Prevalêncıa e fatores predıtıvos assocıados à posıtıvıdade dos marcadores serológıcos do SARS-COV-2 em pacıentes com doença ınflamatórıa ıntestınal em um centro de referêncıa em DII / Prevalence and predictive factors associated with positivity of sars-cov-2 serological markers in patients with inflammatory bowel disease at an ibd referral center

ABSTRACT Background: Data related to SARS-CoV-2 exposure rates in patients with inflammatory bowel diseases (IBD) are scarce. Objective - Our aim was to determine the prevalence of serological markers of SARS-Cov-2 and the predictive factors for positivity in patients with IBD. Methods: This is a cross-sectional, observational study carried out from May to September 2020. SARS-CoV-2 serological markers were determined using chemiluminescence immunoassay in 233 IBD patients without evidence of COVID-19 symptoms. Patient age was 36.6±11.1 years, 118 patients were male (50.6%), and 63.1% had Crohn's disease. Patient clinical data were extracted from individual electronic medical records and complemented by a structured interview. Results: Twenty-six out of the 233 patients with IBD had positive serum markers for SARS-CoV-2 (11.2%). Female sex (P<0.003), extra-intestinal manifestations (P=0.004), use of corticosteroids (P=0.049), and previous contact with individuals with flu-like symptoms (P<0.001) or confirmed diagnosis of COVID-19 (P<0.001), were associated with a significant increased rate of positive SARS-Cov-2 serological markers. No significant difference was observed regarding to adherence to protection measures and positivity of SARS-Cov-2 serological markers (P>0.05). Conclusion: SARS-CoV-2 previous infection in IBD patients was not that uncommon, and its prevalence was 11.2% in our series. Positivity to SARS-CoV-2 serological markers was associated with female sex, extra-intestinal manifestations, use of corticosteroids, and contact with individuals with suspected or confirmed COVID-19. Studies with longer follow-up periods are needed to confirm these findings.

RESUMO Contexto: Dados relacionados às taxas de exposição ao SARS-CoV-2 em pacientes com doenças inflamatórias intestinais (DII) são escassos. Objetivo Nosso objetivo foi determinar a prevalência de marcadores sorológicos do SARS-Cov-2 e os fatores preditivos de positividade em pacientes com DII. Métodos: Este foi um estudo transversal observacional realizado no período de maio a setembro de 2020. Os marcadores sorológicos SARS-CoV-2 foram determinados por imunoensaio de quimioluminescência em 233 pacientes com DII sem evidência de sintomas de COVID-19. A idade dos pacientes foi 36,6±11,1 anos, 118 pacientes eram do sexo masculino (50,6%) e 63,1% tinham doença de Crohn. Os dados clínicos dos pacientes foram extraídos de prontuários médicos eletrônicos individuais e complementados por meio de uma entrevista estruturada. Resultados: Vinte e seis dos 233 pacientes com DII apresentaram marcadores sorológicos positivos para SARS-CoV-2 (11,2%). Sexo feminino (P<0,003), manifestações extra-intestinais (P=0,004), uso de corticosteroides (P=0,049) e contato prévio com indivíduos com sintomas gripais (P<0,001) ou diagnóstico confirmado de COVID -19 (P<0,001), foram associados a um aumento significativo da taxa de positividade para marcadores sorológicos do SARS-Cov-2. Não foi observada diferença significativa em relação à adesão às medidas de proteção e positividade dos marcadores sorológicos para o SARS-Cov-2 (P>0,05). Conclusão: A infecção prévia pelo SARS-CoV-2 não é tão incomum em pacientes com DII e sua prevalência em nossa série foi de 11,2%. A positividade aos marcadores sorológicos SARS-CoV-2 foi associada ao sexo feminino, manifestações extra-intestinais, uso de corticosteroides e contato com indivíduos com suspeita ou diagnóstico confirmado de COVID-19. Estudos com períodos de acompanhamento mais longos são necessários para confirmar esses achados.

Anemia e deficiência de ferro em pacientes com doença inflamatória intestinal em um centro de referência no Brasil: prevalência e fatores de risco / Anemia and iron deficiency in inflammatory bowel disease patients in a referral center in brazil: prevalence and risk factors

ABSTRACT BACKGROUND: Data regarding the prevalence of anemia in inflammatory bowel disease (IBD) patients are scarce in Brazil. Anemia and iron deficiency anemia have been known to cause significant functional impairment, lower quality of life, and higher morbidity and mortality and may be correlated with an impact on the cost of treatment. OBJECTIVE: The aim of this study was to estimate the prevalence and risk factors for anemia and iron deficiency anemia in patients with IBD in a tertiary IBD unit in Southeast Brazil. METHODS: We conducted an Institutional Review Board-approved retrospective analysis of an adult IBD cohort (IBD Unit, Ribeirão Preto Medical School, University of São Paulo, Brazil) consisting of 579 patients between January 2014 and July 2018. Clinicoepidemiological data, hemoglobin measurements and serum ferritin were extracted from electronic medical records. Anemia prevalence was calculated among ulcerative colitis (UC) and Crohn's disease (CD) phenotypes. Risk factors for anemia were also calculated. RESULTS: A total of 529 (91%) patients had complete blood counts available in their medical records. Only 35.5% of IBD patients were fully screened for anemia. The prevalence of anemia in IBD patients was 24.6% (29.1% in CD and 19.1% in UC, P=0.008). The anemia was moderate to severe in 16.9% (19.8% in CD and 11.4% in UC, P=0.34). The prevalence of iron deficiency was 52.3% (53.6% in CD and 51.2% in UC, P=0.95). Anemia of chronic disease was present in 14.1% of IBD patients. A total of 53.8% of patients with anemia were in clinical remission. CD was associated with an increased prevalence of anemia (P=0.008; OR=1.76; CI 95% =1.16-2.66) compared to UC. The penetrant disease phenotype in CD was associated with a lower risk of anemia (P<0.0001; OR=0.25; CI 95% =0.14-0.43). Active disease compared to the disease in clinical remission was associated with an increased risk of anemia (P=0.0003; OR=2.61; CI 95% =1.56-4.36) in CD. The presence of anemia was less frequent in patients with CD who underwent surgical bowel resection compared to those who did not undergo surgery (P<0.0001; OR=0.24; CI 95% =0.14-0.40). No differences in anemia prevalence were observed regarding CD localization, age at diagnosis, UC extension or biological therapy (P>0.05). CONCLUSION: Despite the low levels of full screening, anemia and iron deficiency anemia were common manifestations of IBD. CD was associated with an increased risk of anemia, especially with active disease. In addition, patients with CD who underwent surgical bowel resection and penetrant disease phenotype in CD were associated with lower risk of anemia.

