The history of liver disease begins at King’s with the work of George Budd (1808-1882). In 1840, Budd was appointed Professor of Medicine at King’s College London and made a special study of liver diseases producing one of the earliest books on the topic. His name is perpetuated in the Budd-Chiari syndrome, a disease of progressive liver failure caused by obstruction to the hepatic vein which he described in 1845.
In 1966, Roger Williams (b 1931) established the Liver Unit at King’s College Hospital and Medical School. Two years later the MRC set up within it a ‘Group for Studies into the Metabolism and Haemodynamics of Liver Disease’ and in the same year, a collaboration began with Professor Sir Roy Calne in Cambridge to perform the first liver transplants in the UK.
In the early 1970s, the first specialist liver intensive care ward for adults in the world was opened at King’s. Over the ensuing twenty-four years and consequent on the strong laboratory base that was set up by Williams (in what became recognised by King’s College London as the Institute of Liver Studies), and with an increasing referral practice, many original contributions were published on the management and outcome of liver failure and liver transplantation as well as on the pathogenesis and treatment of autoimmune liver disease, viral hepatitis and the causes of chronic liver disease.
Today the Instititue of Hepatology includes the adult and paediatric liver services and has the largest liver transplant programme in Europe with 2,500 transplants performed since 1990. Several new surgical techniques have been pioneered, such as reduced liver, split-liver and living-related transplantation which effectively increase the supply of donated organs. As an example, one donor liver can provide three grafts – right lobe for an adult, left lateral segment for a child and the remaining tissue for harvesting cells for transplantation. The last is a different approach to transplantation which is being explored at King’s. Using isolated human liver cells (hepatocytes) has several advantages: it reduces reliance on donor organ availability, it can buy time to allow the damaged organ to recover or until a donor organ is available, and it avoids major surgery.
The first requirements for hepatocyte transplantation are for effective isolation of hepatocytes from a donor or fetal liver and then preservation. Research has resulted in high yields and viability of 90 per cent being achieved. The second requirement is that the hepatocytes, when infused into the liver, should remain and repopulate the liver, ie successful engraftment. Methods being investigated to promote this includes the application of growth factors and ex vivo gene therapy to induce growth factor production in the hepatocytes themselves.
The first successful human liver transplants in the world using cryopreserved hepatocytes have been performed at King’s College Hospital. The patients were children with various metabolic disorders: the bleeding disorder congenital Factor VII deficiency; ornithine transcarbamylase deficiency, diagnosed antenatally, and usually fatal within weeks; progressive familial intrahepatic cholestasis, which causes severe jaundice. These initial results pave the way for an alternative treatment to transplanting part or whole of the liver. If it becomes widely available it will solve two major problems for patients needing an urgent liver transplant, which are the lack of a hepatic equivalent to dialysis in renal failure and the difficulty with donor organ availability.
Hugh De Wardener is described as the single most influential nephrologist in the UK in the second half of the last century, Hugh De Wardener (b 1916) is internationally known for his work on salt and its relation to blood pressure, and natriuretic hormones. He qualified from St Thomas’ in 1939 and, after distinguished service in the Royal Army Medical Corps in World War 2, returned there to a lecturer’s post when his research work on sodium began. It was during this time that he wrote his famous monograph The Kidney which over its several editions influenced many young physicians towards nephrology.