Histological findings and NAFLD/NASH Status in liver biopsies of patients subjected to bariatric surgery

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.

A avaliação de níveis sérios de infliximabe favorece a manutenção do tratamento em pacientes com doença inflamatória intestinal / The evaluation of infliximab trough level favors maintenance therapy of patients with inflammatory bowel disease

ABSTRACT Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases that result from the deregulation of the mucosal immune system of the gastrointestinal tract. The use of biological therapies, including infliximab (IFX), is one of the strategies to treat both CD and UC. The IFX treatment is monitored by complementary tests, namely: fecal calprotectin (FC); C-reactive protein (CRP); and endoscopic and cross-sectional imaging. Besides, serum IFX evaluation and antibody detection are also used. Objective: To evaluate trough levels (TL) and antibodies in a population with inflammatory bowel (IBD) disease undergoing treatment with IFX, and the factors that might impact the treatment effectiveness. Methods: Retrospective, cross-sectional study with patients with IBD that were assessed for TL and antibody (ATI) levels in a southern Brazilian hospital, from June 2014 to July 2016. Results: The study assessed 55 patients (52.7% female) submitted to serum IFX and antibody evaluations (95 blood samples, 55 first test; 30 second test, and 10 as third testing. Forty-five (47.3%) cases were diagnosed with CD (81.8%), and ten with UC (18.2%). Serum levels were adequate in 30 samples (31.57%), subtherapeutic in 41 (43.15%), and supratherapeutic in 24 (25.26%). IFX dosages were optimized for 40 patients (42.10%), maintained for 31 (32.63%), and discontinued for 7 (7.60%). The intervals between infusions were shortened in 17.85% of the cases. In 55 tests (55.79%), the therapeutic approach was exclusively defined according to IFX and/or serum antibody levels. The assessment of patients one year later indicated that: the approach was maintained with IFX for thirty-eight patients (69.09%); the class of biological agent was changed for eight (14.54%); changes using the same class of biological agent occurred for two patients (3.63%); the medication was discontinued and not replaced for three patients (5.45%), and four patients (7.27%) were lost to follow-up. Conclusion: There were no differences in TL between groups with or without immunosuppressants, serum albumin (ALB), erythrocyte sedimentation rate (ESR), FC, CRP, and endoscopic and imaging examinations. Current therapeutic approach could be maintained for almost 70% of patients. Thus, serum and antibody levels are a useful tool in the follow-up of patients undergoing maintenance therapy and after treatment induction in patients with inflammatory bowel disease.

RESUMO Contexto: A doença de Crohn e a colite ulcerativa são doenças crônicas nas quais existem desregulação do sistema imune da mucosa do trato gastrointestinal. Uma das terapias usadas no tratamento dessas doenças são as medicações biológicas, entre elas o Infliximabe. A monitorização do tratamento dos pacientes com Iinfliximabe é feita por exames complementares: calprotectina fecal, pesquisa de atividade inflamatória, exames endoscópicos e imagem. Utiliza-se, também a dosagem do nível sérico do Infliximabe e a pesquisa de anticorpos. Objetivo: Analisar uma população com doenças inflamatórias intestinais, em tratamento com Infliximabe, submetida a avaliação do nível sérico do Infliximabe e do anticorpo, além de possíveis fatores que possam alterar ou contribuir no tratamento. Métodos: Trata-se de estudo retrospectivo, transversal, realizado por meio da revisão dos prontuários dos pacientes com doença inflamatória intestinal, em um hospital sul-brasileiro, no período de junho de 2014 até julho de 2016, que foram submetidos a avaliação dos níveis séricos de Infliximabe e do anticorpo. Resultados: Foram incluídos 55 pacientes, submetidos a dosagem do Infliximabe e do anticorpo, totalizando 95 coletas sanguíneas. Destes, 55 realizaram uma primeira coleta, 30 tiveram uma segunda amostra coletada e 10 coletaram uma terceira vez. Vinte e nove pacientes eram do sexo feminino (52,7%) e vinte e seis do sexo masculino (43.2%). Quarenta e cinco (47,3%) casos tinham diagnóstico de doença de Crohn (81,8%) e 10 de colite ulcerativa (18,2%). Em relação ao nível sérico encontrou-se nível adequado em 30 coletas (31,57%), subterapêutico em 41 coletas (43,15%) e supraterapêutico em 24 coletas (25,26%). A prescrição foi otimizada em 40 (42,10%) casos, mantida em 31 (32,63%) pacientes, suspensa em 7 (7,60%) ou que o intervalo entre as infusões fosse aumentado (17,85%). Na análise geral, em 53 coletas (55,79%) a conduta foi definida em função exclusivamente da dosagem sérica do Infliximabe e/ou do anticorpo, já em relação, apenas a primeira coleta obteve-se 33 (60%) pacientes. Avaliando-se os pacientes um ano após, obteve-se: em 38 (69,09%) pacientes a conduta foi mantida com Infliximabe e, em 8 (14,54%) foi optado por troca de classe, em 2 (3,63%) foi optado por troca da medicação na mesma classe, em 3 (5,45%) pacientes a medicação foi suspensa e não foi substituída e, em 4 (7,27%), perdeu-se o seguimento. Conclusão: Não encontrou-se diferença entre os níveis de Infliximabe entre os grupos com ou sem imunossupressor, albumina sérica, velocidade de hemossedimentação, Calprotectina, Proteína C reativa, exames endoscópicos e exames de imagem. A conduta atual pode ser mantida em quase 70% dos pacientes. Concluindo, a dosagem do nível sérico e do anticorpo é ferramenta útil no acompanhamento dos pacientes em terapia de manutenção e após a indução de tratamento em pacientes com Doença Inflamatória Intestinal.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Experience of a gastroenterology center in fecal microbiota transplantation in the treatment of Clostridioides Difficile / Experiência de um centro de gastroenterologia em transplante de microbiota fecal no tratamento de Clostridioides difficile

Background: The treatment of Clostridioides difficile is based on an antibiotics cycle, but for individuals who have more than two recurrences, fecal microbiota transplantation can be considered as a therapeutic option. Objective: To describe the technique and results of fecal microbiota transplantation performed for recurrent infection by Clostridioides difficile. Methods: Retrospective, cross-sectional study based on a review of medical records of patients undergoing transplantation of fecal microbiota. Data were obtained on the criteria used to select the donor, the preparation of stools in the laboratory and the method of delivery of the material offered, as well as information regarding the characteristics of the recipient, such as: gender, age, comorbidities, hospitalizations, use of antibiotics prior to infection, clinical presentation, diagnosis and treatments performed for Clostridioides difficile. After transplantation, data on efficacy, outcome, follow-up time and procedure complications were considered. Results: Between 2012 and 2019, 11 patients underwent fecal microbiota transplantation. The use of antibiotics prior to infection occurred in 9 patients, no patient was hospitalized in the previous 6 months due to another etiology. All had at least 2 cycles of vancomycin for recurrent disease. Of the total of 11 patients, 2 required 2 infusions and 1 patient required 3, totaling 15 fecal microbiota transplants. The success rate was 81.8% with only one infusion and 90.9% resolution considering patients who needed more than one infusion. Conclusion: Fecal microbiota transplantation is a feasible therapy with resolution in 90.9% of cases as a treatment for recurrent Clostridioides difficile infection.

Contexto: O tratamento do Clostridioides difficile é baseado em ciclo antimicrobiano, mas para os indivíduos que apresentam mais de duas recorrências, pode-se considerar o transplante de microbiota fecal como opção terapêutica. Objetivo: Descrever a técnica e os resultados do transplante de microbiota fecal realizados para infecção recorrente por Clostridioides difficile. Métodos: Estudo retrospectivo, transversal, baseado em revisão de prontuários de pacientes submetidos ao transplante de microbiota fecal. Foram obtidos dados sobre os critérios empregados para seleção do doador, o preparo das fezes e o método de entrega do material, além de informações referentes às características do receptor, como: sexo, idade, comorbidades, internamentos, uso de antimicrobiano prévio à infecção, apresentação clínica, diagnóstico e tratamentos realizados para o Clostridioides difficile. Após o transplante, dados sobre eficácia, desfecho, tempo de seguimento e complicações do procedimento foram considerados. Resultados: Entre 2012 e 2019, 11 pacientes foram submetidos ao transplante de microbiota fecal. O uso de antimicrobiano prévio à infecção ocorreu em 9 pacientes, nenhum paciente internou nos 6 meses anteriores por outra etiologia. Todos fizeram pelo menos 2 ciclos de vancomicina para doença recorrente. Do total de 11 pacientes, 2 necessitaram de 2 infusões e 1 paciente necessitou de 3, totalizando 15 transplantes de microbiota fecal. O sucesso foi de 81,8% com apenas uma infusão e resolução de 90,9% considerando pacientes que necessitaram de mais de uma infusão. Conclusão: O transplante de microbiota fecal é uma terapia factível e com resolução em 90,9% dos casos como tratamento de infecção recorrente por Clostridioides difficile.

Não aderência ao tratamento para hepatite C: um estudo brasileiro / Non-adherence to hepatitis c treatment: a brazilian report

ABSTRACT BACKGROUND: In Brazil, since 2015, the treatment of hepatitis C is provided by SUS (Public Health System) with direct-acting antiviral (DAA). OBJECTIVE: To describe the rate of non-adherence patients to hepatitis C treatment by DAA, investigating the epidemiological data in a large database from Curitiba, Brazil. METHODS: Retrospective study with patients treated between January 2015 and June 2019. Patients were considered adherent when received all medication doses during their treatment. The following data were evaluated: gender, age, type of treatment, period of treatment, presence of diabetes or HIV, previous therapy, originated from SUS or private medicine, fibrosis grade and HCV genotype. RESULTS: 1248 patients (56.8% males) were studied and 102/1248 (8.2%) were non-adherent to treatment. Age or gender not influenced significantly; 10.2% patients from SUS and 3.7% individuals from private medicine were non-adherent (P<0.0001; OR=2.9; CI95%=1.6-9.1); 13.1% patients were co-infected with HIV and among them, 15.9% abandoned treatment. Individuals without co-infection presented 7.0% of non-adherence (P<0.0001; OR=2.5; CI=1.5-4.1). All the other variables showed no differences in the adhesion rate. CONCLUSION: Our study showed that 8.2% of patients were non-adherent to HCV treatment, and that patients from the Public Health System and co-infected with HIV were significantly less adherent.

RESUMO CONTEXTO: No Brasil, desde 2015, o tratamento da hepatite C é prestado pelo Sistema Público de Saúde (SUS) com antivirais de ação direta. OBJETIVO: Avaliar a taxa de não adesão de pacientes ao tratamento da hepatite C pelo antiviral de ação direta investigando os dados epidemiológicos em um banco de dados de Curitiba, Brasil. MÉTODOS: Estudo retrospectivo com pacientes atendidos entre janeiro de 2015 e junho de 2019. Os pacientes foram considerados aderentes quando receberam todas as doses da medicação durante o tratamento. Foram avaliados os seguintes dados: sexo, idade, tipo de tratamento, tempo de tratamento, presença de diabetes ou HIV, terapia anterior, proveniente do SUS ou medicina privada, grau de fibrose e genótipo da hepatite C. RESULTADOS: Um total de 1.248 pacientes (56,8% homens) foram estudados e desses, 102/1248 (8,2%) não aderiram ao tratamento. Idade ou sexo não influenciou significativamente; 10,2% pacientes do SUS e 3,7% da medicina privada eram não aderentes (P<0,0001; OR=2,9; IC95%=1,6-9,1); 13,1% dos pacientes foram coinfectados pelo HIV e, entre eles, 15,9% abandonaram o tratamento. Indivíduos sem coinfecção apresentaram 7,0% de não adesão (P<0,0001; OR=2,5; IC=1,5-4,1). Todas as outras variáveis não mostraram diferenças na taxa de adesão. CONCLUSÃO: Nosso estudo mostrou que 8,2% dos pacientes não aderiram ao tratamento para hepatite C e que os pacientes do SUS e coinfectados pelo HIV eram significativamente menos aderentes.

A cura da hepatite C crônica com os novos antivirais de ação direta não resultou em melhora da resistência insulínica a curto prazo / Curing hepatitis c with the new direct acting antivirals did not improve insulin resistance after one year

ABSTRACT BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).

RESUMO CONTEXTO: A hepatite C crônica ainda figura como importante causa de morbimortalidade na população brasileira, e está associada a alterações metabólicas, incluindo a resistência insulínica (RI), que pode ser avaliada pelo índice HOMA-IR. A RI pode inclusive implicar em menores taxas de reposta virológica sustentada (RVS) em certos regimes terapêuticos e à uma mais rápida progressão para fibrose hepática avançada. Com o advento dos novos antivirais de ação direta (DAA) oferecidos para hepatite C, há crescente necessidade de observar o impacto dos mesmos no perfil de RI em pacientes submetidos à tais terapêuticas. OBJETIVO: - 1) Comparar os valores do HOMA-IR dos pacientes com hepatite C crônica antes do tratamento com os DAAS com os valores deste índice após 12 meses do término do tratamento com RVS. 2) Avaliar evolução do peso após obtenção da cura da hepatite C crônica. MÉTODOS: Foram incluídos pacientes maiores de 18 anos de dois serviços terciários de Curitiba - PR, de ambos os sexos, portadores de hepatite C crônica, com tratamento com os antivirais de ação direta, no período de julho de 2015 a setembro de 2017. Tais pacientes também foram submetidos a dosagem dos níveis de insulina de jejum, glicemia de jejum e hemoglobina glicada antes de iniciar o tratamento da hepatite C e até 12 meses após o término. Também foram utilizados dados como idade, sexo, grau de fibrose hepática, índice de massa corporal, circunferência abdominal, genótipo viral e presença de diabetes mellitus antes e depois do tratamento. A RI foi estimada antes e após 12 meses do término do tratamento e calculada pelo HOMA-IR. Os resultados de variáveis quantitativas foram descritos por médias, medianas, valores mínimos, valores máximos e desvios padrões. Valores de P<0,05 indicaram significância estatística. RESULTADOS: Foram incluídos 75 pacientes no estudo com média de idade de 55,2 anos, sendo 60% do sexo masculino. Destes pacientes, 43 tinham fibrose avançada. Vinte e um (28%) pacientes tinham o diagnóstico de diabetes mellitus. A RI foi observada em 31 (41,3%) pacientes antes do tratamento antiviral, sendo que este número aumentou para 39 (52%) de acordo com a dosagem do HOMA-IR 12 meses após o término do tratamento. Não houve diferença estatística entre os valores de insulina, glicemia e HOMA-IR antes e após a cura da hepatite. Houve um ganho de peso inicial após a obtenção da cura da hepatite C, mas que não se manteve ao final do estudo. CONCLUSÃO: Não foi vista diferença estatística significante entre os valores do HOMA-IR apresentados pelos pacientes portadores de hepatite C crônica antes do tratamento e 12 meses após a cura da doença. Embora tenha ocorrido ganho de peso após obtenção da cura da doença, este não se deu de forma estatisticamente significativa (P=0,131) ao final de um ano.

Avaliação da progressão da fibrose hepática em um grupo de pacientes com doença hepática gordurosa não alcoólica acompanhados por 10 anos / Evaluation of progression of hepatic fibrosis in a group of patients with non-alcoholic fatty liver disease accompanied for 10 years

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease has been progressively diagnosed in the general population as a consequence of the increased prevalence of obesity and type 2 diabetes mellitus, its main risk factors. It is characterized by accumulation of fat in the hepatocytes associated with lobular inflammation and balonization, which can lead to cirrhosis and hepatocarcinoma. Thus, a characterization and follow-up of a progression of the fibrosis level of these patients becomes important, being that the transient hepatic elastography is a reliable method for this evaluation with a measure of the kapa index. OBJECTIVE: To evaluate the progression of hepatic fibrosis through elastography in patients with non-alcoholic fatty liver disease. METHODS: Patients who had previously performed hepatic biopsy and noninvasive scores for non-alcoholic steatohepatitis (NASH) and fibrosis were included in the study. These same subjects were then submitted to current clinical evaluation, laboratory and liver elastography tests, defining the level of liver fibrosis, about 10 years after the first evaluation. RESULTS: Data were analyzed for 66 patients previously submitted to liver biopsy. Of these, 16 were not found, four could not participate because they were debilitated due to hepatic cirrhosis, two had died from an automobile accident and five from complications of cirrhosis of the liver. Therefore, of the 50 patients with a known history, 9 (18%) had died of cirrhosis or were unable to attend the examination because of their liver disease. The remaining population was predominantly female (61.5%), mean age of 63 years, being overweight, dyslipidemia (76.9%), disorders of the glycemic profile (76.9%), and metabolic syndrome (82.1%). Of the 39 cases evaluated, 35% had the same degree of fibrosis at the initial evaluation (biopsy) and at the current evaluation (elastography), 33% had an increase in the degree of fibrosis and another 30% had a decrease in the degree of fibrosis. Twenty-eight patients had NASH at baseline. Regarding these patients, it was observed in the current evaluation, that 25% remained stable in the degree of fibrosis, 39% progressed, and 35% regressed. CONCLUSION: Despite some limitations of our study, such as the small number of patients, and the use of two different methods of evaluation (biopsy and elastography), the data obtained allow us to conclude that of the 39 evaluated cases, 33% (13) presented progression of fibrosis and the total group of 50 patients, 42% had cirrhosis or died due to liver disease. The presence of NASH on hepatic biopsy did not prove to be, in our study, a predictive of the evolution of hepatic fibrosis in the patients.

RESUMO CONTEXTO: A doença hepática gordurosa não alcoólica vem sendo diagnosticada com frequência progressivamente maior na população geral, como consequência do aumento da prevalência da obesidade e do diabetes mellitus tipo 2, considerados seus principais fatores de risco. Caracteriza-se por acúmulo de gordura nos hepatócitos associada à inflamação lobular e balonização, podendo levar à cirrose e hepatocarcinoma. Desta forma, torna-se importante a caracterização e acompanhamento do nível de fibrose hepática destes pacientes, sendo que a elastografia hepática transitória, tem se mostrado um método confiável para esta avaliação com a medida do índice kapa. OBJETIVO: Avaliar a progressão da fibrose hepática através de elastografia em pacientes com doença hepática gordurosa não alcoólica. MÉTODOS: Foram incluídos no estudo pacientes que haviam realizado anteriormente biópsia hepática e cálculo de escores não invasivos para avaliação de esteato-hepatite não alcoólica (EHNA) e fibrose. Estes mesmos indivíduos foram então submetidos à avaliação clínica, laboratorial e exame de elastografia hepática atuais, definindo o nível de fibrose hepática, cerca de 10 anos após a primeira avaliação. RESULTADOS: Foram analisados dados relativos a 66 pacientes previamente submetidos a biópsia hepática. Destes, 16 não foram localizados, quatro não puderam participar por estarem incapacitados em função de cirrose hepática, dois haviam falecido por acidente automobilístico e cinco, por complicações de cirrose hepática. Portanto, do grupo de 50 pacientes com evolução conhecida, nove (18%) haviam falecido por cirrose ou estavam incapacitados de comparecer ao exame em função de sua doença hepática. A população restante era predominantemente do sexo feminino (61,5%), com idade média de 63 anos, apresentando sobrepeso, dislipidemia (76,9%), distúrbios do metabolismo glicêmico (76,9%) e síndrome metabólica (82,1%). Dos 39 casos avaliados, 35% tiveram o mesmo grau de fibrose na avaliação inicial (biópsia) e na avaliação atual (elastografia), 33% tiveram aumento no grau de fibrose e outros 30% tiveram diminuição no grau de fibrose. Vinte e oito pacientes apresentavam EHNA na avaliação inicial. Em relação a esses pacientes observou-se na avaliação atual que, 25% mantiveram-se estáveis no grau de fibrose, 39% progrediram e, 35% regrediram. CONCLUSÃO: Apesar de algumas limitações do nosso estudo, como o pequeno número de pacientes e o uso de dois métodos diferentes de avaliação (biópsia e elastografia), os dados obtidos nos permitem concluir que dos 39 casos avaliados, 33% apresentaram progressão da fibrose e do grupo total de 50 pacientes, 42% apresentam cirrose ou faleceram em decorrência de doença hepática. A presença de EHNA à biópsia hepática não se mostrou um dado capaz, no nosso estudo, de predizer a evolução da fibrose hepática nos pacientes.

How are HCV-infected patients being identified in Brazil: a multicenter study

ABSTRACT Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 ± 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.

Fibrose hepática congênita e venopatia portal obliterativa sem hipertensão portal - revisão da literatura com base em um caso assintomático / Congenital hepatic fibrosis and obliterative portal venopathy without portal hypertension - a review of literature based on an asymptomatic case

ABSTRACT The disease and the case reported here are relevant especially because of their varied clinical presentation, possibility of being associated with other disorders affecting several organs and possible differential diagnoses. Congenital Hepatic Fibrosis is an autosomal recessive disease due to mutation in the PKHD1 gene, which encodes the fibrocystin/polyductine protein. It is a cholangiopathy, characterized by varying degrees of periportal fibrosis and irregular proliferation of bile ducts. Affected patients are typically diagnosed in childhood, but in some cases the disease may remain asymptomatic for many years. The exact prevalence and incidence of the disease are not known, but it is consider a rare disease, with a few hundred cases described worldwide. It can affect all ethnic groups and occur associated with various hereditary and non-hereditary disorders. The clinical presentation is quite variable, with melena and hematemesis being initial symptoms in 30%-70% of the cases. More rarely, they may present episodes of cholangitis. The disease has been classified into four types: portal hypertension, cholestasis / cholangitis, mixed and latent. Diagnosis begins with imaging tests, but the definition is made by the histopathological sample. So far, there is no specific therapy that can stop or reverse the pathological process. Currently, the therapeutic strategy is to treat the complications of the disease.

RESUMO A patologia e o caso aqui reportados são relevantes especialmente devido sua variada apresentação clínica, possibilidade de estar associada com outras desordens acometendo diversos órgãos e pelos possíveis diagnósticos diferenciais. A fibrose hepática congênita é uma doença autossômica recessiva, devido mutação no gene PKHD1, que codifica a proteína fibrocistina/poliductina. É uma colangiopatia, caracterizada por variados graus de fibrose periportal e proliferação irregular de ductos biliares. Os pacientes acometidos são tipicamente diagnosticados na infância, mas em alguns casos a doença pode permanecer assintomática por muitos anos. Exatas prevalência e incidência da doença não são conhecidas, mas sabe-se que é uma doença bastante rara, com algumas centenas de casos descritos no mundo. Pode afetar todos grupos étnicos e ocorrer associada com diversas desordens hereditárias e não-hereditárias. A apresentação clínica é bastante variável, com melena e hematêmese sendo sintomas iniciais em 30%-70% dos casos. Mais raramente, podem apresentar episódios de colangite. A doença tem sido classificada em quatro tipos: hipertensão portal, colestática/colangite, mista e latente. O diagnóstico inicia com exames de imagem, mas a definição é feita pela amostra histopatológica. Até o momento, não há terapia específica que possa parar ou reverter o processo patológico e a estratégia terapêutica atual é tratar as complicações da doença.

Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil

ABSTRACT Background This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. Methods This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. Results A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p < 0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. Conclusions The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

Importância da medida dos níveis de infliximabe em pacientes com doença inflamatória intestinal: uma coorte Brasileira / Importance of measuring levels of infliximab in patients treating inflammatory bowel disease in a brazilian cohort

ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

RESUMO CONTEÚDO: Doença de Crohn e retocolite ulcerativa são doenças inflamatórias intestinais crônicas. Nelas, ocorre aumento da produção de fator de necrose tumoral alfa (TNF-α). Pacientes que falham no tratamento convencional imunossupressor, requerem uso de terapia imunobio­lógica, que são anticorpos monoclonais, principalmente os anti-TNF-α. O infliximabe é uma droga anti-TNF-α, uma imunoglobulina quimérica, com componente murino. Este é responsável pela imunogenicidade da droga e a formação de anticorpos. Presença de anticorpos antidroga pode ser responsável pelos eventos adversos e redução da eficácia da droga. Pacientes com doenças inflamatórias intestinais, em terapia imunossupressora com medicação biológica como o infliximabe, podem ter recaída da doença e muitas vezes isso não se relaciona com a sintomatologia do paciente. Por isso há a necessidade de um método de avaliação do efeito da droga como a dosagem do nivel sérico do infliximabe, bem como da pesquisa de anticorpos. OBJETIVO: O estudo tem como objetivo conhecer os níveis séricos do infliximabe e dos anticorpos anti-infliximabe em pacientes com doença inflamatória intestinal em terapia de manutenção ou pós-indução e descrever as condutas terapêuticas que foram modificadas em função dos níveis séricos de infliximabe e anticorpos para infliximabe. MÉTODOS: Trata-se de estudo restrospectivo, com análise da dosagem dos níveis séricos de infliximabe e anticorpos para Infliximabe. Foram incluídos 45 pacientes, num total de 63 coletas de dosagem de infliximabe. RESULTADOS: Vinte e um paciente estavam com o nível sérico de infliximabe adequado, níveis subterapêuticos em 31 pacientes e níveis supraterapêuticos em 11 pacientes. Sete pacientes tiveram a medicação suspensa por falha terapêutica ou altos níveis de anticorpos para infliximabe. CONCLUSÃO: Apenas um terço dos pacientes apresentavam níveis adequados de infliximabe e 36% dos pacientes apresentavam níveis subterapêuticos ao término da indução. Em cerca de 46% das amostras a conduta adotada se baseou nos níveis de infliximabe e anticorpos para infliximabe demonstrando a importância de se ter esta ferramenta para auxílio no manejo clínico dos pacientes portadores de doenças inflamatórias intestinais em terapia biológica.

Hepatite E crônica - relato de um caso brasileiro / Chronic hepatitis E - a brazilian case report

Hepatite é a quinta forma conhecida de hepatites humanas virais. Apesar de ser muito incomum em nossa prática clínica, a incidência em países ocidentais vem aumentando. O vírus da Hepatite E (HVE) pode estar relacionado à doença aguda, falência hepática, hepatite crônica e cirrose. O HVE é um RNA vírus, com 5 genótipos descritos (1, 2, 3, 4 e 5), sendo que quatro deles podem afetar humanos. Além das manifestações hepáticas, o genótipo 3 pode também levar a manifestações extra-hepáticas, como alterações neurológicas, renais e reumatológicas. O diagnóstico pode ser difícil porque existem poucos testes validados e ainda com baixa sensibilidade e especificidade. A hepatite aguda não precisa ser tratada, já a hepatite E crônica deve ser tratada. Relatamos aqui um caso brasileiro de Hepatite E crônica em um paciente imunossuprimido.

Hepatitis E is the fifth known form of human viral hepatitis. Although not very common in our clinical practice, the incidence in Western countries is increasing. Hepatitis E virus (HEV) may be related to acute illness, liver failure, chronic hepatitis and cirrhosis. HEV is an RNA virus, with 5 described genotypes (1,2,3,4,5), 4 of them can affect humans. Besides liver manifestations, genotype 3 is also related to extra-hepatic manifestations, such as neurological, renal and rheumatological. The diagnosis may be difficult because of the low availability of tests and due to low sensibility and specificity. The acute illness does not have to be treated, but the chronic one does. We presente here a Brazilian case of chronic hepatitis E in an immunosuppressed patient.

Can FIB4 and NAFLD fibrosis scores help endocrinologists refer patients with non-alcoholic fat liver disease to a hepatologist?

ABSTRACT Objective The objective of this study is to evaluate the performance of mathematical models used in non-invasive diagnosis of liver fibrosis in nonalcoholic fatty liver disease (NAFLD) patients to determine when the patient needs to be referred to a hepatologist. Subjects and methods Patients referred by endocrinologists to the liver outpatient departments in two hospitals in Curitiba, Brazil, over a 72-month period were analyzed. The results calculated using the APRI, FIB 4, FORNS and NAFLD Fibrosis Score non-invasive liver fibrosis assessment models were analyzed and compared with histological staging of this population. Results Sixty-seven patients with NAFLD were analyzed. Forty-two of them (62.68%) were female, mean age was 54.76 (±9.63) years, mean body mass index 31.42 (±5.64) and 59 (88.05%) of the 67 cases had glucose intolerance or diabetes. A diagnosis of steatohepatitis was made in 45 (76.27%) of the 59 biopsied patients, and advanced liver fibrosis (stages 3 and 4) was diagnosed in 18 (26.86%) of the 67 patients in the study population. The FIB 4 and NAFLD Fibrosis Score models had a high negative predictive value (93.48% and 93.61%, respectively) in patients with severe liver fibrosis (stages 3 and 4). Conclusion In conclusion, use of the FIB 4 and NAFLD Fibrosis Score models in NAFLD patients allows a diagnosis of severe liver disease to be excluded.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.

ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE / Exame de sonoelastografia é equivalente a biópsia hepática na análise de fibrose em pacientes portadores de hepatite C crônica e doença hepática gordurosa não alcoólica

BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

ContextoA biópsia hepática é considerada padrão-ouro para definição de fibrose hepática em pacientes com doença hepática crônica. No entanto, é um método invasivo, com potenciais riscos e complicações. A elastografia é uma técnica de ultrassonografia que fornece informações sobre variações no tecido hepático, avaliando elasticidade tecidual e sonoelastografia é uma das técnicas disponíveis.ObjetivoO principal objetivo do estudo é avaliar a sensibilidade e especificidade da sonoelastografia comparada a biópsia hepática para análise do grau de fibrose hepática em pacientes com hepatite C crônica e doença hepática gordurosa não alcoólica.MétodosVinte e quatro pacientes foram incluídos no estudo, submetidos a biópsia hepática e sonoelastografia. Os resultados obtidos foram comparados a valores descritos na literatura por diferentes autores.ResultadosNa população de pacientes com hepatite C crônica, os dados melhor se correlacionaram com resultados publicados por Carmen Fierbinteanu-Braticevici e col, com uma acurácia de 82,4%, sensibilidade de 71,4% e especificidade de 90%. Para doença hepática gordurosa não alcoólica, a melhor correlação se deu com dados publicados por Masato Yoneda e col, com acurácia de 85,7%, sensibilidade de 80% e especificidade de 100%.ConclusãoSonoelastografia é um método com boa acurácia para diferenciar fibrose avançada de fibrose inicial e pode substituir a biópsia hepática na maioria das vezes.

Doenças hepatobiliares eosinofílicas: relato de dois casos e revisão de literatura / Eosinophilic hepatobiliary diseases: a report of two cases and literature review

As doenças hepatobiliares eosinofílicas são patologias raras de origem e de fatores etiológicos ainda não esclarecidos, sendo muitas vezes relacionadas à gastroenterite eosinofílica ou síndrome hipereosinofílica. Caracterizam-se por infiltração de eosinófilos em tecidos hepatobiliares e podem estar associadas à eosinofilia periférica na ausência de outras causas de eosinofilia. A raridade e conhecimento incompleto dessas doenças refletem na dificuldade de diagnóstico e de escolha terapêutica. O diagnóstico é feito através da exclusão de outras causas de eosinofilia periférica, tais como parasitoses, reações medicamentosas e doenças malignas, e também por análise histopatológica do tecido infiltrado. A maioria dos casos é responsiva ao tratamento com corticosteroides. Descrevemos dois casos clínicos, um de colecistite eosinofílica e outro de hepatite eosinofílica, avaliando, segundo revisão de literatura, a possibilidade de uma gastroenterite eosinofílica ou de uma síndrome hipereosinofílica em ambos os casos.

The eosinophilic hepatobiliary diseases are rare pathologies of origin and etiologic factors not yet clarified, being many times related to eosinophilic gastroenteritis or hipereosinophilic syndrome. They are characterized by an infiltration of eosinophils in hepatobiliary tissues and can be associated to peripheral eosinophilia, in the absence of other eosinophilia causes. The rareness and incomplete knowledge about these diseases reflect on the difficulty of diagnosis and choice of treatment. The diagnosis is made through exclusion of other causes of peripheral eosinofilia, such as parasitosis, drug reactions and malignant diseases, and also through histopathological analysis of the infiltrated tissue. Most cases respond to treatment with corticosteroids. We reported two cases, one of eosinophilic colecistitis and other of eosinophilic hepatitis, evaluating, according to literature review, the possibility of eosinophilic gastroenteritis or hipereosinophilic syndrome in both cases.

Change in platelet count in patients with hypersplenism subjected to liver transplantation / Modificação no número de plaquetas de pacientes com hiperesplenismo submetidos a transplante hepático

CONTEXT: Most patients subjected to liver transplantation presents hypersplenism, which is reversed after the operation. However, some patients remain with moderate to intense hypersplenism. OBJECTIVES: To study the effect of liver transplantation on platelet count in patients with hypersplenism. METHOD: Of a total of 233 patients who underwent liver transplantation, 162 were excluded from the present study because of occurrence of steroid-resistant rejection, absence of hypersplenism before the transplantation, absence of follow-up for at least 2 years or incomplete exams data. The electronic study protocols of the remaining 71 patients were reviewed to determine the demographics, etiology of cirrhosis, and results of pathologic examination of the explanted liver. Serial platelet count was obtained from the study protocol on the day before liver transplantation and 1, 2, 4, and 6 months and 1 year after liver transplantation. Statistical analysis was performed using the Student's t-test, chi-square test, and Spearman's correlation test. RESULTS: Posttransplant platelet count at all time intervals was significantly higher than the pretransplant value (P<0.001 for all time intervals). Thrombocytopenia was reversed (platelet count >100,000/mm³) in 58 patients (81.7 percent) 1 month after liver transplantation. Twelve patients (16.9 percent) remained with thrombocytopenia 1 year after liver transplantation. Three patients (4.2 percent) had recurrence of thrombocytopenia within 1 year after liver transplantation. There was no correlation between pretransplant platelet count and the Child-Pugh class or the MELD score. CONCLUSION: Liver transplantation reverses hypersplenism in most patients.

CONTEXTO: A maioria dos pacientes submetidos a transplante hepático apresenta hiperesplenismo, que é revertido após a operação. Entretanto, alguns pacientes permanecem com hiperesplenismo moderado a intenso. OBJETIVO: Avaliar o efeito do transplante hepático na contagem de plaquetas de pacientes com hiperesplenismo. MÉTODOS: De um total de 233 pacientes que foram submetidos a transplante hepático, 162 foram excluídos do presente estudo devido à ocorrência de rejeição resistente a corticóide, ausência de hiperesplenismo antes do transplante, ausência de seguimento pós-transplante por pelos menos 2 anos ou dados de exames incompletos. O protocolo eletrônico de estudo dos demais 71 pacientes foi revisado para determinar os aspectos demográficos, a etiologia da cirrose e o resultado do exame patológico do fígado explantado. Contagem seriada de plaquetas foi obtida do protocolo de estudo no dia antes do transplante e 1, 2, 4 e 6 meses e 1 ano após o transplante. Análise estatística foi realizada empregando o teste t de Student, o teste qui ao quadrado e o teste de correlação de Spearman. RESULTADOS: A contagem de plaquetas pós-transplante em todos os intervalos de tempo foi significantemente maior que os valores pré-transplantes (P<0,001 para rodos os intervalos de tempo). Trombocitopenia foi revertida (contagem de plaquetas >100.000/mm³) em 58 pacientes (81,7 por cento) 1 mês após o transplante. Doze pacientes (16,9 por cento) permaneceram com trombocitopenia 1 ano após o transplante. Três pacientes (4,2 por cento) tiveram recurrência da trombocitopenia dentro de 1 ano após o transplante. Não houve correlação entre a contagem de plaquetas pré-transplante e a classe de Child-Pugh e o escore de MELD. CONCLUSÃO: O transplante hepático reverte o hiperesplenismo na maioria dos pacientes.

High prevalence of hepatitis C associated with familial history of hepatitis in a small town of south Brazil: efficiency of the rapid test for epidemiological survey

This report describes a cross-sectional survey on the prevalence of hepatitis C antibodies (anti-HCV) in Tamboara, a small community in the northwest area from Paraná State, south of Brazil with a high rate of accumulated detection for HCV. Eight hundred and sixteen residents (17.87 percent from all the population), independently of the age and time living in Tamboara were included in this study by an epidemiologic questionnaire and by testing for anti-HCV. The rapid immuno-chromatographic test was applied for detection of HCV antibodies. The anti-HCV prevalence by rapid test was 4.28 percent. The median age for positive and negative test was 60.49 ± 14.14 and 41.67 ± 20.25, respectively (p < 0.001). By multivariate analysis, only familial history of hepatitis (p = 0.001; OR = 6.41; CI 95 percent = 2.08-19.78) and age (p = 0.007; OR 1.06;95 percent CI = 1.02-1.10) showed statistical significance for positive anti-HCV. The rapid test sensitivity and specificity were 100 percent and 92.7 percent respectively, with an accuracy of 95.8 percent (95 percent CI = 91-100). These findings demonstrated a high prevalence of anti-HCV in Tamboara. The familial history of hepatitis was a significant risk factor to the infection and HCV rapid test showed to be accurate and feasible for epidemiological survey.

Extrahepatic biliary atresia: current concepts and future directions

OBJETIVOS: Apresentar uma revisão atualizada sobre atresia das vias biliares extra-hepáticas, com ênfase em etiopatogenia, abordagens diagnósticas e terapêuticas e prognóstico. FONTES DOS DADOS: Foram selecionadas pelos sites de busca médica (MEDLINE e PubMed) pesquisas relacionadas à atresia biliar, utilizando as seguintes palavras-chave: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SíNTESE DOS DADOS A atresia das vias biliares extra-hepáticas é a principal indicação de transplante hepático na faixa etária pediátrica. Quanto à etiologia, o citomegalovírus, o reovírus e o rotavírus têm sido os agentes mais estudados como possíveis desencadeadores da obstrução imunomediada da árvore biliar. A resposta imune, especialmente o predomínio da resposta TH1 e do interferon gama, a susceptibilidade genética e as alterações do desenvolvimento embrionário da árvore biliar são aspectos que podem participar na etiopatogênese da obliteração das vias biliares extra-hepáticas. Ainda hoje, o único tratamento disponível é a portoenterostomia, cujos resultados são melhores quando realizada nos primeiros 2 meses de vida. Em relação ao prognóstico, as crianças não tratadas vão a óbito na totalidade, por complicações relacionadas à hipertensão portal e à cirrose hepática, e mesmo os casos tratados necessitam, em sua maioria, do transplante hepático. CONCLUSÃO: A atresia das vias biliares extra-hepáticas continua sendo a principal indicação de transplante hepático em crianças, e a mudança deste panorama depende de um melhor entendimento da etiopatogenia da obstrução biliar nos diferentes fenótipos da doença. Investigações futuras a respeito do papel do interferon gama e de outras citocinas são necessárias para avaliar se esses aspectos seriam potenciais alvos de intervenção terapêutica.

OBJECTIVE: To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. SOURCES: MEDLINE and PubMed databases were searched using the following keywords: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SUMMARY OF THE FINDINGS: Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. CONCLUSIONS: Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.