Johannesburg, 30 July 2026: The Wits University Liver Transplant Programme has reached its 1000th liver transplant, marking a defining milestone for South African medicine and for one of Africa’s most comprehensive transplant programmes.
A collaboration between Wits Donald Gordon Medical Centre and Charlotte Maxeke Johannesburg Academic Hospital, the liver transplant programme has become a national and regional referral hub for patients across the healthcare system.
Of the 1000 liver transplants, 637 were performed in adults and 363 in children.
Since performing its first liver transplant in 2004, the programme has introduced living donor liver transplantation for both adults and children, expanded expertise in split liver transplantation and ABO (blood group)-incompatible transplantation, pioneered HIV-positive donor liver transplantation, performed monosegment liver transplantation and, most recently, introduced liver machine perfusion technology to help maximise the use of scarce donor organs.
The 1 000th transplant milestone demonstrates what is possible when academic medicine, scientific research, education and healthcare partners work together in pursuit of a common purpose, increasing access to healthcare for all.
Professor Jerome Loveland, Academic Head of Transplantation at Wits, says the programme has continually expanded the boundaries of what is possible through clinical innovation, multidisciplinary expertise, research and academic training in a country facing a severe shortage of donor organs.
“People often see the transplant operation as the defining moment. In reality, it is the culmination of years of expertise and systems development across highly specialised teams. The 1000th transplants reflect the legacy handed to us by those who built the programme, past and present, the extraordinary multidisciplinary expertise that sustains it today and our responsibility to train the people who will carry it forward.”
While the programme celebrates its 1000th transplant, it also highlights one of South Africa’s greatest ongoing healthcare challenges. Many patients continue to wait for life-saving donor organs. Advances such as living donor transplantation, split liver transplantation and liver machine perfusion are helping to expand access to transplantation, but increasing awareness of organ donation remains essential if more patients are to receive the chance of a longer, healthier life.
An international research team led by the Medical University of Vienna reports on a new treatment strategy that has made a kidney transplant possible for a patient with no realistic chance of receiving a suitable donor organ. As the case study demonstrates for the first time, the use of a new drug from the field of cancer medicine can achieve a substantial and sustained reduction in antibodies against potential transplants, a level not previously attained. This significantly improves the prospects of a successful organ transplant even in cases with a particularly unfavourable initial immunological profile. The results have recently been published in the New England Journal of Medicine and could open up new perspectives in transplant medicine.
The new drug Teclistamab is currently used to treat blood cancer (myeloma). It specifically eliminates those cells in the blood and bone marrow that produce antibodies against foreign structures. Due to this unique mechanism of action, the substance has now also come to the attention of transplant medicine: the research team led by Georg Böhmig and Martina Schatzl (Clinical Department of Nephrology and Dialysis, Department of Medicine III, MedUni Vienna) applied it for the first time as part of a case study in a dialysis-dependent patient with a highly unfavourable initial immunological profile.
The 37-year-old had developed particularly pronounced HLA sensitisation following two previous kidney transplants. In this process, the immune system produces antibodies against tissue markers of potential donor organs, known as HLA (Human Leukocyte Antigens). These antibodies significantly limit the availability of suitable organs. In the specific case of the study, the calculated probability (cPRA value) of ever finding a compatible donor kidney for the patient was actually zero. Consequently, the study participant’s name had been on the waiting list for more than twelve years, whilst his condition progressively deteriorated.
Successful transplant after 31 weeks of therapy
Treatment with teclistamab over a period of 31 weeks turned the tide: the drug achieved such a substantial and sustained reduction in antibodies against tissue antigens as is not possible with the methods currently available for HLA sensitisation. “During the course of therapy, HLA markers from donor kidneys, against which there had previously been strong antibody reactions, were gradually classified as acceptable,” reports lead author Martina Schatzl. Eventually, a suitable organ was found and successfully transplanted. “The patient is doing very well today; his kidney function is excellent, and he no longer needs dialysis,” adds study leader Georg Böhmig.
Further studies on benefits and risks needed
20 to 30 per cent of patients on the waiting list for donor kidneys are affected by significant HLA sensitisation, some of whom have no chance of receiving a suitable organ. Existing procedures for so-called desensitisation aim to reduce the number of antibodies prior to transplantation, but are only effective to a limited extent and for a short period. The treatment approach described in the case study, by contrast, directly intervenes in antibody production and sustainably reduces the immune response over a longer period. “This could herald a paradigm shift in transplant medicine and open up new prospects for a group of patients who have been particularly disadvantaged until now,” says Böhmig.
Detailed immunological results from the current case study also suggest that the new treatment strategy might also be applicable in xenotransplantation – that is, the transplantation of organs from genetically modified pigs – as well as in blood-group-incompatible transplants. “Looking ahead, an extension to other forms of organ transplantation, such as heart transplantation, as well as use in the post-transplant setting to treat antibody-mediated rejection reactions, also seems conceivable,” says Böhmig. However, before the new treatment strategy can be used in clinical practice, its benefits and risks must be systematically investigated. A study of this kind is already being planned at MedUni Vienna.
Human kidneys sell for up to £150 000 on the black market, but donors receive as little as £1000. Dr Saradamoyee Chatterjee exposes the criminal syndicates exploiting the desperate on both sides of the illegal organ trade, and asks how we can stop them.
Slums are a goldmine for organ traders. The brokers exploit people who are trapped in poverty and debt, and lure them into selling their kidneys.
Dr Saradamoyee Chatterjee
How much does a human kidney cost on the black market? It depends on who you are in the transaction.
Buyers can pay between £60 000 and £150 000. But donors only receive between £1000 and £7500, if they are lucky.
Where does the rest of the money go? The lion’s share goes to the organ brokers: criminal organisations who act as middlemen between donors and buyers.
These syndicates are sophisticated, exploitative, and international.
“One racket, operating from Israel, brought together Brazilian donors with American buyers, with the transplant taking place in South Africa.” So says Dr Saradamoyee Chatterjee, Bye-Fellow and Director of Studies in Land Economy at Lucy Cavendish College.
Chatterjee unpicks the illegal trade of human organs. She gives voice to the desperate players trapped inside its transactions, and suggests ways to stamp it out.
The organ bazaars
Beginning in the 1950s, science radically improved the success rate of human organ transplantation. Researchers found ways to suppress the immune response of the recipient, so that new organs are not rejected. Transplants now have a high degree of success between strangers, provided that donors and recipients match in blood and tissue type.
Kidneys are by far the most commonly transplanted organ, but transplants of heart, lungs, liver lobes and corneas are also possible.
In countries like India, Pakistan and the Philippines, these advancements initially led to completely unregulated human organ markets. Whichever country had the fewest regulations attracted international patients.
“In the 1980s, these countries were like an organ bazaar,” Chatterjee says. “Patients from the Middle East, UK and USA flocked to get their transplants done.”
Currently, only Iran has a legalised system for paying donors for their organs. Everywhere else relies on legal means, like organ donor lists, or illegal ones, which are still rampant in some countries. The persistence of organ trafficking reflects the desperation on all sides of the transaction.
The need for healthy organs is ever-increasing. Modern ‘lifestyle’ diseases such as diabetes and hypertension lead to kidney failure. Among the 2 current treatments – dialysis and organ transplantation – the latter significantly enhances the quality of life. Many people wait decades on donor lists and will do anything for a healthy organ.
Among slum-dwellers and asylum seekers, there is both a supply of valuable organs and the desperation required to part with them.
Here is where the middlemen come in, servicing an unsavoury gap in the market.
The sellers
Chatterjee travelled to Mumbai, Delhi, Chennai and Kolkata to seek out people with first-hand knowledge of the organ trade. In these cities she found a network of medical professionals, transplant coordinators, buyers and donors willing to share their views.
“Slums are a goldmine for organ traders,” Chatterjee says. “The brokers exploit people who are trapped in poverty and debt, and lure them into selling their kidneys.”
Many people are in need of a lump sum to escape dire circumstances – the organ traders supposedly offer that.
Once a broker gets a kidney, the sellers seldom receive the promised compensation and the vital post-operative care. Even the nominal fee would not provide any relief from poverty.
“One woman I spoke to was a cleaner for weddings,” recalls Chatterjee. “She sold her kidney to save the life of her husband. He’d fallen into debt after buying a tuktuk via a money lender, and couldn’t afford the interest payments. In the end, she only received half the offered price for her kidney.
“She was left weakened, deeply disappointed, and regretful of the whole organ-selling experience.”
In matching sellers with buyers, the syndicates respond to pleas for organ transplants on social media.
