Good morning, liver people, and welcome to TLM 2023 from the AASLD. This is a liver transplant debrief. I'm Lorna Dove, transplant hepatologist from the New York Presbyterian Hospital, which includes Columbia University and Weill Cornell Medical Center. I'm here to give you an update on just a few of the hits from Boston. It was a fantastic meeting with thousands of papers presented. In the next 30 minutes, I will discuss just a few of the titles from the liver transplant catalog. I will cover three broad categories. Number one, new frontiers, two, promoting equity in transplant, and three, an update on the basics. What's hot? Dr. Leslie Saxon, leader of the USC Body Computing Center, encouraged us to embrace technology and to transition into a new era of care. She challenged us to not only capture all that is good about technology, but to also engage the patient in the process. Hopefully, this approach will lead to better understanding of health, more adherence, and better outcomes. That theme set the tone for the meeting, and the overflow rooms were dominated by machine learning, artificial intelligence, and telemedicine. Liver transplant was no exception. Many authors presented on topics to show us how to utilize technology to advance the field. In the last year, the use of normothermic machine perfusion has begun to change the face of liver transplant, and it has changed the way we look at donors. Dr. Tang and her colleagues from the University of Pennsylvania captured this by using NUNOS data to evaluate the utilization of the normothermic machine perfusion pump between 2016 and 2022 in the United States. Specifically, they compared the use of the normothermic pump to traditional static cold storage in DCD organs. They found both an increase in the use of DCD organs, shown in pink, and an increase in the percent utilization of the machine perfusion pump, shown along this line, with the most dramatic increase from 2021 to 2022, where pump use increased from 3% to 11%. I anticipate that this will be even higher at the conclusion of 2023. With this, they also noted that the use of the normothermic perfusion pump appears to have expanded the use of donors, and with higher donor risk index patients. This is noted in the box plot, and has been used to expand the use in higher mailed recipients, shown below in this scatter plot. Hopefully they will continue to analyze this data and again present next year as pump use increases across the country. Continuing in the surgical realm, but moving to machine learning, W with his partners at the University of Hong Kong and collaborators in Taiwan, sought to use machine-based learning to predict the likelihood of HCC recurrence after surgery. Their paper was entitled RecurNet, which is the name of the model. A multi-phasic deep learning model on CT is superior to microvascular invasion in predicting hepatocellular carcinoma recurrence after curative surgery. Let's walk through the paper. Histologic demonstration of microvascular invasion is associated with increased risk of early HCC recurrence. However, this does not provide preoperative prognostication, as this data can only be obtained from the surgical specimen. Thus, the goal was to develop a model that could be utilized prior to surgery and predict if a cancer would recur. If successful, this model could help providers know who should potentially receive adjuvant therapy to prevent recurrence. However, I included this paper in the transplant section as I believe that this same technology could be applied to the decisions about transplantation. Knowing a patient could have early recurrence after resection may encourage providers to consider transplant as the better option as opposed to resection. Or in the future, perhaps further development of the model could help predict who recurs after transplantation. Now let's walk through the presentation. They chose 671 patients with histology-confirmed resection HCC from five centers in Hong Kong. Using this data, they trained the program on 536 and then validated that data on another 135 local samples, and then they obtained 560 samples from Taiwan for further validation. The preoperative data chosen was CT data and clinical data, including variables such as age, sex, AST. What they found was that RecurNet achieved excellent diagnostic performance, and it significantly outperformed microvascular invasion as a predictor of recurrence every year post-surgery. In addition, RecurNet was significantly better with a p-value of less than 0.001 in predicting liver-related and all-cause mortality. Now I'll move on to health care equity, which I'm excited to say many investigators in transplant explored this year. The comparison of the liver transplant process to the subway train system was discussed in more than one abstract. The patient takes a journey from organ failure to transplant, but there are many junctions along the way that represent challenges to reaching that final goal. Many investigators explored how to make sure that