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Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.
Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.
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BACKGROUND: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. OBJECTIVE: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. METHODS: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea-sured utilizing immunoassay techniques. RESULTS: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. CONCLUSION: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis. BACKGROUND: ⢠Exploration of intestinal inflammation in chronic pancreatitis patients with altered bowel habits. BACKGROUND: ⢠Assessment of 23 patients using lactoferrin and calprotectin as intestinal inflammation biomarkers. BACKGROUND: ⢠Intestinal inflammation was detected in all patients; positive correlation between both biomarkers. BACKGROUND: ⢠Established connection between altered bowel habits and intestinal inflammation in chronic pancreatitis.
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Lactoferrina , Pancreatitis Crónica , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Crónica/complicaciones , Diarrea/etiología , Complejo de Antígeno L1 de Leucocito , Biomarcadores , InflamaciónRESUMEN
ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were measured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.
RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.
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Abstract Objective: To determine the frequency and interobserver reproducibility of the magnetic resonance imaging (MRI) features considered diagnostic for autoimmune hepatitis. Materials and Methods: Two abdominal radiologists, blinded to pathology data, reviewed the MRI examinations of 20 patients with autoimmune hepatitis, looking for liver enhancement, lymphadenopathy, portal hypertension, and chronic liver disease. The pattern of liver fibrosis was categorized as reticular, confluent, or mixed. Interobserver agreement was assessed by calculating intraclass correlation coefficients and kappa statistics. Results: The most common abnormal finding on MRI was surface nodularity (in 85%), followed by liver fibrosis with a reticular pattern (in 80%)—categorized as mild (in 25.0%), moderate (in 43.8%), or severe (in 31.2%)—; heterogeneous liver enhancement (in 65%); splenomegaly (in 60%); caudate lobe enlargement (in 50%); and lymphadenopathy (in 40%). The interobserver agreement was almost perfect for surface nodularity (0.83), ascites (0.89), and liver volume (0.95), whereas it was just slight and fair for the degree of fibrosis and for heterogeneous liver enhancement (0.12 and 0.25, respectively). It was also slight and fair for expanded gallbladder fossa and enlarged preportal space (0.14 and 0.36, respectively), both of which are indicative of chronic liver disease. Conclusion: The interobserver agreement was satisfactory for surface nodularity (the most prevalent abnormal MRI finding), ascites, liver volume, and splenomegaly. Conversely, it was only slight or fair for common but less objective criteria.
Resumo Objetivo: Determinar a frequência e reprodutibilidade interobservador das características de imagem por ressonância magnética na hepatite autoimune. Materiais e Métodos: Dois radiologistas abdominais, cegos para dados patológicos, revisaram ressonâncias magnéticas de 20 pacientes com hepatite autoimune quanto ao realce hepático, linfadenopatia, hipertensão portal e doença hepática crônica. A fibrose foi classificada como reticular, confluente ou ambas. A concordância interobservador foi avaliada por coeficientes de correlação intraclasse e estatística kappa. Resultados: O achado anormal mais comum foi nodularidade superficial (85%), seguido de fibrose reticular hepática (80%) — leve (25%), moderada (43,8%), grave (31,2%) —, realce heterogêneo (65%), esplenomegalia (60%), aumento do lobo caudado (50%) e linfadenopatia (40%). A concordância interobservador foi quase perfeita para nodularidade superficial (0,83), ascite (0,89) e volume hepático (0,95); entretanto, foi apenas leve (0,12) e razoável (0,25) para grau de fibrose e realce heterogêneo, respectivamente. Também foi leve (0,14) ou regular (0,36) para achados de doença hepática crônica, como fossa da vesícula biliar expandida e espaço pré-portal alargado, respectivamente. Conclusão: A concordância geral foi satisfatória para nodularidade superficial (achado anormal mais prevalente), ascite, volume hepático e esplenomegalia. Critérios frequentes, porém menos objetivos, tiveram apenas concordância leve a razoável.