To dodge India’s prohibitions, the syndicates exploit loopholes in the law, including the forging of fake backstories. They generate false documents and testimonies to convince doctors and clinicians that 2 strangers know each other.
The transplant can then take place as if it were happening legally – as an agreement between friends or family, without money changing hands. These tactics make it difficult for doctors to detect potential exploitation.
The buyers
Organ trades are a bad deal for buyers too. Both the buying patients Chatterjee interviewed died shortly after their operations.
“In one case, the broker took payment before providing a mis-matched donor,” Chatterjee says. “In the second case, a female doctor saw that her new husband’s kidneys were failing. She placed an advertisement in the local newspaper, and a broker responded. But on the day of the planned transplant, the donor ran away.”
Operating with no regulation, the middlemen don’t uphold medical standards. They often don’t screen donors for existing conditions, exposing recipients to blood diseases like HIV or hepatitis.
The proliferation of lifestyle diseases in massive populations means that the organ trade isn’t only for the super rich: buyers only need to be rich relative to the poverty-stricken sellers.
Both of the buyers Chatterjee spoke to came from the middle class. They were compelled to borrow money from their relatives to pay the broker.
How can we make things better?
Meaningfully reducing the illegal trade of human organs requires action on many fronts.
Reducing the gap in supply means encouraging more legal donations. Other countries have focused on deceased donations, where people donate their organs after death. In Spain, everyone is an organ donor by default, meaning they have the world’s highest deceased donors rate (49 per million people; by comparison, India has only 0.77).
India claims to be tackling the black market with increased regulations and harsher sentences for perpetrators. Information campaigns targeting potential sellers should warn people about the dangerous middlemen. Further exposure of the black market by researchers like Chatterjee and Dr Sean Columb may also prevent people from being dragged into it.
On the demand side, societies need to properly fund their citizens’ healthcare. More successful countries focus on the prevention of lifestyle diseases that are leading causes of renal failure.
Encouraging people into healthier lifestyles – with fewer carbohydrates and more exercise – would decrease the prevalence of conditions like diabetes. Better screening programmes would also encourage patients to adjust before their condition deteriorates, reducing the demand for new organs.
“Organ traffickers exploit the vulnerabilities of both the donors and buyers,” says Chatterjee. To wipe out the middlemen, we need to make people on all sides of organ transplantation less vulnerable and more resilient.
L-R – Dr Bilal Bobat, Professor Jerome Loveland, Dr Sharan Rambarran and Dr Dinen Parbhoo, the transplant team at Wits Donald Gordon Medical Centre alongside the liver perfusion machine, the first of its kind to be implemented on the African continent.
Johannesburg, 12 June 2026:For a patient waiting for a liver transplant in South Africa, the hardest part is not the surgery. It is the wait and the knowledge that an organ may never come. In a country facing severe organ shortages, every decision to accept or decline a donor liver carries immense weight and every viable organ that goes unused represents a lost opportunity to save a life.
At the centre of changing this reality is the Wits Donald Gordon Medical Centre (WDGMC), home to one of the leading liver transplant programmes in Africa and a unit internationally recognised for its contribution to specialised transplant care, research and surgical training. Having performed over 1 000 liver transplants, the programme represents decades of expertise, innovation and collaboration.
Now, WDGMC, in partnership with Surgeons for Little Lives and with support from key corporate sponsor Weelee, has introduced a state-of-the-art liver perfusion machine, becoming the first transplant centre on the African continent to implement this technology for liver transplantation.
This technology keeps donor livers viable outside the body while clinicians assess, monitor and actively improve the condition of the organ before transplantation. By allowing transplant teams to better maintain organ viability, the machine has the potential to increase organ utilisation, reduce complications and improve transplant outcomes for patients who may otherwise not survive the wait.
“As a transplant programme, our responsibility extends far beyond the operating theatre,” says Professor Jerome Loveland, Head of Solid Organ Transplantation at WDGMC. “This technology will help us better assess donor organs and increase the number of livers that can safely be transplanted, whilst simultaneously improving results. In a country where every donor organ matters, this will have a significant impact on organ utility and patient outcomes.”
South Africa’s transplant programmes continue to achieve strong outcomes despite operating within a severely resource-constrained environment and against the backdrop of ongoing organ shortages. As a result, transplant teams are often required to make difficult decisions under significant pressure.
