The liver was seen as a sort of imperial organ throughout history in some cultures. In fact, the German word for liver is “leber”, which is derived from the verb “to live”. The Roman anatomist, Galen, who lived in 2nd and 3rd century, referred to the organ as the principal organ of the human body. Avicenna, an Islamic medical philosopher from the 10th and 11th century, artfully noted the liver as “the seat of the nutritive or vegetative faculties.” (https://web.stanford.edu/class/history13/…/liverpages/livergallbladderspleen.html). It was during the mid-20th century that the secret to successfully transplanting this noble organ was unlocked.
As was the case with various organ transplantation attempts, the first experiments to transplant the liver were performed on animals. Dogs were the specialty animals for early liver replacement trials. C. Stuart Welch of Albany Medical College wrote about inserting a liver into a dog in 1955, while three years later, Francis Moore described the first surgery on a dog where the original liver was removed and replaced by a donor liver. Further, Dr. Thomas E. Starzl performed over 150 dog experiments to investigate the various issues involving liver transplantation.
The early 1960s was a time of the first human liver transplant attempts, but none were successful. To note, Dr. Starzl performed five such human liver replacement attempts, with one patient dying during the surgery due to massive blood loss, with the remaining four living from between 6.5 to 23 days following the procedure (http://www.starzl.pitt.edu/transplantation/organs/liver.html). These cumulative failed attempts led to a moratorium on liver transplant activity in humans until the summer of 1967. Undeterred, Dr. Starzl did not stop pursuing liver transplantation activities, but under a different model, as he and his colleagues performed three chimpanzee to human children procedures between 1966 and 1973. True to practice, none of those transplants were successful.
The much sought-after success in this realm finally occurred in July 1967, as Dr. Starzl, termed “The Father of Liver Transplantation”, transferred a liver into nineteen-month-old Julie Rodriguez. This girl became the first person to survive for more than a year, post liver transplant, only to succumb to a type of liver cancer 400 days later (http://www.nickspicks.org/nicks-voice/dr-thomas-starzl-the-father-of-liver-transplantation/).
At the time, 70% of deaths occurred in liver transplantation due, in large part, to organ rejection. The common immunosuppressant drugs utilized at the time were steroids and azathioprine, and based on the lagging success rate, were not largely effective (https://emedicine.medscape.com/article/431783-overview). As such, the one-year survival rate was at 15% in 1970.
A significant barrier to the success of liver transplantation was pierced with the discovery of the immunosuppressant drug Cyclosporine by J.F. Borel in 1976. Cyclosporine was effective, as it allowed selective immunoregulation of T cells without excessive toxicity (http://www.davidmoore.org.uk/Sec04_01.htm). An illustration of the drug’s effectiveness is exhibited by a report showing that prior to the discovery of Cyclosporine, the one year survival rate following liver transplantation was between 30% to 50%, while the survival rate of that same period of time climbed to 74% for the first 1,000 recipients treated with Cyclosporine in the early 1980s at the University of Pittsburgh (https://www.intechopen.com/books/liver-transplantation-basic-issues/history-and-evolution-of-liver-transplantation).
This type of procedure obtained a significant boost in the medical field in 1981, when C. Everett Koop, the United States Surgeon General, initiated an international conference for liver transplantation. The input provided from experts, including those from several European centers, led to the consensus that liver transplantation had become a “clinical service”, as opposed to the experimental service as it had been previously recognized.
Finally, a new immunosuppressive drug Tacrolimus, which promotes the development of T cells vital to the body’s learned immune system, was introduced in 1990. It was later found that when Tacrolimus is used in conjunction with Cyclosporine, this combination further reduced instances of organ rejection when compared to past anti-rejection medications.
As of 2015, more than 10 million liver transplantations had been performed worldwide, with patient survival within the first year ranging from roughly 80% to 90%.
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Topic for Tuesday, February 6th posting – Transplantation Firsts, Part 3 – First Heart Transplants
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