Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

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 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

Características histopatológicas, clínicas e epidemiológicas da esclerose hepatoportal em um centro de referência para doenças do fígado no Nordeste do Brasil / Histopathological, clinical and epidemiological features of hepatoportal sclerosis in a referral center for liver disease in northeastern brazil

ABSTRACT BACKGROUND: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE: To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS: We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS: From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION: HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.

RESUMO CONTEXTO: Esclerose hepatoportal EHP ou venopatia portal obliterativa VPO, um dos diagnósticos diferenciais para a hipertensão portal não cirrótica, é caracterizada pelo desaparecimento dos ramos portais, fibrose portal e septal, fibrose sinusoidal e hiperplasia nodular regenerativa HNR. A EHP é um doença espectral, que pode progredir para hipertensão portal severa. Sua etiopatologia é ainda pouco compreendida, especialmente no Brasil, onde ela é provavelmente subdiagnoticada devido as suas similaridades com a forma hepatoesplênica da esquistossomose. OBJETIVO: Analizar o perfil dos pacientes com EHP no Nordeste do Brasil, e demontrar as características patológicas da EHP. MÉTODOS: Analisamos restrospectivamente os casos de VPO em biópsias hepáticas e explantes de um centro de referência em fígado na Bahia, Brasil. A análise qualiquantitativa dos tratos portais e parênquima hepático foi realizada, permitindo a comparação entre os nossos paciente e os achados descritos por outros autores. RESULTADOS: Entre os 62 paciente identificados com EHP, 42% era do sexo masculino, 58% era do sexo feminino. A média de idade no diagnótico foi 48,3 anos. Desse grupo, analizamos a biópsia hepática de 10 pacientes nos quais o diagnóstico de esquistossomose pode ser excluído. Desses pacientes, 100% 10/10 se apresentou com fibrose portal densa e obliteração venosa portal. Atrofia do perênquima hepático estava presente em 60% 6/10 dos pacientes, dilatação sinusiodal em 30% 3/10 a presença de septos portais ocorreu em 50% 5/10 e fibrose portal densa foi achada em todos os pacientes. Hiperplasia nodular regenerativa foi encontrada em 30% dos pacientes. CONCLUSÃO: A EHP parece ser negligenciada e subdiagnosticada no Brasil, devido as suas similaridades com esquistossomose. Em nosso estudo, fibrose portal densa, obliteração dos ramos da veia porta, atrofia do parênquima, dilatação sinusoidal e hiperplasia nodular do parênquima foram os principais achados histopatológicos e foram semelhantes aos descritos em outros países.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Drug induced liver damage in a universitary hospital / Lesão hepática induzida por drogas em um hospital universitário

Introdução: lesão hepática induzida por drogas (DILI) é responsável por um amplo espectro de lesão hepática. Clinicamente, esses eventos são apresentados de várias formas e, para alcançar um diagnóstico diferente, outras causas de lesões devem ser excluídas. Objetivo: identificar e caracterizar casos de hepatotoxicidade induzida por medicamentos, fitoterápicos e suplementos alimentares em Hospital Universitário no Brasil. Metodologia: estudo observacional, retrospectivo. Os dados foram coletados em prontuários do Hospital Universitário, entre agosto de 2009, em agosto de 2014. A causalidade das reações medicamentosas suspeitas foi avaliada pelo Conselho de Organizações Internacionais de Ciências Médicas (CIOMS). Resultados: foram selecionados 30 casos suspeitos, 50% do sexo feminino e média de 39 anos. As classes terapêuticas mais comuns foram: anti-infecciosos; agentes antineoplásicos; drogas do sistema nervoso central, esteroides anabolizantes e suplementos herbáceos e dietéticos (HDS). Lesão colestática ou mista foi observada em 73% desses casos; 60% eram altamente prováveis, de acordo com o CIOMS. Conclusão: DILI é causada por uma grande variedade de drogas, suplementos dietéticos e suplementos dietéticos. Anti-infecciosos e quimioterapia foram responsáveis por grande parte da resposta.

