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Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Background: Cytomegalovirus (CMV) is the most common viral pathogen after liver transplantation (LT). Although reactivation of CMV infection is generally described in the context of immunosuppression, it has also been described in critically ill immunocompetent patients including cirrhotic patients., Aim: To determine the incidence of reactivated CMV prior to LT., Methods: This was a prospective cohort study evaluating adult patients who underwent LT between 2014 and 2016. A plasma sample was obtained from all patients for CMV quantitative real-time PCR testing right before transplantation. Patients were followed for at least 1 year to assess the following outcomes: Incidence of CMV infection, organ rejection and overall mortality., Results: A total of 72 patients were enrolled. Four patients died before transplantation, thus 68 patients were followed up for a median of 44 mo (20-50 mo). In 23/72 patients (31.9%) CMV was reactivated before transplantation. Post-transplantation, 16/68 (23.5%) patients had CMV infection and that was significantly associated with the recipient being CMV negative and a CMV-positive donor. Pre-transplant CMV reactivation was not associated with overall mortality (log rank: 0.9)., Conclusion: This study shows that CMV infection is common in patients with chronic liver disease just before LT, but the clinical impact of this infection seems to be negligible., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic Hepatitis C relapse after liver transplantation can lead to graft failure within a short time period. The high efficacy and good safety profile of direct-acting antivirals has led to consensual recommendations for using interferon-free treatment after liver transplantation. However, pegylated interferon may still be required for genotype 3 non-responders. We treated a liver graft recipient with grade 1 fibrosis in the biopsy with daclatasvir and sofosbuvir for 12 weeks. He did not respond and progressed to grade 3 fibrosis. Lacking other options, we obtained a sustained virological response with pegylated interferon, ribavirin and sofosbuvir for 12 weeks. The combination of pegylated interferon, ribavirin and sofosbuvir is a viable option after the failure of direct acting antivirals in economically disadvantaged countries.

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., Methods: We report our real-world results in liver transplant (LT) recipients. All patients were hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course, followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months before treatment and stratified as early (0-1) or moderate to advanced (2-4) according to the Metavir score., Results: Median postoperative time was 5.2 years. Genotype 3 was found in 66.7% of the sample. The following regimens were prescribed: daclatasvir-sofosbuvir with (n = 11) or without (n = 28) ribavirin. Genotypes 1 and 3 were evenly distributed between the regimens. Sustained virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who received daclatasvir-sofosbuvir and in all patients (100%) who received daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample: 48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin was more commonly prescribed (P = .001)., Conclusions: The SVR rate in our LT recipients was similar to that previously reported in the literature. The addition of ribavirin to DAA treatment appears to be justified in this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

MLVI has been used to assess adherence. To determine the MLVI in children <12 years of age at transplantation and to identify demographic correlates and consequences for the graft. This is a retrospective study of 50 outpatients (4.0 ± 3.5 years), at least 13-month post-liver transplantation. The outcomes evaluated were MLVI, ALT > 60 IU/L, ACR, death, and graft loss. We analyzed demographic and socioeconomic characteristics, indication for transplantation, and type of donor. Student's t test and the chi-square test were used. Statistical significance was set at P ≤ .05. Seventy-two percent were infants or preschoolers, 62% biliary atresia. Seventy-four percent of the mothers had middle-school education, and 54% of the families had an income ≤3632.4 US$/y. Twenty-two (44%) patients had a MLVI ≥ 2 SD; this was more prevalent in families with higher incomes (P = .045). ALT levels > 60 IU/L were more common in MLVI ≥ 2 SD group (P = .035). ACR episodes were similar between groups (P = 1.000). No patient died or lost the graft. MLVI ≥ 2 SD may be an indicator of the risk of medication non-adherence., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to disclose.

This retrospective study evaluated the ability of the Metroticket model to predict five-yr post-transplant survival in patients with hepatocellular carcinoma (HCC) based only on explant data. Five-yr survival after transplant was estimated using the Metroticket Calculator, and observed survival was calculated using the Kaplan-Meier method. Metroticket-predicted survival was compared between deceased and surviving patients using the Mann-Whitney test. The accuracy of Metroticket estimates in discriminating between these two patient groups was assessed using the c-statistic. Median patient age (n = 109) was 55.7 yr, and 72.5% of the sample were men. Metroticket-predicted and observed post-transplant survival at five yr was 71.1% and 58.7%, respectively. Predictions were calculated using the explant data of the 64 survivors and 45 deceased patients. Median five-yr survival was 72.9% in the former and 69.7% in the latter. The c-statistic of the Metroticket model for distinguishing surviving from deceased patients was 0.55. In this cohort, the Metroticket model was unable to accurately predict five-yr post-transplant survival based only on explant data., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 recipient's 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 solution's particularities. The preservation solution availability in each transplantation center must guide its use at the present moment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The D-MELD score was designed to prevent donor-recipient matches with a high risk of unfavorable outcome. The main objective of the present study was to assess the predictive value of the DMELD score for 1-month and 3-month post-transplant mortality in a cohort of patients who underwent deceased-donor liver transplantation in Southern Brazil., Material and Methods: A cohort study was conducted. Receiver operating characteristic c-statistics were used to determine the ability of the D-MELD score to predict mortality. The Kaplan-Meier method was used to analyze survival as a function of time regarding D-MELD scores, and the Cox model was employed to assess the association between D-MELD and mortality., Results: Most recipients were male, with a mean age of 54.3 ± 9.6 years (n = 233 transplants). Mean donor age was 44.9 ± 16.8 years (19.3% of donors were aged ≥ 60 years). Mean MELD and D-MELD scores were 16.3 ± 7.1 and 733.1 ± 437.8 respectively. Overall survival at 1 and 3 months was 83.6%. The c-statistic value for 1- and 3-month mortality was < 0.5 for the D-MELD. Analysis of Kaplan-Meier curves for groups with D-MELD scores < 1,600 and ≥ 1,600 did not show statistically significant differences in survival (p = 0.722)., Conclusion: D-MELD scores were unable to predict survival in this cohort of Brazilian liver transplant recipients.

