Liver transplants: From ‘macabre’ experiment to life-saving procedure
Monday, April 02, 2018
Early liver transplantation was such a terrible failure that anesthesiologists in England refused to participate in clinical trials, calling the surgery "macabre and unethical." Today, the liver is the second-most commonly transplanted organ.
Liver transplantation replaces a patient's diseased liver with a whole or partial healthy liver from a human donor. Common reasons for liver transplant include non-cholestatic cirrhosis, cholestatic liver disease/cirrhosis, biliary atresia, acute hepatic necrosis, metabolic diseases and malignant neoplasms.
Dr. Thomas E. Starzl performed the first human liver transplant on March 1, 1963. Sadly, it was an utter failure as the patient — 3-year-old Bennie Solis — bled to death on the operating table, Anish Koka wrote recently for The Health Care Blog.
The young patient had biliary atresia, a condition characterized by damage or obstruction to the extrahepatic biliary system, which can obstruct bile flow. Biliary atresia, like many liver diseases, interferes with the liver's production of clotting factors. Clearly, Starzl would have to address clotting.
Undaunted, Starzl pressed on and performed liver transplantation on four more young patients that year. None made it past 23 days post-op.
All four of Starzl's subsequent patients died with functioning grafts that showed no signs of rejection or preservation injury upon autopsy. Instead, those patients succumbed to multiple infections and pulmonary emboli.
Other surgeons were attempting liver transplants at that time, including attempts in Boston and in Paris in 1963 and 1964, but all were failing. The procedure gained a reputation of being too difficult to try again. Scientists worldwide stopped performing liver transplants until the summer of 1967.
During the self-imposed moratorium on liver transplants, Starzl focused his attention on kidney transplants and on studies of tissue (HLA) matching. Kidney transplantation flourished during those years, but few believed liver transplantation was possible. However, Starzl never fully let go of the idea that liver transplantation could succeed.
Many medical professionals were steadfastly against performing liver transplantation because of the poor success rate to that point; they saw the procedure as a death sentence. Starzl saw it differently — he knew patients with biliary atresia and other types of liver disease would likely suffer terrible deaths without the life-saving treatment of a liver transplant.
Starzl had to fight hard to perform the procedure again. The surgeon defended liver transplantation at the 48th annual session of the American College of Physicians in 1967. The chairman of pediatrics at Starzl's home institution in Colorado, who happened to be little Bennie's pediatrician, supported liver transplant trials in children. The Department of Internal Medicine did not.
The surgeon's next seven patients were children. The surgeries were long and difficult. A surgeon from Sweden, Carl Groth, provided around-the-clock care for the young patients. Groth inserted breathing tubes, surgically removed infections and massaged hearts that had stopped. Incredibly, all seven children left the hospital.
Sadly, four of the children died within six months from infections. The three remaining children died one to two years later. Two of these three patients died from cancer that had metastasized; the third died after complications associated with chronic rejection.
By 1969, 26 patients had received liver transplants. Six lived beyond one year, but all perished within two and a half years of receiving their transplant.
The discovery of cyclosporine by the Sandoz Corporation finally broke the barrier to long-term survival by narrowly suppressing the immune system. This breakthrough almost did not happen, as executives of the company nearly abandoned the drug due to high costs and a perceived limited market. An appeal by English transplant surgeon Roy Calne cleared the way to use the drug in kidney transplants in England.
Starzl worried that monotherapy with cyclosporine would cause drug-related nephrotoxicity and opted instead to use prednisone concomitantly with cyclosporine. He was right, as it turns out — all of the English liver transplant patients showed signs of kidney damage; three developed leukemia, and five died.
Negative reports about liver transplant attempts poured in from England and elsewhere. Undeterred, Starzl pressed on. Even pressure from the public did not stop him. He opened a private surgical service in Pittsburgh in 1980 and began performing liver transplants there.
By 1982, the medical community and Consensus Development Conference had come to the conclusion that liver transplantation was no longer an experimental procedure — it had become a clinical service. In 1989, Starzl and his team reported that they had performed liver transplantation on a series of 1,179 consecutive patients; these patients had a survival rate of between one and five years of 73 percent and 64 percent, respectively. Liver transplantation was finally possible.
As of June 2014, nearly 72,000 adults were living with functional liver allografts. That year, doctors performed 6,729 liver transplants in adults; of these, 6,449 were from deceased donors and 280 were from living donors.
About 13,800 people are currently on the waiting list for a liver transplant, according to the Organ Procurement and Transplantation Network (OPTN). Without the tenacity of dedicated surgeons, none of these liver transplants would be possible.
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