“This technology changes the level of information we have available before transplantation. Traditionally, organs are preserved on ice and assessment is limited. Machine perfusion allows us to monitor how the liver is functioning outside the body. Beyond the valuable information it provides, the machine has the ability to resuscitate the liver by delivering oxygen to the liver cells, creating the best metabolic environment outside the body. This helps us make more informed clinical decisions and potentially increases the number of organs that can safely be transplanted,” says Dr Sharan Rambarran, Transplant Surgeon at WDGMC.
The introduction of the machine is also expected to contribute to reduced post-operative complications, shorter hospital stays and improved recovery outcomes.
“Too many patients in South Africa deteriorate while waiting for a transplant because there are simply not enough donor organs available,” says Dr Bilal Bobat, Transplant Hepatologist at WDGMC. “Anything that helps us safely expand organ utilisation has the potential to directly impact survival and quality of life for patients and families facing end-stage liver disease.”
“Weelee is always looking for opportunities to contribute to causes that create real and lasting impact,” says Errol Levin, CEO of Weelee. “Supporting advancements in liver perfusion technology aligns perfectly with our commitment to innovation that improves lives. This ground-breaking initiative has the potential to save countless lives and we are proud to be associated with a project of such significance.”
WDGMC plays a unique role within South Africa’s healthcare system. As a private academic hospital affiliated with the University of the Witwatersrand, the Centre combines highly specialised clinical care with academic medicine and collaboration across both the private and public healthcare sectors.
While the technology represents an important advancement in liver transplantation, clinicians stress that increasing organ donation awareness remains critical to improving access to life saving transplants in South Africa.
For the transplant teams, this marks not only a clinical advancement but the beginning of a broader effort to continue strengthening transplant medicine in South Africa.
Changes in personality following a heart transplant have been noted pretty much ever since transplants began. In one case, a person who hated classical music developed a passion for the genre after receiving a musician’s heart. The recipient later died holding a violin case.
In another case, a 45-year-old man remarked how, since receiving the heart of a 17-year-old boy, he loves to put on headphones and listen to loud music – something he had never done before the transplant.
A recent study suggests that heart transplant recipients may not be unique in experiencing personality changes. These changes can occur following the transplantation of any organ.
However, there is some evidence to suggest that these personality changes aren’t all psychological. Biology may play a role, too.
The cells of the transplanted organ will perform their expected function – heart cells will beat, kidney cells will filter and liver cells will metabolise – but they also play a role elsewhere in the body. Many organs and their cells release hormones or signalling molecules that have an effect locally and elsewhere in the body.
The heart seems to be most commonly associated with personality changes. The chambers release peptide hormones, including “atrial natriuretic peptide” and “brain natriuretic peptide”, which help regulate the balance of fluid in the body by affecting the kidneys.
Around two hundred heart transplants are performed in the UK each year. VesnaArt/Shutterstock
They also play a role in electrolyte balance and inhibiting the activity of the part of our nervous system responsible for the fight-or-flight response. The cells in charge of this are in the hypothalamus – a part of the brain that plays a role in everything from homeostasis (balancing biological systems) to mood.
So the donor organ, which may have a different base level of hormones and peptide production from the original organ, could change the recipient’s mood and personality through the substances it releases.
It has been shown that natriuretic peptide levels are higher following transplantation – and never return to normal. Although some of the elevation is probably a response to the trauma of surgery, it may not account for everything.
Memories stored outside the brain
The body stores memories in the brain. We access them when thinking or they can be triggered by sight or smell. But memories are basically neurochemical processes where nerves convey impulses to each other and exchange specialised chemicals (neurotransmitters) at the interface between them.
While in transplant surgery, many of the nerves that govern the function of the organ are cut and are not able to be reattached, this doesn’t mean that the nerves within the organ do not still function. In fact, there is evidence that they may be partially restored a year after surgery.
These neurochemical actions and interactions could feed into the nervous system of the recipient, enacting a physiological response that then affects the recipient’s personality according to memories from the donor.
One thing it does is stimulate immune responses. These immune responses may be enough to trigger personality changes as long-term, low-level inflammation is known to be able to change personality traits, such as extroversion and conscientiousness.
Whichever mechanism, or combination of mechanisms, is responsible, this area of research warrants further investigation so that recipients can understand the physical and psychological changes that could occur following surgery.
The public health sector serves roughly 84% of South Africans, yet per-person spending in private healthcare is around five times higher. The National Health Insurance (NHI) is designed to change that equation. As President Ramaphosa stated, the right to healthcare “cannot depend on where you were born, how much you earn or where you live.”
