GENES EXPRESSION AND SERUM BIOMARKERS FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA, CIRRHOSIS AND HEPATITIS C.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. OBJECTIVE: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), ß-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. METHODS: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. RESULTS: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of ß-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). CONCLUSION: The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.

Expressão gênica e biomarcadores séricos para diagnóstico de carcinoma hepatocelular, cirrose e hepatite C / Genes expression and serum biomarkers for diagnosis of hepatocellular carcinoma, cirrhosis and hepatitis c

ABSTRACT Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. Objective: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), β-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. Methods: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. Results: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of β-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). Conclusion The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.

RESUMO Contexto: Carcinoma hepatocelular (CHC) é o tipo mais comum de câncer de fígado. Os fatores de risco para CHC incluem infecção pelo vírus da hepatite C (VHC) e B (VHB), cirrose alcoólica e alterações genéticas que podem afetar diversas vias celulares. Objetivo: Este estudo teve como objetivo analisar a expressão gênica e proteica sérica de VEGF, AFP, CSTB, β-catenina e GPC3 em grupos com CHC, cirrose ou VHC e controles, e sua relação com o estadiamento clínico nos grupos CHC e cirrose, bem como sua valores de sensibilidade e especificidade. Métodos: Duzentos e trinta indivíduos foram distribuídos no Grupo 1 (G1) - 80 pacientes com CHC; Grupo 2 (G2) - 76 pacientes com cirrose de qualquer etiologia; Grupo 3 (G3) - 33 pacientes com VHC; Grupo 4 (G4 - Controles) - 41 indivíduos sem sinais clínicos ou bioquímicos de qualquer doença hepática. A expressão gênica foi analisada por qRT-PCR e as proteínas séricas foram realizadas pelo método ELISA. Resultados: Aumento da expressão de VEGF e AFP pode ser observado em pacientes BCLC estágio D em comparação com pacientes estágio B, e pacientes estágio C apresentaram maior expressão de CTNNB1, em comparação com pacientes estágio B (P<0,05). Para VEGF e GPC3, foi observado poder discriminatório entre pacientes com CHC e controles (AUC = 0,71; 0,82, respectivamente). O CSTB mostrou poder discriminatório na comparação entre pacientes com VHC e controles (AUC =0,74). Conclusão: O presente estudo confirma a sensibilidade do CSTB sérico no diagnóstico da hepatite C, e a expressão gênica de VEGF e GPC3 sérica conferem sensibilidade e especificidade para o diagnóstico de CHC.

Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case-control study.

This study was performed to investigate the relationship between polymorphisms in microsomal epoxide hydrolase (mEH; Tyr113His and His139Arg substitution) and glutathione S-transferase (GST; GSTM1 deletion, GSTT1 deletion, and GSTP1.Ala114Val substitution) and their correlation with clinico-histopathological features in hepatocellular carcinoma (HCC).We evaluated environmental risk factors and genetic alterations in 556 individuals (86 cases and 470 controls). PCR multiplex for GSTM1 and GSTT1, polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for GSTP1, and real-time PCR for mEH were performed. Statistical analyses were performed using multiple logistic regression tests.Age over 48 years (p < 0.001) and alcohol consumption (p = 0.021) were the predictors of increased risk of developing HCC. GSTP1.Ala114Val for all regression models (p < 0.05), except the recessive model, and the GSTT1 null genotype (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.21-0.87, p = 0.019) were predictors of an increased risk of developing HCC. Polymorphic GSTT1, GSTM1, GSTP1.Ala114Val, and mEH.His139Arg and wild-type mEH.Tyr113His (OR = 5.04; 95% CI = 1.59-16.04; p = 0.006) were associated with HCC.Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.

PREVALENCE AND TIME OF DEVELOPMENT OF SYSTEMIC ARTERIAL HYPERTENSION IN PATIENTS AFTER LIVER TRANSPLANTATION.

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.

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.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

Atualização das recomendações da Sociedade Brasileira de Hepatologia para o diagnóstico e tratamento do carcinoma hepatocellular / Brazilian society of hepatology updated recommendations for diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

NEW IMMUNIZATION SCHEDULE EFFECTIVENESS AGAINST HEPATITIS B IN LIVER TRANSPLANTATION PATIENTS.

BACKGROUND: Although liver transplantation is considered to be a high-risk procedure, it is well-established as a treatment option for the cure and quality of life enhancement for individuals who suffer from diseases. Preventing an infection by hepatitis B virus through immunization schedules has been the most effective way to reduce complications, since it decreases the number of people who suffer from chronic hepatitis caused by the hepatitis B virus and eradicates its transmission. OBJECTIVE: 1. Analyzing evidence in the literature on various schedules employed for immunization against hepatitis B in patients who have received a liver transplantation. 2. Suggesting potential immunization schedules against hepatitis B in patients who suffer from liver cirrhosis, without previous verifying documentation, using the Child-Turcotte Pugh score, according to evidences found in the literature. METHODS: Systematic review of the literature, conducted on the data bases MedLine, PubMed, and Lilacs, between September, 2017 and January, 2018, by using the following keywords: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". In order to analyze the articles, a summary figure was especially designed and both the results and discussion were presented in a descriptive way. RESULTS: We included 24 studies; among them, eight had accelerated immunization schedules, 13 followed the conventional schedules, and three had super accelerated schedules. Regarding immunization, 21 studies were conducted with patients in the pre-transplant period, one with a transplanted patient, one with a pre-transplant group, and one with a post-transplant group. Found articles suggest that, disregarding the chosen immunization schedule, seroconversion rates tended to be lower as the liver disease advanced, compared to the healthy population. CONCLUSION: The studies did not find seroconversion superiority between the different immunization schedules (conventional and unconventional). However, since candidates to liver transplantation are usually very vulnerable, results show that super accelerated immunization schedules are possibly recommended for such group of patients; serologic test results will be higher when the immunization schedule is completed in the pre-transplant period.

Eficácia de um novo esquema vacinal contra hepatite B em pacientes submetidos a transplante de fígado / New immunization schedule effectiveness against hepatitis b in liver transplantation patients

ABSTRACT BACKGROUND: Although liver transplantation is considered to be a high-risk procedure, it is well-established as a treatment option for the cure and quality of life enhancement for individuals who suffer from diseases. Preventing an infection by hepatitis B virus through immunization schedules has been the most effective way to reduce complications, since it decreases the number of people who suffer from chronic hepatitis caused by the hepatitis B virus and eradicates its transmission. OBJECTIVE: 1. Analyzing evidence in the literature on various schedules employed for immunization against hepatitis B in patients who have received a liver transplantation. 2. Suggesting potential immunization schedules against hepatitis B in patients who suffer from liver cirrhosis, without previous verifying documentation, using the Child-Turcotte Pugh score, according to evidences found in the literature. METHODS: Systematic review of the literature, conducted on the data bases MedLine, PubMed, and Lilacs, between September, 2017 and January, 2018, by using the following keywords: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". In order to analyze the articles, a summary figure was especially designed and both the results and discussion were presented in a descriptive way. RESULTS: We included 24 studies; among them, eight had accelerated immunization schedules, 13 followed the conventional schedules, and three had super accelerated schedules. Regarding immunization, 21 studies were conducted with patients in the pre-transplant period, one with a transplanted patient, one with a pre-transplant group, and one with a post-transplant group. Found articles suggest that, disregarding the chosen immunization schedule, seroconversion rates tended to be lower as the liver disease advanced, compared to the healthy population. CONCLUSION: The studies did not find seroconversion superiority between the different immunization schedules (conventional and unconventional). However, since candidates to liver transplantation are usually very vulnerable, results show that super accelerated immunization schedules are possibly recommended for such group of patients; serologic test results will be higher when the immunization schedule is completed in the pre-transplant period.

