Maria Lucia Zanotelli

MELD and other predictors of survival after liver transplantation

Abstract:  Background:  This study examined how reliable is the pre‐transplant model for end‐stage liver disease (MELD) score in predicting post‐transplantation survival and analyzed variables associated with patient survival.

Frequency of and factors associated with vascular complications after pediatric liver transplantation

OBJECTIVE to evaluate the frequency and factors associated with vascular complications after pediatric liver transplantation. METHOD risk factors were evaluated in 99 patients under 18 years of age with chronic liver disease who underwent deceased donor liver transplantation (DDLT) between March of 1995 and November of 2009 at the Hospital de Clínicas de Porto Alegre, Brazil. The variables analyzed included donor and recipient age, gender, and weight; indication for transplant; PELD/MELD scores; technical aspects; postoperative vascular complications; and survival. RESULTS vascular complications occurred in 19 patients (19%). Arterial events were most common, occurred earlier in the postoperative period, and were associated with high graft loss and mortality rates. In the multivariate analysis, the following factors were identified: portal vein diameter ≤ 3mm, donor-to-recipient body weight ratio (DRWR), prolonged ischemic time, and use of arterial grafts. CONCLUSION the choice of treatment depends on the timing of diagnosis; however, in this study, surgical revision or correction produced worse outcomes than percutaneous angioplasty. The reduction of risk factors and early detection of vascular complications are key elements to a successful transplantation.

Survival benefit of liver transplantation and the effect of underlying liver disease

BACKGROUND The benefit of liver transplantation relative to initial degree of underlying liver disease and time on the waiting list remains poorly defined. We sought to examine the survival benefit attributable to liver transplantation across a wide range of Model for End-Stage Liver Disease (MELD) scores. METHODS The study population included patients with end-stage liver disease enlisted in Rio Grande do Sul, Brazil, between 2001 and 2005. Survival and hazard function for enlisted and transplanted patients were estimated using parametric and nonparametric methods. MELD score was utilized to account for underlying liver disease. RESULTS Of 1,130 eligible patients, 520 (46.0%) were transplanted, 266 (23.5%) died on the waiting list, 141 (12.5%) were excluded from the waiting list, and 203 (18.0%) remained enlisted and were awaiting transplantation at the time of last observation. At 1 year after transplantation, a MELD score of 15 represented a transition point in terms of overall survival benefit (MELD 10, 90% vs 83%; MELD 15, 81% vs 80%; MELD 20, 63% vs 78%; MELD 25, 42% vs 74%; MELD 30, 21% vs71%; enlisted vs transplant patients, respectively). MELD scores at which transplantation seemed to be beneficial relative to the amount of follow-up time was MELD 23, 17, 15, and 12 at 6 months, and 1, 2, and 5 years, respectively, from time of transplantation/enlistment. CONCLUSION Although patients with greater MELD scores enjoy a pronounced and early benefit from transplantation, patients with lesser MELD scores do gain from transplantation, although a greater period of time is needed to realize the survival benefit.

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.

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.

Comparison Between IGL-1 and HTK Preservation Solutions in Deceased Donor Liver Transplantation.

The effectiveness of liver preservation solutions remains in evidence. Cold ischemia time, steatosis, expanded criterion donors, operational cost, and survival represent important roles in its success. In a prospective cohort study between August 2009 and April 2014, 178 patients were allocated into an Institut Georges Lopez - 1 (IGL-1) solution group (63.5%) or histidine-tryptophan-ketoglutarate (HTK) group (36.5%). There were no differences among recipients characteristics including age, skin color, gender, Model for End-stage Liver Disease score, acute rejection, cholestasis, and reperfusion syndrome incidences. Also, donors, age average, skin color, donor risk index, time in intensive care unit, hemodynamic variables, infections, and steatosis incidences were similar. The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group (P = .77). Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL, respectively, with IGL-1 and 1298 and 2291 mg/dL, respectively, with HTK (P = .016) and similar at day 15 (P > .88). The incidence of delayed graft function was 4.5% with IGL-1 and 4.6% with HTK (P = .90). The incidence primary nonfunction was 2.7% with IGL-1 and 3.1% with HTK (P = .71). The incidence of perioperative death was 11.5% with IGL-1 and 13.8% with HTK (P = .94). The survival in 30 months was 86% in IGL-1 group and 82% in HTK group (P = .66). Both preservation solutions are efficient to liver transplantations with deceased donors. Major prospective trials are necessary to evaluate each preservation solutions particularities. The preservation solution availability in each transplantation center must guide its use at the present moment.

Alpha-fetoprotein Level Predicts Recurrence After Transplantation in Hepatocellular Carcinoma.

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplantation. In an attempt to predict their recurrence after liver transplantation, evaluation of tumor number and size, degree of histologic differentiation, and the presence of vascular invasion already have their importance established. In this context, the role of biologic markers such as alpha-fetoprotein (AFP) is still not clear. This retrospective cross-sectional study analyzed the AFP relationship with recurrence of HCC after orthotopic liver transplantation. The current study retrospectively analyzed data from 206 patients with a histopathologic confirmed HCC between 1997 and 2010. The overall survival rates at 1, 3, 5, and 14 years were 78.6%, 65.4%, 60.5%, and 38.7%, respectively. The frequency of recurrence was 15.5%, and recurrence was significantly associated with a lower survival rate (P < 0.001). No association was observed between survival and AFP level (P = 0.153). A correlation, however, was found between tumor recurrence and AFP level (P = 0.002). Univariate analysis of risk factors for recurrence revealed that an AFP level greater than 200 ng/mL, the number of tumors, the degree of cellular differentiation, and the presence of vascular invasion or satellite nodules were associated with relapse. By multivariate analysis, only an AFP level greater than 200 ng/mL remained as a risk factor. Although an elevated AFP level did not correlate with survival in HCC patients undergoing orthotopic liver transplantation, a high AFP level was associated with a 3.32-folds increase in the probability of HCC recurrence.

Liver glutathione depletion after preservation and reperfusion in human liver transplantation

PURPOSE The oxidative stress is an important mechanism responsible for dysfunction after orthotopic liver transplantation (OLT). Glutathione (GSH) low levels after cold storage render the grafts vulnerable to reperfusion injury. Aim of this study was to evaluate GSH and oxidized glutathione (GSSG) liver concentrations, the hepatocellular injury and function in optimal and suboptimal grafts after human OLT. METHODS Liver biopsies were taken in 33 patients before the implant and two hours after reperfusion, allowing determination of GSH, GSSG and oxidative stress ratio (GSH/GSSG). Serum transaminases, prothrombin activity (PT) and factor V were measured to evaluate injury and function respectively. Histopathological injury was analyzed by an index of five parameters. RESULTS There was a decrease in GSH (p<0.01) after reperfusion (0.323 +/- 0.062 ìmol/g to 0.095 +/- 0.01 ìmol/g and 0.371 +/- 0.052 ìmol/g to 0.183 +/- 0.046 ìmol/g) in suboptimal and optimal groups, respectively. An increase of GSSG (p<0.05) occurred after reperfusion (0.172 +/- 0.038 ìmol/g to 0.278 +/- 0.077 ìmol/g and 0.229 +/- 0.048 ìmol/g to 0.356 +/- 0.105 ìmol/g) in suboptimal and optimal groups, respectively. A decrease (p<0.01) occurred in the GSH/GSSG ratio after reperfusion (2.23 +/- 0.31 to 0.482 +/- 0.042 and 2.47 +/- 0.32 to 0.593 +/- 0.068) in suboptimal and optimal groups, respectively. Histopathological injury scores were higher (p<0.05) in the suboptimal group than in optimal (6.46 +/- 0.4 vs. 5.39 +/- 1.1) and showed correlation with PT and factor V in the optimal group (p<0.05). Multivariate analysis pointed steatosis as an independent risk factor to histopathological injury (p<0.05). CONCLUSION There was a significant GSH depletion and GSSG formation after cold storage and reperfusion due to a similar oxidative stress in optimal and suboptimal grafts, but these levels were not related to graft viability.

Living related versus deceased donor liver transplantation for maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9-13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19 ± 12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224 ± 306 μM to 143 ± 44 μM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management.

Post-transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.