Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

Background

The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD.

Impact of the Model for End-Stage Liver Disease (MELD) Score on Liver Transplantation in Greece

IntroductionThe impact of preoperative Model for End-stage Liver Disease (MELD) score in postoperative mortality remains unclear. The assumption that patients with a higher MELD score will have a higher mortality rate is not confirmed and studies are contradictory.AimThe study of the clinical course of patients with a higher MELD score and its impact in immediate and later mortality in comparison with patients with a lower MELD score in the only liver transplantation center in Greece.MethodWe retrospectively studied 71 patients who underwent orthotopic liver transplantation (OLT) in the time period between 1-1-2011 and 31-12-2013. The patients were divided into 2 groups: Group A with a MELD score ≥23 and Group B with a MELD score <23.ResultsIn the patients with a MELD score ≥23 the duration of mechanical ventilation and length of stay in the ICU were prolonged (P = .013 and .009, respectively), the transfusions were more (P = .005), and the rates of ICU readmissions (22.5% vs 7.31%, P = .001) and infections (42.5% vs 17.5%, P = .011) were higher. Thirty-day mortality did not differ between the 2 groups (P = .420), but there was a statistically significant difference in morbidity and in 180-day mortality.ConclusionThe patients with a higher MELD score have more complex pathophysiology. This score seems to affect morbidity and late, but not early, mortality.     

Liver Transplantation in Recipients With High Model for End-stage Liver Disease Score

Objectives

The score in the Model of End-stage Liver Disease, or MELD, is a good indicator of the survival in patients on the liver transplant waiting list. In this study, an analysis is performed on the benefits of liver transplant on those patients with a very high MELD score and who thus start from a very severe baseline state that could affect the surgical outcome.

Clinical Analysis of Factors Affecting Hospital Mortality After Liver Transplant in Patients With High Model for End-Stage Liver Disease Score

BackgroundThis study was undertaken to identify poor prognostic factors in patients with high Model for End-Stage Liver Disease (MELD) scores.MethodsFrom September 2001 to December 2017, living donor liver transplant and deceased donor liver transplant were performed in 851 (84.4%) and 157 patients (15.6%), respectively, in our center. Eighty-one patients (8.0%) with MELD scores ≥ 35 were classified as patients with high MELD scores.ResultsThe overall survival rates in patients with high MELD scores were significantly worse than those in patients with low MELD scores (P = .005). However, no significant difference in survival was found between the 2 groups when in-hospital mortality was excluded. In-hospital mortality occurred in 18 patients (22.2%), and the main cause of death was sepsis (n = 14, 77.8%). On univariate analysis, the risk factors for in-hospital mortality were mean age (P = .028), mean MELD score (P = .045), intubation status (P < .001), culture positivity (P = .042), and encephalopathy grade 3 or 4 (P = .014). On multivariate analysis, age (P = .006), intubation status (P = .042), and culture positivity (P = .036) were significant.ConclusionsThe main cause of in-hospital mortality was sepsis, and the risk factors for in-hospital mortality of patients with high MELD score were older age, preoperative intubation, and culture positivity. Special attention should be paid to the prevention and treatment of infection in the liver transplant of patient with high MELD scores.     

Model for End-Stage Liver Disease (MELD) predicts nontransplant surgical mortality in patients with cirrhosis

OBJECTIVE: We sought to determine the ability of the Model for End-Stage Liver Disease (MELD) score to predict 30-day postoperative mortality for patients with cirrhosis undergoing nontransplant surgical procedures. SUMMARY BACKGROUND DATA: The Child-Pugh class historically has been used by clinicians to assist in management decisions involving patients with cirrhosis. However, this classification scheme has a number of limitations. Recently, MELD was introduced. It has been shown to be highly predictive of mortality in a variety of clinical scenarios. METHODS: Adult patients with a diagnosis of cirrhosis undergoing nontransplant surgical procedures between January 1, 1996, and January 1, 2002, at a single center were analyzed. The preoperative MELD score was calculated for all patients, and the MELD's performance in predicting 30-day mortality was determined using multivariate regression techniques. RESULTS: A total of 140 surgical procedures were identified and analyzed. The 30-day mortality rate was 16.4%. The mean admission MELD score for the patients who died (23.3, 95% confidence interval 19.6-27.0) was significantly different from those patients surviving beyond 30 days (16.9, 15.6-18.2), P = 0.0003. The c-statistic for MELD score predicting 30-day mortality was 0.72. Further subgroup analysis of 67 intra-abdominal surgeries showed an in-hospital mortality of 23.9%. The mean MELD score for patients dying (24.8, 20.4-29.3) was significantly different from survivors (16.2, 14.2-18.2), P = 0.0001. The c-statistic for this subgroup was 0.80. CONCLUSIONS: The MELD score, as an objective scale of disease severity in patients with cirrhosis, shows promise as being a useful preoperative predictor of surgical mortality risk.     

Analysis of Model for End-Stage Liver Disease (MELD) score in a liver transplantation waiting list

BACKGROUND: The Model for End-Stage Liver Disease (MELD) was introduced in 1999 to quantify the 3-month prognosis of cirrhotic patients after a transjugular intrahepatic portosystemic shunt (TIPS). Because of the imbalance between organ donors and patients on the waiting list, the MELD was adopted by the United States in 2002 to allocate liver grafts for transplantation. Preliminary results have indicated a reduction in waiting list deaths and an increase in transplantation rates for candidates. Seeking to find a new model to predict death on the waiting list and after liver transplantation, retrospective studies have examined MELD scores in waiting list patients. The aim of this study was to analyze the MELD scores of patients on the liver waiting list for comparisons between transplanted patients. PATIENTS AND METHODS: A retrospective study was performed analyzing 131 registrations of 127 orthotopic liver transplant (OLT) patients (4 underwent retransplantation) grafted between November 2000 and January 2006, excluding 24 patients: 2 had urgent retransplantations due to hepatic artery thrombosis and 22 had incomplete data. These patients were divided into 3 groups: group I (transplanted patients)-53 patients underwent 55 OLT; group II-29 patients who died on the waiting list; group III-patients on the waiting list including 23 patients still waiting as of the date of the study. RESULTS: The main indication for OLT was hepatitis C virus cirrhosis (50.50%), followed by alcoholic liver cirrhosis (23.30%), cryptogenic cirrhosis (12.60%), autoimmune hepatitis (5.80%), hepatitis B virus cirrhosis (4.85%), and primary biliary cirrhosis (2.91%). Group I: MELD score 15.62 (range, 6-39) on admission to the list, and 18.87 (range, 7-39) at transplantation. The mean waiting time for OLT was 478.39 days (range, 2-1270 days). The 38 patients who survived underwent 39 OLT (1 retransplantation). The MELD score at entrance to the list was 14.62 (range, 7-30) and at transplantation, 17.70 (range, 7-39). The mean time between admission to the list and transplantation was 505.37 days (range, 6-1270 days). The 15 patients who died had received 16 OLT (1 retransplantation). Their MELD scores were 17.80 (range, 6-39) and 21.81 (range, 9-39) at admission to the list and at transplantation, respectively, with a mean time on the waiting list of 417.93 days (range, 2-872 days). Group II: 29 patients died before OLT, at a mean age of 52.60 years (range, 22-67 years). Their MELD score was 19.24 (range, 7-45), and the interval between admission to the waiting list and death was 249.55 days (range, 3-1247 days). Group III: 23 patients still active on the OLT waiting list at the time of study displayed a mean MELD score of 13.65 (range, 6-28) and 354.30 days (range, 2-905 days) waiting until the moment. In conclusion, MELD score at the time of admission to the waiting list was higher among those patients who died either awaiting a liver graft (19.24) or after OLT (17.80) compared with those who survived after OLT (14.60) or are still awaiting OLT (13.65).     

Hazards of Stroke in Renal Transplant Recipients and Patients With End-Stage Renal Disease

BackgroundSeveral comparison studies have suggested that kidney transplant (KT) could reduce stroke risk in patients with end-stage renal disease (ESRD). To avoid the selection criteria bias of using dialysis patients as control groups, we compared the risk of stroke between KT recipients and comparable propensity score-matched dialysis patients.MethodsWe used Taiwan's National Health Insurance Research Database to identify patients with newly diagnosed ESRD between 2000 and 2009. We separated them into 2 groups: a KT group and a non-KT dialysis-only group. To evaluate the stroke outcome, we compared each patient with KT to a patient on dialysis without KT using propensity score matching.ResultsIn total, 2735 KT recipients and 10,940 propensity score-matched dialysis patients were identified. The incidence rates of overall stroke were 9.1 and 23.4 per 1000 person-years in KT recipients and non-KT dialysis patients. Compared with the propensity score-matched dialysis patients, the patients who received KT exhibited significantly lower overall stroke risk, hemorrhagic stroke, and ischemic stroke, the adjusted hazard ratios were 0.37 (95% CI, 0.31–0.45), 0.19 (95% CI, 0.12–0.29), and 0.46 (95% CI, 0.37–0.56), respectively (all P < .001).ConclusionsThrough a propensity score-matched cohort, this study confirms that KT is associated with a reduced risk of stroke more than dialysis alone in patients with newly diagnosed ESRD.     

