Background The liver transplantation (LT) landscape is continuously evolving. We sought to evaluate trends in indications for LT in Canada and the impact of primary liver disease on post‐LT outcomes using a national transplant registry. Methods Adult patients who underwent a primary LT between 2000 and 2018 were retrospectively identified in the Canadian Organ Replacement Registry. Outcomes included post‐LT patient and graft survival. Results A total of 5,722 LTs were identified. The number of LT per year increased from 251 in 2000 to 349 in 2018. The proportion of patients transplanted for HCV decreased from 31.5% in 2000 to 3.4% in 2018. In contrast, the percentage of transplants for HCC increased from 2.3% in 2000 to 32.4% in 2018, and those performed for NASH increased from 0.4% in 2005 to 12.6% in 2018. Year of transplant (per 1‐year) was protective for both patient (HR:0.96,95%CI:0.94‐0.97;p<0.001) and graft survival (HR:0.97,95%CI:0.96‐0.99;p=0.001). Conclusion Post‐LT outcomes have improved over time in this nation‐wide analysis spanning 18 years. Moreover, trends in the indications for LT have changed, with HCC becoming the leading etiology. The decrease in the proportion of HCV patients and increase in those with NASH has implications on the evolving management of LT patients.

Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs.

Background The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short‐ and long‐term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. Methods First‐time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short‐term (first 90 days) and longer‐term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. Results Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non‐HCC recipients. The 3‐year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short‐term than in long‐term mortality, both for recipients with HCC (0–90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non‐HCC recipients (0–90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). Conclusion In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short‐term and longer‐term mortality.

Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008–2011 and 2012–2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142). Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.

Background: Most kidneys for transplantation come from deceased donors, though healthy live individuals may also donate. Living donor transplants generally show better outcomes than deceased donor transplants, but it is unclear whether this reflects inherent benefits of having a living donor kidney or differences in donor and recipient characteristics. Using data from 10 915 UK kidney-only transplants, the aim of this study was to determine the causal effect of living donors on graft survival, considering all-cause death without graft failure as a competing risk. Methods: This study used inverse probability of treatment weighting based on propensity scores to adjust for imbalances in baseline variables between recipients of living and deceased donor kidneys implanted between 2010 and 2021. The mean treatment effect, had all patients received kidneys from living donors, was estimated from differences in survival probabilities and restricted mean survival time using weighted competing risks models. Results: After adjustment for key confounders, living donor kidney transplantation (LDKT) was associated with a 6.03% (95% c.i. 4.71% to 7.35%) lower 5-year risk of graft failure compared with deceased donor kidney transplantation (DDKT). Over 7 years, living donor recipients experienced an additional 0.36 (95% c.i. 0.29 to 0.43) years of graft survival. Benefits persisted across clinically relevant LDKT subgroups. Conclusion: LDKT is associated with superior graft survival compared with DDKT after adjusting for confounders. Findings highlight the importance of promoting living donor programmes whilst simultaneously identifying opportunities to enhance DDKT. Future work may clarify whether factors such as reduced cold ischaemia time drive these benefits.