Association of Karnofsky Performance Status with waitlist mortality among older and younger adults awaiting kidney transplantation

Patients with end-stage renal disease (ESRD) have impaired functional status compared with the general population. We sought to explore the association between Karnofsky Performance Status (KPS) and death/delisting from the kidney transplantation waitlist and whether this association differed by age. Patients listed for single-organ kidney transplantation in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2015, to January 1, 2018, were included. We performed competing-risk regression analyses to determine the association between KPS (“Severely impaired”, “Moderately impaired”, “Non-impaired”) and death/delisting, with deceased-donor kidney transplantation as a competing risk. We tested for interactions between age and KPS on death/delisting. Of the 89,819 patients analyzed, 39% were impaired (KPS < 80) and 20% were aged ≥ 65 years. Older age and lower KPS were independently associated with higher risk of death/delisting (age 45-64 years, HR 1.97 [95% CI 1.73-2.24]; age ≥ 65 years, HR 3.62 [95% CI 3.33-3.92] compared with age < 45 years; moderately impaired, HR 1.68 [95% CI 1.45-1.95]; severely impaired, HR 4.80 [95% CI 3.71-6.21] compared with non-impaired). Lower KPS was associated with higher risk of death/delisting among all ages, but this effect was slightly less pronounced among individuals aged ≥ 65 years. Performance status should be used when counseling patients with ESRD on their risks for death/delisting.     

Comparison of seven liver allocation models with respect to lives saved among patients on the liver transplant waiting list

The patients with end-stage liver disease (ESLD) on the liver transplant waiting list are prioritized for transplant based on the model for end-stage liver disease (MELD) score. We developed and used an innovative approach to compare MELD to six proposed alternatives with respect to waiting list mortality. Our analysis was based on United Network for Organ Sharing data of patients with ESLD on the waiting list between January 2006 and June 2009. We compared six allocation models to MELD. Two models were based on reweighting the variables used by MELD: an "updated" MELD, and ReFit MELD. Four models also included serum sodium: MESO, MeldNa, UKELD, and ReFit MELDNa. We estimated that UKELD and the updated MELD would result in significantly fewer lives saved. There were no significant differences between the other models. Our new approach can supplement standard methods to provide insight into the relative performance of liver allocation models in reducing waiting list mortality. Our analysis suggests that UKELD and the updated MELD score would not be optimal for reducing waiting list mortality in the United States.     

Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation

The current policy for organ allocation in liver transplantation is to give priority to the sickest patients mostly using model for end-stage liver disease (MELD) score in ranking. However, other factors as serum sodium may be of value in predicting early mortality. In this single-center study, patients with cirrhosis over age 14 on the liver transplant wait-list from September 1998 to June 2007 were followed for six months from the time of listing to evaluate the value of hyponatremia on mortality. Of 612 listed patients, 51 were transplanted who were excluded from survival analysis and 55 died without transplantation within the first three months. The numbers of transplanted and dead patients during months 3-6 were 29 and 24, respectively. Both MELD score and serum sodium at the time of listing were independent predictors of early mortality. On bivariate analysis, serum sodium of <130 mEq/L beside MELD was a significant predictor of mortality within 90 and 180 d. Serum sodium level <135 mEq/L masked the difference in mortality between patients with refractory and non-refractory ascites. Serum sodium level of <130 mEq/L and an increased MELD score are significant predictors of early mortality in patients listed for liver transplantation.     