Performance of Posttransplant Model for End-Stage Liver Disease (MELD) and Delta-MELD Scores on Short-Term Outcome After Living Donor Liver Transplantation

The performance of the Model for End-stage Liver Disease (MELD) and delta-MELD scores in predicting posttransplant survival has been variable and the results are conflicting, suggesting that posttransplantational factors are more important than pre- or peritransplantational factors in outcomes following liver transplantation (OLT). We assessed the value of posttransplant MELD and delta-MELD scores to predict short-term (90-day) posttransplant survival. We evaluated 279 consecutive patients undergoing living donor OLTs. The MELD scores were calculated serially from pretransplantation as well as 3, 7, and 14 days after transplantation. Twenty-seven (9.7%) among 279 patients died within 90 days after transplantation. Pretransplant MELD score was not associated with short-term posttransplant mortality. The area under the receiver operating characteristic (AUROC) curve in predicting 90-day mortality was 0.637 for posttransplant 3-day MELD, 0.746 for posttransplant 7-day MELD, and 0.859 for posttransplant 14-day MELD score (P = .047, <.001, and <.001, respectively); AUROC was 0.582, 0.646, and 0.784 for 3-day, 7-day, and 14-day delta-MELD scores (P = .235, .034, <.001, respectively). Upon multivariate analysis, posttransplant 14-day MELD (≥20 vs <20), and 14-day delta-MELD scores (≥−3 vs <−3) were independent short-term prognostic factors with risk ratios of 18.875 (95% confidential interval [CI]: 4.625-77.028, P < .001) and 13.577 (95% CI: 2.641-69.791, P = .002), respectively. In conclusion, determination of posttransplant 14-day MELD and 14-day delta-MELD scores may afford suitable short-term prognostic predictors for patients following living donor OLT.     

Correlation Between Functional Capacity and Respiratory Assessment of End-Stage Liver Disease Patients Waiting for Transplant

IntroductionEnd-stage liver disease has metabolic complications associated with malnutrition, which involves a great loss of muscle mass. This complication can lead to changes in the diaphragm, which along with ascites may impair daily activities and result in global motor disability and physical inactivity of patients on the waiting list for liver transplantation.ObjectivesThis study sought to delineate the profile of candidates for liver transplantation while on the waiting list at the Clinical Hospital of State University Campinas (UNICAMP), and to assess and verify whether there is a correlation between functional status of the individuals tested using the 6-minute walk test (6MWT), pulmonary function test (PFT), and respiratory muscle strength with end-stage liver disease candidates for liver transplantation.MethodsThis study was carried out in the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, 6MWT, PFT, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP), and SF-36.ResultsCorrelations were found between the respiratory variables 6MWT and PFT. The walked distance was correlated with MIP and MEP. There was no correlation between the 6MWT and the variables body mass index and age.ConclusionCandidates for liver transplantation have decreased muscle strength, normal lung function, and impaired quality of life, mainly due to physical limitations. Functional status may be correlated with the respiratory assessment (muscle strength and pulmonary function test) in liver disease candidates for transplantation.     

Model for End-Stage Liver Disease (MELD) system to allocate and to share livers: experience of two Italian centers

BACKGROUND: The use of the Model for End-stage Liver Disease (MELD) score to prioritize patients on liver waiting lists and to share organs among centers was effective according to US data, but few reports are available in Europe. MATERIALS AND METHODS: We evaluated the outcome of 887 patients listed between April 2004 and July 2006 in a common list by two transplant centers (University of Bologna [BO] and University of Modena [MO] ordered according to the MELD system. Patients with hepatocellular carcinoma had a score calculated according to their real MELD, tumor stage, and waiting time. RESULTS: Five hundred eighty-six (67%) patients were listed from BO and 291 (33%) from MO. The clinical features of recipients (sex, age, blood group, and real MELD) were comparable between centers. The number of liver transplantations performed was 307, and 273 (89%) recipients had a calculated MELD >or=20. Liver transplantations were equally distributed according to the number of patients listed: 215 out of 586 (36.7%) for BO and 92 out of 291 (31.6%) for MO. The median real MELD of patients transplanted was 20, and 246 out of 307 (80.1%) grafts transplanted were functioning. The dropouts from the list were 124 (14%), and 87 (70%) of these patients had a calculated MELD >or=20. CONCLUSION: The MELD system was effective to share livers among the two Italian centers. According to this policy, livers were allocated to the recipients with the highest probability of dropout and who had a satisfactory survival after liver transplantation.     