transplant was available to all by exploring the social barriers that patients encounter at each junction. One place to start is at the beginning. How do you find all the patients that have advanced liver disease? This paper marries both health care equity and technology. Dr. Prince and his group developed and explored the Liver Toolkit, an innovative information technology solution to screen patients in general practice for undiagnosed cirrhosis. This was a two-year multi-center study based in primary care practices throughout central and eastern Sydney. It utilized a novel cloud-based software platform, and the primary aim was to evaluate the effectiveness of the Liver Toolkit in identifying patients in primary care with undiagnosed advanced chronic liver disease. Let's walk through the study. The Liver Toolkit utilized data accessed from the electronic medical record of the primary care practices. De-identified names with results and records were uploaded into the toolkit software. The kit then used APR score, FIB4 score, a diagnosis of NAFL with the presence of a metabolic risk factor, and an elevated NASH fibrosis score. After analysis, names of the patients considered at risk were then downloaded, and patients were re-identified, and a recall list was created. All patients recalled were brought in to undergo elastography, and patients with cirrhosis or advanced fibrosis were then linked to specialty care. Here are the results. Approximately 115,000 patients were in the practice, 32,000 had results available for review. The Liver Toolkit reviewed this group and flagged 703 patients for callback. 25% of them were successfully recalled and had elastography, and with this, 23 patients with newly identified advanced chronic liver disease were linked to specialist care. The system was not perfect. The positive predictive value was 13%, but a start in being able to screen large populations and identify patients who may need to start the transplant journey. If patients are referred for specialty care, evaluated for transplant, and then even listed, have we achieved equity? Well, many continue, many patients continue to have challenges, and investigators are looking at those obstacles. Dr. Strauss and the group from Johns Hopkins noted that during the COVID pandemic, some of their patients appeared to have difficulty having the necessary labs required to be active on the liver transplant list. They decided to explore this and presented racial and ethnic disparities in waitlist maintenance, updating labs, and remaining active. Their hypothesis, social determinants of health disproportionately impact patients, leading to racial disparities in recertifying male labs and remaining active. For those who are not familiar, patients must have labs on a regular schedule that's based on their male score in order to remain active on the liver transplant list. If they miss their scheduled labs, they are penalized by losing their points, can potentially be made inactive, and they can miss an opportunity for transplantation. To evaluate this, they looked at three models. Model one, patients who were either inactive or missed recertification of labs. Model two, patients who were inactive. And model three, patients that merely missed their recertification. What they found was that in every model, Black and Hispanic patients were significantly more likely to be inactive or miss recertification. Clearly, further study needs to be completed to understand the barriers that prevent patients from recertifying labs. With this knowledge, we can develop strategies and solutions to help vulnerable populations maintain their listing status. Now, advancing our knowledge of the basics. Metabolic-associated liver disease dominated much of the discussion at this year's meeting, and this was true in transplant as well. Dr. Younasi presented a paper evaluating the probability of having NASH in patients with a pedocellular carcinoma. Non-alcoholic steatohepatitis has become the most common indication for liver transplantation among candidates with a pedocellular carcinoma in the United States. On this slide, you see that among patients listed for liver transplant, NASH with a pedocellular carcinoma, NASH, which is in the red line, has steadily grown from 9.5% in 2013 to 31.6% in 2022. This is in direct contrast to hepatitis C, which has decreased. The increasing trend for NASH remains significant after adjustment for changes in candidates' age, sex, ethnicity, obesity, and type 2 diabetes. The average magnitude of increase in the proportion of NASH in liver candidates with HCC in 2018 to 2022 was plus 2.8 percentage points per year. In contrast, in patients listed without cancer, alcohol continues to be the number one indication. Patients with alcohol-associated liver disease represented 48% of patients in 2022, followed by NASH or MASH at 27%. As we will see, metabolic syndrome will be a diagnosis that the transplant community will be battling for the next decade. Let's look at this abstract presented by Dr. Serrano entitled Impact of Comorbidities on Liver Transplantation, a Prospective and Multicentric Analysis. 1,400 consecutive patients included on the liver transplant waiting list in 18 hospitals in Spain were analyzed between October, 2019 to 2022. There were comorbidities identified at the time of transplant. Comorbidities were more common in men, which is shown in green, than in women. The most common comorbidities were hypertension and diabetes, and only 8% of the listed patients had no comorbidities. The number of comorbidities was associated with survival after transplant. What they found was that there were clusters of patients that could be characterized by distinct comorbidities, and these clusters had significant differences in post-transplant survival. And specifically, metabolic syndrome is a disease that best characterizes the group with the highest post-transplant mortality. So, do we need to address metabolic syndrome in some way? Some think that we should. Dr. Larson and the Mayo Clinic group presented simultaneous liver transplant and sleeve gastrectomy is a safe surgical option that improves metabolic syndrome and reduces allograft steatosis. All Mayo Clinic transplant sites were included, and they performed 73 simultaneous liver transplant and sleeve gastrectomy starting in 2009. To qualify, the patients had to have a BMI greater than 35. This was a retrospective analysis of the outcome of those patients, compared to 185 patients diagnosed with MASL and with a BMI greater than 30 who had transplant alone in the same period. I am unsure of the additional matching criteria. What did they find? First, patients with liver transplant alone, represented in blue, had no change in diabetes after transplant, but in patients who received the sleeve, the prevalence of diabetes decreased from 43% to 20%, and this was statistically significant. Steatosis recurrence after transplant was present in 39.6% in patients who received liver transplant alone, but only 20% in patients who underwent the sleeve at the time of transplant. Fibrosis recurrence, though more common in patients who received liver transplant alone, was not significantly different between the two groups. BMI decreased approximately 10 points for at least nine years in the patients who received the sleeve. However, despite these described changes, there was no difference in overall survival, graft, or cardiac events between the two groups, so a lot more to learn. Okay, a few odds and ends. An evaluation of the effectiveness of prehab to improve post-transplant survival was undertaken at the University of Pittsburgh, and Dr. Lin presented this paper, Prehabilitation in Liver Transplant Candidates, Improves Frailty Metrics Leading to Improved Survival. They analyzed liver transplant candidates who attended physical therapy consultation between 2018 and 2022. 1,275 patients received a personalized prehab prescription. Using the LFI model, 23% of patients were identified as frail. Frail patients tended to be older, of female sex, and have a higher male, and they were less likely to be transplanted during the study period. Multivariable models, survival models, including a risk model against liver transplant, were fit to investigate the impact of frailty metrics and prehab engagement on mortality, and what did they find? Frailty, as defined by LFI, had a strong association with survival, with non-frail patients having improved survival. In addition, improvement in LFI by at least 0.4 was associated with improved survival. This makes an argument that both assessing and addressing frailty could result in better outcomes. Given both the number of patients transplanted with alcohol-associated liver disease, as identified in the previous study, and the recent change in listing criteria adopted by many centers, we are steadily accruing new data and developing strategies to provide support and care for this population post-transplant. One test often proposed as a monitoring tool is the phosphatidylethanol, or PETH. This multi-center study from the Transplant Research Center entitled Phosphatidylethanol Monitoring of Post-Transplant Alcohol Consumption Among Alcohol and Non-Alcohol-Related Liver Transplant Recipients was presented by Mayan Telus. PETH is a blood biomarker that can detect moderate or heavy alcohol use for up to four weeks following consumption. The time-to-event analysis to compare time to first alcohol use after transplant was performed on three groups. Number one, the standard group were patients who received a liver transplant for alcohol-associated liver disease with greater than six months of sobriety prior to transplant. Group two was early liver transplant. This represents patients with alcohol-associated liver disease who had sobriety for less than six months at time of transplant. And group three are patients who were not transplanted for alcohol-associated liver disease. What did they find? Routine PETH testing revealed that there was no significant difference in time of at least moderate alcohol use after transplant when you compared the standard and the early groups, 102 days versus 76 days. The non-alcohol group did have a significantly lower risk of moderate or heavy alcohol use post-transplant, but it was not zero. This suggests that routine PETH testing may be helpful to identify harmful alcohol use patterns and guide supportive addiction therapy. Now, the use of hep C positive organs has become so frequent that offering these organs may not substantially change wait times. Our success with these organs has been tied to our ability to effectively treat hepatitis C after transplant. Standard protocols in the past have often offered 12 weeks of therapy. The Toronto group has previously described a shortened protocol, and they presented additional data at this meeting. Ongoing experience of implementing the Toronto protocol, an ultra short course of GPE for solid organ transplantation from HCV infected donors to HCV uninfected recipients. Hepatitis C positive donors were offered to 32 kidney, 14 lung, six heart, three pancreas, and three kidney pancreas patients. Some of the lung patients received ex vivo lung perfusion with or without ultraviolet light, which is important as this may decrease hep C RNA. And patients received one dose of medication prior to transplant, and then daily medication for seven days post-transplant. These medications were given either by mouth or by NG tube. What did the follow-up show? So follow-up was for a mean of 125 weeks. SVR 12 was 100%. There were no late viral relapses, no graft losses, and no hepatitis C related complications. This data suggests that not only is the use of hepatitis C positive organs safe, an abbreviated course of therapy may be adequate. I will finish with COVID-19, because though it did not dominate the center stage at the meeting this year, there is still great concern about the impact of COVID-19 on the immunocompromised patient and on transplant. Dr. Sohel looked at predictors of hospital related outcomes of COVID-19 infection in liver transplant recipients in the United States, a nationwide inpatient study. He utilized the 2020 National Inpatient Sample Database to identify liver transplant recipients with COVID-19 hospitalizations who underwent liver transplant either in the index hospitalization or had a history of liver transplantation. This was at the peak of the pandemic. 2,259 adult liver transplant patients with concurrent COVID-19 infection were identified, and they were compared to a group of liver transplant patients without COVID who were also admitted to the hospital. Patients with liver transplant and COVID-19 infection had higher mortality, developed more receptive shock, but no increase in ICU utilization, no increase in mechanical ventilation, and no difference in length of stay when compared to the non-COVID group. On univariate and multivariate logistic regression, COVID-19 infection, septic shock, mechanical ventilation, and ICU were all independent predictors of mortality. Of note, this data predates most of the COVID vaccine data and therapy. Many liver transplant patients are now vaccinated. We need to evaluate trends as the more recent data is released. However, most of us feel much more comfortable with management of COVID-19, and this has prompted the use of donor, utilization of donor organs from patients with COVID-19 infection. And therefore, the next study I will present is Trends in Utilization and Post-Transplant Outcomes in COVID-19-Positive Deceased Donor Liver Transplantation, which was presented by Dr. Wang. This was a retrospective cohort study using data from the UNOS registry to evaluate the use of COVID-positive livers with patient and allograft survival. The population was all adults who underwent deceased donor liver transplant from July of 2020 to July of 2022. The primary exposure was a COVID-positive liver donation. The analysis, this was a propensity score matching for recipients of a COVID-positive liver donation to controls, and there was a generated three-to-one control to cases sub-cohort, and they did a survival analysis to evaluate post-transplant outcomes and compare the two groups. They looked to demonstrate that both transplant and discard of COVID-positive organs increased over the course of the pandemic. But there was no difference in patient and graft survival at one year post-transplant based on COVID status. So this was encouraging that utilization of COVID-positive livers appears to be safe with this preliminary data, and it may increase opportunities for transplantation in the future. With that, I will conclude. I thank you for your attention. We're all thankful that you attended the meeting. We hope you enjoyed the meeting, and we will see you again next year in San Diego.

liver transplant trends

TLM 2023

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machine learning

normothermic machine perfusion

metabolic-associated liver disease

COVID-19 positive deceased donor liver transplantation