Association of thrombocytopenia with outcome following adult living donor liver transplantation

This study aimed to evaluate the association of postoperative thrombocytopenia with outcome following adult living donor liver transplantation (LDLT) for end‐stage liver disease (ESLD). It was a prospective study of 120 consecutive adult LDLT from September 2012 to May 2015. Preoperative platelet counts (PLTs) and postoperative PLTs were recorded at regular intervals till 3 months after LDLT. Univariate and multivariate analyses were performed. The median pretransplant PLT was 61 × 10⁹/l. The lowest median PLT after LDLT was observed on POD 3. Patients were stratified into low platelet group (n = 83) with PLT <30 × 10⁹/l and high platelet group (n = 37) with PLT ≥30 × 10⁹/l. Patients with PLT <30 × 10⁹/l had statistically significant higher grade III/IV complication (P = 0.001), early graft dysfunction (P = 0.01), sepsis (P = 0.001), and prolonged ascites drainage (P = 0.002). On multivariate analysis, PLT<30 × 10⁹/l was identified as an independent risk factor for grade III/IV complications (P = 0.005). Overall, patients survival was significantly different between two groups (P = 0.04), but this predictive value was lost in patients who survived more than 90 days (P = 0.37). Postoperative PLT of <30 × 10⁹/l was a strong predictor of major postoperative complications and is associated with early graft dysfunction, prolonged ascites drainage, and sepsis. The perioperative mortality rate was high in the thrombocytopenia group.     

Model for the end-stage liver disease and death prediction in a cohort of Brazilian patients on the waiting list for liver transplantation

Abstract: Background/aim: To examine the performance of the model for end‐stage liver disease (MELD) score to predict mortality three and six months after enlistment of patients with chronic diseases for their first liver transplantation (LT) and to compare the performances of the Child–Turcotte–Pugh (CTP) and the Erasmus Model for End‐stage Resistant‐to‐therapy All etiology Liver Disease (EMERALD) scores with the MELD to predict mortality. Methods: Cohort study. Receiver operating characteristics curve (ROC) curves were used to determine the ability of the scores for predicting three and six month mortality, the c‐statistic to establish the predictive power of each score and the Cox proportional hazard model to estimate the risk of dying. Results: We studied 271 patients. At enlistment, the mean MELD and EMERALD scores were 14.8 and 26.6, respectively. Approximately 61% of the cases were in the CTP B category. During the three or six month follow‐up period, the percentage of patients dying, receiving LT or remaining on the list were 11.8%, 9.2%, and 79.0% or 19.2%, 17.7%, and 63.1%, respectively. The three‐month mortality was similarly predicted by the scores MELD, EMERALD and CTP (c‐statistic of 0.79, 0.74, and 0.70, respectively). Six‐month mortality presented similar AUC and ROC curves. Conclusion: The scores predicted mortality for the three or six months, but the performance of the MELD was better than CTP and EMERALD scores.     

Donation after cardiac death liver transplantation is associated with increased risk of end‐stage renal disease

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end‐stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty‐three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow‐up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long‐term renal outcomes in liver transplant recipients.     

Identifying a targeted population at high risk for infections after liver transplantation in the MELD era

Sun H‐Y, Cacciarelli TV, Singh N. Identifying a targeted population at high risk for infections after liver transplantation in the MELD era.
Clin Transplant 2011: 25: 420–425. © 2010 John Wiley & Sons A/S. Abstract: Impact of model for end‐stage liver disease (MELD) scoring system on post‐transplant infections and associated risk factors are unknown. Infections <90 d post‐transplant were assessed in 277 consecutive liver transplant recipients from 1999 to 2008. “High‐risk” factors for infections were pre‐defined as MELD score >30, ICU stay >48 h prior to transplant, intraoperative transfusion ≥15 units, retransplantation, post‐transplant dialysis, or reoperation. Of the 240 recipients in the MELD era (2002–2008), 48.5% had any high‐risk factor. The OR for infection was 1.69, 2.00, 18.00, and 4.50 in recipients with any 1, 2, 3, and ≥4 high‐risk factors, respectively (χ² for trend, p < 0.001). In logistic regression model, recipient age (OR 1.12, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) were associated with infections. Compared with 37 pre‐MELD recipients, the overall infections and mortality at 12 months did not differ in the two eras. In Cox regression model, recipient age (OR 1.09, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) remained associated with infections. The overall frequency of infections did not increase in the MELD era. Pre‐defined risk factors accurately predicted the risk of infections in these patients.     