Liver transplantation for hepatocellular carcinoma: lessons from the first year under the Model of End-Stage Liver Disease (MELD) organ allocation policy.

We examined the impact of the Model for End-Stage Liver Disease (MELD) organ allocation scheme on 44 patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) between February 2002 and January 2003, and compared the outcome with 58 patients listed in the 4 years before MELD implementation. Patients undergoing living-donor liver transplantation were excluded. The Kaplan-Meier probabilities for OLT at 3, 6, and up to 8.5 months were 22.5%, 64.0%, and 88.0%, respectively, under MELD versus 17.2%, 24.7%, and 35.8% at 3, 6 and 9 months, respectively, in the pre-MELD group (P =.0006). In Cox regression analysis, non-O blood group (hazard ratio 2.5; P =.047 versus blood group O) and 3 tumor nodules (hazard ratio 5.5; P =.005) were associated with a significantly higher probability for OLT under MELD. The probabilities of dropout were 5.6% at 6 and 8.5 months under MELD versus 7.2% and 37.8% at 6 and 12 months, respectively, in the pre-MELD group (P =.74). The lack of a significant difference in dropout may be due to low dropout rates in the first 6 months in either group. No HCC was found in the explant in 1 patient from each group. In conclusion, the HCC-adjusted MELD system significantly improved the probability of timely OLT, albeit a significant disadvantage for blood group O was evident. Compared with preliminary UNOS data, in which 90% of patients with HCC have received OLT within 3 months, our results reflect the wide regional variation in the impact of MELD.     

Looking Beyond Respiratory Cultures: Microbiome‐Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune‐response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture‐positive samples across the groups. Bayesian regression analysis identified non–culture‐based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia‐colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.     

Daclatasvir and Sofosbuvir With or Without Ribavirin in Liver Transplant Recipients: A Single-Center Real-World Study

Background

Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out.

Model for End-Stage Liver Disease (MELD) score and organ allocation from cadaveric donors for 198 liver transplantation procedures performed in a single center

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.     

Inadequate Blood Pressure Control in Most Kidney Transplant Recipients and Patients With Coronary Artery Disease With and Without Complications

Background

Hypertension is a widely accepted risk factor for coronary artery disease (CAD), chronic heart failure, and chronic kidney disease (CKD). In kidney transplant recipients, the prevalence of hypertension is 60% to 80%.

Objective

To assess the prevalence of target blood pressure in 2 high-risk populations: patients with CAD and kidney allograft recipients.

Patients and Methods

The study included 520 patients with CAD and 150 kidney allograft recipients. In the CAD population, 30% of patients had diabetes mellitus and 33% had CKD. In kidney allograft recipients, 52% had diabetes (15%) or CKD. Hypertension was diagnosed and treated in 72% of patients with CAD and 90% of kidney allograft recipients. In the CAD population without diabetes but with CKD, target blood pressure was achieved in 47% compared with 31% in the CKD population. Treatment included angiotensin-converting enzyme (ACE) inhibitors in 72% of patients, calcium channel blockers in 28%, diuretic agents in 27%, and β-blockers in 89%. In allograft recipients, more than 60% required 3 or more hypotension agents. Only 40% demonstrated target blood pressure. In the latter group, the most commonly used hypotension agents were ACE inhibitors in 38%, calcium channel blockers in 84%, diuretic agents in 51%, β-blockers in 68%, and α-blockers in 15%.

Conclusion

Both cohorts demonstrated a high prevalence of hypertension. Despite polytherapy, optimal blood pressure control was not achieved in most patients. Greater efforts should be expended to optimize blood pressure control, in particular in the presence of comorbidities. In transplant recipients, β-blockers are widely used, whereas ACE inhibitors are used infrequently.     

Risk Factors for Mortality in Liver Transplant Recipients With ESKAPE Infection

BackgroundAlthough infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections.MethodsA retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified.ResultsFifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1–40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7–244.8, P = .001), and lymphocyte counts <300/mm³ (OR = 20.2, 95% CI = 2.9–142.2, P = .003).ConclusionsTo improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts.     

Early indicators of prognosis in fulminant hepatic failure: an assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital criteria.

While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 +/- 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age >or=50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time >or=35 seconds, and creatinine >or=1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of >or=33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c-statistic [95% confidence interval]: CPI 0.802 [0.726-0.878], MELD 0.717 [0.636-0.789], and KCH criteria 0.676 (0.588-0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis.