The liver is reportedly the second most-transplanted organ worldwide. One of the most common liver diseases that would require a liver transplant, up until five years ago, was Hepatitis C. A liver transplant is a surgical procedure that removes a liver that no longer functions properly and replaces it with a healthy liver from a deceased donor or a portion of a healthy liver from a living donor. Like how medical treatments manage diseases, transplantation, whether for the liver, kidney, or heart, replaces a failing or a failed organ.
According to Dr. Rolf Barth, Director of Liver, Kidney and Pancreas Transplantation and Associate Director of the Transplant Institute at the University of Chicago Medicine, clinically today, in the majority of Western countries, the portion of the population needing transplants because of Hepatitis C has been replaced by people suffering from fatty liver disease, or Nonalcoholic Steatohepatitis (NASH). There has also been an increase in alcoholic liver disease, including alcoholic hepatitis.
Dr. Barth highlighted: “Currently, the above mentioned metabolic and alcoholic liver disease indications are higher, with a decrease in the Hepatitis C cases, worldwide. However, Hepatitis C, Hepatitis B, and some autoimmune diseases continue to play a significant role. We also do transplants for people with liver tumors and patients with either unresectable liver tumors (tumors that cannot be surgically removed) or tumors in the context of having some liver disease. The diseased liver does not safely tolerate normal surgical resection, thus leaving transplant as the only potential curative option.”
When asked about what life is like for a patient after a transplant, the doctor emphasized that it’s a second chance at life for many people. He explained that there are two categories of people that get transplanted. There are those who are quite unwell and are “at the top of the waiting list” in a particular region. There are also those who are acutely ill and may die within days or weeks without a transplant. UChicago Medicine has invested in the latest tools to help support these patients with a liver dialysis machine. The medical center also has a dedicated intensive care unit staff of medical and critical care doctors who can help the patients survive those critical days while waiting for the liver. Post-operation, and when patients start to recover, they will find their bodies getting strengthened and gradually get back to fully functional lifestyles. Once they get used to their medicines, it does become life as usual, he added.
“But, once you’re transplant patient, you’re always a transplant patient,” stressed Dr. Barth. “So, they do need to take medicines for the rest of their lives. The liver rejects less than any other organ, immunologically. So, these patients generally need less immunosuppression medications than heart or kidney transplant patients. Some patients take one pill twice a day, which needs to be maintained in the long term.”
There’s another group of patients who are not the sickest on the list. These are people who have liver disease, whether it’s a tumor or complications that have caused them to stop working or be admitted to the hospital at frequent intervals. But they are not at the risk of dying within weeks or months. For these patients, transplant allows them to re-establish normalcy in their lives. Their energy levels increase, and they may start being able to work again if they had to stop because of the disease. “For the right patient nowadays, the transplant will be able to last over 30 years. However, it is dependent on a case-by-case basis. For many people, it’s a return to normal life with the caveat of remembering to take their medications,” he added.
Does COVID-19 impact the liver?
According to Dr. Barth, COVID-19 is not a liver-specific disease, and it doesn’t appear that transplant patients are more susceptible than other cohorts. But there are certain considerations to keep in mind for the transplant patient population. There are hepatic and systematic effects that patients who have COVID-19 may demonstrate.
There is also some evidence that when transplant patients get infected or become symptomatic, they tend to do worse than normal patients.
Recent data published in the New England Journal of Medicine found that transplant patients may not respond to the vaccine antibodies as robustly as other patients. However, it does appear that it’s likely that they’re protected by cellular immunity in different ways. In addition, transplant patients are a little more sophisticated than the average population, the doctor explained. They live with a chronic medical condition of their transplanted organ that requires them to take immunosuppression medications. So, they are more educated about avoiding sick contacts.
He said: “I think, if there was a group that’s already thinking about their vulnerability, it is the transplant patient population. The patients have come to this pandemic with an experience that makes them well prepared in terms of how to deal with some of the things the rest of us are experiencing.”
A lot of times, liver transplantation could be a matter of life and death, which means the surgeries can’t be postponed. But due to the pandemic, several programs in the U.S. had to take a brief pause.
“Our program continued transplanting during the pandemic,” said Dr. Barth. “We did take a break from living donor transplants. But now, we are back into the full speed of getting those transplants scheduled. Now we have the benefit of getting our patients vaccinated. So, for the ones who have diagnosed liver disease and don’t need a transplant urgently, we can vaccinate them first.”
Liver transplant program at UChicago Medicine
One of the biggest challenges is making sure people with liver disease get appropriately referred and start discussions about transplantation early on. The almost three-decade-old transplant program at UChicago Medicine, shared Dr. Barth, has an extensive history of being the first institution to successfully do living donor liver transplants worldwide. In the last few years, the transplant program has been revamped and has recruited worldwide leaders in liver transplantation and medicine. The Transplant Institute is led by Dr. John Fung and Dr. Michael Charlton. Dr. Fung is one of the initial developers of the liver transplantation field and one of the most cited surgical scientists and surgeons in the literature worldwide.
“We have recruited teams particularly oriented to living donor liver transplants for extended indications, including special types of tumors, alcoholic liver disease, nonalcoholic liver disease, and other autoimmune ideologies. The program is in a phase of significant investment, with other health specialties supporting it. It is increasingly looking at what is the next step in the field of transplantation and what are the next indications that will need to be addressed for people who need transplants,” Dr. Barth highlighted.
Some of the success stories of the transplantation program include the first recipient of a living donor liver transplant, who recently celebrated the 30th anniversary of her procedure. The program also receives patients traveling from around the United States and worldwide, especially the Middle East.
UChicago Medicine also has a transplant oncology program, which intersects normal medical and surgical oncology with transplantation. This kind of approach uses strengths from both disciplines to offer transplants to diseases that may not have usually been considered or have historically been attempted with inferior outcomes. It combines oncologic principles and approaches of downstaging tumors, periods of surveillance to understand tumor biology and next-generation sequencing of biopsies to see if there are special targets. Patients can go through a period of new adjuvant therapies, and those that demonstrate favorable responses can then be offered liver transplantation.
Curative therapy
According to Dr. Barth, the future of transplantation revolves around expanding the list of diseases that can be cured through organ transplantation. And then, correspondingly, to increase the number of organs available for transplantation. “For those of us who practice transplant, we view it as the best and curative therapy for a list of diseases,” he stressed.
The doctor said that with continuous improvements in the field, transplantation could be expanded to other diseases. He said that the idea of managing diseases medically versus offering organ replacements for transplantation would continue to show that transplant is, in fact, a superior therapy than these other strategies of disease management.
Today, several new therapies can be used for organs that traditionally had not been used for transplant. For example, UChicago Medicine has recently started a clinical trial of hypothermic organ perfusion for organs donated from deceased donors. In addition, there is work going on in laboratories in the use of organ manipulation and modification, as well as ongoing research in the use of animal organs for transplanting genetically engineered animals. The goal in the long-term, said Dr. Barth, is to increase the organ supply proportionate to the number of patients waiting for transplants.
In conclusion, he said that for people with liver disease, screening is critical. There are therapies available now that can cure liver disease before it becomes end-stage. Therefore, getting access to those therapies at early stages before irreversible damage has occurred to an organ is essential. Likewise, when patients have been diagnosed with cirrhosis, or an end-stage liver disease, getting access to transplant programs and evaluations for therapies is critical.
Dr. Barth is multi-organ abdominal transplant surgeon specializing in living donor kidney and liver transplantation. His clinical practice emphasizes both advanced support and transplantation for critically patients and living donor transplantation for expanded oncologic and other indications. He has pioneered minimally invasive surgery for living kidney donation and has performed over 500 “scarless,” single-port laparoscopic donor nephrectomies. His research interests include novel immunosuppressive therapies, immunologic tolerance, and the use of genetically engineered animal organs for human transplantation (xenotransplantation). In addition, he has investigated transplant tolerance and preclinical models of composite facial and limb transplantation, which resulted in a successful clinical trial in face transplantation.
