Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

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.

Magnetic resonance imaging findings in autoimmune hepatitis: how frequent and reproducible are they? / Achados de imagem por ressonância magnética na hepatite autoimune: quão frequentes e reprodutíveis são eles?

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.

Autonomic dysfunction is common in liver cirrhosis and is associated with cardiac dysfunction and mortality: prospective observational study

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.

Cholestatic pruritus: a knowledge update

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.

Study protocol: epidemiological and clinical characteristics of acute viral hepatitis in Brazilian health services.

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.

Autoimmune hepatitis in practice, from diagnosis to complications: What is the role of imaging? A clinicoradiological review.

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.

Socioeconomic profile and degree of satisfaction of patients attending Gastroenterology Outpatient Clinics of a University Institution.

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.

Socioeconomic profile and degree of satisfaction of patients attending Gastroenterology Outpatient Clinics of a University Institution / Perfil socioeconômico e grau de satisfação de pacientes que são atendidos em clínicas externas de gastrenterologia de uma instituição universitária / Perfil socioeconómico y grado de satisfacción de pacientes atendidos en clínicas externas de gastroenterología de un centro universitario

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.

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.

Acute pancreatitis associated with boceprevir: a case report

Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30-50%. In an attempt to improve the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.

Histological evolution of hepatitis C virus infection after renal transplantation.

BACKGROUND: information regarding histological progression of hepatitis C after renal transplant (RTx) is scarce. AIMS: To analyze clinical and laboratory evolution and histological progression of hepatitis C in patients evaluated before and after RTx. METHODS: Twenty-two HCV-infected patients submitted to liver biopsy pre- and post-RTx were included. A semiquantitative analysis of necroinflammatory activity and fibrosis staging was performed and the two biopsies were compared. RESULTS: Patients were mostly men (73%) with mean age of 36±9 yr. Time post-transplant was 4±2 yr and time between biopsies was 5±2 yr. An elevation of alanine aminotransferase (p=0.041) and aspartate aminotransferase (p=0.004) levels was observed in the post-transplant period. Fibrosis progression after renal transplantation was observed in 11 (50%) of the patients, and necroinflammatory activity worsening was observed in 7 (32%) of the patients. The histological progression occurred even among those without significant histological lesions in pre-transplant biopsy. CONCLUSION: The findings of this study suggest that the practice of indicating treatment in the pre-transplant phase based mainly on histological disease should be revised, because a high proportion of patients present disease progression. Because interferon cannot be used safely after RTx, treatment should be indicated for all ESRD patients with hepatitis C.

Câncer da próstata: recurso diagnósticos atuais / Prostate carcinoma: current diagnostic strategy

Câncer da próstata é a segunda causa de morte por câncer na populaçäo masculina ocidental. Apesar do progresso no tratamento dos estádios avançados, näo há dúvidas de que a única possibilidade de reduçäo da mortalidade é o diagnóstico precoce, quando a doença ainda está localizada. Neste estudo, objetivamos rever os recursos atuais disponíveis para o diagnóstico do carcinoma prostático. Antígeno prostático específico (PSA) é importante marcador tumoral e tem demonstrado ser efetivo na detecçäo, na monitorizaçäo terapêutica e na identificaçäo de recorrência. Mesmo assim, métodos alternativos têm sido propostos, como a relaçäo entre o PSA livre e o total, a densidade e a velocidade do PSA, os quais podem melhorar a sensibilidade e a especificiddade diagnósticas. Métodos de imagem incluem ultra-som transretal, tomografia computadorizada, ressonância magnética e mapeamento ósseo. O ultra-som é o melhor método para direcionar a realizaçäo de biópsias e, juntamente com a ressonância magnética, pode ser útil no estadiamento locorregional. Tanto a tomografia como a ressonância podem ser utilizadas para a identificaçäo de comprometimento linfonodal. O mapeamento ósseo é o melhor método para diagnóstico de metástases à distância