For patients with blood cancer and blood disorders, that promise could not be more urgent. On World Health Day 2026, Palesa Mokomele, Head of Community Engagement and Communication at DKMS Africa, says this is an opportunity to ask whether the NHI is being designed to reach them. “Blood cancer and blood disorder patients depend on highly specialised treatment pathways – exactly the kind the NHI has an opportunity to strengthen. They cannot be an afterthought in the benefit package conversation.”
The NHI Act was signed into law in May 2024 but has not yet commenced, with key constitutional challenges set to be heard in May 2026. Despite legal uncertainty, the government has been clear that foundational work will continue.
The Reality on the Ground
Stem cell transplantation is one of the most effective treatments for blood cancers and blood disorders, and among the most resource-intensive, requiring specialist physicians, trained nurses, dedicated infrastructure, and in 70% of cases, a matched unrelated donor (MUD).
The capacity to deliver these treatments is already under severe strain. Just 25% of South Africa’s oncologists serve more than 75% of the population. Long treatment delays, limited resources, high patient volumes, and advanced disease at presentation make for a deeply challenging environment.
“What we see is a system doing its best under enormous pressure,” says Mokomele. “The NHI has a real opportunity to address those structural gaps, but it requires deliberate investment where the need is greatest.”
What Universal Coverage Must Include
The NHI benefit packages for the treatment of blood cancer and disorders have yet to be finalised. With South Africa projected to see a 78% increase in cancer incidence by 2030, whether those packages cover the full cost of finding, matching, and transplanting an unrelated donor will be a test of whether universal health coverage means what it says.
“We are not here to debate the merits of the NHI,” shares Mokomele. “We are here to make sure that when it is implemented, it works for every patient. The full treatment pathway must be funded, and the clinical infrastructure to deliver it must be in place.”
President Ramaphosa has called for genuine partnerships between the public and private health sectors, academic institutions, NGOs, and communities. “That vision of cross-sector collaboration reflects exactly how we believe this challenge must be met,” notes Mokomele.
A Blueprint for Access
DKMS Africa’s Access to Transplant programme offers a practical example of barrier-free access in the public sector. Working across six provinces, it aims to invest in infrastructure upgrades at public hospitals, training for specialist nurses and mobilises its global network to collaborate with physicians, and patient support services addressing practical barriers, such as transport and housing, that often cause patients to abandon treatment.
“When you remove barriers systematically, outcomes improve,” points out Mokomele. “Each barrier removed is a patient who makes it to transplant. That is the model the NHI needs to learn from and scale.”
The organisation is also preparing for a more centralised system, ensuring its programmes can integrate into national frameworks while maintaining global standards – through early diagnosis education, donor registry diversification, stronger referral pathways, and local research capacity.
Your Health System, Your Voice
The decisions being made about the NHI benefit package today will shape healthcare for decades. Young South Africans will inherit both the growing burden of disease and the system designed to address it.
“World Health Day is a reminder that universal means everyone,” concludes Mokomele. “We are asking young South Africans to support us in uniting towards a healthcare system that works for everyone.”
Monthly infusion could replace daily drug regimen with a less toxic treatment that improves renal function.
Photo by Robina Weermeijer on Unsplash
Anew study offers hope that kidney transplant patients could one day have a monthly treatment instead of multiple pills every day. The new treatment also may reduce side effects and increase the lifespan of the donor organ.
Currently, patients who have had a kidney transplant must take a cocktail of pills every day for the rest of their lives. These standard immunosuppressants prevent the immune system from attacking the new organ, but over time may damage kidney function and become less effective.
Plus, standard immunosuppressants are also lead to diabetes, hypertension, high cholesterol, and weight gain that can lead to transplant patients skipping doses, noted the study’s first author Flavio Vincenti, MD, professor of medicine and surgery in the Division of Nephrology at UC San Francisco. Other side effects include fatigue, muscle weakness, sexual dysfunction, hair loss, and sleeplessness.
Patients showed improvement
In the phase 2 pilot study, 23 patients received infusions of belatacept and dazodalibep, proteins that disrupt the immune system’s attack on the new organ but that do not affect non-immune cells the way standard treatment does.
Kidney function improved in all patients who completed the study and was similar for those who experienced organ rejection. No patient experienced rejection due to antibodies produced by the immune system, which is a major cause of transplant failure. Results were published Feb. 3 in the American Journal of Transplantation.
“We would hope to see better medication compliance with the new regimen since it does not involve taking multiple medications every day,” Vincenti said.
Study patients received standard immunosuppressants at first, but these were discontinued by day 28 in favour of the infusions for the remainder of the 48-week study.
Two of the first three patients experienced organ rejection, which was effectively treated and the rejection reversed. Drug frequency and dosing were revised in response for the remaining patients, 13 of whom completed the study. Seven patients withdrew due to acute kidney rejection, side effects, or for unspecified reasons.
The next phase of the study will determine if these early findings are replicated in a large patient pool, said senior author Allan D. Kirk, MD, PhD, professor of surgery at Duke University School of Medicine.
“We hope that most patients can be spared the toxic effects of immunosuppressants, which would be reserved for those with certain high-risk factors,” said Kirk.
When Karina Ledesma’s kidneys failed in high school, she was told she’d need a transplant – and a lifetime of immunosuppressive drugs to keep it working. But thanks to an experimental UCLA clinical trial, she’s now living with a kidney donated by her sister and no longer needs daily medications to protect it.
“It was such a relief to finally throw all the drugs away,” said Ledesma, 26. “I didn’t need to keep them here. I didn’t need to see them every day as a reminder. Tossing them all out was just a really great feeling.”
For nearly a year after her transplant, and before enrolling in the trial, Ledesma experienced troubling side effects from the immunosuppressive medications – insomnia, burning sensations in her fingers and toes and the constant need to plan her day around taking pills at 8am and 8pm.
Now she’s finally free from those burdens. Ledesma has been off her medications for just over a month, and her sister Rosa Rivera, 28, who donated the kidney, supported her through every step of the journey.
More patients may soon have the same opportunity. UCLA’s Dr. Jeffrey Veale has received a $6.7 million grant from the California Institute for Regenerative Medicine to expand the clinical trial that helped Ledesma.
His study explores delayed immune tolerance, which involves infusing donor-derived blood stem cells months or even years after a kidney transplant to retrain the recipient’s immune system with the aim of eliminating the need for lifelong immunosuppressive drugs currently required to prevent organ rejection.
Veale and his team have already demonstrated early success with this approach, focusing solely on patients with a close-sibling match who had their transplant within the last five years. Starting in January 2026, the clinical trial will open to patients who have had kidney transplants up to 20 years ago.
Veale’s method works like this: After infusion, the donor stem cells integrate into the recipient’s bone marrow and immune system, creating a mixed population of donor and recipient immune cells — a state known as chimerism. This helps the recipient’s immune system recognize the transplanted kidney as “self,” reducing the risk of rejection and eliminating the need for ongoing immunosuppressive medications.
Of the six patients treated in the phase 1/2 trial to date, three are completely off immunosuppressive drugs, and the others are on a lower dose or successfully tapering.
“This could be the difference between managing end-stage renal disease as a chronic condition and actually curing it,” said Veale, professor of urology at the David Geffen School of Medicine at UCLA and a member of the UCLA Broad Stem Cell Research Center. “A kidney transplant takes recipients most of the way there, but patients say being able to get off immunosuppressive drugs feels like truly being cured.”
Expanding the trial
The new grant will fund the enrollment of 10 additional patients in the trial and support research into the science behind immune tolerance, helping Veale and his team identify the biological mechanisms that make tolerance possible and uncover biomarkers that could predict which patients are most likely to benefit.
The clinical trial is currently only open to patients who have received a kidney donation from a well-matched sibling. Veale hopes that by understanding how tolerance occurs, he and others can pinpoint ways to make it possible in a broader range of donor-recipient types — and in more kinds of organ transplant cases.
“Right now, only a select group of patients qualify for this therapy,” said Veale, who is also director of the UCLA Kidney Exchange Program. “But if we can understand why tolerance works at the cellular level, we may be able to offer it to patients with less well-matched donors – or even extend it to liver and other transplants. That’s what makes this research so exciting. It’s not just about improving outcomes – it’s about unlocking immune tolerance for many more patients.”
Freeing more patients from the burden of immune suppression
Immunosuppressive medications, while essential for transplant success, come with serious — and sometimes life-threatening — side effects including infections, cardiovascular disease, diabetes and cancer. Ironically, they can also cause damage to the very organ they’re meant to protect.
