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LIVER TRANSPLANTATION IN MAN.

ABSTRACT: Until quite recently it was possible to give only highly tentative opinions on the role of liver transplantation in the treatment of patients dying of incurable liver disease. Now, a much more authoritative position concerning clinical liver transplantation can be taken, since there have been six patients who have lived for more than a year after removal of their own diseased livers and replacement with cadaveric organs.The mortality has been high, just as it was in the first trials with renal transplantation. Nevertheless, we believe that the future role of liver transplantation in hepatic disease will not be fundamentally different than cadaveric kidney transplantation in the field of renal disease. In this paper we will give the justification for this optimistic view, mention the indications for such operations as they have become clear in the last year and, above all, focus attention upon the errors in technique or judgment we have made which have accounted for most of the early deaths in our experience.

SUBMITTER: Penn I

PROVIDER: S-EPMC3000223 | biostudies-literature | 1970 Jul

REPOSITORIES: biostudies-literature

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LIVER TRANSPLANTATION IN MAN.

Penn Israel I Halgrimson Charles G CG Starzl Thomas E TE

Annals of the New York Academy of Sciences 19700701

Until quite recently it was possible to give only highly tentative opinions on the role of liver transplantation in the treatment of patients dying of incurable liver disease. Now, a much more authoritative position concerning clinical liver transplantation can be taken, since there have been six patients who have lived for more than a year after removal of their own diseased livers and replacement with cadaveric organs.The mortality has been high, just as it was in the first trials with renal t ...[more]

PMID: 21151748

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Project description:Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV.

Project description:Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676?±?251 g (mean?±?SD), and percentage reconstitution was 80%?±?13%. Among recipients, GRWR was 1.3%?±?0.4% (8?<?0.8%). Graft weight was 60%?±?13% of SLV. Three-month absolute growth was 549?±?267 g, and percentage reconstitution was 93%?±?18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P?=?0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR?=?4.50, P?=?0.001) but not by GRWR or graft fraction (P?>?0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

Dataset Information

LIVER TRANSPLANTATION IN MAN.

Publications

LIVER TRANSPLANTATION IN MAN.

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