ABSTRACT Purpose: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. Methods: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient’s total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. Results: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). Conclusions: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed. Purpose VEGFa, , (VEGFa) KappaLightChainEnhancer Kappa Light Chain Enhancer (NFkB ischemiareperfusion ischemia reperfusion Methods clamping IL6, IL6 IL 6, IL-6 IL10, IL10 10, IL-10 assessed times n= n (n recipient s n=6, n6 n=6 (n=6) Results 0.62±0.19 062019 0 62 19 (0.62±0.1 0.39±0.08 039008 39 08 p 0.016. 0016 0.016 . 016 0.016) (IL-6) (IL-10) Notch1. (Notch1) Conclusions (VEGFa IL- IL1 IL-1 (n=6 0.62±0.1 06201 (0.62±0. 0.39±0.0 03900 3 001 0.01 01 (IL-6 (IL-10 (Notch1 0.62±0. 0620 (0.62±0 0.39±0. 0390 00 0.0 (IL- (IL-1 (Notch 0.62±0 062 (0.62± 0.39±0 039 0. (IL 0.62± 06 (0.62 0.39± 03 0.62 (0.6 0.39 0.6 (0. 0.3 (0 (

Abstract Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were “COVID-19” and “Liver transplantation”. Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5-44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)

Non-tumoral portal vein thrombosis (PVT) is associated with higher morbidity and mortality in liver transplantation (LT). In this study, we aimed to evaluate the impact of PVT in LT outcomes and analyze the types of surgical techniques used for dealing with PVT during LT. A systematic review was conducted in Cochrane, MEDLINE, and EMBASE databases, selecting articles from January 1990 to December 2019. The MESH-terms used were (“Portal Vein”[Mesh] AND “Thrombosis”[Mesh] NOT “Neoplasms”[Mesh]) AND (“Liver Transplantation”[Mesh]). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendation was used, and meta-analysis was performed with Review Manager Version 5.3 software. A total of 1,638 articles were initially found: 488 in PubMed, 289 in Cochrane Library, and 861 in EMBASE, from which 27 were eventually selected for the meta-analysis. Surgery time of LT in patients with PVT was longer than in patients without LT (p<0.0001). Intraoperative red blood cell (p<0.00001), fresh frozen plasma (p=0.01), and platelets (p=0.03) transfusions during LT were higher in patients with PVT. One-year (odds ratio [OR] 1.17; p=0.002) and 5-year (OR 1.12; p=0.01) patient survival after LT was worse in the PVT group. Total occlusive PVT presented higher mortality (OR 3.70; p=0.00009) and rethrombosis rates (OR 3.47 [1.18-10.21]; p=0.02). PVT Yerdel III/IV classification exhibited worse 1-year [2.04 (1.21-3.42); p=0.007] and 5-year [0.98 (0.59-1.62); p=0.93] patient survival. Thrombectomy with primary anastomosis was associated with better outcomes. LT in patients with non-tumoral PVT demands more surgical time, needs more intraoperative transfusion, and presents worse 1- and 5-year patient survival. Total occlusive PVT and Yerdel III/IV PVT classification were associated with higher mortality. (PROSPERO, registration number: CRD42020132915).

RESUMO Racional: A incidência de hérnia abdominal em pacientes cirróticos é elevada, em torno de 20%. Em casos de ascite volumosa, a incidência atinge valores até 40%. Uma das principais e mais graves complicações no pós-operatório de correção de hérnias de pacientes cirróticos é a insuficiência renal aguda (IRA). Objetivo: Analisar a função renal de pacientes cirróticos submetidos a herniorrafias, comparando aqueles que apresentavam IRA pós-operatório com os demais, para determinar os fatores relacionados à sua ocorrência. Método: Seguimento de pacientes cirróticos submetidos à cirurgia de hérnia entre 2001 e 2014 no Serviço de Transplante de Fígado. Foram coletados exames laboratoriais para avaliar a função renal no pós-operatório rotineiramente. A IRA foi definida com base no consenso do clube da ascite em 2015. Resultados: Dos 174 pacientes incluídos, ocorreu IRA em 58 pacientes (34,9%). Houve diferença entre grupos para as seguintes variáveis: MELD inicial, creatinina basal e creatinina, o grupo com IRA apresentou medias superiores ao grupo que não apresentou IRA. No grupo IRA PO, 74,1% das cirurgias, foram realizadas em caráter de emergência, enquanto que no grupo sem IRA no pós-operatório, 34,6%. No grupo IRA, 90,4% dos indivíduos apresentaram complicações no pós-operatório, enquanto no grupo sem IRA, 29,9%. As variáveis idade, MELD inicial, creatinina basal e creatinina no pós-operatório inicial foram estatisticamente significantes na análise de sobrevida. Conclusões: Existe uma associação entre IRA pós-operatória e cirurgia de emergência e IRA pós-operatóri e complicações pós-operatórias. Os fatores relacionados à maior ocorrência de IRA em pacientes cirróticos submetidos à cirurgia de hérnia são o MELD inicial, creatinina basal, creatinina pós-operatória inicial. O preparo de pacientes cirróticos com hérnia abdominal antes de procedimentos cirúrgicos deve ocorrer sistematicamente, pois apresentam alta incidência de IRA pós-operatória.

ABSTRACT Background: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). Aim: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. Methods: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . Results: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. Conclusions: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

OBJECTIVES: The number of pancreatic transplants has decreased in recent years. Pancreatic grafts have been underutilized compared to other solid grafts. One cause of discard is the macroscopic appearance of the pancreas, especially the presence of fatty infiltration. The current research is aimed at understanding any graft-related association between fatty tissue infiltration of the pancreas and liver steatosis. METHODS: From August 2013 to August 2014, a prospective cross-sectional clinical study using data from 54 multiple deceased donor organs was performed. RESULTS: Micro- and macroscopic liver steatosis were significantly correlated with the donor body mass index ([BMI]; p=0.029 and p=0.006, respectively). Positive gamma associations between pancreatic and liver macroscopic and microscopic findings (0.98; confidence interval [CI]: 0.95-1 and 0.52; CI 0.04-1, respectively) were observed. Furthermore, comparisons of liver microscopy findings showed significant differences between severe versus absent (p<0.001), severe versus mild (p<0.001), and severe versus moderate classifications (p<0.001). The area under the receiver operating curve was 0.94 for the diagnosis of steatosis by BMI evaluation using a cut-off BMI of 27.5 kg/m2, which yielded 100% sensitivity, 87% specificity, and 100% negative predictive value. CONCLUSIONS: We observed a positive association of macroscopic and microscopic histopathological findings in steatotic livers with adipose infiltration of pancreatic grafts.

RESUMO Racional: A volumetria por tomografia computadorizada (VTC) é uma ferramenta útil para a previsão do peso do enxerto (PE) para o transplante hepático com doador vivo (TFDV). Poucos estudos examinaram a correlação entre o VTC e PE no parênquima hepático normal. Objetivo: Analisar a correlação entre VTC e PE em uma população adulta de doadores para o TFDV e realização de revisão sistemática dos modelos matemáticos existentes para calcular o peso de enxertos hepáticos parciais. Métodos: Foram revisados retrospectivamente 28 doadores consecutivos submetidos à hepatectomia direita para o TFDV entre janeiro de 2009 a janeiro de 2013. Todos os doadores eram adultos saudáveis com VTC pré-operatório. Os enxertos foram perfundidos com solução de preservação HTK. O volume estimado foi obtido por VTC e estes valores foram comparados com o peso real do enxerto, o qual foi aferido depois da hepatectomia e perfusão do enxerto. Resultados: A mediana do PE real foi de 782,5 g, média de 791,43±136 g, variando de 520-1185 g. A mediana do volume estimado do enxerto foi de 927,5 ml, média de 944,86±200,74 ml e variou de 600-1477 ml. A regressão linear volume estimado do enxerto e PE real foi significativamente linear (PE=0.82 do volume estimado do enxerto, r2=0,98, declive=0,47, desvio-padrão de 0,024 e p<0,0001). Correlação linear de Spearman foi de 0,65, com IC de 95% do 0,45-0,99 (p<0,0001). Conclusão: A regra de "um-para-um" não deve ser empregada em pacientes com parênquima hepático normal. A melhor estimativa do peso do enxerto hepático de doador vivo pode ser alcançado através da multiplicação do VTC por 0,82.

ABSTRACT Background: Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. Aim: To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Methods: Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Results: Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82.

RESUMO Introdução: A rejeição aguda tardia apresenta resultados com pior sobrevida do paciente e do enxerto após o transplante de fígado. Objetivo: Analisar os resultados publicados na literatura nos últimos anos pelos principais centros de transplante sobre o tema rejeição aguda tardia para a tualização analisando suas manifestações clínicas, diagnóstico e tratamento. Método: Foi realizado uma revisão sistemática da literatura, utilizando o banco de dados PubMed/Medline com os descritores relacionados à rejeição aguda tardia nos artigos publicados até novembro de 2013. Foram analisados dados demográficos, imunossupressão, rejeição, infecção, bem como as taxas de sobrevida do enxerto e do paciente. Resultados: A rejeição aguda tardia no pós transplante de fígado mostra pior resultado na sobrevida do enxerto e do paciente. A grande maioria dos estudos foram coortes retrospectivas e descritivas. A incidência de rejeição aguda tardia variou de 7-40% a partir destes estudos. A rejeição aguda tardia é uma das causas de perda do enxerto. Rejeição aguda tardia tem sua definição variável definida em relação ao tempo. Sua evolução apresenta resultado diferente em relação à sobrevida do enxerto, podendo evoluir para rejeição crônica, apresentando pior prognóstico. A rejeição aguda tardia está presente no momento em que se tende a manter menor imunossupressão, alguns meses depois transplante. Conclusão: Os artigos atuais mostram a importância da rejeição aguda tardia. O benefício real está no diagnóstico precoce e no tratamento adequado durante o episódio e no seguimento tardio após transplante de fígado.

Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion: The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation.

RACIONAL: A insuficiência hepática aguda está associada à alta taxa de mortalidade e os principais efeitos do tratamento são para evitar o edema cerebral e as infecções, que muitas vezes são responsáveis pela morte do paciente. O transplante hepático é o tratamento padrão-ouro e melhora a sobrevida de um ano. OBJETIVO: Descrever uma técnica alternativa para transplante de fígado auxiliar na insuficiência hepática aguda. MÉTODO: Transplante de fígado auxiliar devido à insuficiência hepática fulminante pela infecção pelo vírus da hepatite B. O paciente preencheu os critérios O´Grady e o racional para indicar o transplante de fígado auxiliar foi a hepatite aguda sem instabilidade hemodinâmica ou insuficiência renal em um paciente com deterioração da consciência. Foi realizado o transplante auxiliar de fígado com enxerto inteiro com uma técnica alternativa para transplante auxiliar parcial de fígado. RESULTADOS: O procedimento demonstrou melhora da função hepática e diminuição da hipertensão intracraniana no pós-operatório. CONCLUSÃO: Esta técnica é viável e pode superar algumas complicações pós-operatórias que estão associadas com enxertos parciais. Tanto quanto sabemos, este é o primeiro caso de transplante de fígado auxiliar descrito no Brasil.

BACKGROUND: Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. AIM: To describe an alternative technique to auxiliary liver transplant on acute liver failure. METHOD: Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. RESULTS: The procedure improved liver function and decreased intracranial hypertension in the postoperative period. CONCLUSION: This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil.