Liver transplantation wasfirst attempted in dogs by Welch in Albany in 1955 and Cannon in California in1956.In the late 1950s and early 1960s two centers, Starzlworking in Denver1 and Moore in Boston wereinterested in the technique of transplanting the liver, which was clearly goingto be a formidable undertaking. Both had realized that dogs would not tolerateclamping of the vena cava and portal vein that is necessary to take out and transplantthe liver.2On 1st March, 1963, Thomas E Starzl (Figure 1.
1) in Denver, Universityof Colorado Health Sciences Center (UCHSC), USA had performed the first humanliver transplantation in the world in a 3 years old child with biliary atresiaand received the liver from another child who died from brain tumor. But theycould not complete the surgery and patient died due to uncontrolled hemorrhage.3 The second liver transplantationin man was performed on 5th May, 1963.Patient died on the 22nd postoperativeday due to pulmonary embolism but with a normal liver. Starzl therefore decidedto have a moratorium on clinical application of liver transplantation thatlasted until 1967when he started his main program. The first long term survivalwas achieved in 1967 by Starzl in Denver,Colorado, USA.
4,5 Despite the developments insurgical techniques, liver transplantation remained experimental till 1970 with1 yr patient survival rate around 25%. Figure 1.1: Prof Thomas E Starzl (World’s 1st Liver transplantation)Contributed and reproducedwith permission of Terry Mangan,UPMC, USA By the end of summer 1967,the Denver experience included 11 liver transplantations. Eight of the patientshad undergone orthotopic liver transplantation, and three had been providedwith an auxiliary liver.
Early immunosuppressivetherapy consisted ofazathioprine andprednisolone, but rejection was usually rapid. None of thesepatients had recovered their health; the longest survival was 34 days. In thesame year, a chamber for the preservation of the liver was developed inDenver.The system included perfusion of the liver with diluted blood underhypothermia and hyperbaric oxygenation.When dog livers were placed in thechamber, it was found that the livers could be preserved for 8 hours.
6 At the same time,Denver group set out to prepare antihuman anti-lymphocyte globulin (ALG).InJuly 1967, a 2½ yrs old child underwent orthotopicliver transplantation on(23rd July, 1967). The donor liver had been maintained for 3 hours in thepreservation chamber. The early postoperative function was satisfactory.Postoperatively, antilymphocyte globulin(ALG) was given for several months incombination with azathioprine, and prednisolone. During the following 2 months,two more infants, both suffering from biliary atresia, underwent orthotopicliver transplantation. The protocol was the same as that for the first child.These three children were the first to achieve extended survival after livertransplantation.
7In 1969, Starzl published a monograph on liver transplantation, and by thattime 25 patients had been treated in Denver and a number of the patients hadsurvived for more than 1 year.8Thomas E Starzl’s pioneering efforts in organ transplantationfor four decades have resulted in clinically proven treatments for patientswith end-staged organ failure, who were previously doomed to death. His contributionsto immunosuppression, organ procurement, organ preservation, tissuematching,surgical transplant technology, and the team approach to organtransplantation paved the way for the acceptance of heart, lung, pancreas,intestinal, liver, and kidney transplantation.
Starzl combined the marginallyeffective drugs, azathioprine and prednisolone, in a strategy (1962-63) thatmade kidney transplantation a viable option for treatment of end-stage renaldisease.Dr Starzl introduced the first major innovation in hypothermia, whencanine liver allografts were cooled by infusion of chilled fluids into thevascular bed of hepatic allografts via the portal vein.9 In the initial stages ofliver transplantation, 1-year survival rates were below 30% due to variouslimitations related to surgical technique, ineffective immunosuppression,andinadequate postoperative care. But results later improved drastically.
Tillnow, 8 patients have survived for more than 30 years after livertransplantation worldwide and 6 of them are from the Denver series.10 The longestsurvivor has had her new liver for 38 years. This patient was only 3 years oldat the time of transplantation. Carl Groth reported that a total of 8 patientstransplanted with livers from non heart-beating donors have by now survived formore than 20 years in Stockholm.11One of Starzl’s early experimental animals survived formany years after the immunosuppressant had been stopped.12 In Cambridge,Roy Y Calne (Figure 1.2) and team were fascinated with the immunologicalstudies of orthotopic liver transplantation and decided to follow Starzl withclinical application in April 1968.13 Clane performed 1st OLT on May 2, 1968,in Addenbrookes Hospital, Europe.
In any immunosuppressed patient with an organgraft, there is a danger of sepsis, or infection,and this was in fact the causeof failure in many of the early cases performed in Cambridge. Figure 1.2: Sir RoyYorke Calne (Introduced cyclosporine, 1st livertransplantation in Europe, and World’s 1stcombined heart, lungand liver transplantation) TABLE 1.
1: Historical milestones of liver transplantation(15) Year Type of liver transplantation Surgeon and Country 1963 1st Liver transplantation (biliary atresia) Starzl TE, Denver, Colorado, USA 1964 1st Liver transplantation in Asia from non-heartbeating donor (biliary atresia ) Nakayama, Chiba Univ., Japan 1967 1st Successful liver transplantation Starzl TE Denver, Colorado, USA 1968 1st Long-term survival (1 yr) of child Denver, Colorado, USA 1968 1st Liver transplantation in Europe Roy Y Calne,Cambridge, Europe 1983 NIH Consensus Conference declares liver transplantation is justified in the treatment of ESLD 1984 1st Reduced-size liver transplantation Bismuth H, Univ Paris Sud, France 1987 1st LDLT in a child Raia S, Univ. of São Paulo Brazil 1987 Introduction of University of Wisconsin Solution 1988 1st Split Liver transplantation (2nd Feb.) Pichlmayr R, Germany 1989 1st Successful LDLT in child Strong RW, Brisbane, Australia 1989 1st LDLT in Asia (Biliary atresia) Nagasue, Japan 1993 1st Adult to adult LDL T Makuuchi, Tokyo Univ., Japan 1997 1st Split Liver transplantation in Asia Chen CL, Chang Gung Univ, Taiwan 2000 1st Dual graft transplantation Lee SG, Ulsan Univ., Korea 2001 UNOS/OPTN Board of Directors approve MELD and PELD scoring system for organ allocation in liver transplantation 2002 MELD and PELD Scoring system becomes effective 2007 1st Dual graft transplantation in Europe Broering DC, H-E Univ, Germany CONCEPT OF LIVING DONOR LIVERTRANSPLANTATION (LDLT)Silvano Raia (Figure1.3) in San Paolo, Brazil, introduced the concept of a living donortransplant to a child15The first attempt was performed in December, 1988 without success (the childdied on the 6th postoperative day during hemodialysis).
The second one wasperformed in July, 21st, 1989 and the girl survived for 4.5 months and diedprobably due to CMV infection. His efforts were not successful but werefollowed up shortly afterward by cases done in Brisbane, Australia by RussellStrong with success.16This provided an opportunity to develop liver transplantation in Japan byMakuuchi M and Tanaka K(16)thatpreviously had been impossible due to the law on organ donation and reluctanceof the public to donate organs. However, parents would frequently offer a lobe ofa liver for their child. The Japanese became the most experienced and skillfulexponents of this technique in the world, although there was also enthusiasmfor it in other centers particularly in the United States.
As results improvedand FK506 (tacrolimus) became available as another calcineurin inhibitor like cyclosporine,but with certain advantages in therapeutic index for liver transplants, thecriteria of selection for living donors widened to people who are notnecessarily parents of a child, but more distant relatives or even friends.Then, adult-to-adult living donation was popularized in Hong Kong by ST Fanwhose excellent techniques showed that good results could be obtained eitherusing the right or left lobe, depending on the size of the donor and recipient.17 In Taiwan,first successful deceased donor liver transplantation was performed in March1984 by CL Chen and his team .
Figure 1.3: Prof Silvano Raia. Professor emeritus at the Faculty subjectof interest.ofMedicine of the University of San Paulo, San Paulo, Brazil (World’sfirstLiving Donor Liver Transplantation in a child) (Contributed andreproducedwith permission of Dr. Sergio Mies, Sao Paulo MedicalSchool – USP, Liver Unit, InstitutoDante Pazzanese de Cardiologia,São Paulo–SP, Brazil ADULT-TO-ADULTLDLTInitially adult-to-adultliver transplantation was considered as hazardous to the donor. The exactmortality is not known but it has been calculated to be around 0.
1-1% eitherdue to complications or inappropriate donor selection with small residualvolume or a fatty liver leading to hepatic failure after surgery. But thetechniques of LDLT are refined with gaining experience the morbidity andmortality rates are less and risk of the donor can be balanced against thebenefits of the recipient.SPLIT LIVER First split livertransplantation was done on 2nd Feb. 1988 by Rudolf Pichlmayr (Figure 1.
4),Germany, later many studies have been reported and is an option to increase thedonor pool in carefully selected deceased donor. In Asia, Chen CL from Taiwanperformed the first split liver transplantation in May 1997, followed by KC Tanin July1997 in Singapore18Initially, split liver was used for one adult and one pediatric patient, but inthe present transplantation scenario, split liver for 2 adults is the subjectof interest. Figure 1.4: Prof Rudolf Pichlmayr(1932-1997) (First split livertransplantation)(Contributed and reproduced withpermission of S.
Karger AG, Medical and Scientific Publishers,Allschwilerstrasse,Basel, Switzerland DOMINOSThelong-term shortage of livers available for transplantation has spurred thedevelopment of many strategies to bolster the donor organ supply. Oneparticularly innovative strategy is domino liver transplantation in which aselect group of liver transplant recipients can donate their explanted nativelivers for use as liver grafts in other patients. Several hereditary metabolicdiseases (such as familial amyloid polyneuropathy, maple syrup urine disease,and familial hypercholesterolemia) are caused by aberrant or deficient proteinproduction in the liver, and these conditions can be cured with an orthotopicliver transplant.
Although their native livers eventually caused severesystemic disease in these patients, these livers are otherwise structurally andfunctionally normal, and they have been used successfully in domino livertransplants for the past 15 years.19 ABO-INCOMPATIBLE (ABO-I)LDLT20: The first ABO-I LDLT wasperformed in November 1991 in Japan to overcome the organ shortage. As per thedata of National Registry of the Japan Study Group for ABO incompatible,291(155 children and 136 adults) ABO-ILDLTs have been performed till March 2006 inJapan from 28 institutions. ABO-incompatible LDLT is a standard practice inchildren (< 2 years), and plasmapharesis, local infusion and rituximabprophylaxis are promising in adults. In adult LDLT, it is exceptionallyperformed only as a rescue option in an emergent situation where suitable donoris not available.
DUALGRAFTSFirst Dual grafts reportedby Lee SG and team from Koreain 2000.21 Several reports suggesting excellentresults of this procedure have already been published22-24