- 19
- Apr.
- 2024
Hepatic Transplantation: A Therapeutic Victory
modified on 24 Apr. 2024 à 03:19 Read : 8 minute(s) A A A
Transplantation offers a crucial hope for patients facing end-stage liver failure. Despite its challenges, it remains the last lifeline to prolong life and restore health. Let's delve into it with Professor Francis Navarro.
Organ transplantation stands as one of the major breakthroughs in modern medicine, offering a glimmer of hope for many patients facing terminal organ failure, notably in the kidneys, liver, heart, lungs, or intestines. The first successful organ transplantation was performed in 1954 by Dr. Joseph Murray and his team at Brigham Hospital in Boston, transplanting a kidney from a donor to his twin brother. Since then, this form of therapy has witnessed significant growth, especially in the past few decades. Indeed, the total number of solid organ transplantations in the United States rose from 15,001 in 1990 to 46,630 in 2023, according to statistics published by the Organ Procurement and Transplantation Network.
Although scientific and medical advancements have expanded treatment options, the use of artificial organs remains limited to certain cases, primarily hemodialysis in cases of end-stage renal failure. For many patients, transplantation thus remains the only solution to restore the function of one or more organs, and thereby prevent premature death. According to a study published in Nature in May 2021, over 34,285 solid organ transplantations were performed in Europe in 2019, with 85% of them being kidney (62%) and liver (23%) transplants.
The figures in France seem to be in line with these numbers. According to data from the French Agency for Biomedicine, 5,634 solid organ transplantations were performed in 2023, including 3,525 kidney and 1,343 liver transplants, which represent 86% of the total number of transplantations.
Epidemiological studies show that liver transplantation is the second most performed organ transplantation after kidney transplantation. This therapeutic choice represents the ultimate solution, even the reference curative treatment, for a number of serious liver pathologies, the most important of which are severe cirrhosis (resulting from chronic viral hepatitis or excessive chronic alcohol consumption), hepatocellular carcinoma, and acute liver failure. So what are the available options for patients awaiting liver transplantation?
"Two approaches are conceivable," says Professor Francis Navarro, Head of the Hepatic, Biliary, Pancreatic Surgery and Transplantation Department at Montpellier University Hospital. "The first involves the transplantation of a whole cadaveric liver from a donor with brain death," he explains to Ici Beyrouth, on the sidelines of a congress on "Medical-surgical updates around digestive pathologies" organized by the French Hospital of the Levant, in collaboration with the IRCAD International (Research Institute against Digestive Cancer) and Montpellier University Hospital.
"The second option consists of transplanting a part of the liver, either the right lobe or the left lobe, taken from a living donor," continues the French surgeon of Spanish origin. However, he specifies that a primordial condition must be met from the outset: the graft in the recipient must correspond to at least 0.8% of their body weight.
Unlike bone marrow transplantation, which requires very close tissue compatibility between the donor and the recipient, liver transplantation is less restrictive in terms of compatibility criteria. "It simply involves blood type," Dr. Navarro emphasizes. The distribution of grafts is thus governed by the ABO system, i.e., the four groups: A, B, O and AB. Conditions are more complex in certain cases, such as hyperimmunized patients undergoing double kidney and liver transplantation, where the situation becomes more complicated. Immunosuppressive treatment is initiated after transplantation to prevent rejection of the new liver by the body.
If liver transplantation seems theoretically within reach due to the less restrictive compatibility requirements, the reality is quite different. According to a study published in March 2022 in the American Journal of Transplantation, only 54.4% of patients in the United States received their graft within the year following their registration on the national waiting list in 2020. "Cadaveric organ donation is not always possible due to cultural, religious, or even dogmatic considerations, as is the case in Southeast Asia, where 95% of liver transplantations are performed from living donors," notes the surgeon. However, he specifies that the living donor is exposed to risks, with a morbidity rate of 9% and a mortality rate of 2%: "It's a heavy surgery, but when done with a robot via laparoscopy, the risk decreases significantly," he points out.
What about these transplantations in Lebanon? The first liver transplantation from a living donor was successfully performed at Hôtel-Dieu de France in July 2000. However, Lebanese archives only mention about twenty cases of liver transplantation in the land of the Cedar. Why is that? "The availability of cadaveric donors seems uncertain in Lebanon for various reasons, while resorting to living donors remains risky in a country where the chain is not yet ready," responds the expert. And he adds, "The introduction of rapid transplantation techniques, i.e., the removal of a liver lobe from a family member, could be a glimmer of hope in Lebanon for patients suffering from cirrhosis or liver metastases." Indeed, a prospective pilot study, called SECA-I, conducted at Oslo University Hospital, reported in 2013 a 5-year overall survival rate of 60% after liver transplantation in 21 patients with unresectable liver metastases from colorectal cancer.
Thanks to the rapid progress in genetics, particularly in the field of genome editing (manipulation of the human genome), a new era is beginning in medicine and biomedical research. The "humanization" of the pig is the most tangible proof of it. By modifying the genetic heritage of these animals, researchers have succeeded in making their organs more compatible with those of humans. And this is to address the serious organ shortage. In January 2022, the very first transplantation of a humanized animal organ took place in the US. David Bennett, then 57 years old, successfully received the genetically modified heart of a pig, when no other therapeutic alternative was available. He survived for two months.
More recently, on March 16, 2024, Richard Slayman, aged 62 and suffering from end-stage chronic kidney failure as well as several comorbidities, was successfully transplanted with a genetically modified pig kidney. He is currently showing positive signs of recovery. However, the durability and effectiveness of this transplantation remain to be confirmed over time. Can we envisage a future for xenotransplantation in the treatment of terminal liver diseases? Professor Navarro seems optimistic: "I am convinced that there is a promising future in this field. The pig represents a particularly promising avenue, being the animal whose organs are closest to those of humans. The next two or three decades will be decisive for this evolution."
Organ transplantation stands as one of the major breakthroughs in modern medicine, offering a glimmer of hope for many patients facing terminal organ failure, notably in the kidneys, liver, heart, lungs, or intestines. The first successful organ transplantation was performed in 1954 by Dr. Joseph Murray and his team at Brigham Hospital in Boston, transplanting a kidney from a donor to his twin brother. Since then, this form of therapy has witnessed significant growth, especially in the past few decades. Indeed, the total number of solid organ transplantations in the United States rose from 15,001 in 1990 to 46,630 in 2023, according to statistics published by the Organ Procurement and Transplantation Network.
Although scientific and medical advancements have expanded treatment options, the use of artificial organs remains limited to certain cases, primarily hemodialysis in cases of end-stage renal failure. For many patients, transplantation thus remains the only solution to restore the function of one or more organs, and thereby prevent premature death. According to a study published in Nature in May 2021, over 34,285 solid organ transplantations were performed in Europe in 2019, with 85% of them being kidney (62%) and liver (23%) transplants.
The figures in France seem to be in line with these numbers. According to data from the French Agency for Biomedicine, 5,634 solid organ transplantations were performed in 2023, including 3,525 kidney and 1,343 liver transplants, which represent 86% of the total number of transplantations.
Ultimate solution
Epidemiological studies show that liver transplantation is the second most performed organ transplantation after kidney transplantation. This therapeutic choice represents the ultimate solution, even the reference curative treatment, for a number of serious liver pathologies, the most important of which are severe cirrhosis (resulting from chronic viral hepatitis or excessive chronic alcohol consumption), hepatocellular carcinoma, and acute liver failure. So what are the available options for patients awaiting liver transplantation?
"Two approaches are conceivable," says Professor Francis Navarro, Head of the Hepatic, Biliary, Pancreatic Surgery and Transplantation Department at Montpellier University Hospital. "The first involves the transplantation of a whole cadaveric liver from a donor with brain death," he explains to Ici Beyrouth, on the sidelines of a congress on "Medical-surgical updates around digestive pathologies" organized by the French Hospital of the Levant, in collaboration with the IRCAD International (Research Institute against Digestive Cancer) and Montpellier University Hospital.
"The second option consists of transplanting a part of the liver, either the right lobe or the left lobe, taken from a living donor," continues the French surgeon of Spanish origin. However, he specifies that a primordial condition must be met from the outset: the graft in the recipient must correspond to at least 0.8% of their body weight.
Heavy surgery
Unlike bone marrow transplantation, which requires very close tissue compatibility between the donor and the recipient, liver transplantation is less restrictive in terms of compatibility criteria. "It simply involves blood type," Dr. Navarro emphasizes. The distribution of grafts is thus governed by the ABO system, i.e., the four groups: A, B, O and AB. Conditions are more complex in certain cases, such as hyperimmunized patients undergoing double kidney and liver transplantation, where the situation becomes more complicated. Immunosuppressive treatment is initiated after transplantation to prevent rejection of the new liver by the body.
If liver transplantation seems theoretically within reach due to the less restrictive compatibility requirements, the reality is quite different. According to a study published in March 2022 in the American Journal of Transplantation, only 54.4% of patients in the United States received their graft within the year following their registration on the national waiting list in 2020. "Cadaveric organ donation is not always possible due to cultural, religious, or even dogmatic considerations, as is the case in Southeast Asia, where 95% of liver transplantations are performed from living donors," notes the surgeon. However, he specifies that the living donor is exposed to risks, with a morbidity rate of 9% and a mortality rate of 2%: "It's a heavy surgery, but when done with a robot via laparoscopy, the risk decreases significantly," he points out.
A glimmer of hope
What about these transplantations in Lebanon? The first liver transplantation from a living donor was successfully performed at Hôtel-Dieu de France in July 2000. However, Lebanese archives only mention about twenty cases of liver transplantation in the land of the Cedar. Why is that? "The availability of cadaveric donors seems uncertain in Lebanon for various reasons, while resorting to living donors remains risky in a country where the chain is not yet ready," responds the expert. And he adds, "The introduction of rapid transplantation techniques, i.e., the removal of a liver lobe from a family member, could be a glimmer of hope in Lebanon for patients suffering from cirrhosis or liver metastases." Indeed, a prospective pilot study, called SECA-I, conducted at Oslo University Hospital, reported in 2013 a 5-year overall survival rate of 60% after liver transplantation in 21 patients with unresectable liver metastases from colorectal cancer.
Humanized animal organs
Thanks to the rapid progress in genetics, particularly in the field of genome editing (manipulation of the human genome), a new era is beginning in medicine and biomedical research. The "humanization" of the pig is the most tangible proof of it. By modifying the genetic heritage of these animals, researchers have succeeded in making their organs more compatible with those of humans. And this is to address the serious organ shortage. In January 2022, the very first transplantation of a humanized animal organ took place in the US. David Bennett, then 57 years old, successfully received the genetically modified heart of a pig, when no other therapeutic alternative was available. He survived for two months.
More recently, on March 16, 2024, Richard Slayman, aged 62 and suffering from end-stage chronic kidney failure as well as several comorbidities, was successfully transplanted with a genetically modified pig kidney. He is currently showing positive signs of recovery. However, the durability and effectiveness of this transplantation remain to be confirmed over time. Can we envisage a future for xenotransplantation in the treatment of terminal liver diseases? Professor Navarro seems optimistic: "I am convinced that there is a promising future in this field. The pig represents a particularly promising avenue, being the animal whose organs are closest to those of humans. The next two or three decades will be decisive for this evolution."
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