Background: drug Induced Liver Injury (DILI) is responsible for wide spectrum of liver injury. Clinically, these events are presented in various forms and for reaching a different diagnosis other injury causes must be excluded. Aim: identify and characterize cases of hepatotoxicity induced by drugs, herbal and dietary supplements in University Hospital in Brazil. Methodology: observational and retrospective study. Was collected in records of University Hospital, between August 2009 at August 2014. The causality of the drug reactions suspected were evaluated Council for International Organizations of Medical Sciences (CIOMS). Results: we selected 30 suspected cases, 50% was female and average was 39 years. the therapeutic classes most common was: anti-infectives; antineoplastic agents; central nervous system drugs, anabolic steroid and herbal and dietary supplements (HDS). Cholestatic or mixed injury was observed in 73% these cases; 60% were highly probable, according to CIOMS. Conclusion: DILI is caused by a wide variety of drugs, dietary supplements and dietary supplements. Anti-infectives and chemotherapy were responsible for much of the response.

Monitoramento prospectivo do uso de medicamentos: lesão hepática induzida por medicamentos em um centro municipal de saúde / Prospective monitoring of drug use: drug-induced liver injury in a primary healthcare center

ABSTRACT BACKGROUND: Drug-induced liver injury is still misunderstood in Brazil due to diagnostic difficulties or lack of reporting incidents. OBJECTIVE: To assess the frequency of adverse events related to the use of medicines in a primary healthcare unit, in a city locate southwestern of the state of Bahia, Brazil. METHODS: Prospective study conducted at the Primary Center for Specialized Health (CEMEA), February at August of 2013 in Vitoria da Conquista, Bahia, Brazil. Interviews were conducted with patients over 18 years old, and their clinical and laboratorial data were collected. The CIOMS scale was used to validate the cases. RESULTS: A total of 149 patients, mainly Afro-Brazilian women, received follow-up. Among these patients, three cases of hepatotoxicity were identified, and the medicines associated to drug-induced liver injuries were: nimesulide, budesonide and valacyclovir. CONCLUSION: Drug-induced liver injury is rare in primary healthcare units. It also allowed estimating the incidence of hepatotoxicity induced by allopathic medicines which are standardized by public healthcare authorities.

RESUMO CONTEXTO: As lesões hepáticas induzidas por drogas (DILI), ainda são mal compreendidas no Brasil devido a dificuldades diagnósticas ou à falta de relatos. OBJETIVO: Avaliar a frequência de eventos adversos relacionados ao uso de medicamentos em uma unidade básica de saúde, em uma cidade do sudoeste baiano. MÉTODOS: Estudo prospectivo realizado no período de fevereiro a agosto de 2013 em Vitória da Conquista, Bahia, Brasil. Entrevistas foram realizadas com pacientes maiores de 18 anos; os dados clínicos e laboratoriais foram coletados. A escala do CIOMS foi usada para avaliar causalidade dos casos. RESULTADOS: Um total de 149 pacientes, principalmente mulheres afro-brasileiras, receberam acompanhamento. Entre esses pacientes, três casos de hepatotoxicidade foram identificados e os medicamentos associados à DILI foram: nimesulida, budesonida e valaciclovir. CONCLUSÃO: DILI é raro em unidades básicas de saúde. Os três casos foram todos reversíveis, sem necessidade de internação hospitalar. Políticas de saúde que fomentam a prática da farmacovigilância são extremamente importantes para a prevenção e detecção de DILI.

Seroepidemiology of hepatitis B in individuals born between 1945-1985 on a Brazilian regional metropolis / Soroepidemiologia da hepatite B em indivíduos nascidos entre 1945-1985 em uma metrópole regional Brasileira

Background: hepatitis B prevalence can be influenced by social/cultural behavior and the Baby Boomer (BB) generation(1945-1964) may have been more susceptible to this infection. Objectives: We investigated the seroprevalence of markers for HBV infection and vaccination and its association with main risk factors. Methodology: a random sample of individuals aged 30-70 years old in a public clinical laboratory from a metropolitan area of Bahia/Brazil were tested for HBsAg/Total Anti-HBc/Anti-HBs/Anti-HBc-IgM and a socio-demographic questionnaire was applied. Results: of the650 participants, 349 were 51-70 yo (BB) and 301 were non-BB. The prevalences were HBsAg (2.3%), Total Anti-HBc (17.1%) and Anti-HBs (27.4%). Anti-HBcIgM (2.7%) was performed in 112 participants sera who had contact/infection with HBV. The laboratory profiles were characterized as susceptibility (68%), vaccine response (14.8%) and contact/infection with HBV (17.2%). BB participants were more susceptible and less vaccinated than non-BB. The higher frequency of contact/infection status was observed in the BB generation. Statistically significant differences were found for the contact/infection status in males(50,9%) illicit drug use (11,6%), syringe/needle sharing (7,1%), and blood transfusion (10,7%). Non-BB with contact/ infection profile reported more tattoo/piercing and BB reported higher use of glass syringes. Conclusion: the majority of the study population was susceptible to infection but participants older than 50 years showed both, a higher frequency of this profile and also a higher frequency of contact/infection status, thus suggesting the need for greater health care attention for this age group.

Introdução: a prevalência de hepatite B pode ser influenciada pelo comportamento sociocultural e a geração Baby Boomer (BB) (1945-1964) pode ter sido mais suscetível a esta infecção. Objetivos: Investigar a soroprevalência de marcadores para a infecção pelo VHB e resposta vacinal e associação com fatores de risco. Metodologia: soro de indivíduos de 30 a 70 anos randomicamente selecionados em um laboratório publico de análises clínicas na área metropolitana do Brasil foram testados para AgHBs/ Anti-HBc Total /Anti-HBs/Anti-HBc-IgM. Todos responderam questionário sociodemográfico contendo perguntas sobre fatores de risco para hepatite B. Resultados: dos 650 participantes, 349 eram BB (51-70 anos) e 301 eram não-BB (30-50 anos). As prevalências estimadas foram: HBsAg (2,3%), Anti-HBs (27,4%). Entre os Anti-HBc Total (17,1%) apenas 2,7% foram Anti-HBc IgM. Os perfis laboratoriais foram caracterizados como suscetibilidade (68%), resposta vacinal (14,8%) e contato com VHB (17,2%). Na distribuição por idade, os BB foram mais susceptíveis, menos vacinados e apresentaram maior frequência de contato/infecção que os não-BB. Diferenças estatisticamente significantes foram encontradas no status contato/infecção e as seguintes variáveis: sexo masculino, uso de drogas ilícitas, compartilhamento de seringas de vidro/agulhas e transfusão de sangue. Não-BB com status contato/infecção relataram ter mais tatuagem/piercing e BB relataram maior uso de seringas de vidro. Conclusão: a maioria da população estudada era suscetível ao VHB, mas os participantes com mais de 50 anos apresentaram tanto uma maior frequência desse status quanto do status contato/ infecção, sugerindo a necessidade de maior atenção à saúde para indivíduos desta faixa etária.

In silico modeling of the molecular structure of micrornas markers for liver fibrosis in hepatitis c

Molecular biology looks for evidence that microRNA (miRNAs) plays a relevant function both in the beginning and advanced stages of hepatic fibrosis (HF), and has been proposed as an additional biomarker for HF forecasting in carriers of hepatitis C virus (HCV) infection. The purpose of this study was to develop an in silico modeling of the two-dimensional (2D) molecular structure of miRNA markers for HF in carriers of HCV. A search was initially performed for the nucleotide sequence of 6 miRNAs defined as biomarkers for HF, performing a computational simulation of the molecular structure of the following miRNAs: miRNA-182, miRNA-183, miRNA-1260b, miRNA-122-3p, miRNA-378i, and miRNA-214-5p. The nucleotide sequences were chosen in the GenBank of the American National Institutes of Health genetic sequence database. The nucleotide sequence alignment was carried out with a text-based format (FASTA) tool. In the molecular modeling, the structures were built with the RNAstructure, a completely automated miRNAs structure modelling server, available through Web Servers for RNA Secondary Structure Prediction. This study presented the nucleotide sequence and the computational simulation of molecular structures for the following miRNA: miRNA-182, miRNA-183, miRNA-1260b, miRNA-122-3p, miRNA-378i, and miRNA-214- 5p. The molecular structure of miRNAs markers for HF in HCV carriers, through computational biology, is essential for designing more efficient optional tools for accurate treatment.

Sequence similarity between thyroid self-protein and hepatitis c virus polyprotein: possible triggering mechanism of autoimmune thyroiditis / Similaridade de sequências entre auto-proteínas da tireoide e poliproteínas do vírus da hepatite C: possível mecanismo de desencadeamento da tireoidite auto-imune

ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.

RESUMO Contexto - A exposição a antígenos virais que compartilham sequência de aminoácidos semelhantes a auto-antígenos pode provocar doenças auto-imunes em indivíduos predispostos geneticamente, e a teoria do mimetismo molecular sugere que o mimetismo entre epítopos de vírus e proteínas humanas pode ativar doenças auto-imunes. Objetivo - O objetivo deste estudo foi explorar a possível semelhança entre as sequências de aminoácidos de auto-proteinas da tireóide e proteínas do vírus da hepatite C, utilizando bancos de dados de proteínas e peptídeos imunogênicos, para explicar a doença auto-imune da tireóide. Métodos - Foram realizadas comparações entre as sequências de aminoácidos de poliproteínas do vírus da hepatite C e auto-proteinas da tireóide humana, disponível na base de dados do National Center for Biotechnology Information no Basic Local Alignment Search Tool. Resultados - A semelhança de sequências foi relacionada para cada genótipo de vírus da hepatite C e proteínas da tireóide. As semelhanças entre proteínas da tireóide e os peptídeos virais variaram de 21,0% (31 resíduos idênticos da sequência de 147 aminoácidos) a 71,0% (cinco resíduos idênticos da sequência de 7 aminoácidos). Conclusão - Dados de bioinformática sugerem uma possível ligação entre vírus da hepatite C e doença auto-imune da tireóide. Através de mimetismo molecular observa-se que as semelhanças entre as sequências de poliproteínas virais e auto-proteínas da tireóide pode ser um mecanismo de indução de resposta imune resultando em doença auto-imune da tireóide.

Avaliação do protocolo clínico e diretrizes terapêuticas para o tratamento para hepatite B crônica nas regiões nordeste e norte do Brasil / Analysis of clinical protocol and guidelines therapeutic for treatment for chronic hepatitis B in northeast Brazil and regions north

No Brasil o tratamento para Hepatite B cônica, tem sido disponibilizado pelo Sistema Único de Saúde há mais de 10 anos. O objetivo foi analisar o tratamento dos pacientes com hepatite B crônica, em dois Centros de Referência em Hepatites Virais na Região Nordeste e Norte do Brasil, comparando com o Protocolo Clínico e Diretrizes Terapêuticas da Hepatite B do Ministério da Saúde. Foram incluídos no estudo 527 pacientes em atendimento ambulatorial. No algoritmo 4.1 foi observado que existe uma dificuldade em seguir a recomendação do Ministério da Saúde, nos dois serviços de referência, 78,9% e 72% Região Nordeste e Norte respectivamente. O algoritmo 4.2, foi o algoritmo que apresentou no geral mais de 90% de seguimento na recomendação do Protocolo Clínico, devido que os pacientes são na sua grande maioria AgHBe negativo. O algoritmo 4.3 aproximadamente 85% dos pacientes da Região Nordeste estava dentro da recomendação do Protocolo Clínico para Hepatite B crônica, entretanto, nenhum paciente da Região Norte. O Protocolo Clínico de Diretrizes Terapêuticas para Hepatite B foi um grande passo e avanço. Uma ferramenta importantíssima dentro da realidade do tratamento para Hepatite B e foi possível incorporar novas drogas e indicadores de tratamento embasados na Medicina Baseada em Evidencias e nos Consensos Internacionais pelo Ministério da Saúde.

In Brazil the treatment for Hepatitis B conical, has been provided by the National Health System for over 10 years. The aim was to analyze the treatment of patients with chronic hepatitis B in two reference centers in Viral Hepatitis in the Northeast and North of Brazil, compared to the Clinical Protocol and Therapeutic Guidelines Hepatitis B of the Ministry of Health. The study included 527 patients in outpatient care. In algorithm 4.1 it was observed that there is a difficulty in following the recommendation of the Ministry of Health in two reference centers, 78.9% and 72% northeast and north respectively. The 4.2 algorithm, the algorithm was presented in general more than 90% follow-up on the recommendation of the Clinical Protocol because patients are mostly negative HBeAg. The algorithm 4.3 approximately 85% of patients in the Northeast was in the recommendation of the Clinical Protocol for chronic hepatitis B, however, no patients in the Northern Region. The Clinical Protocol Therapeutic Guidelines for Hepatitis B was a big step and advance. An important tool within the reality of treatment for hepatitis B and it was possible to incorporate new drugs and treatment indicators grounded in Evidence-Based Medicine and the International Consensus by the Ministry of Health.

Dano hepático induzido por medicamentos em pacientes ambulatoriais: análise retrospectiva da utilização de medicamentos / Drug-induced liver injury in outpatients: retrospective analysis of medication use

Introdução: pouco se sabe sobre a hepatotoxicidade no Brasil, principalmente na assistência básica do Sistema Único de Saúde, devido à subnotificação. Objetivo: determinar a prevalência de Dano Hepático Induzido por Medicamentos (DHIM), em pacientes ambulatoriais. Método: estudo retrospectivo. Foram coletados os dados dos pacientes atendidos em clínica especializada por gastroenterologistas no período de 01 a 31 de agosto de 2010. Resultados: dos 139 pacientes atendidos, foram encontrados quatro casos com suspeita de DHIM (2,87%). A idade média foi de 47,3 anos, 66,2% eram mulheres e média de medicamentos utilizados de 3,36/paciente. Os casos foram validados com a utilização da escala de RUCAM, por especialistas, confirmando um caso por uso de rifampicina e dapsona de sódico e três casos classificados como possível DHIM. Paciente 1- antissecretores; Paciente 2- glicocorticoides; Paciente 3- antimicrobianos. Conclusão: apesar da baixa incidência de DHIM, o quadro resultante pode ser grave, acarretando em grandes perdas econômicas para o paciente e para o sistema de saúde.

Introduction: little is known about hepatotoxicity in Brazil, especially in the basic care of the Unified Health System, due to underreporting of cases. Aims: to determine the prevalence of Drug-Induced Liver Injury (DHIM) in outpatients. Methods: retrospective study. We collected data from medical records, of patients seen in a specialized clinic by gastroenterologists from August 01 to August 31, 2010. Results: of 139 patients enrolled, four cases were found with suspected DHIM (2.87%): The mean age was 47.3 years, 66.2% were women and average medication used 3.36 per patient. The cases were validated with the use of RUCAM scale, by specialists, confirming a case caused by rifampicin and dapsone and three cases classified as possible DHIM: Patient 1- antisecretory; Patient 2- glucocorticoids; Patient 3- antimicrobials. Conclusion: despite the low incidence of DHIM, the resulting picture can be severe, causing huge economic losses for both the patient and the healthcare system.

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature / Impacto da gama glutamiltransferase na resposta terapêutica da hepatite C crônica: revisão sistemática da literatura

BackgroundThe standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase.ObjectiveTo evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C.MethodsThis is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013.ResultsA total of 4,785 titles were iden tified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study - six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %).ConclusionGamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin.

ContextoO tratamento padrão da hepatite C crônica consiste na administração de interferon peguilado α2a ou α2b associado à ribavirina. Contudo, podem ser observados efeitos adversos além do alto custo desta terapêutica. Por isso há interesse no conhecimento dos fatores preditivos de resposta virológica sustentada como a gama glutamiltransferase.ObjetivoAvaliar os níveis séricos da gama glutamiltransferase como fator preditivo de resposta terapêutica com interferon peguilado α e ribavirina na hepatite C crônica.MétodosTrata-se de uma revisão sistemática da literatura, conduzida através de consulta às bases eletrônicas de dados PUBMED, LILACS, MEDLINE, SCOPUS e COCHRANE, e busca ativa das referências dos artigos selecionados, no período de janeiro de 2000 a abril de 2013.ResultadosForam identificados 4.785 títulos. Destes, seguindo os critérios de inclusão e exclusão, foram selecionados 273 resumos para a leitura por dois pesquisadores independentes. Após a leitura dos artigos, na íntegra e em consenso, os revisores incluíram dez estudos, para sistematização e qualificação, segundo os critérios da Escala de Oxford. Predominaram os estudos 1B A (Coorte prospectivo - seis estudos), publicações da Alemanha. A frequência de resposta virológica rápida foi identificada em três estudos e resposta virológica precoce em dois estudos, com um total de 392 e 413 pacientes respectivamente; a resposta virológica sustentada foi registrada em nove artigos correspondendo a 3.787 pacientes (76,5%).ConclusãoO nível sérico da gama glutamiltransferase é um fator preditivo de resposta virológica sustentada no tratamento da hepatite C crônica com interferon peguilado α2a ou α2b associado à ribavirina.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

Grading scale o visceral adipose tissue thicknss and their relation to the noonalcoholic fatty liver disease / Escala de classificação da espessura do tecido adiposo visceral e sua relação com a doença gordurosa hepática não alcoólica

Context The mesenteric fat is drained by the portal system, being related to the metabolic syndrome which is an impor­tant risk factor for non-alcoholic fatty liver disease (NAFLD). Objectives Graduate of visceral fat thickness and correlate with the NAFLD degree through ultrasonography method. Methods We studied 352 subjects for age, gender, measures of subcutaneous fat thickness and visceral fat thickness as well as the presence and degree of liver fatty. Was analyzed the independent relationship between visceral fat thickness and NAFLD, and linear regression analysis was used in order to predict the visceral fat thickness from subcutaneous fat thickness. Results The mean age of 225 women (63.9%) and 127 men (36.1%) was 47.5 ± 14.0 (18-77) years, 255 subjects had normal examinations, 97 had NAFLD thus distributed, 37 grade 1, 32 grade 2, and 28 grade 3. The subcutaneous fat thickness ranged from 0.26 to 3.50 cm with a mean of 1.3 ± 0.6 cm and visceral fat thickness ranged from 0.83 to 8.86 cm with a mean of 3.6 ± 1.7 cm. Linear regression showed that for every increase of 1 cm in subcutaneous fat thickness the visceral fat thickness will increase 0.9 cm. Conclusions The visceral fat thickness measured by ultrasonography is a useful and seems to be able to help estimate the risk of NAFLD. .

Contexto A gordura mesentérica é drenada pelo sistema venoso portal, estando relacionada à síndrome metabólica, que é um importante fator de risco para doença de infiltração gordurosa do fígado. Objetivos Graduar a espessura do tecido adiposo visceral e correlacionar com o grau de doença de infiltração gordurosa do fígado através do exame ultrassonográfico. Métodos Foram estudados 352 indivíduos, avaliando-se idade, gênero, medidas da espessura da gordura subcutânea e tecido adiposo visceral, a presença e o grau de doença de infiltração gordurosa do fígado. Foi analisada a relação independente entre tecido adiposo visceral e doença de infiltração gordurosa do fígado, e a regressão linear foi utilizada para prever a tecido adiposo visceral pela espessura da gordura subcutânea. Resultados A idade média de 225 (63,9%) mulheres e 127 (36,1%) homens foi 47,5 ± 14,0 (18-77) anos, 255 indivíduos apresentaram exames normais, 97 apresentaram doença de infiltração gordurosa do fígado assim distribuídos: 37 grau 1, 32 grau 2 e 28 grau 3. A espessura da gordura subcutânea variou de 0,26 e 3,50 cm, com uma média de 1,3 ± 0,6 cm e a tecido adiposo visceral variou de 0,83 a 8,86 cm, com uma média de 3,6 ± 1,7 cm. A regressão linear demonstrou que para cada aumento de 1 cm da espessura da gordura subcutânea o tecido adiposo visceral aumentará 0,9 cm. Conclusão O tecido adiposo visceral medido por ultrassonografia é um instrumento útil e parece ser capaz de estimar o risco de doença de infiltração gordurosa do fígado. .

Estudio sobre la sobrecarga de hierro en pacientes con hepatitis C crónica / [A study on hepatic iron overload in chronic hepatitis C patients].

BACKGROUND: Hepatitis C is a worldwide chronic liver disease. Different factors have been found to be associated with an increased progression to severe liver fibrosis, such as alcohol intake higher than 30 g/day, older age at infection and co-infection. Nevertheless, different research centers have found conflicting data concerning the liver iron overload fibrogenic role. AIM: To assess the association between hepatic iron overload and fibrosis stage grades in hepatitis C Virus carriers, hepatic steatosis and demographic variables. METHODS: In this descriptive study we recruited 290 positive anti-HCV and qualitative HCV-RNA, treatment naive chronic hepatitis C outpatients registered fom 2007 to 2009 at the Federal University of Bahia’s Hospital. The variables studied in the liver biopsy results were: 1) fibrosis stage according to META VIR score (F0-F4), 2) iron overload presence or absence according to Perls staining, and 3) presence or absence of steatosis. Fibrosis stages were categorized as mild/moderate (F0-F2) and severe (F3-F4). Exclusion criteria were hepatitis B virus and human immunodeficiency virus co-infection, and primary or secondary hemochromatosis. The statistical analysis was performed using Chi-square and Student’s t tests, with the ssoftware: SPSS 17. A P value < 0.05 was considered as significant. RESULTS: Severe fibrosis was statistically associated with older age, iron overload presence (P = 0.003) and steatosis (P = 0.01). CONCLUSIONS: In this study hepatic iron overload and hepatic steatosis were associated with severe hepatic fibrosis (METAVIR F3-F4).

Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease / Infecção pelo vírus da hepatite D na Amazônia brasileira - longe de uma doença em declínio

INTRODUCTION: A decline in hepatitis D virus (HDV) occurrence was described in Europe and Asia. We estimated HDV prevalence in the Brazilian Amazon following hepatitis B vaccination. METHODS: This is a cross-sectional survey of HDV measured by total antibodies to HDV (anti-HD T). RESULTS: HDV prevalence was 41.9% whiting HBsAg carries and was associated with age (PR = 1.96; 95% CI 1.12-3.42; p = 0.01), hepatitis B virus (HBV) infection (PR = 4.38; 95% CI 3.12-6.13; p < 0.001), and clinical hepatitis (PR =1.44; 95% CI 1.03-2.00; p = 0.03). Risk factors were related to HDV biology, clinical or demographic aspects such as underlying HBV infection, clinical hepatitis and age. CONCLUSIONS: Our study demonstrated that HDV infection continues to be an important health issue in the Brazilian Amazon and that the implementation of the HBV vaccination in rural Lábrea had little or no impact on the spread of HDV. This shows that HDV has not yet disappeared from HBV hyperendemic areas and reminding that it is far from being a vanishing disease in the Amazon basin.

INTRODUÇÃO: É descrito declínio na ocorrência do vírus da hepatite D (VHD) na Europa e Ásia. Estimamos a prevalência de infecção pelo VHD na Amazônia Ocidental, após a introdução da vacinação contra hepatite B. MÉTODOS: Este é um estudo de corte transversal da prevalência do VHD medido pela ocorrência de anticorpos totais (anti-HD T). RESULTADOS: A prevalência do VHD encontrada foi 41,9% entre os portadores do HBsAg, e esteve associado à idade (RP = 1,96; IC 95% 1,12-3,42; p = 0,01), infecção pelo HBV (RP = 4,38; IC 95% 3,12-6,13; p < 0,001) e história clínica de hepatite (RP =1,44; IC 95% 1,03-2,00; p = 0,03). Fatores de risco mostraram-se associados à biologia do HDV, aspectos clínicos e demográficos como infecção prévia pelo VHB e idade. CONCLUSÕES: O estudo demonstra que a infecção pelo VHD continua sendo um importante problema de saúde pública na região, e que a implantação da vacinação contra o VHB na área rural de Lábrea teve um impacto pouco significativo no controle do VHD, percebe-se que este ainda não desapareceu de áreas hiperendêmicas do VHB, e está longe de poder ser classificado como uma doença em declínio na bacia Amazônica.

