Deceased Donor Liver Transplantation Recipients Research Articles

Evaluating the yield of digital single operator cholangioscopy in posttransplant biliary strictures after unsuccessful guidewire placement with ERCP.

Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D-SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods. This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased-donor liver transplant recipients undergoing D-SOC for biliary strictures who have failed conventional methods to achieve biliary access were included. Between July 2017 to April 2022, eighteen patients underwent D-SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D-SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D-SOC. In two of these patients, use of D-SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D-SOC cholangitis. D-SOC is effective at achieving guidewire access in post-liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery.

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

Changes in Criteria for Indication of Deceased Donor Liver Transplant Recipients

Changes in Criteria for Indication of Deceased Donor Liver Transplant Recipients

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

A305 ANONYMOUS LIVING LIVER DONATION IMPROVES ACCESS FOR MEDICALLY UNDERSERVED CHILDREN IN NEED OF LIVER TRANSPLANTATION

Abstract Background Since our first pediatric anonymous non-directed live donor liver transplant (A-LDLT) performed in April 2005, 62 children have undergone live donor liver transplant (LDLT) with an anonymous non-directed graft. Anon-LDLT organs being allocated as per our deceased donor liver transplant (DDLT) wait list. Aims To evaluate clinical outcomes, recipient characteristics and social determinants of health of pediatric recipients of A-LDLT in comparison to those who received a directed LDLT (Dir-LDLT) and DDLT. Methods Retrospective analysis of all recipients of LDLT performed between January 2005 and March 2023. Demographic and clinical data included age, sex, race, ethnicity, single-parent households, primary diagnosis, recipient blood type, time on waiting list, post-LT intensive care unit (ICU) length of stay (LOS), time to extubation, and post-transplant comorbidities were assessed as covariates. A comparative analysis was conducted between children receiving A-LDLT, Dir-LDLT versus DDLT. Results A total of 422 (50% male, 57% white, 23% Asian, 7% Black, 5% indigenous) childrenunderwent LT during the study period. Biliary atresia (40%) and metabolic diseases (19%) were the commonest primary indications. A-LDLT was done in 62 children (15%) with no directed donor options. Dir-LDLT was in 174 children (41%). Of 186 DDLTs (44%), 25% were split grafts, 26% reduced, and 49% whole liver grafts. In A-LDLT recipients, the primary diseases were more frequently characterized by metabolic disorders (31%), while the incidence of acute liver failure was notably lower (0%). Recipients of Anon-LDLT were more often Indigenous recipients in comparison to Dir-LDLT or DDLT recipients (p=0.044). Anon-LDLT recipients were more frequently living in single parent households (18% vs 3% vs 10%, pampersand:003C0.001) and to require interpreter assistance (11% vs 3% vs 0.5%, pampersand:003C0.001) (Table), compared to children who received Dir-LDLT or DDLT. Median time on the wait list was longer for Anon-LDLT (92 days) compared to Dir-LDLT (62 days) and DDLT (72 days) recipients (p=0.004). Post-LT ICU LOS, time to extubation, other post-LT complications or patient prognosis were better in the A-LDLT and Dir-LDLT recipients than DDLT recipients. Conclusions This retrospective analysis of 422 children undergoing LT at a single institution confirms excellent patient and graft survival for A-LDLT recipients. Patients from Indigenous communities, single parent and households where English is a second language, are more frequently the beneficiaries of Anon-LDLT grafts. Anon-LDLT, as utilized in this single center analysis, benefits medically underserved pediatric patients who otherwise have limited access to the advantages of LT. Funding Agencies None

Use of 50 years or older donors in septuagenarian recipients for liver transplantation: Potential to expand the donor pool: Old livers for old transplant recipients

BackgroundWhile younger donors have better liver transplant (LT) outcomes, the median age of both the donor and recipient pools is rising. The impact of using donors ≥50 years on the LT outcomes of septuagenarians is unknown. MethodsFrom 2011–2021, outcomes in septuagenarian LT recipients from donor livers <50 year-old (DON<50) and donor livers ≥50 year-old (DON≥50) were analyzed using the United Network for Organ Sharing database. Post-LT survival analysis was performed with the Kaplan-Meier method and multivariable Cox proportional-hazards model. A propensity score was utilized to conduct one-to-one matching using 14 recipient variables (1230-pairs). ResultsThere were 2797 septuagenarian deceased-donor LT recipients during the study period. Of these, 1487 (53.2 %) were DON <50 with median age of 34 years and 1310 (46.8 %) were DON ≥50 with median age of 60 years. The number of LT for septuagenarians has increased over the last decade. The causes of donor and recipient deaths were different between two groups. Post-LT one-year survival (DON<50: 89.3 % vs. DON≥50: 88.3 %) and five-year survival (DON<50: 41.4 % vs DON≥50: 42.8 %) were comparable. Multivariable Cox proportional-hazards model showed that donor age ≥50 years is not associated with increased mortality after LT in the matched cohort (HR: 1.04, 95 % CI: 0.88–1.24, P = 0.63). ConclusionsThe utilization of carefully selected donor livers older than 50 years may be a viable option for septuagenarian LT candidates by lowering their waitlist time and can maximize the organ utilization without compromising the outcomes.

Neighborhood-level social determinants of health measures independently predict receipt of living donor liver transplantation in the United States.

Disparities exist in the access to living donor liver transplantation (LDLT) in the United States. However, the association of neighborhood-level social determinants of health (SDoH) on the receipt of LDLT is not well-established. This was a retrospective cohort study of adult liver transplant recipients between January 1, 2005 and December 31, 2021 at centers performing LDLT using the United Network for Organ Sharing database, which was linked through patients' ZIP code to a set of 24 neighborhood-level SDoH measures from different data sources. Temporal trends and center differences in neighborhood Social Deprivation Index (SDI), a validated scale of socioeconomic deprivation ranging from 0 to 100 (0=least disadvantaged), were assessed by transplant type. Multivariable logistic regression evaluated the association of increasing SDI on receipt of LDLT [vs. deceased donor liver transplantation (DDLT)]. There were 51,721 DDLT and 4026 LDLT recipients at 59 LDLT-performing centers during the study period. Of the 24 neighborhood-level SDoH measures studied, the SDI was most different between the 2 transplant types, with LDLT recipients having lower SDI (ie, less socioeconomic disadvantage) than DDLT recipients (median SDI 37 vs. 47; p < 0.001). The median difference in SDI between the LDLT and DDLT groups significantly decreased from 13 in 2005 to 3 in 2021 ( p = 0.003). In the final model, the SDI quintile was independently associated with transplant type ( p < 0.001) with a threshold SDI of ~40, above which increasing SDI was significantly associated with reduced odds of LDLT (vs. reference SDI 1-20). As a neighborhood-level SDoH measure, SDI is useful for evaluating disparities in the context of LDLT. Center outreach efforts that aim to reduce disparities in LDLT could preferentially target US ZIP codes with SDI > 40.

Impact of Median MELD at Transplant Minus 3 National Policy on Quality of Transplanted Livers for Patients With and Without Hepatocellular Carcinoma.

Patients with hepatocellular carcinoma (HCC) have been overprioritized in the deceased donor liver allocation system. The United Network for Organ Sharing adopted a policy in May 2019 that limited HCC exception points to the median Model for End-Stage Liver Disease at transplant in the listing region minus 3. We hypothesized this policy change would increase the likelihood to transplant marginal quality livers into HCC patients. This was a retrospective cohort study of a national transplant registry, including adult deceased donor liver transplant recipients with and without HCC from May 18, 2017, to May 18, 2019 (prepolicy) to May 19, 2019, to March 1, 2021 (postpolicy). Transplanted livers were considered of marginal quality if they met ≥1 of the following: (1) donation after circulatory death, (2) donor age ≥70, (3) macrosteatosis ≥30% and (4) donor risk index ≥95th percentile. We compared characteristics across policy periods and by HCC status. A total of 23 164 patients were included (11 339 prepolicy and 11 825 postpolicy), 22.7% of whom received HCC exception points (prepolicy versus postpolicy: 26.1% versus 19.4%; P = 0.03). The percentage of transplanted donor livers meeting marginal quality criteria decreased for non-HCC (17.3% versus 16.0%; P < 0.001) but increased for HCC (17.7% versus 19.4%; P < 0.001) prepolicy versus postpolicy. After adjusting for recipient characteristics, HCC recipients had 28% higher odds of being transplanted with marginal quality liver independent of policy period (odds ratio: 1.28; confidence interval, 1.09-1.50; P < 0.01). The median Model for End-Stage Liver Disease at transplant in the listing region minus 3 policy limited exception points and decreased the quality of livers received by HCC patients.

Impact of Renal Replacement Therapy on Rejection among Liver Transplant Recipients.

Introduction: Renal dysfunction in liver transplant recipients is associated with an increased risk of morbidity and mortality, with an even higher risk among patients requiring renal replacement therapy. There is limited data evaluating rejection outcomes in patients requiring renal replacement therapy after liver transplant. Program evaluation aims: To evaluate the incidence of biopsy-proven acute rejection, recipient and graft survival, infection, renal dysfunction, and immunosuppression practices. Design: This was a single-center, retrospective, cohort study. To be eligible, patients were deceased donor liver transplant recipients ≥18 year of age transplanted between January 2017 and August 2019 who received steroid-only induction and tacrolimus as part of their initial immunosuppression regimen. Results: Recipients that required renal replacement therapy (N = 86) were compared to those who received no renal replacement therapy (N = 158). Biopsy-proven acute rejection at 1-year posttransplant was significantly higher among those requiring renal replacement therapy (36% vs 13%, P < .001). Patient survival at 12 months was 77% for those requiring renal replacement therapy and 94% for those not requiring renal replacement therapy (P < .001). Infection (HR 3.8, 95% CI 1.6-8.8; P < .001), but not rejection (HR 0.7, 95% CI 0.3-1.7; P = .5) was an independent predictor of mortality. The use of renal replacement therapy after liver transplant necessitated careful titration of immunosuppression to balance the detrimental risks of infection versus rejection in this high-risk population.

Sex and racial disparities in living donor liver transplantation in the United States.

Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.

O048 Vote counting and sign testing methodology to assess the effect of tissue typing in liver transplantation

Abstract Introduction Liver grafts are currently matched by blood group and size. Due to immune privilege of transplanted livers, tissue typing (HLA matching) is not routinely undertaken. Emerging evidence suggests typing may be beneficial for specific patient groups. This systematic review aimed to determine patient and graft outcomes in HLA matched liver transplant patients. Methods Criteria included primary articles exploring effects of typing for liver transplantation, identified from PubMed/MEDLINE and Web of Science databases until January 2022, excluding articles published pre-2000. The Newcastle-Ottawa scale assessed risk of bias. Cochrane protocols for synthesis without meta-analysis (vote counting and sign testing) determined proportions of studies favouring typing. Results All 28 included articles were cohort studies with low-medium bias risk. Graft survival syntheses favoured typing across all patients in studies of both living (LDLT) and deceased donor liver transplantation (DDLT), where 1 study showed a beneficial effect, and 1 showed no effect. In LDLT-only studies, 2 showed benefit, 4 showed no effect, and 1 showed harm. Additionally, typing was favoured in adult-only DDLT recipients. Rejection syntheses favoured typing across all patients for studies of LDLT, DDLT, and both, and for subgroups including adult-only, paediatric-only, tacrolimus-treated, and negative lymphocyte crossmatch. Patient survival syntheses favoured typing across all patients, and for adult-only, PBC, and hepatitis/viral/cirrhosis diseases subgroups, in DDLT studies. Graft failure syntheses favoured typing across all patients in LDLT-only studies, and both LDLT &amp; DDLT. Conclusion Findings evidenced disparate subgroup benefits of typing, and numerous studies reported no effect, or harmful effects.

Impact of living donor liver transplantation on long-term cardiometabolic and graft outcomes in cirrhosis due to nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). This study aimed to determine whether living donor LT (LDLT) recipients experienced less recurrent NASH, cirrhosis, and cardiometabolic complications compared to deceased donor LT (DDLT). Patients with LDLT and DDLT for NASH between February 2002 and May 2018 at University Health Network (UHN) were compared. Cox Proportional Hazard model was used to analyze overall survival (OS), Fine and Gray's Competing Risk models were conducted to analyze cumulative incidence of post LT outcomes. One hundred and ninety-nine DDLTs and 66 LDLTs were performed for NASH cirrhosis. Time and rate of recurrence of NAFLD and NASH were comparable in both groups. Graft cirrhosis was more common in DDLT recipients (n=14) versus LDLT (n=0) (p<.0001). Significant fibrosis (Fibrosis≥F2) developed in 50 recipients (12 LDLT and 38 DDLT) post LT (DDLT vs. LDLT: HR=1.00, 95% CI=(.52-1.93), p=.91) and there was no difference in time to significant fibrosis (p=.57). There was no difference in development of post-transplant diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, and cancers. LDLT group had better renal function at 10years (MDRD eGFR of 57.0mL/min vs. 48.5mL/min, p=.047). Both groups had a comparable OS (HR=1.83 (95% CI=.92-3.62), p=.08). Overall, LDLT recipients had significantly better renal function by virtue of having early transplantation in their disease course. LDLT was also associated with significantly less graft cirrhosis, although OS and cardiometabolic outcomes were comparable between LDLT and DDLT.

A model for calculating the long-term estimated post-transplant survival of deceased donor liver transplant patients.

The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent. Using the Scientific Registry of Transplant Recipients (SRTR) database, we developed, calibrated, and validated a nonlinear regression equation to calculate liver-EPTS (L-EPTS) for 5- and 10-year outcomes in adult DDLT recipients. The population was randomly split (70:30) into two discovery (N=26,372 and N=46,329) and validation cohorts (N=11,288 and N=19,859) for 5- and 10-year post-transplant outcomes, respectively. Discovery cohorts were used for variable selection, Cox proportional hazard regression modeling, and nonlinear curve fitting. Eight clinical variables were selected to construct the L-EPTS formula, and a five-tiered ranking system was created. Tier thresholds were defined and the L-EPTS model was calibrated (R2=0.96 [5-year] and 0.99 [10-year]). Patients' median survival probabilities in the discovery cohorts for 5- and 10-year outcomes ranged from 27.94% to 89.22% and 16.27% to 87.97%, respectively. The L-EPTS model was validated via calculation of receiver operating characteristic (ROC) curves using validation cohorts. Area under the ROC curve was 82.4% (5-year) and 86.5% (10-year). L-EPTS has high applicability and clinical utility because it uses easily obtained pre-transplant patients characteristics to accurately discriminate between those who are likely to receive a prolonged survival benefit and those who are not. It is important to evaluate medical urgency alongside survival benefit and placement efficiency when considering the allocation of a scarce resource. There are no funding sources related to this project.

Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation

Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/μL), mid (500-1000/μL), and high ALC (>1000/μL). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P = .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P = .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P = .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P = .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.

OPTN/SRTR 2021 Annual Data Report: Liver

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle–based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle–based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Changing Landscape of Liver Transplantation in the Post-DAA and Contemporary ART Era.

Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.

Artificial intelligence for predicting survival following deceased donor liver transplantation: Retrospective multi-center study

BackgroundPrevious studies have indicated that the model for end-stage liver disease (MELD) score may fail to predict post-transplantation patient survival. Similarly, other scores (donor MELD score, balance of risk score) that have been developed to predict transplant outcomes have not gained widespread use. These scores are typically derived using linear statistical models. This study aimed to compare the performance of traditional statistical models with machine learning approaches for predicting survival following liver transplantation. Materials and methodsData were obtained from 785 deceased donor liver transplant recipients enrolled in the Korean Organ Transplant Registry (2014–2019). Five machine learning methods (random forest, artificial neural networks, decision tree, naïve Bayes, and support vector machine) and four traditional statistical models (Cox regression, MELD score, donor MELD score and balance of risk score) were compared to predict survival. ResultsAmong the machine learning methods, the random forest yielded the highest area under the receiver operating characteristic curve (AUC-ROC) values (1-month = 0.80; 3-month = 0.85; and 12-month = 0.81) for predicting survival. The AUC-ROC values of the Cox regression analysis were 0.75, 0.86, and 0.77 for 1-month, 3-month, and 12-month post-transplant survival, respectively. However, the AUC-ROC values of the MELD, donor MELD, and balance of risk scores were all below 0.70. Based on the variable importance of the random forest analysis in this study, the major predictors associated with survival were cold ischemia time, donor ICU stay, recipient weight, recipient BMI, recipient age, recipient INR, and recipient albumin level. As with the Cox regression analysis, donor ICU stay, donor bilirubin level, BAR score, and recipient albumin levels were also important factors associated with post-transplant survival in the RF model. The coefficients of these variables were also statistically significant in the Cox model (p < 0.05). The SHAP ranges for selected predictors for the 12-month survival were (−0.02,0.10) for recipient albumin, (−0.05,0.07) for donor bilirubin and (−0.02,0.25) for recipient height. Surprisingly, although not statistically significant in the Cox model, recipient weight, recipient BMI, recipient age, or recipient INR were important factors in our random forest model for predicting post-transplantation survival. ConclusionMachine learning algorithms such as the random forest were superior to conventional Cox regression and previously reported survival scores for predicting 1-month, 3-month, and 12-month survival following liver transplantation. Therefore, artificial intelligence may have significant potential in aiding clinical decision-making during liver transplantation, including matching donors and recipients.

Risk Factors of Early Allograft Dysfunction in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure After Deceased Donor Liver Transplant

Hepatitis B virus-related acute-on-chronic liver failure remains a life-threatening syndrome, and transplant is the definitive treatment. Early allograft dysfunction is a postoperative complication and affects morbidity and mortality. We studied the risk factors associated with early allograft dysfunction in livertransplantrecipients with hepatitis B virus-related acute-on-chronic liver failure. This single-center retrospective study of early allograft dysfunction is based on data from January 2015 to June 2020 for 323 recipients with hepatitis B virus-related acute-on-chronic liver failure and 445 with only hepatitis B virus infection (control group). Data that correlated with early allograft dysfunction and outcome were analyzed. Incidence of early allograft dysfunction in patients with hepatitis B virus-related acute-on-chronic liver failure was significantly higher versus the control group (39.3% vs 21.1%; P < .001). Transplant recipients with hepatitis B virus-related acute-onchronic liver failure who developed early allograft dysfunction had lower 90-day, 180-day, and 360-day patient survival rates versus patients with no early allograft dysfunction (89.0% vs 98.0%, 82.7% vs 97.5%, and 80.3% vs 96.4%, respectively; P < .001). Pretransplant kidney failure (odds ratio, 2.644; 95% CI, 1.019-6.864; P = .046), pretransplant coagulation failure (odds ratio, 2.162; 95% CI, 1.291-3.621; P = .003), and operative time (odds ratio, 1.005; 95% CI, 1.002-1.008; P = .003) were independent risk factors for early allograft dysfunction in liver transplant recipients with hepatitis B virus-related acute-onchronic liver failure. There was a synergistic effect of early allograft dysfunction and preoperative kidney/coagulation failure on survival rates of liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. Preoperative kidney/coagulation failure and operative time were independent risk factors of early allograft dysfunction in deceased donor liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. The combination of early allograft dysfunction and preoperative kidney/coagulation failure was significantly associated with lower survival of these recipients.

