The saga of liver transplantation

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Figure 28.1 First three human recipients to have prolonged survival after liver replacements in July and August 1967. The adult, Carl Groth, was a senior surgical resident from the University of Stockholm who was a Fulbright Scholar and transplant fellow at the University of Colorado during 1966–1968.

Transplantation of other extrarenal organs followed close behind the liver, using similar immunosuppression. Hearts were successfully transplanted in 1968 in Capetown by Barnard [62] and in Palo Alto by Shumway [63]. In 1969, the first prolonged survival after human lung [64] and pancreas transplantation [65] was accomplished in Ghent and Minneapolis, respectively. But transplantation of the extra-renal organs, and especially of the liver, remained controversial for another decade, because of the high mortality. Swimming against the stream, the German and French teams of Rudolf Pichlmayr and Henri Bismuth entered the field in the early 1970s, as did the Dutch group of Rudi Krom later in the decade.

The unusual tolerogenicity of the hepatic allograft previously demonstrated in dogs and pigs was evident in human liver recipients of the 1970s. In 1995, 12 of our 42 patients (28%) surviving from this era already had been off all immunosuppression for 1–17 years [66,67]. Since then, many of the remaining 30, who are now out to 45 years post-transplantation, also have stopped drugs and remain well. Such drug-free tolerance was almost unheard of with the other kinds of cadaveric organs.

28.8.1  Advent of better drugs

Despite such encouraging notations, the widespread use of the liver and other extrarenal organs was precluded for another decade by the high mortality. The outlook for all organs improved after cyclosporine was introduced clinically in England in 1978 by Calne [68] and combined with prednisone in Denver 1 year later [69]. Results further improved when tacrolimus was substituted for cyclosporine in the 1990s [70,71].

The increases in liver recipient survival with the two new drugs were particularly striking, but less dramatic gains were recorded with the other organs. By the end of the twentieth century, transplantation of the liver and all of the other vital organs had become an integral part of sophisticated medical practice in every developed country in the world.

BOX 28.1

The lesson is clear. History is neither dull nor dead. It is a uniquely human survival tool, aiding those in the present by the ability to draw on the past to meet current needs, and to predict needs yet to come.

Thomas E. Starzl

BOX 28.2

Liver transplantation … was a therapeutic modality for end-stage liver disease that deserves broader application.

NIH Consensus Development Conference on Liver Transplantation, 1983

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Nicholas Eck, Russian military surgeon who at 29 years old published a one-page pamphlet on the creation of a complete portacaval shunt in dogs. Only one of eight survived.

*  Based on a presentation to the American College of Surgeons, Annual Clinical Congress, San Francisco, October 2002, and published in Journal of the American College of Surgeons 195 (5), 2002 (edited by Mark Davenport) © 2002 by the American College of Surgeons. Published by Elsevier Science Inc.