Fontan-associated liver disease current status and transplantation consideration / 中华肝脏病杂志

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.

Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation / 中南大学学报(医学版)

OBJECTIVES@#Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections.@*METHODS@#In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed.@*RESULTS@#Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001).@*CONCLUSIONS@#Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Nonalcoholic fatty liver disease and liver transplantation / 中华肝脏病杂志

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is now the second largest indication for liver transplantation in Western countries, but viral hepatitis B and end-stage alcohol-related liver disease are still the main indications in China. With the improvement of people's living standards, the prevalence of metabolic syndrome, and the number of NAFLD patients has also gradually increased. At the same time, with the hepatitis B vaccination popularization and the nucleos(t)ide analogues and other drugs uses, it is predicted that NAFLD-related end-stage liver disease may become one of the main indications for liver transplantation in our country in the future. This article reviews the research progress of NAFLD and liver transplantation.

Consensus on diagnosis and treatment of postoperative infections in pediatric liver transplant recipients / 中华外科杂志

With the breakthrough in surgical technology, pediatric liver transplantation (PLT) has achieved landmark development in China in recent years. In some high-volume centers, postoperative outcomes have even been comparable to the world-leading levels. However, postoperative infection remains a major factor affecting graft and recipient survivals. Thus, the Enhanced Recovery After Surgery Committee of the Chinese Research Hospital Association organized experts from multiple disciplines and formulated the consensus to improve the diagnosis, treatment and prevention of postoperative infections in PLT recipients. This consensus is based on the progress of domestic and international researches in this field and followed the principles of evidence-based medicine. It covers general and transplantation-specific infection, and is expected to provide reference for centers conducting or planning to conduct PLT.

Preservation fluid cultures. Clinical significance in liver transplantation / Cultivos de líquido de preservación en trasplante hepático. Significancia clínica

Abstract The aim of this study was to determine the incidence of preservation fluids (PF) bacterial positive cultures, identify the germs involved, determine their correlation with infections in recipients during the postoperative period and compare outcomes in terms of morbidity, hospital stay and both patient and graft survival. We describe incidence and etiology of germs developed in PF cultures in our series and evaluate its impact on recipients. A prospective study in deceased donor liver transplants (LT) recipients was carried out from January 2014 to December 2017. Back table PF cultures were analized considering positive the development of any germs and negative to no signs of growth after 5 days. PF were classified as contamination or pathogens. Targeted antibiotic therapy was administered in the last ones. Recipients were divided in: PF (-) and PF(+). Recipients infections related to positive PF were analyzed. These were identified as "direct correlation" when the same germ grew up in PF. Hospital stay and 30 days follow up were compared. Eighty-eight patients PFs were included, 38% (33) had positive cultures, 28 (85%) of these were considered contamination and only 5 as pathogens. We found no differences in postoperative infections (p 0.840), ICU and total hospital stay (p 0.374 and 0.427) between both groups. Postoperative infections and hospital stay seem not to be influenced by PF cultures positivity. Treatment of isolated pathogens could have prevented infections, therefore, those groups that perform PF cultures should consider treatment in these cases and conclude prophylaxis when PF is negative or contaminated.

Resumen Las infecciones bacterianas son frecuentes en pacientes sometidos a trasplante hepático. Describimos la incidencia y etiología de los cultivos de líquidos de preservación (LP) positivos en nuestra serie y analizamos su importancia clínica. Se trata de un trabajo prospectivo de pacientes trasplantados hepáticos, entre enero 2014 a diciembre 2017. Se analizaron muestras de LP tomadas al finalizar la mesa de banco, considerándose positivo el desarrollo de cualquier germen y negativo la ausencia del mismo luego de 5 días. Los LP positivos se clasificaron en: con contaminantes y con patógenos. Los pacientes con LP patógenos recibieron tratamiento antibiótico de acuerdo al antibiograma. Los pacientes fueron divididos en dos grupos: con LP + y LP-. Las infecciones relacionadas a los LP fueron analizadas. Se consideró "correlación directa" cuando el mismo germen desarrolló en el LP y en el recipiente. Se comparó estadía hospitalaria en ambos grupos. Se incluyeron 88 pacientes, 38% (33) presentaron LP+, de los que el 85% (28) fueron por contaminación y 5 por pa tógenos. No se hallaron diferencias significativas en infecciones postoperatorias (p 0.840) y estadía hospitalaria (p 0.427) entre ellos. No hubo casos de "correlación directa". Las infecciones postoperatorias y la estadía hospitalaria de los pacientes no parecen estar influidas por la positividad de los cultivos de LP. El tratamiento dirigido a los gérmenes aislados como patógenos pudo prevenir infecciones, por lo tanto, los grupos que realizan cultivos de rutina deberían considerar el tratamiento en estos casos y finalizar la profilaxis cuando el LP sea negativo o contaminado.