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

OBJECTIVE: To investigate the frequency of thyroid disorders (TD) in patients with chronic hepatitis C before and during interferon-alpha (IFN-α) and ribavirin (RIB) treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males) was 49.61 ± 11.83 years. Seven (10.76 percent) patients presented baseline thyroid disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92 percent) patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A total of 18 patients (27.69 percent) developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of developing hypothyroidism found in this study was 1.3 (95 percent CI: 1.1 to 1.6), hyperthyroidism 1.2 (95 percent CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95 percent CI: 3.9 to 14.5). The study showed a significant association between female sex and thyroid disease (p = 0.009). CONCLUSION: Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8 percent and cryoglobulinemia was demonstrated in 36.9 percent patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

Impact of psychiatric disorders on the quality of life of brazilian HCV-infected patients

The aim of our study was to determine the impact of psychiatric comorbidities on the health-related quality of life of HCV-infected patients. Assessment of clinical, socio-demographic and quality of life data of the patients followed up at a Hepatology unit was performed by using a standard questionnaire and the SF-36 instrument. Psychiatric diagnoses were confirmed by using the Mini International Neuropsychiatric Interview, Brazilian version 5.0.0 (MINI Plus). Evaluation using the MINI plus demonstrated that 46 (51 percent) patients did not have any psychiatric diagnosis, while 44 (49 percent) had at least one psychiatric diagnosis. Among patients with a psychiatric comorbidity, 26 (59.1 percent) had a current mental disorder, out of which 22 (84.6 percent) had not been previously diagnosed. Patients with psychiatric disorders had lower scores in all dimensions of the SF-36 when compared to those who had no psychiatric diagnosis. Scores of physical functioning and bodily pain domains were lower for those suffering from a current psychiatric disorder when compared to those who had had a psychiatric disorder in the past. Females had lower scores of bodily pain and mental health dimensions when compared to males. Scores for mental health dimension were also lower for patients with advanced fibrosis. The presence of a psychiatric comorbidity was the variable that was most associated with the different scores in the SF-36, compared to other variables such as age, gender, aminotransferase levels, and degree of fibrosis.

Occult B infection in the Brazilian northeastern region: a preliminary report

A sentinel study on viral hepatitis is currently being carried out in the village of Cavunge in a semiarid rural region of the state of Bahia, northeastern Brazil. This study has identified individuals in whom anti-HBc IgG was the only serological marker for hepatitis B virus (HBV). This serological pattern may constitute evidence of occult HBV infection. This study Investigated the possibility of occult hepatitis B virus infection in individuals in a rural community who tested positive for anti-HBc IgG alone. A cross-sectional population-based study. ELISA III was performed on serum samples to test for serological viral markers, and ultrasensitive PCR (US-PCR) was used to assess viremia. Among the 1,536 serum samples, 3.6 percent (n=55) were positive for anti-HBc alone. Four years after this first serological survey, 31 of those 55 individuals (56.3 percent) were retested, and 11 (35.5 percent) remained anti-HBc positive alone. Two of these 31 (6.5 percent) were HBV-DNA positive based on US-PCR, with normal aminotransferase levels in both cases. Cases of occult hepatitis B infection were identified in this semiarid rural community of northeastern Brazil, where endemicity of HBV is moderate.

Hepatotropic viruses in the Brazilian Amazon: a health threat: [review]

Viral Hepatitis B, C and D are a serious public health problem in Brazil and other South American countries, mainly in the Amazonian region. Despite the paucity of clinical and epidemiological studies, a high prevalence of Hepatitis viruses has often been described in this area. Genotype F of Hepatitis B and Genotype III of Hepatitis D have been found to be quite prevalent in this area and preliminary studies have implicated both genotypes in carcinogenesis and peculiar pathogenic liver mechanisms. Initial epidemiological studies have further demonstrated a high prevalence of Hepatitis C in the western Brazilian Amazon. The geographic, cultural, ethnic and environmental aspects of this region may favor hepatotropic virus dissemination, as well as rendering difficult the implementation of governmental programs in the treatment of patients and prevention of disease dissemination.