. Although I don’t have a direct link with her as everybody of my generation and also the generation after mine, we all have a major debt and admiration to her,” he commented.

Dr Thorburn has also felt her impact throughout his time at the hospital. “In those days the concept of a liver unit didn’t exist. Almost everything that was being done in clinical care generated new knowledge and publications,” he stated. “The current structure of our and most liver units developed very much from Sheila Sherlock’s vision of multidisciplinary working for the care of patients with liver disease, particularly the collaboration between physicians, pathologist, radiologists, and surgeons.”

She has also left an enduring legacy of attracting research and clinical fellows from around the world. Prof Pinzani explained that this was not just in commonwealth countries, but in areas of the world not usually closely tied to the UK, such as in South America. This legacy was continued through Prof Andrew Burroughs, who had previously been a registrar with her. Prof Burroughs sadly died in 2014.

The achievements of Sheila Sherlock have been vast and well known in the hepatology community, contributing to all aspects of liver disease. One particular advance lauded by Prof Pinzani was her introduction of the day-to-day use of the Menghini needle, enabling much enhanced classification of liver diseases.

Advances in Hepatology

Pioneering techniques such as this have paved the way for the huge advances in hepatology Prof Pinzani has observed and been part of during his career. He has seen both the discovery of hepatitis C virus in 1989 and the introduction of highly effective treatment through an oral antiviral in recent years; so within the space of a generation. Another major advance has been the introduction and subsequent improvement of liver transplantation, ironically a technique that Sheila Sherlock was fairly sceptical about. “When I was a student the mortality for cancer was about 40%; now a transplant at the Royal Free has a 96% survival at 1 year so almost all our transplanted patients start a second life. This is due to the improvement of the surgical technique, the way you preserve the donor liver, and also immune suppression, so it’s a major change,” said Prof Pinzani.

The growth of liver transplantations has been a major aspect of the work of the Royal Free, which has a renowned programme and expertise in this area. “Over the last 10 years we’ve worked very hard to try and develop our liver transplant programme by creating a liver transplant referral network,” stated Dr Thorburn. “There’s been a greater than doubling in the number of liver transplants we’ve undertaken. Ten years ago, we were doing 40–60 at the Royal Free and last year we undertook 118 transplants so there’s been a substantial growth in the activity of the unit.”

One area that Prof Pinzani is currently heavily involved in and believes will have a substantial impact in the future is regenerative medicine; the ability to create a new liver using scaffold from discarded organs. His own role is in biotechnology, such as developing bioreactors for tissue engineering, using gels made with an extracellular matrix of the human liver that is discarded from donor patients. He pointed out that about 25% of donor liver are not transplanted for various reasons, so being able to put this to effective use is very positive. He is also excited by the possibilities brought about by 3D bioprinting for parts of the human body such as a biliary duct or blocks of liver tissue. This comes from extracellular matrix coming from the normal human liver, which is then reconstituted into a gelling solution. “We have now escalated that programme in collaboration with UCL Biochemistry, who use two specific polymers to make this bioink, where you can print any cell with a high stability,” he explained.

Challenges in the Field

Both Dr Thorburn and Prof Pinzani believe that despite major progression in the field in recent decades, a number of challenges remain. One relates to the increasing prevalence of liver conditions, largely caused by lifestyle-related issues such as misuse of alcohol and drugs, and obesity. The NCEPOD report into alcohol-related liver disease in 2013 for example found that there is insufficient liver disease expertise nationally within the UK. “There’s an increasing need for people who are more fully trained as liver physicians, as hepatologists, and this gap has not been adequately addressed at the moment,” said Dr Thorburn. “Currently hepatology and gastroenterology training remains integrated so hepatology is a subset of gastro training, but this becomes increasingly challenging as the specialist training has been shortened to 4 years instead of 5.”

In keeping with their innovative legacy in hepatology, a number of initiatives have taken place at the Royal Free to try and ensure many more liver disease patients get the right treatment in the context of higher demand for services. Community-based solutions lie at the heart of this, providing greater levels of efficiency and cost-effectiveness. “The community-based system that we’ve developed with local Clinical Commissioning Groups (CCGs) is a pathway for investigating abnormal liver function tests, which involves making a diagnosis but also staging the severity of liver disease in the course of the patient’s workup,” explained Dr Thorburn. “The purpose of this is, without having to refer the patient to the hospital, to better understand the significance of abnormal liver function when they’re identified. And this provides a mechanism to then ensure that the right patients are being referred to the right place for further management. Historically, when patients were found to have abnormal liver function, some people would ignore them and others would be referring them immediately to the hospital without investigation. What we’ve developed is an algorithm that’s run through primary care so that only patients with advanced stage disease are referred into secondary care, whereas those with milder disease are looked after in the community with recommendations about lifestyle change and weight reduction.”

An area that Prof Pinzani would now like to see more progress in is immunotherapy. “We hear everyday in the media about cancer treated with immunotherapy. Many liver diseases can also be targeted with immunotherapies. In the future we need 50% of hepatologists to also be immunologists and here at the Royal Free we have joint programmes with immunology because it’s becoming increasingly important to have this competence,” he stated.

The profound impact that Sheila Sherlock has and continues to have on the field of hepatology cannot be overstated. This is particularly so at the Royal Free, where not only does a legacy of attracting international clinical and research fellows continue, but also pioneering and innovative solutions to the challenges faced in liver disease today.