Transplant benefit-based offering of deceased donor livers in the United Kingdom.

BACKGROUND & AIMS: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant. METHODS: UK Transplant Registry data on patient registrations and transplants were analysed to build survival on the list (M1) and survival post-transplantation (M2) statistical models. A separate cohort of registrations - not seen by the models before - was analysed to simulate what liver allocation would have been under M1, M2 and a Transplant Benefit Score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the Registry. Number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme. RESULTS: The TBS was identified as the optimal model to offer livers from donors after brain death (DBD) to adult and large paediatric elective recipients and, in the first two years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p<0.0001), and that patient survival post-listing is significantly greater post-than pre-NLOS (p=0.005). CONCLUSIONS: In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives. IMPACT AND IMPLICATIONS: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit; the Transplant Benefit Score (TBS). The results are important to the transplant community - from healthcare practitioners to patients - and demonstrate that, in the first two years of NLOS offering, waiting-list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the TBS remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated.

Outcomes after liver transplantation using deceased after circulatory death donors: A comparison of outcomes in the UK and the US.

BACKGROUND AND AIMS: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. METHODS: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes. RESULTS: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001). CONCLUSIONS: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries.

Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study.

BACKGROUND: The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS: In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS: 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION: GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING: Junta de Andalucía and EDRF.

Predicting Early Allograft Function After Normothermic Machine Perfusion.

BACKGROUND: Normothermic ex situ liver perfusion is increasingly used to assess donor livers, but there remains a paucity of evidence regarding criteria upon which to base a viability assessment or criteria predicting early allograft function. METHODS: Perfusate variables from livers undergoing normothermic ex situ liver perfusion were analyzed to see which best predicted the Model for Early Allograft Function score. RESULTS: One hundred fifty-four of 203 perfused livers were transplanted following our previously defined criteria. These comprised 84/123 donation after circulatory death livers and 70/80 donation after brain death livers. Multivariable analysis suggested that 2-h alanine transaminase, 2-h lactate, 11 to 29 mmol supplementary bicarbonate in the first 4 h, and peak bile pH were associated with early allograft function as defined by the Model for Early Allograft Function score. Nonanastomotic biliary strictures occurred in 11% of transplants, predominantly affected first- and second-order ducts, despite selection based on bile glucose and pH. CONCLUSIONS: This work confirms the importance of perfusate alanine transaminase and lactate at 2-h, as well as the amount of supplementary bicarbonate required to keep the perfusate pH > 7.2, in the assessment of livers undergoing perfusion. It cautions against the use of lactate as a sole indicator of viability and also suggests a role for cholangiocyte function markers in predicting early allograft function.

A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID-19 pandemic.

INTRODUCTION: Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers. METHODS: Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD > 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019. RESULTS: The retrieval rate for deceased donor livers (71% vs. 54%; P < .0001) and conversion from offer to completed transplant (63% vs. 48%; P < .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort. CONCLUSIONS: We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Risk-adjusted survival in liver transplant patients assessed and managed by a non-transplanting centre: South West Liver Unit experience.

BACKGROUND: Liver transplant services remain a scarce resource not reflective of geography or burden of liver disease within the UK. To address geographical concerns in the South West (SW), a devolved network model of care for liver transplantation was established in 2004 between the SW Liver Unit (SWLU) at Derriford Hospital, Plymouth and King's College Hospital, London. The SWLU has evolved to deliver both pre-transplant and post-transplant care for patients across the SW Peninsula. We determined whether risk-adjusted survival in patients assessed and managed at the SWLU compared with existing UK transplant centres. DESIGN: Retrospective analysis of records at National Health Service Blood and Transplant (NHSBT) for patients ≥18 years listed or undergoing first liver only deceased donor transplantation from 1 January 2006 to 31 December 2017. Data collected and used were in accordance with standard NHSBT outcome measures. RESULTS: We identified 8492 patients registered for first liver only transplant and 6140 patients who subsequently underwent transplantation. Of these, 215 patients listed and 172 patients transplanted were registered at the SWLU. The 1-year, 5-year and 10-year risk-adjusted post-listing survival for patients registered at the SWLU were 86%, 75% and 67%, respectively, with 1-year and 5-year risk-adjusted post-transplant survival 94.9% and 84.4%, respectively. CONCLUSIONS: Risk-adjusted post-listing 1-year, 5-year and 10-year survival outcomes and risk-adjusted 1-year and 5-year post-transplant survival outcomes at the SWLU are good and comparable with the seven UK transplant centres. These outcomes provide assurance that care delivered by our regional programme is equivalent to well-established liver transplant programmes.

