Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil.

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.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT 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.

Impact of cytomegalovirus reactivation just before liver transplantation: A prospective cohort study.

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.

Sofosbuvir, ribavirin and pegylated interferon for a daclatasvir-resistent genotype 3 hepatitis C virus: case report and review.

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.

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

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.

Validation of the "Metroticket" model in a cohort of patients transplanted for hepatocellular carcinoma in southern Brazil.

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.

D-MELD does not predict post-liver transplantation survival: a single-center experience from Brazil.

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.

Liver retransplantation in adults: a 20-year experience of one center in southern Brazil.

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.

Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.

For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.

Impact of MELD score implementation on liver allocation: experience at a Brazilian center.

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.

Impact of creatinine values on MELD scores in male and female candidates for liver transplantation.

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.

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.

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.

MELD and other predictors of survival after liver transplantation.

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.

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

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.

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Liver glutathione depletion after preservation and reperfusion in human liver transplantation

OBJETIVO: O estresse oxidativo é um importante mecanismo responsável pela disfunção dos enxertos após transplante de fígado (TF). Sabe-se que níveis baixos de Glutationa reduzida (GSH) deixam os enxertos vulneráveis aos danos de reperfusão. O objetivo deste estudo foi avaliar as concentrações de GSH e da Glutationa oxidada (GSSG), os danos hepatocelulares e a função em enxertos ótimos e subótimos após TF. MÉTODOS: Foram realizadas biópsias em 33 pacientes imediatamente antes do implante e duas horas após a reperfusão, permitindo a determinação do GSH, GSSG e o cálculo do índice de stress oxidativo (GSH/GSSG). Foram medidas as transaminases hepáticas e as atividades da Protrombina (TP) e do Fator V para avaliação dos danos hepatocelulares e da função do enxerto, respectivamente. O dano histopatológico foi avaliado através de um índice de cinco parâmetros. RESULTADOS: Houve uma diminuição nos níveis de GSH (p<0.01) 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) e aumento nos níveis de GSSG (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) (p<0.05). Houve diminuição do GSH/GSSG (2.23 ± 0.31 to 0.482 ± 0.042 and 2.47 ± 0.32 to 0.593 ± 0.068). Nenhuma diferença entre os grupos ótimo e subótimo foi vista após duas horas de reperfusão. Os escores de danos histopatológicos foram maiores no grupo subótimo (6.46 ± 0.4 vs. 5.39 ± 1.1) (p<0.05) e mostraram correlação com o TP e fator V no grupo Ótimo (p<0.05). A análise multivariada apontou a esteatose como um fator de risco independente para a ocorrência de danos histopatológicos (p<0.05). CONCLUSÃO: Houve uma significativa depleção de GSH e formação de GSSG após a preservação em solução devido a um intenso estresse oxidativo nos enxertos ótimos e subótimos, porém estes níveis não se correlacionaram com a viabilidade dos enxertos.

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.

Zigomicose após transplante hepático em adultos: relato de três casos / Zygomycosis following liver transplantation in adults: report of three cases

Relatam-se três casos de zigomicose após transplante hepático em uma série de 300 pacientes. O diagnóstico foi anatomopatológico (dois casos à necropsia e um à cirurgia). A doença manifestou-se de diferentes formas: rinomaxilar, gastrointestinal e, em um paciente, comprometeu a anastomose da artéria hepática. Neste caso, retirada cirúrgica da região comprometida e uso de anfotericina-B possibilitaram a cura.