Disseminated paracoccidioidomycosis in a liver transplant patient

Abstract Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.

Prevalência e tempo de desenvolvimento da hipertensão arterial sistêmica em pacientes após transplante de fígado / Prevalence and time of development of systemic arterial hypertension in patients after liver transplantation

ABSTRACT BACKGROUND: The use of immunosuppressive drugs after liver transplantation (LT) is associated with the development of systemic arterial hypertension (SAH), in addition to other comorbidities of metabolic syndrome. OBJECTIVE: Therefore, the purpose of this study was to analyze the time after use immunosuppressive drugs the patient progresses to SAH, as well as to identify its prevalence and the factors that may be correlated to it. METHODS: A retrospective and longitudinal study was conducted, based on the analysis of medical records of 72 normotensive patients, attended in the transplant unit of a university hospital, between 2016 and 2019. RESULTS: It was observed, on average, 9±6.98 months after immunosuppressive use, the patients were diagnosed with hypertension, and the prevalence of transplanted patients who evolved to SAH in this study was 59.64% (41 patients). In addition, there was a correlation between serum dosage of tacrolimus and the development of SAH (P=0.0067), which shows that tacrolimus has a significant role in the development of SAH. Finally, it was noticed that the development of post-transplantation hypertension indicates a higher risk of the patient presenting the other parameters of metabolic syndrome, as well as a higher impairment in its renal function (P=0.0061). CONCLUSION: This study shows that the patients evolved to SAH in an average of 9±6.98 months after immunosuppressive drug use. We have also found high prevalence of systemic arterial hypertension (59.64%) in patients after liver transplantation, who used calcineurin inhibitors, especially when associated with the use of tacrolimus.

RESUMO CONTEXTO: O uso de imunossupressores pós-transplante de fígado (TF) está associado ao desenvolvimento de hipertensão arterial sistêmica (HAS), além de outras alterações da síndrome metabólica. OBJETIVO: Sendo assim, o objetivo deste estudo foi analisar a partir de quando tempo após o uso do imunossupressor o paciente evolui para HAS, assim como, identificar a sua prevalência e outros fatores que podem estar relacionados, como injuria renal. MÉTODOS: Realizou-se um estudo retrospectivo, longitudinal, baseado em análise de 72 prontuários de pacientes, atendidos na unidade de transplante de um hospital universitário, que não apresentavam hipertensão arterial prévia, entre período de 2016 a 2019. RESULTADOS: Observou-se que, em média, 9±6,98 meses após uso do imunossupressor, os pacientes foram diagnosticados com hipertensão arterial sistêmica, sendo que a prevalência de pacientes transplantados que evoluíram para HAS, neste estudo, foi de 59,64% (41 pacientes). Além disso, verificou-se uma correlação entre a dosagem sérica de tacrolimus e o desenvolvimento de HAS (P=0,0067), o que evidencia que o tacrolimus tem uma atuação significativa no desenvolvimento da hipertensão arterial sistêmica. Por fim, percebeu-se que o desenvolvimento de HAS pós-transplante indica um maior risco de paciente apresentar os outros parâmetros da síndrome metabólica, como também maior prejuízo na sua função renal (P=0,0061). CONCLUSÃO: Este estudo mostra que os pacientes evoluíram para HAS em média 9±6,98 meses após o início do uso do imunossupressor. Verificou-se também alta prevalência de hipertensão arterial sistêmica (59,64%) em pacientes pós-transplante de fígado, que usavam inibidores de calcineurina, principalmente, quando associado ao uso de tacrolimus.

