Reduced Priority MELD Score for Hepatocellular Carcinoma Does Not Adversely Impact Candidate Survival Awaiting Liver Transplantation

The liver organ allocation policy of the United Network for Organ Sharing (UNOS) is based on the model for end-stage liver disease (MELD). The policy provides additional priority for candidates with hepatocellular carcinoma (HCC) who are awaiting deceased donor liver transplantation (DDLT). However, this priority was reduced on February 27, 2003 to a MELD of 20 for stage T1 and of 24 for stage T2 HCC. The aim of this study was to determine the impact of reduced priority on HCC candidate survival while on the waiting list. The UNOS database was reviewed for all HCC candidates listed after February 27, 2002, The HCC candidates were grouped into two time periods: MELD 1 (listed between February 27, 2002, and February 26, 2003) and MELD 2 (listed between February 27, 2003 and February 26, 2004). For the two time periods, the national DDLT incidence rates for HCC patients were 1.44 versus 1.53 DDLT per person-year (p = NS) and the waiting times were similar for the two periods (138.0 +/- 196.8 vs. 129.0 +/- 133.8 days; p = NS). Furthermore, the 3-, 6- and 12-month candidate, patient survival and dropout rates were also similar nationally. Regional differences in rates of DDLT for HCC were observed during both MELD periods. Consequently, the reduced MELD score for stage T1 and T2 HCC candidates awaiting DDLT has not had an impact nationally either on their survival on the waiting list or on their ability to obtain a liver transplant within a reasonable time frame. However, regional variations point to the need for reform in how organs are allocated for HCC at the regional level.     

Association of Center Volume with Outcome After Liver and Kidney Transplantation

Outcomes for certain surgical procedures have been linked with volume: hospitals performing a high number of procedures demonstrate better outcomes than do low-volume centers. This study examines the effect of volume on hepatic and renal transplant outcomes. Data from the Scientific Registry of Transplant Recipients were analyzed for transplants performed from 1996-2000. Transplant centers were assigned to volume quartiles (kidney) or terciles (liver). Logistic regression models, adjusted for clinical characteristics and transplant center clustering, demonstrate the effect of transplant center volume quantile on 1-year post-transplant patient mortality (liver) and graft loss (kidney). The unadjusted rate of renal graft loss within 1 year was significantly lower at high volume centers (8.6%) compared with very low (9.6%), low (9.9%) and medium (9.7%) volume centers (p = 0.0014). After adjustment, kidney transplant at very low [adjusted odds ratio (AOR) 1.22; p = 0.043) and low volume (AOR 1.22 p = 0.041) centers was associated with a higher incidence of graft loss when compared with high volume centers. Unadjusted 1-year mortality rates for liver transplant were significantly different at high (15.9%) vs. low (16.9%) or medium (14.7%) volume centers. After adjustment, low volume centers were associated with a significantly higher risk of death (AOR 1.30; p = 0.0036). There is considerable variability in the range of failure between quantiles after kidney and liver transplant. Transplant outcomes are better at high volume centers; however, there is no clear minimal threshold volume.     

Preoperative Delta-MELD Score Does Not Independently Predict Mortality After Liver Transplantation

Changes in model for end-stage liver disease (MELD) score of > or = 5 points over 30 days (delta-MELD) is an independent predictor for death in patients awaiting liver transplantation. The aim of the current study was to determine if a positive change in MELD score occurring over the 30 days immediately prior to liver transplantation was predictive of posttransplant mortality. MELD scores from the day of transplantation and 30 days prior to transplantation were calculated for 1510 UNOS patients and used to compute a delta-MELD score. Multivariate modeling determined predictors of posttransplant mortality. Patients with a preoperative delta-MELD > or = 5 had higher absolute MELD scores at transplant, shorter mean posttransplant survival and higher mortality. However, multivariate analysis showed that none of the excess mortality was attributable to the high delta-MELD score (p = 0.43 for delta-MELD > or = 5) and the majority of the excess risk was attributable to absolute MELD score (p < 0.001) at the time of transplantation. Mortality of patients with rapidly worsening chronic liver disease who undergo transplantation depends substantially on absolute MELD score at the time of transplantation but not the rate of change immediately preceding transplant. Allocation policymakers should consider that a high delta-MELD in the immediate pretransplant period does not indicate greater posttransplant mortality.     

MELD and Other Factors Associated with Survival after Liver Transplantation

Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end-stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre-transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 +/- 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow-up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre-transplant renal dysfunction requiring dialysis, Child-Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow-up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre-OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long-term follow-up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.     

Adult Liver Transplant Candidate Attitudes Toward Graft Sharing Are Not Obstacles to Split Liver Transplantation

Split liver transplantation (SLT) benefits society by increasing the total number of transplants that can be performed, but it is yet unknown if a decreased post-transplant survival (in comparison to whole liver transplantation) would make participation in SLT less appealing to adult liver transplant candidates. A 20-item questionnaire was administered to 50 adult candidates to assess attitudes toward SLT and organ sharing. The overall attitudes of 60% of participants were classified as utilitarian (maximizing benefit to greatest number of candidates), while 26% were classified as self-preserving (maximizing individual benefit) and 14% were undecided. Ninety percent of participants would be willing to share even if expected survival was less than that of whole liver transplantation, and 69% felt that pediatric candidates should have priority over adult candidates. In conclusion, attitudes toward graft sharing and the possibility of compromised survival benefit are not barriers to SLT for most adult liver transplant candidates.     

MELD is MELD is MELD? Transplant center–level variation in waitlist mortality for candidates with the same biological MELD

Recently, model for end-stage liver disease (MELD)-based liver allocation in the United States has been questioned based on concerns that waitlist mortality for a given biologic MELD (bMELD), calculated using laboratory values alone, might be higher at certain centers in certain locations across the country. Therefore, we aimed to quantify the center-level variation in bMELD-predicted mortality risk. Using Scientific Registry of Transplant Recipients (SRTR) data from January 2015 to December 2019, we modeled mortality risk in 33 260 adult, first-time waitlisted candidates from 120 centers using multilevel Poisson regression, adjusting for sex, and time-varying age and bMELD. We calculated a "MELD correction factor" using each center's random intercept and bMELD coefficient. A MELD correction factor of +1 means that center's candidates have a higher-than-average bMELD-predicted mortality risk equivalent to 1 bMELD point. We found that the “MELD correction factor” median (IQR) was 0.03 (−0.47, 0.52), indicating almost no center-level variation. The number of centers with “MELD correction factors” within ±0.5 points, and between ±0.5–± 1, ±1.0–±1.5, and ±1.5–±2.0 points was 62, 41, 13, and 4, respectively. No centers had waitlisted candidates with a higher-than-average bMELD-predicted mortality risk beyond ±2 bMELD points. Given that bMELD similarly predicts waitlist mortality at centers across the country, our results support continued MELD-based prioritization of waitlisted candidates irrespective of center.     

Improved Survival After Liver Transplantation in Patients with Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is present in 10–32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO₂) ≤50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow‐up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO₂ or SaO₂ were recorded. PaO₂ increased from 52.2 ± 13.2 to 90.3 ± 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.     

Impact of Adult Living Donor Liver Transplantation on Waiting Time Survival in Candidates Listed for Liver Transplantation

Studies comparing adult living donor liver transplantation to deceased donor liver transplantation have focused on post-transplant survival. Our aim was to focus on the impact of living donor liver transplant on waiting time mortality and overall mortality. We analyzed the affect of living donor liver transplantation on waiting time mortality and overall mortality (from listing until last follow up) in a cohort of 116 transplant candidates. Fifty-eight candidates who had individuals present as potential living donors (volunteer group) were matched by MELD score to 58 liver transplant candidates who did not have individuals present as a potential living donor (no volunteer group). Twenty-seven percent of candidates in the no volunteer group and 62% of candidates in the volunteer group underwent liver transplantation, p = 0.0003. One-year waiting list mortality for the volunteer group and no volunteer group was 10% and 20%, respectively, p = 0.03. Patient survival from the time of listing to last follow up was similar between the two groups. In our study group, living donor liver transplantation is associated with a higher rate of liver transplantation and lower waiting time mortality. In the era of living donor liver transplantation, estimates of patient survival should incorporate waiting time mortality.     

Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States

Open in a separate window     

Living Donor Adult Liver Transplantation: A Longitudinal Study of the Donor''s Quality of Life

We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF-36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty-nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between 0 dollars and 25,000 dollars in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.     

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT)_n polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT) _n allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT) _n genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (≥25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT) _n polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT) _n polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation.     

Health Status in Young Adults Two Decades After Pediatric Liver Transplantation

We conducted a cross‐sectional study of patients who underwent pediatric liver transplant (LT) between 1988 and 1992 to evaluate long‐term health status. Survivors completed socio‐demographic, medical and Health‐Related Quality of Life (HRQOL) surveys by mail including the SF‐36v2, PedsQL?4.0 Generic Core Scale, PedsQL? Cognitive Functioning Scale and PedsQL?3.0 Transplant Module. SF‐36 scores were converted to SF6D‐based utilities and risk factors for lower outcomes were assessed. Eighty‐five of 171 patients had survived. Fifty‐six were contacted with a response rate of 66%. Median age at LT was 0.86 years (IQR 0.58–3.0) and 64.3% had biliary atresia. Mean age at survey was 23.0 ± 4.4 years: 62% attended college, 68% lived with parents and 80% of those over 23 were employed. Patient health utilities were lower than norms (0.75 ± 0.12 vs. 0.82 ± 0.18, p < 0.01) and correlated with unemployment (p < 0.042), hospitalizations (p < 0.005) and lower education level (p < 0.016). Lower PedsQL?3.0 Transplant Module and PedsQL? 4.0 Generic Core Scale scores correlated with unemployment (p = 0.006, p = 0.009) and hospitalizations (p = 0.006, p = 0.02). Pediatric transplant recipients who survive to adulthood have lower physical HRQOL, measurable transplant‐related disability and lower health utility. Transplantation is life saving; however, physical and psychological sequelae continue to affect health status up to two decades later.     

The Prognostic Value of Kidney Transplant Center Report Cards

SRTR report cards provide the basis for quality measurement of US transplant centers. There is limited data evaluating the prognostic value of report cards, informing whether they are predictive of prospective patient outcomes. Using national SRTR data, we simulated report cards and calculated standardized mortality ratios (SMR) for kidney transplant centers over five distinct eras. We ranked centers based on SMR and evaluated outcomes for patients transplanted the year following reports. Recipients transplanted at the 50th, 100th and 200th ranked centers had 18% (AHR = 1.18, 1.13?1.22), 38% (AHR = 1.38, 1.28?1.49) and 91% (AHR = 1.91, 1.64?2.21) increased hazard for 1‐year mortality relative to recipients at the top‐ranked center. Risks were attenuated but remained significant for long‐term outcomes. Patients transplanted at centers meeting low‐performance criteria in the prior period had 40% (AHR = 1.40, 1.22?1.68) elevated hazard for 1‐year mortality in the prospective period. Centers' SMR from the report card was highly predictive (c‐statistics > 0.77) for prospective center SMRs and there was significant correlation between centers' SMR from the report card period and the year following (ρ = 0.57, p < 0.001). Although results do not mitigate potential biases of report cards for measuring quality, they do indicate strong prognostic value for future outcomes. Findings also highlight that outcomes are associated with center ranking across a continuum rather than solely at performance margins.

     

Liver Transplantation for Alcoholic Liver Disease in Europe: A Study from the ELTR (European Liver Transplant Registry)

Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988–2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10 943 VIR, 1478 ALD + VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p = 0.04, p = 0.05). By multivariate analysis, ALD + VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.     

Improved Survival After Live Donor Adult Liver Transplantation (LDALT) Using Right Lobe Grafts: Program Experience and Lessons Learned

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.