Liver transplantation for late-onset presentations of acute liver failure in Wilson's disease: The UK experience over 2 decades.

BACKGROUND & AIMS: Acute liver failure as the initial presentation of Wilson's disease is usually associated with onset in childhood, adolescence or early adulthood. Outcomes after transplantation for late-onset presentations, at or after 40 years, are seldom reported in the literature. METHODS: We report a case, review the literature and provide unpublished data from the UK Transplant Registry on late-onset acute liver failure in Wilson's disease. RESULTS: We describe the case of a 62-year-old man presenting with acute liver failure who was successfully treated with urgent liver transplantation. We identified 7 cases presenting at age 40 years or over in the literature, for which individual outcomes were reported; 3 were treated with transplantation and 2 survived. We identified a further 8 cases listed for transplantation in the UK between 1995 and 2014; 7 were treated with transplantation and 6 survived. One patient was de-listed for unknown reasons. CONCLUSIONS: Wilson's disease should be considered in older adults presenting with acute liver failure. We suggest that urgent liver transplantation has good outcomes for late-onset presentations and recommend that urgent transplantation should always be considered in Wilson's disease presenting as acute liver failure. LAY SUMMARY: Wilson's disease is a rare inherited disease that causes copper accumulation in the liver and brain and usually manifests during childhood, adolescence or early adulthood. We report the case of a 62-year-old who developed acute liver failure and was successfully treated with urgent liver transplantation. We discuss the outcomes of other late-onset cases of acute liver failure due to Wilson's disease in the literature and provide additional data from the UK Transplant Registry.

Prioritising transplantation for adult congenital heart disease, UK national data.

OBJECTIVE: There are no multi-centre data on the outcomes of transplant for adult congenital heart disease (ACHD) outside of North America. The literature has identified a number of concerns for this population such as increased wait-list and early post-operative mortality. We investigated outcomes in a national cohort to see if these problems are replicated outside of America. METHODS: Adults (aged ≥16 years) undergoing primary heart transplantation 1995-2014 were identified in the UK Registry and registration, operative and post-transplantation related clinical factors were compared to non ACHD recipients. RESULTS: Of 3026 adults who underwent primary heart transplantation, 134 (4.4%) had ACHD (median age 30 years; 40.3% female). For the ACHD patients listed as urgent status, the time to transplant was not significantly different to non ACHD patients and ACHD were not more likely to die or be removed from the wait list. Despite ACHD recipients having longer hospital stays (27 vs. 22 days; p = 0.003) and worse 90-day survival (79.5% vs. 86.6%; p = 0.02), long-term post-transplantation survival was not significantly different. Creatinine clearance was significantly better in ACHD patients at follow-up. In the last 10 years of our study period, all single ventricle transplants have been restricted to experienced ACHD teams, one year survival for Fontan patients was 89.5%. CONCLUSIONS: The use of urgent listing appears to have benefited the ACHD group by allowing equal access to transplantation, and recent concentration of expertise for single ventricle transplants has been associated with excellent early survival.

Impact of Regional Organ Sharing and Allocation in the UK Northern Liver Alliance on Waiting Time to Liver Transplantation and Waitlist Survival.

BACKGROUND: In the United Kingdom, liver transplantation (LT) is undertaken in 7 supraregional centers. Until March 2018, liver grafts were offered to a center and allocated to a patient on their elective waiting list (WL) based on unit prioritization. Patients in Newcastle, Leeds, and Edinburgh with a United Kingdom Model for End-Stage Liver Disease (UKELD) score ≥62 were registered on a common WL and prioritized for deceased-donor liver allocation. This was known as the Northern Liver Alliance (NLA) "top-band scheme." Organs were shared between the 3 centers, with a "payback" scheme ensuring no patient in any center was disadvantaged. We investigated whether the NLA had improved WL survival and waiting time (WT) to transplantation. METHODS: Data for this study were obtained from the UK Transplant Registry maintained by National Health Service Blood and Transplant. This study was based on adult patients registered for first elective liver transplant between April 2013 and December 2016. Non-NLA centers were controls. The Kaplan-Meier method was used to estimate WL survival and median WT to transplant, with the log-rank test used to make comparisons; a Bonferroni correction was applied post hoc to determine pairwise differences. RESULTS: WT was significantly lower at NLA centers compared with non-NLA centers for top-band patients (23 versus 99 days, P < 0.001). However, WL survival was not significantly different for top-band patients (P > 0.999) comparing NLA with non-NLA centers. WL survival for nontop-band patients was no different (P > 0.999) comparing NLA with non-NLA centers. CONCLUSIONS: The NLA achieved its aim, providing earlier transplantation to patients with the greatest need. Nontop-band patients did not experience inferior survival.