Encapsulating peritoneal sclerosis in liver transplant

Encapsulating peritoneal sclerosis occurs due to chronic irritation of the peritoneal surface resulting in inflammation and fibrosis. Encapsulating peritoneal sclerosis usually occurs in patients requiring peritoneal dialysis (PD); however, it may also occur in liver transplant patients. The fibrosis in encapsulating peritoneal sclerosis could be severe enough to cause small bowel obstruction (SBO). Herein, we report a case of encapsulating peritoneal sclerosis secondary to liver transplantation that presented with SBO. The patient was started on Tamoxifen for encapsulating peritoneal sclerosis and evaluated at follow-up without any other intestinal obstruction episodes. This case demonstrates that encapsulating peritoneal sclerosis can occur as a liver transplant complication and present with small bowel obstruction.

Postoperative serum triglyceride levels in predicting risk of new-onset diabetes mellitus in patients following liver transplantation / 浙江大学学报·医学版

To investigate the postoperative serum triglyceride (TG) levels in predicting the risk of new-onset diabetes mellitus (NODM) in patients following allogeneic liver transplantation. One hundred and forty three patients undergoing allogeneic liver transplantation in Shanghai General Hospital from July 2007 to July 2014 were enrolled in this study. The NODM developed in 33 patients after liver transplantation. The curve of dynamic TG levels in the early period after liver transplantation was generated. Independent risk factors of NODM were determined by univariate and multivariant logistic regression analyses. The clinical value of TG in predicting NODM was analyzed by area under the ROC curve (AUC). Serum TG levels were gradually rising in the first week and then reached the plateau phase (stable TG, sTG) in patients after surgery. The sTG in NODM group were significantly higher than that in non-NODM group (=-2.31, <0.05). Glucocorticoid therapy (=4.054, <0.01), FK506 drug concentration in the first week after operation (=3.482, <0.05) and sTG (=3.156, <0.05) were independent risk factors of NODM. ROC curve analysis showed that the AUC of sTG in predicting NODM was 0.72. TG shows a gradual recovery process in the early period after liver transplantation, and the higher TG level in stable phase may significantly increase the risk of NODM in patients.

Há lugar para a avaliação colangioscópica na estenose biliar anastomótica pós-transplante hepático de doador cadáver? / Is there a place for cholangioscopic evaluation of biliary anastomotic stricture after deceased donor liver transplant?

ABSTRACT BACKGROUND Biliary complications remain one of the most important causes of morbidity and graft loss after liver transplant (LT). Endoscopic therapy of biliary complications has proven to be effective over time, leaving surgical treatment restricted to only very few cases. However, we cannot yet predict which patients will have the greatest potential to benefit from endoscopic treatment. OBJECTIVE On this premise we decide to conduct this study to evaluate the role and safety of single operator cholangioscopy (SOC) in the endoscopic treatment of post-LT biliary anastomotic strictures (AS). METHODS: Between March/2016 and June/2017, 20 consecutive patients referred for endoscopic treatment for biliary anastomotic stricture were included in this prospective observational cohort study. Inclusion criteria were age over 18 years old, and a deceased LT performed within at least 30 days. Exclusion criteria were non-anastomotic biliary stricture, biliary leakage, cast syndrome, any previous endoscopic therapy, pregnancy and inability to provide informed consent. All patients underwent SOC before endoscopic therapy with fully covered self-expandable metal stent (FCSEMS) and after stent removal. RESULTS: At pre-treatment SOC, stricture orifice and fibrotic changes could be visualized in all patients, vascular changes and surgical sutures in 60% and acute inflammatory changes in 30%. SOC was essential for guidewire placement in five cases. FCSEMS was successfully deployed in all patients. Stricture resolution rate was 44.4% (median stent indwelling 372 days). Stricture recurrence was 12.5% (median follow-up of 543 days). Adverse events were distal (66.6%) and proximal (5.5%) stent migration, stent occlusion (16.6%), severe abdominal pain (10%) and mild acute pancreatitis (10%). SOC was repeated after FCSEMS removal. Post-treatment SOC showed fibrotic changes in all but one patient; vascular and acute inflammatory changes were less frequent in comparison to index procedure. The disappearance of suture material was remarkable. None of the cholangioscopic findings were statistically correlated to treatment outcome or stricture recurrence. CONCLUSION: Endoscopic retrograde cholangiography with SOC is feasible in post-LT patients with AS. Cholangioscopic findings can be classified into fibrotic, vascular and acute inflammatory changes. Cholangioscopy may be helpful to assist guidewire passage, but Its overall role for changing management is post-LT patients was not demonstrated.