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Objective: To determine the frequency and interobserver reproducibility of the magnetic resonance imaging (MRI) features considered diagnostic for autoimmune hepatitis. Materials and Methods: Two abdominal radiologists, blinded to pathology data, reviewed the MRI examinations of 20 patients with autoimmune hepatitis, looking for liver enhancement, lymphadenopathy, portal hypertension, and chronic liver disease. The pattern of liver fibrosis was categorized as reticular, confluent, or mixed. Interobserver agreement was assessed by calculating intraclass correlation coefficients and kappa statistics. Results: The most common abnormal finding on MRI was surface nodularity (in 85%), followed by liver fibrosis with a reticular pattern (in 80%)-categorized as mild (in 25.0%), moderate (in 43.8%), or severe (in 31.2%)-; heterogeneous liver enhancement (in 65%); splenomegaly (in 60%); caudate lobe enlargement (in 50%); and lymphadenopathy (in 40%). The interobserver agreement was almost perfect for surface nodularity (0.83), ascites (0.89), and liver volume (0.95), whereas it was just slight and fair for the degree of fibrosis and for heterogeneous liver enhancement (0.12 and 0.25, respectively). It was also slight and fair for expanded gallbladder fossa and enlarged preportal space (0.14 and 0.36, respectively), both of which are indicative of chronic liver disease. Conclusion: The interobserver agreement was satisfactory for surface nodularity (the most prevalent abnormal MRI finding), ascites, liver volume, and splenomegaly. Conversely, it was only slight or fair for common but less objective criteria.
Objetivo: Determinar a frequência e reprodutibilidade interobservador das características de imagem por ressonância magnética na hepatite autoimune. Materiais e Métodos: Dois radiologistas abdominais, cegos para dados patológicos, revisaram ressonâncias magnéticas de 20 pacientes com hepatite autoimune quanto ao realce hepático, linfadenopatia, hipertensão portal e doença hepática crônica. A fibrose foi classificada como reticular, confluente ou ambas. A concordância interobservador foi avaliada por coeficientes de correlação intraclasse e estatística kappa. Resultados: O achado anormal mais comum foi nodularidade superficial (85%), seguido de fibrose reticular hepática (80%) leve (25%), moderada (43,8%), grave (31,2%) , realce heterogêneo (65%), esplenomegalia (60%), aumento do lobo caudado (50%) e linfadenopatia (40%). A concordância interobservador foi quase perfeita para nodularidade superficial (0,83), ascite (0,89) e volume hepático (0,95); entretanto, foi apenas leve (0,12) e razoável (0,25) para grau de fibrose e realce heterogêneo, respectivamente. Também foi leve (0,14) ou regular (0,36) para achados de doença hepática crônica, como fossa da vesícula biliar expandida e espaço pré-portal alargado, respectivamente. Conclusão: A concordância geral foi satisfatória para nodularidade superficial (achado anormal mais prevalente), ascite, volume hepático e esplenomegalia. Critérios frequentes, porém menos objetivos, tiveram apenas concordância leve a razoável.
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This review is focused on updating knowledge about cholestatic pruritus. It summarizes clinical-epidemiological characteristics, pathophysiology, diagnostic approach, and evidence-based therapeutic recommendations regarding this form of pruritus. Pruritus is a frequent symptom that accompanies several liver diseases, particularly cholestatic ones. The symptom may be mild and tolerable, but it can also dramatically reduce the quality of life. Although the exact pathophysiology of this form of pruritus remains unclear, current evidence supports a mixed origin. It is extremely important for dermatologists to have knowledge about cholestatic pruritus since they are usually the first physicians to be sought by the patient when they experience the symptom. In the absence of specific dermatological alterations, cholestasis must always be considered as a possible cause of pruritus. In addition to allowing an adequate diagnosis, a better pathophysiological understanding of hepatic pruritus provides the identification of new therapeutic targets and, consequently, optimization of the approach in patients with this condition.
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Colestasis , Calidad de Vida , Colestasis/complicaciones , Humanos , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Prurito/etiologíaRESUMEN
ABSTRACT BACKGROUND: Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. OBJECTIVE: To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. DESIGN AND SETTING: Prospective observational study conducted in the Federal University of São Paulo. METHOD: A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. RESULTS: The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. High-risk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. CONCLUSION: Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.
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Humanos , Niño , Arritmias Cardíacas , Electrocardiografía Ambulatoria , Estudios Prospectivos , Frecuencia Cardíaca/fisiología , Cirrosis Hepática/complicacionesRESUMEN
BACKGROUND: Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. OBJECTIVE: To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. DESIGN AND SETTING: Prospective observational study conducted in the Federal University of São Paulo. METHOD: A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. RESULTS: The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. High-risk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. CONCLUSION: Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.
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Arritmias Cardíacas , Electrocardiografía Ambulatoria , Niño , Frecuencia Cardíaca/fisiología , Humanos , Cirrosis Hepática/complicaciones , Estudios ProspectivosRESUMEN
Abstract This review is focused on updating knowledge about cholestatic pruritus. It summarizes clinical-epidemiological characteristics, pathophysiology, diagnostic approach, and evidence-based therapeutic recommendations regarding this form of pruritus. Pruritus is a frequent symptom that accompanies several liver diseases, particularly cholestatic ones. The symptom may be mild and tolerable, but it can also dramatically reduce the quality of life. Although the exact pathophysiology of this form of pruritus remains unclear, current evidence supports a mixed origin. It is extremely important for dermatologists to have knowledge about cholestatic pruritus since they are usually the first physicians to be sought by the patient when they experience the symptom. In the absence of specific dermatological alterations, cholestasis must always be considered as a possible cause of pruritus. In addition to allowing an adequate diagnosis, a better pathophysiological understanding of hepatic pruritus provides the identification of new therapeutic targets and, consequently, optimization of the approach in patients with this condition.
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INTRODUCTION: Acute viral hepatitis is a disease of great clinical importance. This study proposes actions to better characterise cases of acute hepatitis in Brazil and to provide relevant information to institutionalised health policies within the Unified Health System. Available data on acute hepatitis in Brazil need to be re-evaluated regarding the different hepatotropic agent (hepatitis A to E virus) frequencies, as well as other agents that can cause similar clinical conditions, such as Herpes Simplex Virus 1 and 2(HSV1, HSV2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Herpes Virus 6 and 7 (HHV6, HHV7), arbovirus (yellow fever, dengue, chikungunya, Zika), parvovirus B19, adenovirus, parechovirus, enterovirus, HIV, leptospirosis, toxoplasmosis and syphilis, in addition to autoimmune hepatitis. In this context, the primary aim of this study is the clinical-epidemiological and molecular characterisation of acute viral hepatitis in Brazilian health services from all geographical regions of the country. The present article describes the study protocol. METHODS AND ANALYSIS: This study will evaluate 2280 patients with symptoms and/or signs suggestive of acute liver disease in Brazilian health institutions in all five geographic Brazilian regions. Demographic, epidemiological and clinical data will be collected, as well as blood samples to be analysed at Hospital Israelita Albert Einstein Clinical Laboratory. ETHICS AND DISSEMINATION: Ethics approval was obtained at the national research ethics committee (Conselho Nacional de Ética em Pesquisa- CONEP-CAAE 00952818.4.1001.0071) and at all participating sites. Results will be published in journals and presented at scientific meetings.
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Infecciones por Virus de Epstein-Barr , Hepatitis Viral Humana , Infección por el Virus Zika , Virus Zika , Brasil/epidemiología , Servicios de Salud , Hepatitis Viral Humana/epidemiología , Herpesvirus Humano 4 , HumanosRESUMEN
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown origin that can lead to liver cirrhosis, hepatocellular carcinoma (HCC), liver transplantation or death. The diagnosis is performed upon a multifactorial score. Treatment is based on the combination of immunosuppressants and aims at clinical, laboratory and histological remission, the latter being the most difficult to be achieved and proven. The absence of liver inflammation, defined by biopsy, is the main determinant in remission or therapeutic modification. Imaging exams have a limited role in this clinical management and the main findings are those related to chronic liver disease. Imaging's relevance, therefore, lies mainly in helping to exclude overlapping syndromes and in assessing complications related to cirrhosis, such as in screening for HCC. In recent years, however, the radiological literature has been witnessing increasing advances with regard to imaging biomarkers in liver disease, leading some authors to consider a future of virtual liver biopsy performed by magnetic resonance imaging. The present study aims to review the role of imaging in the management of AIH in the light of recent advances in the current literature and to provide an illustrated guide with the main findings described in the disease.
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Carcinoma Hepatocelular , Hepatitis Autoinmune , Neoplasias Hepáticas , Trasplante de Hígado , Hepatitis Autoinmune/diagnóstico por imagen , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico por imagenRESUMEN
INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries
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Humanos , Masculino , Femenino , Hepatitis C/tratamiento farmacológico , Terapia Antirretroviral Altamente ActivaRESUMEN
INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/uso terapéutico , Cirrosis Hepática/patología , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Anciano , Brasil , Carbamatos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Pirrolidinas , Factores Sexuales , Respuesta Virológica Sostenida , Valina/análogos & derivadosRESUMEN
OBJECTIVE: To evaluate the degree of satisfaction and the socioeconomic profile of patients attending Gastroenterology Outpatient Clinics at a University institution linked to the Brazilian Unified Health System. METHOD: A researcher-administered questionnaire was applied during a structured interview in outpatient clinics. RESULTS: Two hundred and forty (240) patients were included in the study (mean age of 53 years, 55% women). About 30% of the patients had incomplete elementary education, 25% had complete secondary education, and 53% were active workers. Approximately 87% attending the outpatient clinics were from the B2, C1 and C2 socioeconomic classes with an estimated family income of USD$275.00 to USD$825.00/month. Ninety-two percent (92%) of patients were satisfied with the care received; the items associated with a lower degree of satisfaction were facilities/comfort, cleanliness, and waiting time for consultation. No relationship was observed between socioeconomic profile and degree of satisfaction. CONCLUSION: Satisfaction surveys are important to identify opportunities for improving healthcare services, and it is incumbent upon managers, health professionals and even users to promote compliance with laws and decrees that seek to improve healthcare.
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Atención Ambulatoria/normas , Gastroenterología/normas , Programas Nacionales de Salud/organización & administración , Satisfacción del Paciente/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria/normas , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
ABSTRACT Objective: To evaluate the degree of satisfaction and the socioeconomic profile of patients attending Gastroenterology Outpatient Clinics at a University institution linked to the Brazilian Unified Health System. Method: A researcher-administered questionnaire was applied during a structured interview in outpatient clinics. Results: Two hundred and forty (240) patients were included in the study (mean age of 53 years, 55% women). About 30% of the patients had incomplete elementary education, 25% had complete secondary education, and 53% were active workers. Approximately 87% attending the outpatient clinics were from the B2, C1 and C2 socioeconomic classes with an estimated family income of USD$275.00 to USD$825.00/month. Ninety-two percent (92%) of patients were satisfied with the care received; the items associated with a lower degree of satisfaction were facilities/comfort, cleanliness, and waiting time for consultation. No relationship was observed between socioeconomic profile and degree of satisfaction. Conclusion: Satisfaction surveys are important to identify opportunities for improving healthcare services, and it is incumbent upon managers, health professionals and even users to promote compliance with laws and decrees that seek to improve healthcare.
RESUMO Objetivo: Avaliar o grau de satisfação e o perfil socioeconômico de pacientes que são atendidos em Clínicas Externas de Gastrenterologia de uma instituição universitária vinculada ao Sistema Único de Saúde brasileiro. Método: Um questionário administrado por pesquisador foi aplicado durante uma entrevista estruturada em clínicas externas. Resultados: Duzentos e quarenta (240) pacientes foram incluídos no estudo (idade média de 53 anos, 55% mulheres). Aproximadamente 30% dos pacientes tinham ensino fundamental incompleto, 25% tinham ensino médio incompleto e 53% eram trabalhadores na ativa. Cerca de 87% dos que eram atendidos nas clínicas externas se encontravam nas classes econômicas B2, C1 e C2 com renda familiar estimada entre 275,00 e 825,00 dólares americanos por mês. Noventa e dois por cento (92%) dos pacientes estavam satisfeitos com o atendimento recebido; os itens associados a baixo grau de satisfação foram as instalações/conforto, limpeza e tempo de espera para consulta. Nenhuma relação foi observada entre perfil socioeconômico e grau de satisfação. Conclusão: Pesquisas de satisfação são importantes para identificar oportunidades para melhorar os serviços de saúde e para que seus gerentes responsáveis, profissionais da saúde e até mesmo usuários possam promover o cumprimento às leis e decretos que visam melhorar o atendimento em saúde.
RESUMEN Objetivo: Evaluar el grado de satisfacción y el perfil socioeconómico de pacientes atendidos en Clínicas Externas de Gastroenterología de un centro universitario vinculado al Sistema Único de Salud brasileño. Método: Un cuestionario administrado por investigador fue aplicado durante entrevista estructura en clínicas externas. Resultados: Doscientos cuarenta (240) pacientes fueron incluidos en el estudio (edad media de 53 años, el 55% mujeres). Un 30% de los pacientes tenían educación básica incompleta, el 25% tenían el bachillerato/secundaria incompleto/a y el 53% eran trabajadores activos. Cerca del 87% de los que eran atendidos en la clínicas externas se hallaban en las clases económicas B2, C1 y C2 con ingresos familiares estimados entre 275,00 y 825,00 dólares estadounidenses por mes. El noventa y dos por ciento (92%) de los pacientes estaban satisfechos con la atención recibida; los puntos asociados con bajo grado de satisfacción fueron las instalaciones/comodidad, limpieza y tiempo de espera para consulta. Ninguna relación fue observada entre perfil socioeconómico y grado de satisfacción. Conclusión: Encuestas de satisfacción son importantes para identificar oportunidades de mejorar los servicios sanitarios y para que sus gerentes responsables, profesionales sanitarios e incluso los mismos usuarios puedan promocionar el cumplimiento a la leyes y decretos a fin de mejorar la atención sanitaria.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Factores Socioeconómicos , Satisfacción del Paciente , Sistema Único de Salud , Servicios de SaludRESUMEN
INTRODUCTION: Hepatitis B virus infection is an important cause of liver disease in hemodialysis patients and renal transplant recipients. Hepatitis Delta virus is a defective virus transmitted by the same route of hepatitis B virus, which requires the helper function of hepatitis B virus. Data about hepatitis B virus/hepatitis delta virus coinfection are scarce and there are no studies regarding the coinfection among hemodialysis patients and renal transplant in our country. OBJECTIVE: This study aimed to investigate the prevalence of hepatitis delta virus infection among hemodialysis patients and renal transplant recipients. METHODS: Cross-sectional study analyzing virological markers of hepatitis B virus and hepatitis delta virus infection and biochemical and clinical features of liver disease of patients infected with hepatitis B virus in hemodialysis and renal transplant. RESULTS: A total of 117 HBsAg-positive patients (46 hemodialysis and 71 renal transplant) were included. The mean age was 48.5 ± 11.8 years and 67% were males. Antiviral therapy was given to 74% of patients. Liver function tests were within the normal range. HBeAg-positive was found in 35% of patients and median hepatitis B virus DNA was 2.98 log (IU/mL). Cirrhosis was detected in 26.5% of patients. The prevalence of anti-hepatitis delta virus total antibody (+) was 1.7% (2/117). None of the 2 patients had active hepatitis delta virus infection, since all samples tested negative for hepatitis delta virus-RNA. CONCLUSION: The results suggest a low prevalence rate of coinfection B and D in hemodialysis and renal transplant recipients in this population.
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Virus de la Hepatitis B , Hepatitis B , Hepatitis D , Virus de la Hepatitis Delta/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Diálisis Renal/efectos adversos , Adulto , Brasil/epidemiología , Coinfección/epidemiología , Estudios Transversales , Femenino , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis D/diagnóstico , Hepatitis D/epidemiología , Humanos , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Diálisis Renal/métodosRESUMEN
New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naïve patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4). Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n = 4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.
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Hepacivirus/genética , Fallo Renal Crónico/virología , Filogenia , Diálisis Renal , Antivirales/uso terapéutico , Biología Computacional , Farmacorresistencia Viral , Evolución Molecular , Variación Genética , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Mutación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Proteínas no Estructurales Virales/genéticaRESUMEN
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.
Asunto(s)
Antivirales/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de Proteasas/administración & dosificación , Anciano , Brasil , Estudios Transversales , Femenino , Genotipo , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Polietilenglicoles/administración & dosificación , Prolina/administración & dosificación , Prolina/análogos & derivados , ARN Viral/genética , Proteínas Recombinantes/administración & dosificación , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antivirales/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de Proteasas/administración & dosificación , Brasil , Estudios Transversales , Genotipo , Hepatitis C Crónica/virología , Interferón-alfa/administración & dosificación , Oligopéptidos/administración & dosificación , Polietilenglicoles/administración & dosificación , Prolina/administración & dosificación , Prolina/análogos & derivados , Proteínas Recombinantes/administración & dosificación , ARN Viral/genética , Resultado del TratamientoRESUMEN
Brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection.