Liver transplantation Historical overview Brian Davidson Consultant HPB and liver transplant surgery Royal Free Hospital Professor of surgery, UCL

Transplantation “The great adventure of the 20th Century” John Hunter 1728-93 Scottish surgeon and scientist Animal transplants and human tooth transplants

Vascular surgery : prelude to organ transplantation Mathieu Jaboulay Vascular anastomosis with everting sutures Alexis Carrel Animal organ transplantation using the triangulating vessel technique for anastomosis.

Organ Tx developments 1900-50 1933 Voronoy Soviet surgeon 1st human renal Tx 60 year old donor 26 yr old recipient. (Uraemic from swallowing mercury). Some urine produced. Graft failed 1954 Moore, Murray, Merrill, Harrison (Brigham Hospital, Boston) First successful renal Tx between twins with life long survival. 1950-60 Sir Peter Medawar UCL 1951-60 Nobel Prize 1960

Liver transplantation 1963 Tom Starzl, USA 1st human liver transplant. Technical success but no patient benefit. Medal of science Feb 2006

Liver transplantation 1963 Roy Calne (Cambridge) Roger Williams (Kings) 1970 35 liver Tx teams globally Starzl 57 cases, Roy Calne 28 cases

Transplant immunosuppression 1960 Azathioprine 1962 Steroids 1976 Cyclosporine First discovered by Sandoz (now Novartis) scientists in in 1969, cyclosporine is isolated from the fungus Tolypocladium inflatum.

Liver Tx in 1970’s End of decade 30% success in 100 cases (Starzl) Poor status of recipient Operative difficulties Infection and immunosuppression 1983 NIH consensus conference on liver Tx. Is liver Tx a therapeutic option? Insurance Co. cover for OLT

Improvements in immunosuppression Tacrolimus (FK506) 1990 Sirolimus 2000

Liver Tx 1980-2000 Organ preservation solutions (UW 1987) Better patient selection Improved surgical technique Reduced vascular occlusion, bile leaks Improved immunosuppressive protocols Coagulation monitoring K Lactobionate 100 mmol/L KH2PO4 25 mmol/L MgSO4 5 mmol/L Raffinose 30 mmol/L GSH 3 mmol/L Adenosine 5 mmol/L Allopurinol 1 mmol/L Pentafraction (HES) 50 g/L Penicillin 200,000 U/L Insulin 40 U/L Dexamethasone 16 mg/L Na + 25 mmol/L K + 125 mmol/L UW solution pH is 7.4 and osmolality is 320 mOsm/L.

Royal Free Hospital Liver Transplant programme Commenced 1988 Over 1300 transplants Excellent results in comparison UK/ International Active research programme.

Liver transplant challenges 2011 Increased indication for transplant Donor organ shortage Optimising donor organ use Use of high risk donors (fatty, preservation injury) Organ preservation strategies Side effects of immunosuppression

Technical developments in Liver Tx Split liver transplant (Bismuth 1987) Now routinely considered in UK with young donors (<40 years)

Live donor liver transplant Tanaka, Kyoto, Japan 1997 First adult living donor transplant

Live donor liver transplant

Non heart beating liver donors

Historical background Conclusions Century of development Vascular anastomosis to routine practise Phenomenal progress in last 30 years Current results excellent Major challenges related to donor organ shortage