RESUMO CONTEXTO: As complicações biliares continuam sendo uma das principais causas de morbidade e perda do enxerto após o transplante hepático. O tratamento endoscópico das complicações biliares provou ser eficaz ao longo do tempo, deixando o tratamento cirúrgico restrito a casos de exceção. No entanto, ainda não podemos prever quais pacientes terão maior potencial de se beneficiar da terapia endoscópica. OBJETIVO: Nesta premissa, decidimos realizar este estudo para avaliar o papel e a segurança da colangioscopia peroral de operador único (CPO) no tratamento endoscópico das estenoses anastomóticas biliares (EA) pós-transplante hepático. MÉTODOS: Entre março de 2016 e junho de 2017, 20 pacientes consecutivos encaminhados para tratamento endoscópico da EA biliar foram incluídos neste estudo prospectivo de coorte observacional. Os critérios de inclusão foram idade superior a 18 anos e um transplante hepático de doador falecido realizado há pelo menos 30 dias. Pacientes com estenose biliar não anastomótica, fístula biliar, "cast" síndrome, qualquer terapia endoscópica prévia, gravidez e incapacidade de fornecer consentimento informado foram excluídos. Todos os pacientes foram submetidos à CPO antes da terapia endoscópica com prótese metálica autoexpansível totalmente coberta (PMAEC) e após a sua remoção. RESULTADOS: Na CPO realizada antes do tratamento endoscópico, o orifício de estenose e alterações fibróticas foram visualizadas em todos os pacientes, alterações vasculares e a presença de suturas cirúrgicas em 60%, enquanto alterações inflamatórias agudas em 30%. A CPO foi determinante para a transposição do fio-guia através da estenose em cinco casos. Uma PMAEC foi implantada com sucesso em todos os pacientes. A taxa de resolução da estenose foi de 44,4% (tempo médio de permanência de 372 dias). A recorrência da EA foi de 12,5% (acompanhamento médio de 543 dias). Os eventos adversos foram migração distal (66,6%) e proximal (5,5%) da prótese metálica, oclusão da PMAEC (16,6%), dor abdominal intensa (10%) e pancreatite aguda leve (10%). A CPO foi repetida após a remoção da PMAEC. A colangioscopia realizada após o tratamento endoscópico mostrou alterações fibróticas em todos, exceto em um paciente; alterações vasculares e inflamatórias agudas foram menos frequentes em comparação à CPO inicial. O desaparecimento do material de sutura, observado em todos os casos, foi notável. Nenhum dos achados colangioscópicos foram estatisticamente correlacionados ao resultado do tratamento ou à recorrência de estenose. CONCLUSÃO: A colangioscopia peroral é viável nos pacientes pós-transplante hepático com estenose biliar anastomótica. Os achados colangioscópicos podem ser classificados em alterações inflamatórias agudas, fibróticas e vasculares. A colangioscopia pode ser útil para auxiliar na passagem do fio-guia, mas seu papel geral na mudança de tratamento nos pacientes pós-transplante hepático não foi demonstrado.

Risk factors associated with hepatic artery thrombosis: analysis of 1050 liver transplants / Fatores de risco associados à trombose de artéria hepática: análise de 1050 transplantes de fígado

ABSTRACT Background: Hepatic artery thrombosis is an important cause of graft loss and ischemic biliary complications. The risk factors have been related to technical aspects of arterial anastomosis and non-surgical ones. Aim: To evaluate the risk factors for the development of hepatic artery thrombosis. Methods: The sample consisted of 1050 cases of liver transplant. A retrospective and cross-sectional study was carried out, and the variables studied in both donor and recipient. Results: Univariate analysis indicated that the variables related to hepatic artery thrombosis are: MELD (p=0.04) and warm time ischemia (p=0.005). In the multivariate analysis MELD=14.5 and warm ischemia time =35 min were independent risk factors for hepatic artery thrombosis. In the prevalence ratio test for analysis of the anastomosis as a variable, it was observed that patients with continuous suture had an increase in thrombosis when compared to interrupted suture. Conclusions: Prolonged warm ischemia time, calculated MELD and recipient age were independent risk factors for hepatic artery thrombosis after liver transplantation in adults. Transplanted patients with continuous suture had an increase in thrombosis when compared to interrupted suture. Re-transplantation due to hepatic artery thrombosis was associated with higher recipient mortality.

RESUMO Racional: Trombose de artéria hepática é importante causa de falência de enxerto e complicações biliares. Fatores de risco para trombose estão relacionados aos aspectos técnicos da anastomose arterial e fatores não cirúrgicos. Objetivo: Avaliar os fatores de risco para o desenvolvimento de trombose de artéria hepática. Métodos: A amostra consta de 1050 casos de transplante hepático. Foi realizado estudo retrospectivo e transversal, e as variáveis foram avaliadas em doadores e receptores. Resultados: A análise univariada mostrou que as variáveis relacionadas a trombose de artéria hepática são: MELD e tempo de isquemia quente. Na análise multivariada, o MELD=14.5 e tempo de isquemia quente =35 min foram fatores de risco independentes para trombose de artéria hepática. No teste de prevalência para avaliação do tipo de anastomose como variável, foi observado que a sutura contínua tem maior risco de trombose quando comparada com aquela em pontos separados. Conclusão: Tempo de isquemia quente prolongado, MELD calculado e idade do recipiente foram fatores de risco independentes para trombose de artéria hepática após transplante de fígado em adultos. Pacientes submetidos à anastomose com sutura contínua apresentaram mais trombose quando comparados com a em pontos separados. Retransplante por trombose está associado com maior mortalidade.

Risk factors for post-liver transplant biliary complications in the absence of arterial complications / Fatores de risco para complicações biliares pós-transplante hepático na ausência de complicações arteriais

ABSTRACT Background - Biliary complications (BC) represent the most frequent complication after liver transplantation, up to 34% of cases. Aim: To identify modifiable risk factors to biliary complications after liver transplantation, essential to decrease morbidity. Method: Clinical data, anatomical characteristics of recipient and donors, and transplant operation features of 306 transplants with full arterial patency were collected to identify risk factors associated with BC. Results: BC occurred in 22.9% after 126 days (median) post-transplantation. In univariate analyses group 1 (without BC, n=236) and group 2 patients (with BC, n=70) did not differ on their general characteristics. BC were related to recipient age under 40y (p=0.029), CMV infection (p=0.021), biliary disease as transplant indication (p=0.018), lower pre-transplant INR (p=0.009), and bile duct diameter <3 mm (p=0.033). CMV infections occurred sooner in patients with postoperative biliary complications vs. control (p=0.07). In a multivariate analysis, only CMV infection, lower INR, and shorter bile duct diameter correlated with BC. Positive CMV antigenemia correlated with biliary complications, even when titers lied below the treatment threshold. Conclusions: Biliary complications after liver transplantation correlated with low recipient INR before operation, bile duct diameter <3 mm, and positive antigenemia for CMV or disease manifestation. As the only modifiable risk factor, routine preemptive CMV inhibition is suggested to diminish biliary morbidity after liver transplant.

RESUMO Racional: Complicações biliares (CB) são os eventos adversos mais frequentes após o transplante de fígado, ocorrendo em até 34% dos procedimentos. Objetivo: Identificar fatores de risco modificáveis para o aparecimento de complicações biliares após transplantes de fígado, essenciais para diminuir morbidade. Método: Investigação dos dados clínicos, características anatômicas de receptores e doadores e informações sobre a operação de 306 transplantes com artéria hepática pérvia, para identificar fatores de risco associados ao aparecimento de CB. Resultados: CB ocorreu em 22,9% após 126 dias (mediana) do transplante. Em análise univariada pacientes do grupo 1 (sem CB, n=236) e grupo 2 (com CB, n=70) não diferiram em suas características gerais. CB esteve relacionada à idade do receptor menor que 40 anos (p=0,029), infecção pelo citomegalovírus (CMV, p=0,021), doença biliar como indicação ao transplante (p=0,018), RNI pré-transplante mais baixo (p=0,009) e diâmetro do ducto biliar <3 mm (p=0,033). Infecções pelo CMV ocorreram mais precocemente em pacientes com CB (p=0,07). Na análise multivariada, somente infecção por ele, INR mais baixo e menor diâmetro do ducto biliar mantiveram correlação com CB. Antigenemia positiva para CMV correlacionou com CB mesmo em títulos inferiores ao cutoff para tratamento. Conclusões: CB após transplante hepático esteve relacionada com menores RNI do receptor antes da operação, diâmetro do ducto biliar <3 mm e antigenemia ou manifestação clínica positiva para CMV. Como único fator de risco evitável, tratamento preemptivo para inibição do CMV é sugerido para diminuir morbidade biliar após o transplante.

COVID-19 in solid organ transplantation patients: A systematic review

Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were "COVID-19" AND "Transplant." Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299)

O custo do transplante hepático adulto em um centro de referência na região sul do Brasil / The cost of adult liver transplantation in a referral center in southern brazil

ABSTRACT BACKGROUND: Liver transplantation (LTx) is the primary and definitive treatment of acute or chronic cases of advanced or end-stage liver disease. Few studies have assessed the actual cost of LTx categorized by hospital unit. OBJECTIVE: To evaluate the cost of LTx categorized by unit specialty within a referral center in southern Brazil. METHODS: We retrospectively reviewed the medical records of 109 patients undergoing LTx between April 2013 and December 2014. Data were collected on demographic characteristics, etiology of liver disease, and severity of liver disease according to the Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores at the time of LTx. The hospital bill was transformed into cost using the full absorption costing method, and the costs were grouped into five categories: Immediate Pretransplant Kit; Specialized Units; Surgical Unit; Intensive Care Unit; and Inpatient Unit. RESULTS: The mean total LTx cost was US$ 17,367. Surgical Unit, Specialized Units, and Intensive Care Unit accounted for 31.9%, 26.4% and 25.3% of the costs, respectively. Multivariate analysis showed that total LTx cost was significantly associated with CTP class C (P=0.001) and occurrence of complications (P=0.002). The following complications contributed to significantly increase the total LTx cost: septic shock (P=0.006), massive blood transfusion (P=0.007), and acute renal failure associated with renal replacement therapy (dialysis) (P=0.005). CONCLUSION: Our results demonstrated that the total cost of LTx is closely related to liver disease severity scores and the development of complications.

RESUMO CONTEXTO: O transplante hepático (TxH) é o principal e definitivo tratamento de casos agudos ou crônicos de doenças hepáticas avançadas ou terminais. Poucos estudos têm avaliado o custo real do TxH categorizado por setores hospitalares. OBJETIVO: Avaliar o custo do TxH categorizado por especialidade da unidade em um centro de referência na região sul do Brasil. MÉTODOS: Analisamos retrospectivamente os prontuários de 109 pacientes submetidos a TxH entre abril de 2013 e dezembro de 2014. Foram coletados dados sobre características demográficas, etiologia da doença hepática e gravidade da doença hepática de acordo com os escores Child-Turcotte-Pugh (CTP) e Model for End-stage Liver Disease (MELD) no momento do TxH. A conta hospitalar foi transformada em custo pelo método de custeio por absorção integral, e os custos foram agrupados em cinco categorias: Kit Pré-Transplante Imediato; Unidades Especializadas; Centro Cirúrgico; Unidade de Terapia Intensiva; e Unidade de Internação. RESULTADOS: O custo médio total do TxH foi de US$ 17.367. O Centro Cirúrgico, as Unidades Especializadas e a Unidade de Terapia Intensiva responderam por 31,9%, 26,4% e 25,3% dos custos, respectivamente. A análise multivariada demonstrou que o custo total do TxH se associou significativamente ao escore CTP classe C (P=0,001) e ao desenvolvimento de intercorrências (P=0,002). As seguintes intercorrências contribuíram para aumentar significativamente o custo do TxH: choque séptico (P=0,006), politransfusão sanguínea (P=0,007) e insuficiência renal aguda associada à terapia renal substitutiva (diálise) (P=0,005). CONCLUSÃO: Nossos resultados demonstraram que o custo total do TxH guarda uma estreita relação com os escores de gravidade da doença hepática e com o desenvolvimento de intercorrências.

Oral ulcerative lesions in a post-liver-transplantation patient

Oral involvement is rarely found in histoplasmosis, except in its disseminated form, which is mostly observed in the severely immunocompromised host. Herein, we presented the case of a 36-year-old female with a previous history of liver transplant, who was hospitalized due to fever, chills, night sweats, diarrhea, and painful oral lesions over the last 3 days. The oral examination revealed the presence of painful shallow ulcers lined by a pseudomembrane in the gingiva and the soft and hard palate. The initial working diagnosis comprised cytomegalovirus reactivation or herpes simplex virus infection. The diagnostic work-up included incisional biopsies of the gingiva and the sigmoid colon. Both biopsies confirmed the diagnosis of histoplasmosis. Intravenous itraconazole was administered with significant improvement after 7 days. Although oral involvement is rare, histoplasmosis should be included in the differential diagnosis of oral lesions, particularly when the patient is immunosuppressed. This study reports a rare presentation of histoplasmosis involving the mucosa of the oral cavity and the colon.

Sarcopenia, obesity and sarcopenic obesity in liver transplantation: a body composition prospective study / Sarcopenia, obesidade e obesidade sarcopênica em pacientes submetidos ao transplante hepático: estudo prospectivo de composição corporal

ABSTRACT Background: Sarcopenia is prevalent before liver transplantation, and it is considered to be a risk factor for morbidity/mortality. After liver transplantation, some authors suggest that sarcopenia remains, and as patients gain weight as fat, they reach sarcopenic obesity status. Aim: Prospectively to assess changes in body composition, prevalence and associated factors with respect to sarcopenia, obesity and sarcopenic obesity after transplantation. Methods: Patients were evaluated at two different times for body composition, 4.0±3.2y and 7.6±3.1y after transplantation. Body composition data were obtained using bioelectrical impedance. The fat-free mass index and fat mass index were calculated, and the patients were classified into the following categories: sarcopenic; obesity; sarcopenic obesity. Results: A total of 100 patients were evaluated (52.6±13.3years; 57.0% male). The fat-free mass index decreased (17.9±2.5 to 17.5±3.5 kg/m2), fat mass index increased (8.5±3.5 to 9.0±4.0; p<0.05), prevalence of sarcopenia (19.0 to 22.0%), obesity (32.0 to 37.0%) and sarcopenic obesity (0 to 2.0%) also increased, although not significantly. The female gender was associated with sarcopenia. Conclusion: The fat increased over the years after surgery and the lean mass decreased, although not significantly. Sarcopenia and obesity were present after transplantation; however, sarcopenic obesity was not a reality observed in these patients.

RESUMO Racional: A sarcopenia é prevalente antes do transplante de fígado e é considerada fator de risco para morbidade/mortalidade desses pacientes. Após o transplante hepático, alguns autores sugerem que a sarcopenia permanece, e os pacientes ganham peso na forma de gordura, atingindo o status de obesidade sarcopênica. Objetivo: Avaliar prospectivamente as mudanças na composição corporal, prevalência e fatores associados em relação à sarcopenia, obesidade e obesidade sarcopênica após o transplante. Métodos: Os pacientes foram avaliados em dois momentos diferentes para composição corporal, 4,0±3,2 e 7,6±3,1 anos e após o transplante. Os dados da composição corporal foram obtidos por meio de bioimpedância elétrica. O índice de massa livre de gordura e o índice de massa gorda foram calculados, e os pacientes foram classificados nas seguintes categorias: sarcopênico; obesidade; obesidade sarcopênica. Resultados: Foram avaliados 100 pacientes (52,6±13,3 anos; 57,0% homens). A prevalência de sarcopenia (19,0% para 22,0%), obesidade (32,0% para 37,0%) e índice de massa livre de gordura (17,9±2,5 para 17,5±3,5 kg/m2), índice de massa gorda aumentou (8,5±3,5 para 9,0±4,0 kg/m2), e obesidade sarcopênica (0 para 2,0%) também aumentaram, embora não significativamente. O gênero feminino foi associado à sarcopenia. Conclusão: Após a operação, a gordura aumentou ao longo dos anos e a massa magra diminuiu, embora não significativamente. A sarcopenia e a obesidade estavam presentes após o transplante; no entanto, a obesidade sarcopênica não foi realidade observada nesses pacientes.

Disfunção e não função primária do enxerto hepático: revisão integrativa / Primary liver graft dysfunction and non-function: integrative literature review

RESUMO Evitar mortes na fila de espera por um órgão não é mais o único foco de atenção das equipes de transplantação. As pesquisas e cuidados na prática clínica têm sido cada vez mais voltados para o funcionamento do enxerto pós-implante. O objetivo desse estudo foi identificar a nomenclatura utilizada na literatura para disfunção e não função de um enxerto hepático, bem como, investigar as incidências e fatores de risco. Trata-se de uma revisão integrativa da literatura de publicações na íntegra em português, inglês e espanhol, entre 2012 e 2016, nas bases: CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE e Web of Science. Foram selecionados 14 estudos em que se identificou incidências variando entre 7% e 27% e a nomenclatura utilizada para descrever o evento foi mau funcionamento inicial, hipofunção do enxerto, função marginal ou retardo na função. Foram encontradas incidências de não função primária do enxerto hepático entre 1,4% e 8,4% dos pacientes e a nomenclatura usada para descrever o evento foi disfunção precoce ou perda do enxerto. Os fatores de risco encontrados são relacionados às variáveis do doador, receptor, enxerto e logística do transplante. Conclui-se que o conhecimento das diferentes nomenclaturas empregadas na literatura, das incidências da disfunção e não função primária e seus fatores de risco são fundamentais para qualificar as intervenções de controle dos eventos na perspectiva de melhorar a sobrevida do paciente pós-transplante hepático.

ABSTRACT Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Hepatitis E seroprevalence and associated risk factors in Croatian liver transplant recipients

Abstract INTRODUCTION Solid-organ transplant recipients are at risk of hepatitis E virus (HEV) infection. We analyzed the seroprevalence/risk factors of HEV in Croatian liver transplant recipients. METHODS Two hundred forty-two serum samples were tested for HEV immunoglobuline IgG/IgM and HEV RNA. Sociodemographic data and risk factors were collected using a questionnaire. RESULTS HEV IgG seroprevalence rate was 24.4%. Positive/equivocal HEV IgM were found in two patients. HEV RNA was not detected. Logistic regression showed that older age, female gender, rural area/farm, water well, and septic tank were associated with HEV seropositivity. CONCLUSIONS This study revealed a high exposure rate to HEV in Croatian liver recipients.