Long-Term Outcomes of Living Donor Versus Deceased Donor Liver Transplant for Hepatocellular Carcinoma in the United States.

Although living donor liver transplant has become a vital treatment option in hepatocellular carcinoma, controversy remains on whether recurrence and survival rates are different versus deceased donor recipients. Here, we compared clinical characteristics and outcomes between recipients of living and deceased donor liver transplants for hepatocellular carcinoma in the United States. Our comparisons used data from the United Network of Organ Sharing/Organ Procurement and Transplantation Network. There were 385 living donor and 25 274 deceased donor liver transplant recipients with diagnosis of hepatocellular carcinoma. Transplant list wait times of ≥6 months were more common in deceased donor(55.9%) versus living donor recipients (45.2%; P < .001). Both recipient groups were comparable with regard to alpha-fetoprotein level <200 ng/mL (P = .18). Only a small percentage in both groups had ≥3 total tumors (P = .73); both groups had similar low transplants outside of Milan criteria (P = .45). Overall, 1-, 5-, and 10-year overall survival rates for deceased versus living donor recipients were similar (91.2% vs 92%, 74% vs 76.4%, 58.9% vs 56.5%; P = .69). On multivariate analysis, Black/African American race/ethnicity was associated with worse outcomes than White race/ethnicity as reference (P < .001), whereas Hispanic and Asian race/ethnicity were more protected. Hepatitis C virus as liver disease etiology was associated with worse outcomes than other etiologies. Tumor characteristics, ≥3 lesions, tumor size, and higher alpha-fetoprotein levels were associated with worse outcomes. Living donor transplant was not associated with higher hazard of death. Among living donor recipients only, largest tumor size was associated with higher risk of death (P = .005). Survival was similarin between the living donor versus deceased donor recipients with hepatocellular carcinoma. With changes in Model for End-Stage Liver Disease exception policies for hepatocellular carcinoma in the United States, living donor transplant for hepatocellular carcinoma could expand the donor pool.

Neurological Screening in Elderly Liver Transplantation Candidates: A Single Center Experience.

Background: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs in over 65-year-old liver transplant patients. Methods: Data were collected, from a retrospective medical chart review, of 22 deceased donor liver transplant recipients aged 65 years or older with a pre-operative brain magnetic resonance imaging (MRI). We used the Fazekas score (0–3) as a quantitative measurement of the vascular lesion load seen in the MRI. We analyzed all post-operative acute NCs occurring during the hospital stay and any other non-NC. Results: cSVD was recognized in all patients. Neurological complications (NCs) occurred in 18.1% of patients with toxic-metabolic encephalopathy the most frequent diagnosis (13.64%). More severe cSVD was associated with seizures (p = 0.0362), longer hospital stay (p 0.0299), and disability (p 0.0134). In our elderly cohort, hepatic encephalopathy (HE) (p 0.0287) and ascites (p 0.0270) were predictors of NCs after liver transplantation. Ascites and/or variceal bleeding and severity of liver disease were associated with adverse post-operative outcomes. The small sample size limited the statistical analysis power. Conclusions: We present the preliminary data of a single-center retrospective study aimed at understanding the cSVD role on NCs and non-NCs after a liver transplantation in elderly patients. This would encourage a more appropriate multicenter prospective study that will definitely confirm if a neurological screening in old age liver transplant candidates is appropriate.