Survival advantage for patients accepting the offer of a circulatory death liver transplant.

BACKGROUND & AIMS: Donation after circulatory death (DCD) in the UK has tripled in the last decade. However, outcomes following DCD liver transplantation are worse than for donation after brainstem death (DBD) liver transplants. This study examines whether a recipient should accept a "poorer quality" DCD organ or wait longer for a "better" DBD organ. METHODS: Data were collected on 5,825 patients who were registered on the elective waiting list for a first adult liver-only transplant and 3,949 patients who received a liver-only transplant in the UK between 1 January 2008 and 31 December 2015. Survival following deceased donor liver transplantation performed between 2008 and 2015 was compared by Cox regression modelling to assess the impact on patient survival of accepting a DCD liver compared to deferring for a potential DBD transplant. RESULTS: A total of 953 (23%) of the 3,949 liver transplantations performed utilised DCD donors. Five-year post-transplant survival was worse following DCD than DBD transplantation (69.1% [DCD] vs. 78.3% [DBD]; p <0.0001: adjusted hazard ratio [HR] 1.65; 95% CI 1.40-1.94). Of the 5,798 patients registered on the transplant list, 1,325 (23%) died or were removed from the list without receiving a transplant. Patients who received DCD livers had a lower risk-adjusted hazard of death than those who remained on the waiting list for a potential DBD organ (adjusted HR 0.55; 95% CI 0.47-0.65). The greatest survival benefit was in those with the most advanced liver disease (adjusted HR 0.19; 95% CI 0.07-0.50). CONCLUSIONS: Although DCD liver transplantation leads to worse transplant outcomes than DBD transplantation, the individual's survival is enhanced by accepting a DCD offer, particularly for patients with more severe liver disease. DCD liver transplantation improves overall survival for UK listed patients and should be encouraged. LAY SUMMARY: This study looks at patients who require a liver transplant to save their lives; this liver can be donated by a person who has died either after their heart has stopped (donation after cardiac death [DCD]) or after the brain has been injured and can no longer support life (donation after brainstem death [DBD]). We know that livers donated after brainstem death function better than those after cardiac death, but there are not enough of these livers for everyone, so we wished to help patients decide whether it was better for them to accept an early offer of a DCD liver than waiting longer to receive a "better" liver from a DBD donor. We found that patients were more likely to survive if they accepted the offer of a liver transplant as soon as possible (DCD or DBD), especially if their liver disease was very severe.

Patient survival and therapeutic outcome in the UK bridge to transplant left ventricular assist device population.

OBJECTIVE: To study the survival and patient outcome in a population of UK patients supported by an implantable left ventricular assist device (LVAD) as a bridge to heart transplantation. METHODS: Data on all adult patients (n=342) who received a HeartMate II or HVAD as a first long-term LVAD between January 2007 and 31 December 2013 were extracted from the UK Ventricular Assist Device (VAD) Database in November 2015. Outcomes analysed include survival on a LVAD, time to urgent listing, heart transplantation and complications including those needing a pump exchange. RESULTS: 112 patients were supported with the Thoratec HeartMate II and 230 were supported with the HeartWare HVAD. Median duration of support was 534 days. During the study period, 81 patients required moving to the UK urgent waiting list for heart transplantation. Of the 342 patients, 85 (24.8%) received a heart transplant, this included 63 on the urgent list. Thirty-day survival was 88.9%, while overall patient survival at 3 years from LVAD implant was 49.6%. 156 patients (46%) died during LVAD support; the most common cause of death on a VAD was a cerebrovascular accident. There was no significant difference between the two devices used in any outcome. CONCLUSIONS: In a population of patients with advanced heart failure, who have a very poor prognosis, support with an implantable LVAD allowed a quarter to receive a heart transplant in a 3-year period. Overall survival of the cohort was about 50%. With improvement in technology and in post-LVAD management, it is likely that outcomes will improve further.

In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.

Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.

Second annual report from the ISHLT Mechanically Assisted Circulatory Support Registry.

The second annual IMACS registry report includes over 14, 000 patients from 35 countries. Survival, adverse events, and an updated risk model is presented. Continuous flow pumps continue to dominate the world's experience. One and Two-year survival remains at 80% and 70%. Congenital heart disease and biventricular support are the most dominant risk factors. The database is poised for major novel analyses.

First Annual IMACS Report: A global International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support.

The first annual report of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) registry provides global data on 5,942 patients from 31 countries. This initial report focuses on patient demographics, survival, device types, adverse events, competing outcomes, and a risk factor analysis.

Trends in long-term mechanical circulatory support for advanced heart failure in the UK.

AIMS: Heart transplantation (HTx) is limited by the scarcity of suitable donor hearts. Consequently, more patients with advanced heart failure require a ventricular assist device (VAD). We report U.K. activity, trends, and outcome for long-term VAD support as a bridging therapy to HTx. METHODS AND RESULTS: Patients were grouped into three eras: E1, February 2004-March 2006; E2, April 2006-March 2009; and E3, April 2009-March 2011. Exclusions were patients who received isolated short-term support or extracorporeal membrane oxygenation without prior or subsequent long-term VAD support. A total of 247 patients received VAD support; 202 left ventricular (LVAD) support alone and 45 both left and right ventricular support. Activity increased over time, from 36 patients implanted in E1 to 123 in E3. Overall, 46 patients received a first-generation device, 80 a second-generation device, and 121 a third-generation device. Use of third-generation devices increased from <6% in E1 to 78% in E3. Median duration of LVAD support increased from 141 days in E1 to 578 days in E3 (P < 0.001). Overall survival to 1 year after LVAD implant rose from 58.3% [95% confidence interval (CI) 40.7-72.4%] in E1 to 72.5% (95% CI 63.3-79.8%) in E3 (P = 0.21), and improved significantly with device generation; at 1 year, 50% of patients with first-generation devices were alive compared with 68.1% and 76.9% of patients with second- and third-generation devices, respectively (P = 0.002). These differences remained after risk adjustment. HTx following LVAD implant reduced over time (P < 0.001). CONCLUSION: VAD activity and duration of support have increased. There has been a shift from first- and second- to third-generation devices, and an associated improvement in survival.

Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry.

BACKGROUND: The risk that a positive smoking history in lung donors could adversely affect survival of transplant recipients causes concern. Conversely, reduction of the donor pool by exclusion of donors with positive smoking histories could compromise survival of patients waiting to receive a transplant. We examined the consequences of donor smoking on post-transplantation survival, and the potential effect of not transplanting lungs from such donors. METHODS: We analysed the effect of donor smoking on 3 year survival after first adult lung transplantation from brain-dead donors done between July 1, 1999, and Dec 31, 2010, by Cox regression modelling of data from the UK Transplant Registry. We estimated the effect of acceptance of lungs from donors with positive smoking histories on survival and compared it with the effect of remaining on the waiting list for a potential transplant from a donor with a negative smoking history donor, by analysing all waiting-list registrations during the same period with a risk-adjusted sequentially stratified Cox regression model. FINDINGS: Of 1295 lung transplantations, 510 (39%) used lungs from donors with positive smoking histories. Recipients of such lungs had worse 3 year survival after transplantation than did those who received lungs from donors with negative smoking histories (unadjusted hazard ratio [HR] 1·46, 95% CI 1·20-1·78; adjusted HR 1·36, 1·11-1·67). Independent factors affecting survival were recipient's age, donor-recipient cytomegalovirus matching, donor-recipient height difference, donor's sex, and total ischaemic time. Of 2181 patients registered on the waiting list, 802 (37%) died or were removed from the list without receiving a transplant. Patients receiving lungs from donors with positive smoking histories had a lower unadjusted hazard of death after registration than did those who remained on the waiting list (0·79, 95% CI 0·70-0·91). Patients with septic or fibrotic lung disease registered in 1999-2003 had risk-adjusted hazards of 0·60 (95% CI 0·42-0·87) and 0·39 (0·28-0·55), respectively. INTERPRETATION: In the UK, an organ selection policy that uses lungs from donors with positive smoking histories improves overall survival of patients registered for lung transplantation, and should be continued. Although lungs from such donors are associated with worse outcomes, the individual probability of survival is greater if they are accepted than if they are declined and the patient chooses to wait for a potential transplant from a donor with a negative smoking history. This situation should be fully explained to and discussed with patients who are accepted for lung transplantation. FUNDING: National Health Service Blood and Transplant.