Introduction: Patients undergoing orthotopic liver transplantation often present with acute kidney injury (AKI) in the postoperative period. It has been associated with a greater number of complications and high mortality rates. The goal of this study was to determine the incidence of AKI during the early posttransplant period and mortality in patients undergoing orthotopic liver transplantation in our hospital., Patients and Methods: In this retrospective cohort study, we reviewed the medical records of all patients aged >18 years undergoing liver transplantation from April 2008 to April 2011. The exclusion criteria were a glomerular filtration rate (estimated by using the Modification of Diet in Renal Disease formula) <60 mL/min/1.73 m(2) or AKI at the time of transplantation. AKI was defined as an increase ≥50% from preoperative baseline serum creatinine levels during the hospitalization period., Results: Of 113 selected patients, 78 (69%) were male. The mean age was 54.03 ± 9.38 years. The mean preoperative baseline creatinine level was 0.94 ± 0.15 mg/dL, and the estimated glomerular filtration rate was 87.09 ± 19.67 mL/min/1.73 m(2). The mean calculated Model for End-Stage Liver Disease score was 13. Hepatitis C serology was present in 70.8%, hepatitis B in 11.5%, hepatocellular carcinoma in 75.2%, and alcohol abuse in 31.9% of patients. The incidence of AKI was 56.6% (64 of 113 patients). The main risk factors for AKI were Model for End-Stage Liver Disease score and diuretic use at baseline. Renal replacement therapy (RRT) was performed in 19.5% (22 of 113) of patients. The hospital mortality rate in the group with AKI was 25% (16 of 64 patients) and 6.1% (3 of 49 patients) between patients without AKI (odds ratio, 5.11 [confidence interval, 1.39-18.7]; P < .01]. Among patients who underwent RRT, the in-hospital mortality rate was 54.5% (12 of 22 patients) compared with 7.7% (7 of 91 patients) from the other remaining patient cohort (odds ratio, 14.40 [confidence interval, 4.60-45.00]; P < .01)., Conclusions: There was a high incidence of AKI in patients undergoing liver transplantation and an increased risk of mortality among patients who needed RRT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Introduction: Liver retransplantation (LReTx) is the therapeutic option for hepatic graft failure. Survival after LReTx is poorer than after primary liver transplantation. Given the organ shortage, it is essential to optimize the use of this resource., Objective: To evaluate rates, indications and patient survival after LReTx and identify factors associated with mortality following LReTx., Material and Methods: We conducted a retrospective cohort study of all adults undergoing LReTx based on registry data from the Liver Transplantation Group (Complexo Hospitalar Santa Casa de Porto Alegre), southern Brazil., Results: Between June 16, 1991 and July 19, 2011, 824 patients underwent 866 liver transplants. Forty-two procedures corresponded to LReTx (4.8% of all liver transplants performed). Thirty-eight patients who underwent a single LReTx procedure were included in this study. The leading indication for LReTx was hepatic artery thrombosis (HAT) (31.6%), followed by primary nonfunction (PNF) (18.4%). The main indication for early LReTx was PNF (58.3%) and for late LReTx was HAT (38.5%). During the follow-up period, 26 patients (68.4%) died after LReTx. Patient survival at 1 and 3 years after LReTx was 44.7% and 44.7%, respectively. Patients infected with hepatitis C virus, serum albumin < 2.5 g/dL and receiving mechanical ventilation immediately before LReTx had a significantly lower survival rate than the other patients., Conclusion: Considering the increased mortality when the graft loss is delayed, it is necessary to define the minimum acceptable results to indicate LReTx and identify the patients who would most benefit from this treatment.

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., (© 2013 John Wiley & Sons A/S.)

Introduction: A systematic bias against women, resulting from the use of creatinine as a measure of renal function, has been identified in Model for End-stage Liver Disease (MELD)-based liver allocation. Correction of this bias by calculation of female creatinine levels using the Modification of Diet in Renal Disease (MDRD) formula has been suggested., Material and Methods: A cohort of 639 cirrhotic candidates for first-time liver transplantation was studied. Creatinine levels were corrected for gender using the MDRD formula. The accuracy of MELD, with or without creatinine correction, to predict 3-and 6-month mortality after inclusion in a transplant waiting list was estimated., Results: Women exhibited significantly lower creatinine levels, glomerular filtration rate, and MELD scores than men. After creatinine correction, female MELD scores had a mean increase of 1.1 points. Creatinine correction yielded an increase of 3 points in the MELD score in 15.2% of patients, 2 points in 22.4%, and 1 point in 17.6% of patients. The likelihood of death at 3 and 6 months after enrollment in the transplant waiting list was similar in males and females and the likelihood of receiving a transplant, as assessed by Kaplan-Meier survival curves, was also similar in males and females., Conclusion: The survival or the likelihood of receiving a transplant while on the waiting list were similar in men and women in both pre- and post-MELD eras and creatinine correction did not increase the accuracy of the MELD score in estimating 3- and 6-month mortality in female candidates for liver transplantation.