The beneficial impact of temporary porto‐caval shunt in orthotopic liver transplantation: a single center analysis

The use of temporary porto‐caval shunt (TPCS) has been shown to improve hemodynamic stability and renal function in patients undergoing orthotopic liver transplantation (OLT). We evaluated the impact of TPCS in OLT and analyzed the differences according to model for end‐stage liver disease (MELD), donor risk index (DRI) and D‐MELD. This is a retrospective single‐center analysis of 148 consecutive OLT. Fifty‐eight OLT were performed using TPCS and 90 without TPCS. Donor and recipient data with pre‐OLT, intraoperative and postoperative variables were reviewed. Overall graft survival was 89.9% at 3 months and 81.7% at 1 year. Graft survival at 3 months and 1 year was 93.1% and 79.2%, respectively, in TPCS group versus 85.6% and 82.2%, respectively, in non‐TPCS group (P = NS). Intraoperative packed red blood cells requirement was lower in TPCS group (7.5 ± 5.8 vs. 12.2 ± 14.2, P = 0.006) and non‐TPCS group required higher intraoperative total dose of phenylephrine (16% vs. 28%, P = 0.04). TPCS group had lower 30‐day postoperative mortality (1.7% vs. 10%, P = 0.04), no difference was observed at 90 days. Graft survival was lower in patients with high DRI; in this group graft loss was higher at 1 month (25% vs. 4.3%, P = 0.005) and 3 months (25% vs. 4.3%, P = 0.005) when TPCS was not used. TPCS improves perioperative outcome, this being more evident when high‐risk grafts are placed into high‐risk patients.     

The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation

Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.     

Outcomes of status 1 liver transplantation for Budd-Chiari Syndrome with fulminant hepatic failure

There is a paucity of data on the outcome of liver transplantation (LT) in Budd-Chiari Syndrome (BCS) patients who are listed as status 1. The objective of our study was to determine patient or graft survival following LT in status 1 BCS patients. We utilized United Network for Organ Sharing (UNOS) database to identify all adult patients (> 18 years of age) listed as status 1 with a primary diagnosis of BCS in the United States from 1998 to 2018, and analyzed their outcomes and compared it to non-status 1 BCS patients. Four hundred and forty-six patients with BCS underwent LT between 1998 and 2018, and of these 55 (12.3%) were listed as status 1. There was no difference in long-term post-liver transplant or “intention-to-treat” survival from the time of listing to death or the last day of follow-up between status 1 and non-status 1 groups. Graft and patient survival at 5 years for status 1 patients were 75% and 82%, respectively. Cox regression analysis showed that patients listed as status 1 (aHR: 0.45, p < .02) were associated with a better survival. BCS patients listed as status 1 have excellent survival following emergency LT.     

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.     

Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant

Liver allocation in the Eurotransplant (ET) region has changed from a waiting time to an urgency‐based system using the model of end‐stage liver disease (MELD) score in 2006. To allow timely transplantation, pediatric recipients are allocated by an assigned pediatric MELD independent of severity of illness. Consequences for children listed at our center were evaluated by retrospective analysis of all primary pediatric liver transplantation (LTX) from deceased donors between 2002 and 2010 (110 LTX before/50 LTX after new allocation). Of 50 children transplanted in the MELD era, 17 (34%) underwent LTX with a high‐urgent status that was real in five patients (median lab MELD 22, waiting time five d) and assigned in 12 patients (lab MELD 7, waiting time 35 d). Thirty‐three children received a liver by their assigned pediatric MELD (lab MELD 15, waiting time 255 d). Waiting time in the two periods was similar, whereas the wait‐list mortality decreased (from about four children/yr to about one child/yr). One‐ and three‐yr patient survival showed no significant difference (94.5/97.7%; p = 0.385) as did one‐ and three‐yr graft survival (80.7/75.2%; and 86.5/82%; p = 0.436 before/after). Introduction of a MELD‐based allocation system in ET with assignment of a granted score for pediatric recipients has led to a clear priorization of children resulting in a low wait‐list mortality and good clinical outcome.     

MELD scores with incorporation of serum sodium and death prediction in cirrhotic patients on the waiting list for liver transplantation: a single center experience in southern Brazil

To compare the accuracy of standard model for end‐stage liver disease (MELD) score with that of four MELD‐based scores incorporating serum sodium (SNa) to predict three‐ and six‐month mortality in cirrhotic patients after their placement on the waiting list for liver transplantation (LT). A cohort study was performed. Receiver operating characteristic (ROC) curves were generated for MELD, MELD incorporating SNa (MELD‐Na, MELD‐Na2), integrated MELD (iMELD), and MELD to SNa ratio (MESO) index to assess the predictive accuracy of these scores to determine three‐ and six‐month mortality. The c‐statistic (area under the ROC curve [AUC]) was used to determine predictive power and the Cox proportional‐hazard ratio to estimate death risk. We studied 558 patients. There was a statistically significant difference in the predictive accuracy of scores at three months (AUCs: MELD = 0.79 [95% CI = 0.72–0.87]; MELD‐Na = 0.84 [95% CI = 0.78–0.90]; MELD‐Na2 = 0.85 [95% CI = 0.80–0.91]; iMELD = 0.85 [95% CI = 0.80–0.90]; MESO = 0.81 [95% CI = 0.80–0.91]) and at six months (MELD = 0.73 [95% CI = 0.67–0.80]; MELD‐Na = 0.79 [95% CI = 0.73–0.84]; MELD‐Na2 = 0.80 [95% CI = 0.74–0.85]; iMELD = 0.80 [95% CI = 0.75–0.85]; MESO = 0.75 [95% CI = 0.69–0.81]) (p < 0.001). Death risk was independent of age and sex. Sodium‐modified MELD scores are able to more accurately predict three‐ and six‐month mortality among cirrhotic patients awaiting LT.     

Model for end‐stage liver disease‐sodium and survival benefit in liver transplantation

There are currently no studies calculating the survival benefit of liver transplantation (LT) according to model for end‐stage liver disease‐sodium (MELD‐Na) and based on the competing risk (CR) method. We enrolled consecutive adult patients with chronic end‐stage liver disease entering the waiting list (WL) for primary LT (WL group = 337) and undergoing LT (LT group = 220) in the period 2006–2009. Two independent multivariable regressions (WL and LT models) were created to measure the prognostic power of MELD‐Na with respect to MELD. For the WL model, both Cox and CR multivariable analyses were performed. Estimates were finally included in a Markov model to calculate 3‐year survival benefit. WL Cox model: MELD‐Na (P < 0.0001) and MELD (P < 0.0001) significantly predicted survival. WL CR model: MELD‐Na (P = 0.0045) and MELD (P = 0.0109) significantly predicted survival. LT Cox model: MELD‐Na (P = 0.7608) and MELD score (P = 0.9413) had not correlation with survival. Benefit model: MELD and MELD‐Na had an overlapping significant impact on 3‐year survival benefit; CR method determined a significant decrease in 3‐year life expectancy (LE) estimations. MELD‐Na and MELD scores similarly predicted 3‐year LT survival benefit, but the gain in LE is significantly lower when a CR method is adopted.     

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non‐alcoholic fatty liver disease undergoing liver transplantation in the US. Our study utilized data from the 2002 to 2012 United Network for Organ Sharing registry to evaluate model for end‐stage liver disease era trends in US liver transplantations focused on patients with non‐alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease (ALD), and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan–Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index (BMI), and had higher prevalence of diabetes and cardiac disease. However, overall long‐term survival was significantly higher in patients with NASH and ALD (p < 0.001). Compared to HCV, patients with NASH had significantly higher post‐transplantation survival (HR 0.69, 95% CI 0.63–0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69–0.83). Despite having higher BMI and higher prevalence of diabetes and cardiac disease, patients with NASH had better post‐liver transplantation survival compared to patients with HCV or HCC. Patients with ALD also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation.