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.

Application of the Validated Social Assessment Instrument for Liver Transplantation Candidates.

The use of appropriate instruments for social assessment in health aims at both the participation of the subject and effectiveness in resolving demands. The objective of this study was to characterize the population assessed by the Validated Social Assessment Instrument and its implications; a descriptive, documental study with participant and dialectical observation. The data survey were taken from the social assessments applied from July 2020 to June 2021 in a transplant center in northwestern São Paulo state in Brazil. Descriptive statistics were performed. The 65 social evaluations of candidates for liver transplantation (LTx) have presented the following sociodemographic characteristics: male sex (n = 47; 72.3%); mean age of 55.05 years (range: 24-75 years old); with a partner (n = 50; 76.9%); low education level (n = 30; 46.2%); and coming from the state of São Paulo (n = 54; 83.1). Of those evaluated, 48 candidates (74%) were professionally inactive and 37 (56.9%) received assistance or social security benefits; 62 (95.4%) had a family caregiver; 61 (93.9%) had a resolutive compliance family response; 57 (87.7%) had facilitated accessibility; 59 (90.8%) met satisfactory housing standards; and 60 (92.3%) had full acceptance for LTx. The 65 candidates' (100%) social opinions were favorable, and 21 (32.3%) had some limitations and required further assistance. All of them received basic and specific social orientations, and 25 (38.5%) required social referrals. The variables have allowed a view at the totality of the social being in addition to widening the subject's participation in order to identify the real demands and facilitate the monitoring of actions, thus contributing for favorable conditions for treatment.

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. MATERIAL AND METHODS: Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). CONCLUSION: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

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.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

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.

Clinical and laboratorial profiles of dengue virus infection in kidney transplant recipients: Report of a single center.

Dengue infection (DI) is the most important arboviral infection in the world. The majority of immunocompetent patients will have asymptomatic or mild infections, but the degree of dengue severity in kidney transplant recipients (KTx) is unknown. In this study, we report the clinical profile and outcomes of 39 dengue cases in KTx. From a total of 1,186 KTx outpatients in follow-up we reviewed clinical and laboratory records of 60 (5%) patients admitted with suspected DI initially screened by NS-1, IgM, and when possible, multiplex nested PCR. The prevalence of DI in KTx was 3% (39/1,118), with symptoms leading to hospital admission being fever, myalgia, malaise, and headache. Laboratory tests showed leucopenia, thrombocytopenia, and liver enzyme elevation. DI was confirmed by positivity of NS-1 (33%), IgM (69%), and/or RT-PCR (59%). Twenty-three patients (59%) had dengue with warning signs, and 15% had severe dengue, 2 of them with a fatal course. Acute graft dysfunction occurred in 59% (mean nadir serum creatinine: 2.9 ± 2.6mg/dL), 4 of them requiring dialysis. CMV coinfection diagnosed in 19% of the cases and patients was associated with worse clinical presentation. Our results suggest that KTx with DI presented initial physical and laboratorial profile similar to the general population. However, DI in KTx seems to have a higher risk for graft dysfunction, severe dengue, and death. Because CMV coinfection aggravates the DI clinical presentation and recovery, it must be evaluated in all cases.

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.

Clinical, Epidemiological and Histopathological Aspects in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Background: Hepatocellular Carcinoma (HCC) is the primary liver cancer with high incidence and mortality rates. Currently one of the major etiologies for liver disease, HCC and liver transplantation is nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the epidemiological, histopathological and clinical aspects of HCC transplant patients, with emphasis on NAFLD etiology. Methods: This study included all HCC patients submitted to liver transplantation from 2010 to 2016 of the University Reference Center. The analyzed variables were age, gender, ethnicity, causes that led to liver transplantation, alpha-fetoprotein (AFP) dosage, histological aspects, recurrence, survival and NAFLD. Results: A total of 60 patients were included in the study being 80% men with a mean age of 58.3 ± 10.6 years. All patients were cirrhotic. The causes that led to the transplantation were the presence of the hepatitis C virus (HCV) (56.6% of the patients), an association of the virus with alcohol (20%), the presence of the hepatitis B virus (HBV) (20%), alcoholic liver disease (ALD) (50.9%) and NAFLD (25%). Of the latter, eight were diagnosed pre-transplantation and seven were NAFLD carriers without a previous diagnosis. Regarding the Edmondson-Steiner histological classification, 58.5% of the patients were classified as grade ≤ II. Conclusions: There is predominance of male patients with a mean age of 58.3 years. Degree ≤ II is the most frequent to the Edmondson-Steiner histological classification in the evaluated casuistic. HCV, ALD and NAFLD is the most common etiological agents found in the study. The (high) underestimated prevalence of NAFLD in the pre-transplanted patients is due to the fact that all patients presented cirrhosis, masking NAFLD signals.

Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy

Hepatocellular carcinoma (HCC) is a cause of several deaths related to cancer worldwidely. In early stage, curative treatments such as surgical resection, liver transplant and local ablation can improve the patient ´s survival. However, the disease is detected in advanced stage; moreover some available therapies are restricted to palliative care and local treatment. Early detections of HCC and adequate therapy are crucial to increase survival as well as to improve the patient´s quality of life. Therefore, researchers have been investigating molecular biomarkers with high sensibility and reliability as Golgi 73 protein (GP73), Glypican-3 (GPC3), Osteopontin (OPN), microRNAs and others. MicroRNAs can regulate important pathways on carcinogenesis, as tumor angiogenesis and progression. So, they can be considered as possible markers of prognosis in HCC, and therapeutic target for this tumor type. In this review, we discuss the recent advances related to the cause (highlighting the main risk factors), treatment, biomarkers, clinic aspects, and outcome in hepatocellular carcinoma.

VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.

Non-alcoholic fatty liver disease (NAFLD) in different populations: A clinical and epidemiological study - sample of São José do Rio Preto.

INTRODUCTION: NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH), in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM), obesity, predisposition, metabolic syndrome (MS), insulin resistance (IR), drugs, and polycystic ovary syndrome. OBJECTIVE: To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. METHOD: Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. RESULTS: Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each). Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38) with high blood pressure (HBP), 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR) (HOMA> 3.5). There was an association between IR and NASH (p=0.013), IR and obesity (p=0.027), IR and MS (p=0.006), and MS and steatosis on medical ultrasound (USG) (p=0.014). CONCLUSION: The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

Non-alcoholic fatty liver disease (NAFLD) in different populations: A clinical and epidemiological study - sample of São José do Rio Preto / Doença hepática gordurosa não alcoólica em diferentes populações: um estudo clínico e epidemiológico - Amostra de São José do Rio Preto

SUMMARY Introduction: NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH), in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM), obesity, predisposition, metabolic syndrome (MS), insulin resistance (IR), drugs, and polycystic ovary syndrome. Objective: To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. Method: Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. Results: Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each). Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38) with high blood pressure (HBP), 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR) (HOMA> 3.5). There was an association between IR and NASH (p=0.013), IR and obesity (p=0.027), IR and MS (p=0.006), and MS and steatosis on medical ultrasound (USG) (p=0.014). Conclusion: The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

RESUMO Introdução: a doença hepática gordurosa não alcoólica (DHGNA) é uma condição heterogênea que inclui esteatose e esteato-hepatite não alcoólica (NASH), na ausência de consumo significante de álcool, podendo atingir 30% da população. Fatores de risco mais comuns são idade, gênero, etnia, diabetes mellitus (DM), obesidade, predisposição, síndrome matabólica (SM), resistência à insulina (RI), drogas e síndrome do ovário policístico. Objetivo: descrever o perfil de portadores de DHGNA assistidos no Hospital de Base de São José do Rio Preto, SP. Método: foram avaliados pacientes com DHGNA e coletados dados clínico-epidemiológicos, após consentimento informado. Resultados: dos 62 pacientes estudados, houve predomínio de mulheres (76%), caucasoides (73%), idade entre a quinta e sexta décadas e assintomáticos (71%). Exame de ultrassonografia (US) mostrou esteatose em 84%. NASH foi diagnosticada em 61% da casuística. Em 21 pacientes, biópsia hepática mostrou cirrose em 36% e câncer de fígado e esteatose pura em um paciente (5%) cada. Dos fatores de risco, 70% dos pacientes apresentavam SM; 87%, cintura abdominal alterada; 63%, dislipidemia; 61% (n=38), hipertensão arterial sistêmica (HAS); 28%, DM; 52%, sedentarismo, e em 44% encontrou-se RI (HOMA>3,5). Houve associação entre RI e NASH (p=0,013), RI e obesidade (p=0,027), RI e SM (p=0,006), SM e esteatose à US (p=0,014). Conclusão: os fatores de risco mais frequentes foram SM e suas variáveis (cintura abdominal aumentada, dislipidemia e HAS), o que ressalta a importância do controle metabólico na DHGNA e corrobora o seu papel como componente hepático da SM.

Perfil de pacientes em pré-operatório para transplante de fígado em hospital de ensino / Profile of patients preoperatively to liver transplant in a teaching hospital

Objetivo - Descrever dados epidemiológicos de pacientes com cirrose hepática internados em um hospital de ensino, com base nos pareceres fisioterapêuticos solicitados. Métodos - Trata-se de um estudo retrospectivo transversal, realizado em um hospital-escola. Foram selecionados os pareceres realizados no período entre janeiro de 2009 a novembro de 2010, e obtidos dados referentes à etiologia, sexo, faixa etária, espirometria e alterações físico-funcionais. Resultados - Verificou-se maior prevalência para a hepatite por vírus C e a hepatite alcoólica, sendo o gênero masculino o mais afetado, com idade de 51 ± 10,9 anos, abdome globoso ascitíco foi a alteração físico-funcional mais relevante. Conclusão - Tais dados se mostraram similares aos da literatura.

Objective - To describe epidemiological data of patients with liver cirrhosis admitted to a teaching hospital, based on advice requested physical therapy. Methods - This is a retrospective study, conducted in a teaching hospital. We selected the opinions in the period between January 2009 to November 2010, and obtained data regarding the etiology, sex, age, spirometry, and physical and functional changes. Results - A higher prevalence of hepatitis C virus and alcoholic hepatitis, and males were the most affected, aged 51 ± 10.9 years, distended abdomen ascites are the change most relevant physical and functional. Conclusion - These data are similar to those shown in the literature.

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.