RESUMO CONTEXTO: O transplante de fígado, apesar de ser um procedimento de elevado risco, está consolidado como recurso terapêutico para cura e melhoria da qualidade de vida de indivíduos acometidos por doenças. A prevenção da infecção pelo vírus da hepatite B através da vacinação tem sido a medida mais efetiva para reduzir complicações, diminuindo o número de pessoas com hepatite crônica pelo vírus da hepatite B e eliminando a transmissão. OBJETIVO: 1. Analisar as evidências na literatura sobre os diferentes esquemas utilizados para a vacina contra a hepatite B em pacientes submetidos a transplante de fígado. 2. Sugerir possíveis esquemas de vacinação contra hepatite B para pacientes com cirrose hepática, sem documentação comprovatória anterior, em relação à classificação de Child-Turcotte Pugh, segundo evidências encontradas na literatura. MÉTODOS: Revisão sistemática da literatura, realizada nas bases de dados MedLine, PubMed e Lilacs, no período de setembro/2017 a janeiro/2018, com as seguintes palavras chaves: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". Para análise dos artigos foi utilizado um quadro sinóptico especialmente construído para esse fim e a apresentação dos resultados e discussão foi feita de forma descritiva. RESULTADOS: Foram incluídos 24 estudos, sendo oito com esquemas vacinais acelerados, 13 com esquemas convencionais e três com esquemas super acelerado. Quanto ao período da vacinação, 21 estudos foram realizados com pacientes no período pré-transplante, um em pacientes transplantados e um com um grupo pré e um grupo pós transplante. Os artigos encontrados sugerem que independente do esquema vacinal escolhido, as taxas de soroconversão tendem a ser menores conforme o avançar da doença hepática, em relação à população saudável. CONCLUSÃO: Os estudos não encontraram superioridade de soroconversão entre os diferentes esquemas de vacinação (convencional e não convencional). Entretanto, sabendo da vulnerabilidade que os candidatos a transplante de fígado estão expostos, os resultados demonstram que o esquema de vacinação superacelerado pode ser indicado para este grupo de pacientes, e que os resultados sorológicos são mais elevados quando o esquema de vacinação é completado no período pré-transplante.

Mortality and complications in patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) - 12 years experience.

CONTEXT: Transjugular intrahepatic portosystemic shunt (TIPS) is the non-surgical treatment option with low level of morbi-mortality and possibility of accomplishment in patients with severe hepatic dysfunction which aims at decompressing the portal system treating or reducing the portal hypertension complications. OBJECTIVE: Outline the profile analyze global and early mortality, and the complications presented by cirrhotic patients who underwent TIPS for treatment of digestive hemorrhage by portal hypertension. METHOD: Retrospective study based on the data bank of cirrhotic patients' medical reports, who underwent TIPS for digestive hemorrhage by portal hypertension treatment who did not respond to clinical endoscopic treatment, and were assisted from 1998 to 2010 in the Liver Transplant Service at a university hospital. The study was approved by the Committee of Ethics and Research. RESULTS: The sample was comprised of 72 (84.7%) patients, being 57 (79.2%) males, average age 47.7 years (age range from 16 to 85 years and SD = 13), 21 (29.2%) patients presented liver disease as cause excessive intake of alcoholic drinks; 21 (29.2%) contamination by hepatitis virus, 16 (22.2%) excessive alcohol intake associated with virus and 14 (19.4%) patients presented other causes. As for initial classification, 14 (20%) had Child-Pugh A, 33 (47.1%) Child-Pugh B and 23 (32.9%) Child-Pugh C. Initial MELD was obtained in 68 patients being 37 (54.4%) higher than 15 points while 31 (45.6%) had up to 15 points. Early death occurred in 19 (26.4%). Global mortality occurred in 41 (60.3%). CONCLUSIONS: Mortality is directly related to clinical factors of patients, being Child-Pugh and MELD classifications predictors of mortality, with more impact in patients with Child-Pugh class C and MELD > 15. The complications found were similar to those described in the literature, although the dysfunction by stent stenosis (26.4%) was lower than in the most of the studies and the encephalopathy incidence (58.3%) was higher. Probably, the high incidence of encephalopathy is explained by the low incidence of stenosis.

Mortality and complications in patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) - 12 years experience / Mortalidade e complicações em pacientes com hipertensão portal submetidos a derivação portossistêmica transjugular intra-hepática (TIPS) - 12 anos de experiência

CONTEXT: Transjugular intrahepatic portosystemic shunt (TIPS) is the non-surgical treatment option with low level of morbi-mortality and possibility of accomplishment in patients with severe hepatic dysfunction which aims at decompressing the portal system treating or reducing the portal hypertension complications. OBJECTIVE: Outline the profile analyze global and early mortality, and the complications presented by cirrhotic patients who underwent TIPS for treatment of digestive hemorrhage by portal hypertension. METHOD: Retrospective study based on the data bank of cirrhotic patients' medical reports, who underwent TIPS for digestive hemorrhage by portal hypertension treatment who did not respond to clinical endoscopic treatment, and were assisted from 1998 to 2010 in the Liver Transplant Service at a university hospital. The study was approved by the Committee of Ethics and Research. RESULTS: The sample was comprised of 72 (84.7%) patients, being 57 (79.2%) males, average age 47.7 years (age range from 16 to 85 years and SD = 13), 21 (29.2%) patients presented liver disease as cause excessive intake of alcoholic drinks; 21 (29.2%) contamination by hepatitis virus, 16 (22.2%) excessive alcohol intake associated with virus and 14 (19.4%) patients presented other causes. As for initial classification, 14 (20%) had Child-Pugh A, 33 (47.1%) Child-Pugh B and 23 (32.9%) Child-Pugh C. Initial MELD was obtained in 68 patients being 37 (54.4%) higher than 15 points while 31 (45.6%) had up to 15 points. Early death occurred in 19 (26.4%). Global mortality occurred in 41 (60.3%). CONCLUSIONS: Mortality is directly related to clinical factors of patients, being Child-Pugh and MELD classifications predictors of mortality, with more impact in patients with Child-Pugh class C and MELD > 15. The complications found were similar to those described in the literature, although the dysfunction by stent stenosis (26.4%) was lower than in the most of the studies and the encephalopathy incidence (58.3%) was higher. Probably, the high incidence of encephalopathy is explained by the low incidence of stenosis.

CONTEXTO: Derivação portossistêmica transjugular intra-hepática (TIPS) é opção de tratamento não cirúrgico com baixo índice de morbimortalidade e possibilidade de realização em pacientes com disfunção hepática grave que visa descomprimir o sistema porta tratando ou reduzindo as complicações da hipertensão portal. OBJETIVO: Traçar o perfil, analisar mortalidade global e precoce, e as complicações apresentadas pelos pacientes cirróticos submetidos a TIPS para tratamento da hemorragia digestiva por hipertensão portal. MÉTODOS: Estudo retrospectivo baseado no banco de dados dos prontuários dos pacientes cirróticos submetidos a TIPS para tratamento da hemorragia digestiva por hipertensão portal que não responderam ao tratamento clínico-endoscópico e atendidos no período de 1998 a 2010 no Serviço de Transplante de Fígado de um hospital universitário. O estudo foi aprovado pelo Comitê de Ética e Pesquisa. RESULTADOS: Amostra foi composta de 72 (84,7%) pacientes, sendo 57 (79,2%) do sexo masculino, idade média de 47,4 anos (entre 16 e 85 anos e DP = 13); 21 (29,2%) pacientes apresentavam como causa da doença hepática o consumo excessivo de álcool; 21 (29,2%) a contaminação por vírus da hepatite, 16 (22,2%) o consumo excessivo de álcool associado a vírus e 14 (19,4%) pacientes apresentavam outras causas. Quanto à classificação inicial, 14 (20%) tinham Child-Pugh A, 33 (47,1%) Child-Pugh B e 23 (32,9%) Child-Pugh C. MELD inicial foi obtido em 68 pacientes, sendo 37 (54,4%) com mais de 15 pontos, enquanto 31 (45,6%) tiveram até 15 pontos. Óbito precoce ocorreu em 19 (26,4%). Mortalidade global ocorreu em 41 (60,3%). CONCLUSÃO: Mortalidade está diretamente relacionada a fatores clínicos dos pacientes, sendo as classificações de Child-Pugh e MELD preditoras de mortalidade, com maior impacto em pacientes com Child-Pugh classe C e MELD >15. As complicações encontradas foram semelhantes às descritas na literatura, porém a disfunção por estenose do stent (26,4%) foi menor que a maioria dos estudos e a incidência de encefalopatia (58,3%) superior. Provavelmente, esta alta incidência seja explicada pela baixa incidência de estenose.

