Wait-list mortality of young patients with Biliary atresia: Competing risk analysis of a eurotransplant registry-based cohort.

Liver transplantation (LT) is the standard treatment for biliary atresia (BA) patients with end-stage liver disease. The prognosis after LT has steadily improved, but overall prognosis of BA patients is also determined by mortality before LT. We aimed to quantify mortality in young BA patients on the Eurotransplant waiting list and to determine the effect of disease severity and age at time of listing on pretransplant mortality. We used a cohort study design, which incorporated data from the Eurotransplant registry. Participants were 711 BA patients who were below 5 years of age from 5 countries and listed for LT between 2001 and 2014. We applied a competing risk analysis to evaluate simultaneously the outcomes death, LT, and still waiting for a suitable organ. We used Cox proportional hazards regression to assess 2-year mortality. In a subcohort of 416 children, we performed multivariate analyses between 2-year mortality and disease severity or age, each at listing. Disease severity at listing was quantified by the Model for End-Stage Liver Disease (MELD) score, which assesses bilirubin, creatinine, albumin, and international normalized ratio as continuous variables. Two-year wait-list mortality was 7.9%. Age below 6 months and MELD score above 20 points, each at listing, were strongly and independently associated with 2-year mortality (each P < 0.001). A total of 21% of infants who fulfilled both criteria did not survive the first 6 months on the waiting list. In conclusion, our findings quantify mortality among young BA patients on the waiting list and the relative importance of risk factors (age and severity of disease at listing). Our results provide both an evidence base to rationally address high mortality in subgroups and a methodology to assess effects of implemented changes, for example, in allocation rules. Liver Transplantation 24 810-819 2018 AASLD.

van der Doef HPJ ，van Rheenen PF ，van Rosmalen M ，Rogiers X ，Verkade HJ ，for pediatric liver transplantation centers of Eurotransplant ... -  《-》

A 10-Year united network for organ sharing review of mortality and risk factors in young children awaiting liver transplantation.

Young children < 2 years of age with chronic end-stage liver disease (YC2) are a uniquely vulnerable group listed for liver transplantation, characterized by a predominance of biliary atresia (BA). To investigate wait-list mortality, associated risk factors, and outcomes of YC2, we evaluated United Network for Organ Sharing registry data from April 2003 to March 2013 for YC2 listed for deceased donor transplant (BA = 994; other chronic liver disease [CLD] = 221). Overall, wait-list mortality among YC2 was 12.4% and posttransplant mortality was 8%, accounting for an overall postlisting mortality of 19.6%. YC2 demonstrated 12.2%, 18.7%, and 20.6% wait-list mortality by 90, 180, and 270 days, respectively. YC2 with CLD demonstrated significantly higher wait-list mortality compared with BA among YC2 (23.9% versus 9.8%; P < 0.05). Multivariate analyses revealed that listing Pediatric End-Stage Liver Disease [PELD] > 21 (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.6-6.5), lack of exception (HR, 5.8; 95% CI, 2.8-11.8), listing height < 60.6 cm (HR, 2.1; 95% CI, 1.4-3.1), listing weight  > 10 kg (HR, 3.8; 95% CI, 1.5-9.2), and initial creatinine > 0.5 (HR, 6.8; 95% CI, 3.4-13.5) were independent risk factors for YC2 wait-list mortality (P < 0.005 for all). Adjusting for all variables, the risk of death among CLD patients was 2 (95% CI, 1.3-3.1) times greater than patients with BA + surgery (presumed Kasai). Furthermore, the risk of death in BA without surgery was 1.9 (95% CI, 1‐3.4) times greater than BA with presumed Kasai. Our data highlight unacceptably high wait-list and early post-liver transplant mortality in YC2 not predicted by PELD and suggest key risk factors deserving of further study in this age group. Liver Transplantation 22 1584-1592 2016 AASLD.

Leung DH ，Narang A ，Minard CG ，Hiremath G ，Goss JA ，Shepherd R ... -  《-》

Variability in acceptance of organ offers by pediatric transplant centers and its impact on wait-list mortality.

Recent data have suggested that pediatric patients wait-listed for a liver transplantation frequently have liver offers declined. However, factors associated with liver offer decisions and center-level variability in practice patterns have not been explored. We evaluated United Network for Organ Sharing data on all match runs from May 1, 2007 to December 31, 2015 in which the liver was offered to ≥1 pediatric patient; the transplant recipient was ranked in the first 40 positions for the organ offer; and the donor was brain-dead and <50 years of age. We used multilevel mixed effects models to evaluate factors associated with organ offer acceptance, among-center variability, and the association between center-level acceptance and wait-list mortality. There were 4088 unique pediatric patients during the study period, comprising 27,094 match runs. Initial Model for End-Stage Liver Disease or Pediatric End-Stage Liver Disease score, history of exception points, recipient region, rank on match run, and geographic share type were all associated with probability of offer acceptance. There was significant among-center variation (P < 0.001) in adjusted liver offer acceptance rates, accounting for donor, recipient, and match-related factors (adjusted acceptance rates: median, 8.9%; range, 5.1%-14.6%). Center-level acceptance rates were associated with wait-list mortality, with a >10% increase in the risk of wait-list mortality for every 1% decrease in a center's adjusted liver offer acceptance rate (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). In conclusion, there is significant among-center variability in liver offer acceptance rates for pediatric patients that is not explained by donor and recipient factors. A center's liver acceptance behavior significantly impacts whether a pediatric patient will be transplanted or die on the waiting list. Liver Transplantation 24 803-809 2018 AASLD.

Mitchell E ，Loomes KM ，Squires RH ，Goldberg D ... -  《-》

Outcomes for liver transplant candidates listed with low model for end-stage liver disease score.

Kwong AJ ，Lai JC ，Dodge JL ，Roberts JP ... -  《-》

Model for end-stage liver disease and model for end-stage liver disease-Na scores predict both before-listing and wait-list mortality.

Due to the organ shortage, many patients die without transplantation, even before completing an evaluation for candidacy. We analyzed outcomes after patient referral and factors associated with mortality both before and after listing for cadaveric donor liver transplantation. We analyzed 132 consecutive patients who were evaluated for candidacy for cadaveric donor liver transplantation between 2003 and 2010. The study included 69 men and 63 women of median age 49 years (range, 1-65). Etiologies of diseases were acute hepatic failure (n=19), liver cirrhosis due to hepatitis B or C (n=36), primary biliary cirrhosis (n=19), nonviral cirrhosis (n=14), hepatocellular carcinoma (n=13), or other causes (n=31). After evaluation for candidacy, we listed 68 (52%), subjects whereas 24 (18%) died before listing. Factors affecting death before listing were the levels of albumin (P<.001), bilirubin (P<.001), sodium (P<.001), international normalized ratio (INR; P<.001), Model for End-stage Liver Disease (MELD) score (P<.001), MELD-Na score (P<.001), and Child-Pugh-Turcotte (CPT) score (P<.001). Based on multivariate Cox regression analysis, MELD score (hazard ratio [HR] 1.201, P=.017), MELD-Na score (HR 1.244, P=.014), CPT score (HR 1.468, P=.033), and INR (HR 0.491, P=.027) were independently associated with death before listing. Among 68 listed candidates, 11 (16%) underwent transplantation, whereas 29 (43%) died without transplantation. Based on multivariate Cox regression analysis, MELD score (HR 1.102, P=.001), MELD-Na score (HR 1.128, P=.001), and CPT score (HR 1.282, P=.038) independently predicted wait-list mortality. All 11 patients who underwent cadaveric liver transplantation were alive at 29 months (range, 1-55) after transplantation. Patients with a higher MELD, higher MELD-Na, and higher CPT score at referral were at greater risk for death without transplantation, especially before listing. Evaluation for transplantation candidacy is a time-consuming process. Therefore, earlier referral is mandatory to achieve successful listing for transplantation.

Yamashiki N ，Sugawara Y ，Tamura S ，Kaneko J ，Nojiri K ，Aoki T ，Sakamoto Y ，Hasegawa K ，Koike K ，Kokudo N ... -  《-》