Introduction. Model for end-stage liver disease (MELD) is an accurate predictor of mortality in patients with cirrhosis, and has been used on liver allocation in Brazil since 2006. However, its impact on organ allocation, waiting list and post-transplant mortality is still poorly characterized. This study aimed to assess the impact of implementation of the MELD system on liver allocation and mortality after liver transplantation (LT) in Southern Brazil. Material and methods. Adult patients with chronic liver disease on the waiting list for primary deceased-donor LT were divided into two cohorts (pre- and post-MELD implementation) according to the date of waiting list placement. Disease severity, as assessed by MELD score at placement, was similar in both cohorts. Patients were followed for at least 18 months to assess the outcomes of interest (death/LT). Results. Higher MELD scores correlated with waiting list mortality, which increased 20% with each additional point (HR 1.2; 95%CI 1.14-2.26; p < 0.001). Waiting list mortality was 30.9% before and 21.7% after MELD implementation (nonsignificant). Transplant rate increased after MELD implementation (52 vs. 40%, p = 0.002). After excluding patients with hepatocellular carcinoma, mean MELD scores at LT were significantly higher in the MELD era (p < 0.01). There was no significant correlation between MELD scores at LT and post-LT survival. During 18-month follow-up, post-LT mortality rate was 25.4% before and 20% after MELD implementation (nonsignificant). Conclusion. MELD implementation was associated with a reduction in waiting list mortality. Although sicker patients received LT in the MELD era, post-transplant survival was similar in both periods.

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., (© 2012 John Wiley & Sons A/S.)

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., (Copyright 2010 Mosby, Inc. All rights reserved.)

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., Methods: A cohort study was conducted. Receiver operating characteristic curve c-statistics were used to determine the ability of MELD score to predict mortality. The Kaplan-Meier (KM) method was used to analyze survival as a function of time regarding the MELD score and Child-Turcotte-Pugh (CTP) category. The Cox model was employed to assess the association between baseline risk factors and mortality., Results: Recipients and donors were mostly male, with a mean age of 51.6 and 38.5 yr, respectively (n = 436 transplants). The c-statistic values for three-month patient mortality were 0.60 and 0.61 for MELD score and CTP category, respectively. KM survival at three, six and 12 months were lower in those who had a MELD score > or =21 or were CTP category C. Multivariate analysis revealed that recipient age > or =65 yr, MELD > or = 21, CTP C category, bilirubin > or = 7 mg/dL, creatinine > or = 1.5 mg/dL, platelet transfusion, hepatocellular carcinoma, and non-white color donor skin were predictors of mortality., Conclusions: Severe pre-transplant liver disease, age > or = 65, non-white skin donor, and hepatocellular carcinoma are associated with poor outcome.

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.

Unlabelled: Cytomegalovirus (CMV) is one of the most common and serious opportunistic infections in solid organ transplant patients. In different series the incidence of CMV infection ranges from 25% to 85%. An indirect effect of infection includes reduced long-term patient and allograft survival. Our objective was to determine the relationship between CMV infection and patient survival after orthotopic liver transplantation., Patients and Methods: From January 1999 to December 2001, 163 orthotopic liver transplantations were performed in 154 patients. The inclusion criteria for this analysis were the absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. CMV infection was detected by positive antigenemia., Results: CMV infection occurred in 65.8% of patients after orthotopic liver transplantation. Their 5-year survival was 85%, with no difference observed between patients with or without infection (P = .8)., Conclusion: CMV infection did not interfere with patient survival after orthotopic 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.

Unlabelled: Our objective was to investigate the potential risk factors associated with cytomegalovirus (CMV) infection., Patients and Methods: From January 1999 to December 2001, 163 liver transplantations were performed in 154 patients. The study inclusion criteria were absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. We determined variables such as age, gender, and number of hemecomponents as well as serum IgG CMV status of donors and recipients. We recorded the immunosuppression used by each patient. CMV infection was detected by positive antigenemia., Results: Recipient mean age was 50 years. The etiology of cirrhosis was viral (n = 57; 49.6%), alcoholic (n = 20; 17.4%), virus and alcohol (n = 15; 13.0%), cryptogenic (n = 14; 12.2%), or other causes (n = 9; 7.8%). CMV infection was positive in 75 patients (65.8%). There was no relation between infection and age, gender, or CMV IgG donor recipient status, or the number of hemecomponent units. The risk was 3.8-fold higher for patients receiving a three-drug compared with a two-drug regimen. When cyclosporine was used instead of tacrolimus, the risk of CMV infection was 4.3-fold higher. Logistic regression analysis revealed cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) to have stronger associations with CMV infection., Conclusion: The use of cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) are risk factors for CMV infection.

University of Wisconsin (UW) solution has been the standard for preservation of liver transplantation grafts since 1989. However, some studies demonstrated that histidine-tryptophan-ketoglutarate (HTK) solution is also effective. The purpose of this study was to compare the efficacy of both solutions in liver transplantation. From January 2003 to August 2004 the livers of deceased donors were randomized into HTK and UW groups. The 102 studied patients included 65 (63.7%) in the UW group and 37 (36.3%) in the HTK group. Sex, race, hemodynamic state, use of adrenergic drugs, and presence of steatosis in the donor were similarly distributed in the two groups (P > .05). The mean age of the donors was 38.1 years (SD +/-14.4) in the UW group and 44.6 years (SD +/-14.2) in the HTK cohort (P = .036). Sex, race, age, etiology of the cirrhosis, retransplant, acute liver failure, portal thrombosis, and Child-Pugh and MELD scores in the recipients were similarly distributed in the two recipient samples (P > .05). Among 89 patients who completed 4 months of follow-up, the HTK group included eight cases (25.8%) of biliary complications versus five cases (8.6%) in the UW group (P = .033; OR = 2.0 95% CI = 1.2-3.5). The incidence of graft dysfunction was 2.8% in the HTK group and 9.4% in the UW group (P = .15). In conclusion, UW and HTK solutions were equally effective for the preservation of the hepatic graft. The routine use of HTK solution can reduce the costs of liver transplantation.

Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

Background: Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Imaging techniques, specially computed tomography and ultrasound, are among the most useful diagnostic tools, although the accuracy of these methods may have a significant variability., Aims: To determine the prevalence of hepatocellular carcinoma in cirrhotic patients undergoing orthotopic liver transplantation at "Santa Casa de Misericórdia" of Porto Alegre, RS, Brazil; to estimate the sensitivity of computed tomography and ultrasound in pretransplantation detection of hepatocellular carcinoma in this population; to correlate the radiological characteristics with anatomopathological findings., Materials and Methods: Retrospective prevalence study., Population: adult, cirrhotic patients undergoing orthotopic liver transplantation from January 1990 to July 2003. Among the 292 transplanted patients, 31 cases of hepatocellular carcinoma were diagnosed, of which 29 were included in the study. Tumor characteristics in both ultrasound and computed tomography were compared to those observed in anatomopathological examination., Results: Prevalence of hepatitis C virus infection among patients with diagnosis of hepatocellular carcinoma was 93.5%, and the prevalence of hepatocellular carcinoma among transplanted patients was 10.6%. The overall sensitivity of the imaging techniques was 70.3% for computed tomography and 72% for ultrasound., Conclusion: The prevalence of hepatocellular carcinoma at our institution, as well as the sensitivity of both ultrasound and computed tomography to detect such tumors at pretransplantation screening were similar to those found by other authors, while the prevalence of hepatitis C virus infection, the most common etiological agent for liver disease in our patients, is one of the highest ever reported in literature. Factors influencing hepatocellular carcinoma detection rates were: time from examination to liver transplantation; acquisition of computed tomography images during arterial phase; lesion size. Arterial phase proved to be the most useful part of computed tomography examination in this study.

Background: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation., Methods: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days., Results: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT., Conclusion: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

The aim of the study was to investigate risk factors associated with cytomegalovirus (CMV)-positive antigenemia in orthotopic liver transplant (OLT) patients. Sixty-nine patients undergoing OLT during 2001 were retrospectively evaluated for CMV antigenemia during a follow-up of 6 months after transplantation for demographic variables, pretransplant donor and recipient CMV serologic status, etiology of liver disease, number of blood transfusions, and type of immunosuppression. Among the 69 patients who underwent 71 OLT in this period, 43 met study criteria. Mean age was 49.7 +/- 10.8 years and 60.5% were men. End-stage liver disease was the indication for liver transplant, except in one case. The most prevalent etiology of liver disease was hepatitis C and/or alcohol in 66% of the cases. CMV-positive status was recorded in 74% of donors and 95% of recipients. None of the CMV-negative recipients received a positive donor allograft. CMV-positive antigenemia was 84% with 12% having two episodes of infection. There was no correlation between CMV infection and age, gender, etiology of liver disease, or number of blood transfusions. However, all patients using cyclosporine had CMV-positive antigenemia compared with 61% using tacrolimus (P <.032). In this study, the incidence of CMV infection after OLT in adult patients was slightly higher than reported in literature. No risk factor was associated with CMV antigenemia; however, this study suggests a higher probability of CMV infection among patients treated with cyclosporine.

Sixty-five children underwent liver transplantation (LTx) from March 1995 to December 2002. Cirrhosis due to biliary atresia was the main indication, and hepatic artery thrombosis (HAT) the most common vascular complication (n = 5). Other vascular problems were portal vein thrombosis and stenosis. Another patient developed hepatomegaly and ascites due to a late stenosis of the left hepatic vein anastomosis. The two cases of venous stenosis were successfully treated by percutaneous angioplasty. One graft with HAT was saved, but four children died awaiting retransplant.

We report three cases of zygomycosis following liver transplant in a series of 300 patients. Diagnosis was determined via anatomicopathological examination (on necropsy in two cases and during surgery in one case). The disease had different manifestations: rhinomaxillary, gastrointestinal and, in one case, it compromised the liver artery anastomosis. In this case, surgical removal of the affected region and use of amphotericin B achieved resolution.

Neurologic complications are important source of morbi-mortality, in liver transplantation. They result from previous factors, alterations during the surgical procedure, effects from immunosuppressor drugs, coagulopathy and infections. We analyzed, retrospectively, the chronology, causes, and frequencies of neurologic alterations in thirty adult patients submitted to liver transplantation, and our results differ slightly from those registered in other series.

Objective: To analyze the evolution of pediatric patients chosen for hepatic transplantation., Methods: A review was made of the clinical charts of the first 65 children and adolescents with chronic liver disease, aged 5 months to 19 years (X = 6.8%), chosen for liver transplantation during the period of August 1994 to March 1996. Data refer to the patients' demographic characteristics, etiology of their liver disease, their psychosocial situation and of their parents, and their clinical and laboratorial evaluation. According to the severity of the disease, patients were classified as active (waiting for a donor), in evaluation, inactive (compensated liver disease), and excluded for psychosocial or medical conditions, or because of bad indication., Results: Eight patients (12%) received transplantation, and one of them died. Seven (11%) died when in evaluation or waiting for a donor. Ten patients (15%) were excluded from the waiting list: 6 for social problems, and 4 for medical problems. No patient was excluded for bad indication. Six patients are in the active list, waiting for donor. The other 23 patients (35%) are in evaluation, and 11 (17%) are classified as inactive in the waiting list., Conclusions: Eleven patients (17%) were not operated on due to the advanced stage of the liver disease. We emphasize the necessity of organ donation, and the early contact of the patients with a reference center.

A case of combined pancreaticoduodeno-renal transplant with good graft function was complicated by recurrent episodes of graft pancreatitis treated by vesical catheter drainage. Four months after transplantation, a fistula from the pancreatic body associated with ascitis was identified. Anastomosis between pancreatic fistula and an individualized jejunal loop was performed. The duodenocystostomy was not disconnected. A splint placed inside the wirsung was exteriorized percutaneously through the jejunal loop and removed 30 days after the operation. Both kidney and pancreas grafts are functioning normally 2 years after transplantation.