Introductory Chapter: Liver Transplantation – The Path to a Bright Future!

1. Introduction

1.1 Evolution of liver transplantation

Liver transplantation by all accounts represents the pinnacle of surgical procedures. The reason is that the concept of saving a human life by removing a diseased organ and replacing it with one from another human excites the human imagination, in addition to the fact that the recipient is usually a patient with cirrhosis and portal hypertension, which makes any type of intervention critical. When the first liver transplantation was performed on March 1st 1963 in Colorado, USA, by Thomas E. Starzl, it was a groundbreaking event that shook the world [1]. However, none of the first five patients undergoing a liver transplantation at that time survived longer than 23 days. This brought severe criticism, and if it wasn’t for the tenacious spirit and stubbornness of Dr. Starzl, we would probably not be where we are today. The challenges were numerous during the first decade and included technical considerations, immunosuppression medication to overcome rejection, and the definition of brain death and ability to identify suitable donors and recipients, among others. The latter meant that it was critical to understand what was the best timing for a liver transplant, meaning that if it occurred too early, then it would not signify the best use of the liver graft, and if it occurred too late in the disease progression, then it would not benefit the recipient.

Over time, liver transplantation overcame the initial appearance of an experimental procedure and became the mainstay treatment for a variety of diseases and tumors of the liver. What this meant was that, eventually, it became a victim of its own success, as the increased acceptance by the medical and surgical world led to increased indications and need, which made the donor identification and management the limiting factor. So, the next hurdle to overcome was finding ways to increase the number of hepatic grafts, as well as improve the allocation process. The lack of donors led to the use of hepatic grafts from donors after circulatory death (DCD), from extended criteria (the definition of which is still a matter of significant debate) donors, and the practice of splitting a hepatic graft into two, so that the smaller one could be used for a child and the larger one for an adult recipient. Additionally, there have been, and continue to be, efforts to develop xenotransplantation, with the hope that it would provide an endless supply of donors, although the obstacles there (at least till recently) have been very high, given the immunological and biological differences across different species. These challenges and the difficulty of finding a proper graft for a child in need played a major role in the development of living donor liver transplantation, which represents a big step if we consider that the living donor undergoes a high-risk surgical procedure without any benefit to their health. Living donor liver transplantation evolved at different speeds in various parts of the world, with cultural and religious beliefs playing a significant role. Apart from the issue of finding a donor, given the scarcity of hepatic grafts, the question of proper allocation was just as important. This was addressed over time with an effort to identify an objective manner to prioritize the need and place on the waiting list, as in liver transplantation, the important issue is not how long someone is on the waiting list, but rather how advanced the liver disease is. The advent of the Model for End-stage Liver Disease (MELD) changed the landscape and over time continues to evolve as a very useful tool in prioritizing patients on the list [2].

The continued progress in the development of liver transplantation has led us to today where we are witnessing a further rapid expansion of liver transplantation globally, with certain key aspects, which can lead to a very promising future. Specifically:

1. Increasing number and quality of donors: an important development toward increasing both the number and quality of available hepatic grafts has been the increasing use of machine perfusion in liver transplantation, which is taking over liver transplantation in the last decade. The goal is to improve organ storage as well as organ quality, especially in recipients with extended criteria or suboptimal livers [3]. This is a work in progress as different types of machine perfusion are being used and evaluated, such as normothermic machine perfusion (NMP), hypothermic oxygenated machine perfusion (HOPE), and normothermic regional perfusion (NRP) compared to the more “traditional” static cold storage [4, 5, 6]. Although, the use of machine perfusion has decreased the number of discarded livers, especially in cases such as DCD donors, there still remain a lot of questions in terms of identifying the advantages and disadvantages of the different modalities, or even combinations thereof [7].

2. Xenotransplantation: with the help of genetic scientists, it has been possible to overcome significant immunologic hurdles in xenotransplantation, as shown by the recent groundbreaking efforts, which have renewed the faith in this overall approach [8].

3. The role of technology: technology moves at a lightning speed in our days, as evidenced by the leaps and bounds of artificial intelligence (AI), the increasing use of 3D printing in medicine and surgery, and the introduction of augmented and virtual reality from the lab to the bedside [9]. The technological imperative makes it crucial that future physicians in transplantation not only acknowledge its existence but also actively make an effort to understand it and make the best use of this huge potential.

The developments mentioned above are critical to the future of liver transplantation; however, what has led to them and what will continue to be the driving force in the future is the realization that liver transplantation is truly a multidisciplinary field, where surgery, hepatology, anesthesiology, intensive care, engineering, informatics, ethics, and law are only some of the fields that have collaborated to get us where we are. Acknowledging, appreciating, and further pursuing this collaboration is the path to a bright future!