Doença coronária obstrutiva em hepatopatas crônicos que aguardam transplante hepático / Obstructive coronary disease in patients with chronic liver disease awaiting liver transplantation / Enfermedad coronaria obstructiva en hepatópatas crónicos que aguardan trasplante hepático

FUNDAMENTO: A insuficiência hepática avançada (IHA) geralmente cursa com hipocolesterolemia. Apesar disso, uma parcela dos pacientes com IHA desenvolve coronariopatia obstrutiva de grau importante com consequente aumento de risco ou até contraindicação para transplante hepático. OBJETIVO: Analisar a contribuição dos fatores de risco clássicos para doença arterial coronariana (DAC) em pacientes portadores de IHA com e sem coronariopatia obstrutiva. MÉTODOS: Avaliação dos fatores de risco para DAC em 119 pacientes, em um serviço de referência para transplante hepático, com as seguintes características: mais de 40 anos de idade, portadores de IHA e submetidos a cinecoronariografia. RESULTADOS: Coronariopatia obstrutiva foi detectada em 21 (17,6 por cento) dos casos. Esses pacientes apresentavam realmente níveis baixos de colesterol, sendo de 129,0 ± 53,5 mg/dl com mediana de 117,0 mg/dl nos hepatopatas com coronárias normais e 135,4 ± 51,7 mg/dl com mediana de 122,0 mg/dl nos hepatopatas com coronariopatia obstrutiva (P=0,8215). Na regressão logística multivariada, a idade, o sexo, o índice de massa corporal, bem como as presenças de diabete, de tabagismo e de etilismo não tiveram significância estatística isolada na diferenciação entre os grupos. Também não houve associação com a etiologia da IHA. Por sua vez, a hipertensão arterial mostrou-se relevante na associação com DAC (P=0,0474). CONCLUSÃO: Apenas a hipertensão arterial foi fator de risco com significância estatística para o desenvolvimento de DAC em pacientes com IHA aguardando transplante hepático. Por ser um fator de risco modificável, esse achado orienta a prática de atitudes terapêuticas na tentativa de evitar ou retardar o desenvolvimento da DAC nesses pacientes.

BACKGROUND: Advanced liver failure (ALF) usually presents hypocholesterolemia. Nevertheless, some patients with ALF develops major coronary obstructive diseases with consequent increased risk or contraindication to liver transplantation. OBJECTIVE: To analyze the contribution of classical risk factors for coronary artery disease (CAD) in patients with ALF with and without obstructive coronary disease. METHODS: Evaluation of risk factors for CAD in 119 patients in a referral center for liver transplantation, with the following characteristics: patients older than 40 years of age with ALV who underwent coronary angiography. RESULTS: Obstructive coronary disease was detected in 21 (17.6 percent) of the cases. These patients had really low cholesterol levels, of which 129.0 ± 53.5 mg/dl averaging 117.0 mg/dl in liver disease patients with normal coronary arteries and 135.4 ± 51.7 mg/dl averaging 122.0 mg/dl in liver disease patients with obstructive coronary artery disease (P = 0.8215). In multivariate logistic regression, age, sex, body mass index and the presence of diabetes, smoking and alcohol consumption were not statistically significant in distinguishing groups. Nor was there an association with the etiology of the ALF. In turn, hypertension was proven to be relevant in association with CAD (P = 0.0474). CONCLUSION: Only hypertension was a risk factor with statistical significance for the development of CAD in patients with ALF awaiting liver transplantation. Because it is a modifiable risk factor, this finding guides the practice of therapeutic attitudes in an attempt to prevent or delay the development of CAD in these patients.