“These immunosuppressive drugs have not changed in decades,” Veale said. “They’re expensive, impair the recipient’s quality of life and decrease graft survival. Once patients start taking them, it’s just a matter of time until they’ll need another transplant.”
Approximately half of all kidney transplants fail within 15 years and many of the 90,000 people currently waiting for a kidney in the U.S. are heading for their second, third or fourth transplant.
Delayed tolerance could help turn the tide. Unlike earlier protocols that required simultaneous kidney and stem cell transplants, Veale’s method opens up immune tolerance for patients who received a kidney transplant years ago.
This not only makes it possible to treat patients who received their kidney transplant elsewhere but also enables the stem cell infusion to take place on an outpatient basis, without placing strain on hospital beds and resources.
Importantly, the delayed protocol opens the door for tolerance beyond kidney transplant, where the recipient can recover from their major surgery prior to receiving conditioning treatment and donor stem cell infusion.
“The beauty of doing it in a delayed fashion is that it takes all the pressure off the hospital,” said Veale. “The transplant has already occurred, whether it was done at UCLA or in another part of the world. Now the patient just comes in for an outpatient conditioning regimen and stem cell infusion. They get their treatment in the morning and are out and about in the afternoon. That’s what makes it so scalable.”
Understanding why tolerance works
Still, more research is needed to fully understand why delayed tolerance works and which patients are most likely to benefit.
Veale’s team will use the CIRM funding to analyse blood and tissue samples from trial participants to look for clues: changes in immune cell populations, cytokine profiles or signs of donor cells persisting in the organ itself. These insights could help researchers predict who will respond best to the protocol and guide the design of future trials involving mismatched pairs.
“With this funding, we can find out why tolerance works. We really don’t fully understand the immunology behind it,” Veale said. “For example, we’ve seen patients lose all signs of donor stem cells over time and yet remain tolerant and off their medications. That tells us something deeper is happening – maybe the donor stem cells re-educate the recipient’s immune system and leave a footprint we can’t yet detect. This grant gives us a chance to finally study what’s going on and learn how to replicate it in more patients.”
Ultimately, Veale hopes the research will help shift the transplant field’s focus from preserving organ function to preventing long-term harm – not just keeping donated kidneys working, but keeping recipients healthy and medication-free.
Patients who took herbal or dietary supplements found to have lowest likelihood of survival
Photo by Myriam Zilles on Unsplash
A newly developed tool, called the DILI-Inpt prognostic score, can predict patients with drug-induced liver injury who are unlikely to survive without a liver transplant.
In study results published in ClinicalGastroenterology and Hepatology, the DILI-Inpt prognostic score outperformed existing systems in identifying which hospitalised patients with severe idiosyncratic drug-induced liver injury were unlikely to recover on their own.
“We have struggled for many years to identify which patients with severe DILI may need to be evaluated for emergency liver transplantation, versus recovery with supportive care,” said Robert Fontana, MD, Michigan Medicine hepatologist, professor of internal medicine and the study’s senior author.
“The stakes are high. And it is made even more a difficult due to the small number of prior cases we have seen. This study provides important data for all of us to use and help manage our patients.”
The acronym DILI refers to idiosyncratic drug-induced liver injury, an uncommon condition caused by a variety of drugs and herbal and dietary supplements.
While most patients who experience such liver injuries recover after discontinuation of the culprit drugs, some advance to acute liver failure and may require liver transplantation.
The DILI-Inpt prognostic score aims to better assess such patients so that they can be more quickly sent to a liver transplant centre or placed on the waiting list.
This study used data from 305 adults from 1998 to 2019, enrolled in a national database of acute liver failure and acute liver injury patients. The drugs that induced liver injuries in these patients varied and included antimicrobials (42.6%), herbal-dietary supplements (16%) and psychoactive drugs (9.8%).
After 21 days, 110 patients (36%) spontaneously survived – ie, recovered on their own after discontinuing the drug – while 115 required liver transplant and 80 died. For these 305 patients, a variety of tests results were analysed, including total bilirubin, serum ALT and creatinine values.
Using multivariable logistic regression modeling, DILI-Inpt prognostic score was developed to predict which patients were mostly likely to require liver transplant and at highest risk of death. The Area Under the Receiver Operating Characteristic Curve for DILI-Inpt prognostic score was 0.86 and significantly higher than that of MELD (0.79 AUROC score) and King’s College Criteria (0.63).
These results suggest that the DILI-Inpt prognostic score, which is composed of two readily available blood tests (total bilirubin and INR values) and two clinical parameters (encephalopathy grade and use of herbal products), better predicts which patients will not spontaneously survive than these existing scoring systems.
Of note, the diagnosis of drug-induced liver injury is frequently delayed or missed by the need to exclude more common causes of liver injury and its low incidence.
Since DILI patients have a low likelihood of recovery, there is an urgent need to quickly identify which patients might require liver transplant.
“Another important finding in our study was that patients with herbal and dietary supplement hepatotoxicity had the lowest likelihood of survival and that the proportion of herbal cases was increasing over time in the United States,” Fontana said.
“Our data indicates that further research as to why and how botanical products may lead to potentially severe liver injury in otherwise healthy people is needed.”
New Northwestern Medicine study provides answers and drug targets
Photo by Natanael Melchor on Unsplash
More than 50% of lung-transplant recipients experience a rejection of their new lung within five years of receiving it, yet the reason why this is such a prevalent complication has remained a medical mystery.
Now, a new Northwestern Medicine study has found that, following transplant and in chronic disease states, abnormal cells emerge and “conversations” between them drives the development of lung damage and transplant rejection.
These findings not only help answer why rejection occurs, but they also have spurred immediate exploration of new drugs to treat transplant rejection and other lung-scarring diseases.
“Chronic lung-transplant rejection has been a ‘black box.’ We knew it happened but did not exactly know why,” said corresponding author Dr Ankit Bharat, professor of thoracic surgery at Northwestern University Feinberg School of Medicine and executive director of the Northwestern Medicine Canning Thoracic Institute. “Our study provides the first comprehensive cellular and molecular roadmap of the disease.”
The study was published in JCI Insight.
Leading cause of death after the first year of transplantation
Surgeons perform approximately 3000 to 3500 lung transplants each year in the U.S., and more than 69 000 have been performed worldwide to date. Chronic lung allograft dysfunction (CLAD), which encompasses several manifestations of chronic lung rejection, remains the leading cause of death after the first year of transplantation. There currently are no effective treatments for CLAD once it develops, leaving patients with only one option: re-transplantation.
In the new study, after evaluating almost 1.6 million cells, scientists distinguished between abnormal cells from the donor lung versus cells from the recipient’s own immune system. They discovered the donor-derived structural cells and recipient’s immune cells talk to each other in harmful ways that perpetuate lung damage. The findings could lead to new drug targets and provide insights that could help patients with various lung-scarring diseases, not just transplant recipients.
Comparing rejection to other scarring lung diseases
The scientists discovered a rogue cell type (KRT17 and KRT5 cells) that drives lung scarring across multiple diseases, including idiopathic pulmonary fibrosis, interstitial lung disease, COPD, COVID-19 lung damage and transplant rejection. By integrating data from this array of scarring lung diseases, the scientists created the first comprehensive reference map showing which molecular features are shared across conditions and which are unique to each disease.
“By comparing chronic rejection to other scarring lung diseases, we identified both shared and unique features,” said Bharat, who also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This means treatments developed for one condition might help others. The benefits extend far beyond transplant patients.”
The scientists also identified previously unrecognised cell populations in rejected lungs. These include “exhausted” T cells that remain activated but dysfunctional, and “super-activated” macrophages that promote inflammation and scarring.
Lastly, the scientists developed new computational methods to analyse data from multiple studies together, overcoming technical barriers that previously prevented this kind of comprehensive analysis, Bharat said.
New drug targets identified
The scientists pinpointed specific genes and signaling pathways (like PDGF, GDF15 and TWEAK) that drive scarring, which allows them to identify potential targets for new drugs, Bharat said. Some existing medications, such as nintedanib, and pirfenidone, which are approved (in the US) for other lung diseases, might be repurposed for transplant rejection, he said.
“The findings have immediate translational potential,” Bharat said. “We’re already exploring therapeutic strategies based on these discoveries.”
Broad impact on pulmonary fibrosis
While addressing CLAD was the main focus of the paper, this research has major implications for understanding and treating all forms of pulmonary fibrosis, Bharat said.
“The molecular pathways and cell types we identified are relevant to conditions affecting hundreds of thousands of patients with various lung-scarring diseases, not just transplant recipients,” Bharat said. “This work essentially provides a ‘Rosetta Stone’ for understanding lung scarring regardless of the initial trigger.”