FUNDAMENTO: La insuficiencia hepática avanzada (IHA) generalmente cursa con hipocolesterolemia. A pesar de eso, una parcela de los pacientes con IHA desarrolla coronariopatía obstructiva de grado importante con consecuente aumento de riesgo o incluso contraindicación para trasplante hepático. OBJETIVOS: Analizar la contribución de los factores de riesgo clásicos para la enfermedad arterial coronaria (EAC) en pacientes portadores de IHA con y sin coronariopatía obstructiva. MÉTODOS: Evaluación de los factores de riesgo para EAC en 119 pacientes, en un servicio de referencia para trasplante hepático, con las siguientes características: más de 40 años de edad, portadores de IHA y sometidos a cinecoronariografía. RESULTADOS: Coronariopatía obstructiva fue detectada en 21 (17,6 por ciento) de los casos. Estos pacientes presentaban realmente niveles bajos de colesterol, siendo de 129,0±53,5mg/dL con mediana de 117,0mg/dL en los hepatópatas con coronarias normales y 135,4±51,7mg/dL con mediana de 122,0mg/dL en los hepatópatas con coronariopatía obstructiva (P=0,8215). En la regresión logística multivariada, la edad, el sexo, el índice de masa corporal, así como las presencias de diabetes, de tabaquismo y de etilismo no tuvieron significancia estadística aislada en la diferenciación entre los grupos. También no hubo asociación con la etiología de la IHA. A su vez, la hipertensión arterial se mostró relevante en la asociación con EAC (P=0,0474). CONCLUSIÓN: Sólo la hipertensión arterial fue factor de riesgo con significancia estadística para el desarrollo de EAC en pacientes con IHA aguardando trasplante hepático. Por ser un factor de riesgo cambiable, este hallazgo orienta hacia una práctica de actitudes terapéuticas en la tentativa de evitarse o retardar el desarrollo de la EAC en estos pacientes.

Obstructive coronary disease in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: Advanced liver failure (ALF) usually presents hypocholesterolemia. Nevertheless, some patients with ALF develops major coronary obstructive diseases with consequent increased risk or contraindication to liver transplantation. OBJECTIVE: To analyze the contribution of classical risk factors for coronary artery disease (CAD) in patients with ALF with and without obstructive coronary disease. METHODS: Evaluation of risk factors for CAD in 119 patients in a referral center for liver transplantation, with the following characteristics: patients older than 40 years of age with ALV who underwent coronary angiography. RESULTS: Obstructive coronary disease was detected in 21 (17.6%) of the cases. These patients had really low cholesterol levels, of which 129.0 ± 53.5 mg/dl averaging 117.0 mg/dl in liver disease patients with normal coronary arteries and 135.4 ± 51.7 mg/dl averaging 122.0 mg/dl in liver disease patients with obstructive coronary artery disease (P = 0.8215). In multivariate logistic regression, age, sex, body mass index and the presence of diabetes, smoking and alcohol consumption were not statistically significant in distinguishing groups. Nor was there an association with the etiology of the ALF. In turn, hypertension was proven to be relevant in association with CAD (P = 0.0474). CONCLUSION: Only hypertension was a risk factor with statistical significance for the development of CAD in patients with ALF awaiting liver transplantation. Because it is a modifiable risk factor, this finding guides the practice of therapeutic attitudes in an attempt to prevent or delay the development of CAD in these patients.

Comportamento do fator de necrose tumoral e da proteína C reativa em hepatectomia simultânea com colectomia em ratos / Behavior of the tumor necrosis factor and C-reactive protein in simultaneous hepatectomy plus colectomy in rats

OBJETIVO: Observar o comportamento do fator de necrose tumoral-a (TNFalfa) e da proteína C reativa (PCR) em cirurgias simultâneas de fígado e intestino. MÉTODO: Para este objetivo foi desenvolvido um modelo experimental, no qual foram operados quarenta ratos da raça Wistar, divididos em quatros grupos: grupo controle, grupo 1 com ratos submetidos à hepatectomia a 70 por cento, grupo 2 com ratos submetidos à colectomia e grupo 3 com cirurgia simultânea de hepactetomia e colectomia. Em todos os grupos foram dosados TNFalfa e PCR uma hora após o procedimento. Os animais foram mortos em seguida. RESULTADOS: Os valores encontrados mostraram alteração nas dosagens desses elementos nos diversos grupos, sendo que no grupo 3 houve aumento significativo do TNFalfa e queda de PCR. CONCLUSÃO: Quanto mais complexo se tornou o ato cirúrgico os níveis sangüíneos de TFNalfa aumentaram e os níveis sangüíneos da PCR diminuíram significativamente.

BACKGROUND: The aim of this experimental study was to observe the behavior of Tumor Necrosis Factor and C-Reative Protein in simultaneous colectomy plus hepatectomy. METHODS: In this experimental model, 40 Wistar rats underwent surgery. They were divided into four groups: the control group; group 1, rats submitted to hepatectomy to 70 percent; group 2, rats submitted to colectomy; and group 3, rats submitted simultaneously to both procedures: hepatectomy plus colectomy. In all groups, TNF and PCR were collected one hour after the surgical procedure. The animals were killed afterwards. RESULTS: The dosage of these elements showed values with some alterations in all groups. Group three showed a significant increase of TNFalpha and decrease of PCR. CONCLUSION: The more complex became the surgical act the blood levels of TFNalpha have increased and the levels of the PCR decreased significantly.

Uso do subgalato de bismuto para hemostasia local em hepatectomias parciais em ratos / Bismuth subgallate for local hemostasis after partial hepatectomy in rats

OBJETIVO: Avaliar os efeitos do subgalato de bismuto (SGB) usado na área cruenta pós-hepatectomia parcial, quanto a sangramento, aderências e estudo histológico. MÉTODO: Foram utilizados 30 ratos divididos em dois grupos iguais,submetidos à hepatectomias parciais com bisturi de lâmina. Para realizar a hemostasia no grupo 1 (G1), foi utilizado bisturi eletrônico e no grupo 2 (G2), SGB. No 7° dia de pós-operatório (PO), os animais foram mortos, e na cavidade abdominal foram observados sangramento, aderências e, a seguir, realizada a hepatectomia total englobando todos os tecidos adjacentes para análise histológica. No estudo histológico foram analisados: trombose da microcirculação, reação granulomatosa, necrose, fibrose, grau de inflamação e aderências. RESULTADOS: Não foi observado sangramento no PO nos dois grupos. No G1 estavam presentes aderências de omento ao fígado, consideradas neste trabalho como fisiológicas em 80 por cento dos ratos, e no G2 estas aderências foram por outros órgãos, consideradas neste trabalho como anômalas em todos os casos. No exame histológico, quanto à reação granulomatosa e aderências, todos os ratos as apresentaram. Quanto à trombose e necrose o G1 apresentou maior intensidade. Quanto à fibrose e grau de inflamação os resultados foram semelhantes em ambos os grupos. CONCLUSÕES: Ambos os métodos são eficientes para prevenir hemorragia. O G2 apresentou aderências anômalas inviabilizando seu uso em humanos. O G1 revelou mais trombose e necrose. Quanto à reação granulomatosa, fibrose, grau de inflamação e aderências microscópicas, os resultados foram iguais nos dois grupos.

BACKGROUND: This study aimed to observe the effects of bismuth subgallate used on bleeding surfaces after hepatectomy, in relation to bleeding, adhesions and histological study. METHODS: A total of 30 rats divided in 2 equal groups were studied. Partial hepatectomy was performed in both groups. In group 1 (G-1) an electric scalpel was used and in group 2 (G-2) bismuth subgallate for hemostasis of the bloody surface was aplied. On the 7th post-operative day, rats were sacrificed and the abdominal cavity was investigated with respect to bleeding and adhesions. A total hepatectomy with the adhesions was performed for histological study. In the histological study, microcirculation thrombosis, granulomatosis reaction, necrosis, fibrosis, degree of inflammation and adhesions were analyzed. RESULTS: There was no post-operative bleeding in both groups. Adhesions were observed on all rats in both groups. G-1 presented omentum adhesions to the liver, here denominated physiological in 80 percent of the rats and the G-2 presented adhesions of other organs, here named pathological in all cases. The histological study showed that all rats presented a granulomatosis reaction and adhesions. G-1 presented a greater intensity of thrombosis and necrosis. There was no significant difference between the two groups in relation to fibrosis or the degree of inflammation. CONCLUSION: This study demonstrated that both methods were efficient to prevent hemorrhage. G-2 presented pathological adhesions suggesting its use is unfeasible in human beings. G-1 presented more thrombosis and also more necrosis. The granulomatosis reaction, fibrosis, degree of inflammation and microscopic adhesions were similar in between groups.

O uso do doador "marginal" no transplante de fígado: Resultados em trinta pacientes

Resumo: Este estudo teve como objetivo avaliar os resultados dos transplantes de fígado, realizados com órgäos de doadores considerados "marginais". Foram estudados, prospectivamente, 213 pacientes submetidos a transplantes de fígado, realizados no período de 18 meses, NO momento da captaçäo dos órgäos, os doadores foram classificados em duas categorias: doadores "marginais" e doadores ideais. Do total, 30 doadores foram considerados "marginais", por serem portadores de uma ou mais das seguintes condiçöes: história de alcoolismo, provas de funçäo hepática alteradas, intoxicaçäo por superdose de paracetamol, doença cardiovascular avançada, infecçäo, período longo de hipotensäo, altas doses de substâncias inotrópicas, doença de von Willebrand, esteatose hepática, idade maior do que 50 anos e obesidade. Os 183 restantes preenchiam os critérios de doadores ideais: idade entre dois e 50 anos, provas de funçäo hepática normais, ausência de hipotensäo, de hipóxia, de parada cardíaca, de infecçäo, de obesidade, de esteatose hepática, de traumatismo e de isquemia do fígado, hematócrito acima de 30 por cento, sem história de alcoolismo, doenças ou antecedentes que pudessem sugerir lesäo hepato-biliar, tempode permenência em UTI menor de cinco dias, e uso de substâncias inotrópicas em dose menor do que 10ug/kg/min. Os resultados dos transplantes realizados com fígados provenientes de doadores "marginais" (grupo A, n=30) foram comparados aos dos que utilizaram fígados de doadores ideais (grupo B,n=183). Os transplantes nos dois grupos foram semelhantes quanto à premência do procedimento (eletivo, urgência ou emergência), volume de sangue transfundido no período intra-operatório, tempo de isquemia fria e quente, tempo de internaçäo na UTI e na enfermaria, falência primária do enxerto e tempo de sobrevida do enxerto em um mês, tempo de sobrevida do receptor e doenxerto, em um ano. Os dois grupos diferiram apenas quanto aos níveis de AST no primeiro e dentro dos primeiros cinco dias de pós-operatórios imediato, sendo significativamente maiores no grupo A, em relaçäo ao grupo B. Estes dados mostram que os transplantes realizados com fígados de doadores "marginais" foram semelhantes àqueles realizados com fígados de doadores ideais.

An anatomical study contributing to partial liver transplantation

Este estudo teve como objetivo contribuir com o transplante hepatico parcial, utilizando um figado para a obtencao de dois enxertos e, consequentemente, aumentar a oferta de enxertos para o receptor pediatrico. Foram estudados 20 figados por meio de disseccao, que simula o ato operatorio. O estudo foi dirigido para a anatomia da veia hepatica esquerda, ramo esquerdo da veia porta, arteria hepatica esquerda e ducto biliar esquerdo. Procurando detectar algum impedimento anatomico que inviabilizasse o ato, tambem apontamos o plano ideal de transeccao hepatica, baseando-nos na anatomia funcional hepatica...