RESUMO CONTEXTO: Dados referentes à prevalência de anemia em pacientes com doença inflamatória intestinal (DII) são escassos no Brasil. Sabe-se que anemia e a anemia ferropriva causam comprometimento funcional significativo, menor qualidade de vida e maior morbimortalidade e podem estar correlacionadas com um impacto no custo do tratamento. OBJETIVO: O objetivo deste estudo foi estimar a prevalência e os fatores de risco de anemia e de anemia ferropriva em pacientes com DII em um centro de referência de DII no Sudeste do Brasil. MÉTODOS: Realizamos uma análise retrospectiva dos pacientes com DII adultos, aprovada pelo Comitê de Ética Institucional do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Brasil, constituída por 579 pacientes no período de janeiro de 2014 a julho de 2018. Dados clínico-epidemiológicos, níveis de hemoglobina e de ferritina sérica foram obtidos dos prontuários eletrônicos. A prevalência de anemia foi calculada entre os fenótipos de retocolite ulcerativa (RCU) e doença de Crohn (DC). Fatores de risco para anemia também foram calculados. RESULTADOS: Um total de 529 (91%) pacientes tinha disponível o exame de hemograma completo em seus prontuários médicos. Apenas 35,5% dos pacientes com DII tinha o rastreamento completo para anemia. A prevalência de anemia nos pacientes com DII foi de 24,6% (29,1% na DC e 19,1% na RCU, P=0,008). A anemia foi moderada a grave em 16,9% (19,8% na DC e 11,4% na RCU, P=0,34). A prevalência de deficiência de ferro foi de 52,3% (53,6% na DC e 51,2% na RCU, P=0,95). Anemia de doença crônica estava presente em 14,1% dos pacientes com DII. Um total de 53,8% dos pacientes com anemia estavam em remissão clínica. A DC esteve associada a um aumento da prevalência de anemia (P=0,008; OR=1,76; IC 95% =1,16-2,66) em comparação à RCU. O fenótipo da doença penetrante na DC foi associado a um menor risco de anemia (P<0,0001; OR=0,25; IC 95% =0,14-0,43). A doença ativa comparada à doença em remissão clínica foi associada a um risco aumentado de anemia (P=0,0003; OR=2,61; IC 95% =1,56-4,36) na DC. A presença de anemia foi menos frequente nos pacientes com DC submetidos à ressecção intestinal em comparação aos que não foram submetidos à cirurgia (P<0,0001; OR=0,24; IC 95% =0,14-0,40). Não foram observadas diferenças na prevalência de anemia em relação à localização da DC, idade ao diagnóstico, extensão da RCU ou terapia biológica (P>0,05). CONCLUSÃO: Apesar do baixo rastreamento completo, tanto a anemia como a anemia ferropriva foram manifestações comuns da DII. A DC foi associada a um risco aumentado de anemia, especialmente com doença ativa. Além disto, pacientes com DC submetidos a ressecção intestinal e/ou com fenótipo penetrante tiveram menor risco de anemia.

Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

BACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.

Distribution of HBV subgenotypes in Ribeirão Preto, Southeastern Brazil: a region with history of intense Italian immigration

Abstract Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases / Características clínicas, demográficas e epidemiológicas dos pacientes com hepatite B em seguimento em hospital universitário no sudeste do Brasil: predominância de casos HBeAg negativos

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60 percent of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4 percent of the patients, among whom the risk of vertical/intrafamily transmission was 43.2 percent (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3 percent of the subjects and was more frequent among men (33 percent) (p < 0.001). Among patients with cirrhosis, 54.1 percent were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4 percent) than in the HBeAg-negative group (10.2 percent) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.

INTRODUÇÃO: No Brasil, a hepatite B é comum. No entanto, há diferenças regionais no que diz respeito ao grau de endemicidade, as formas de transmissão mais encontradas e a presença dos diferentes estágios evolutivos da doença crônica. O objetivo deste trabalho foi o de conhecer características clínicas, demográficas e epidemiológicas de pacientes cronicamente infectados pelo vírus da hepatite B (HBV), residentes na região de Ribeirão Preto, no sudeste do Brasil. MÉTODOS: Foi realizada a análise retrospectiva de 529 prontuários de indivíduos com monoinfecção pelo HBV. RESULTADOS: Mais de 60 por cento eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4 por cento dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2 por cento (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3 por cento dos indivíduos, sendo mais frequente entre os homens (33 por cento) (p < 0,001). Entre os pacientes com cirrose, 54,1 por cento faziam uso abusivo de bebidas alcoólicas (p = 0,04), sendo todos estes do gênero masculino. A presença de cirrose foi maior no grupo HBeAg positivo (24,4 por cento) que no grupo HBeAg negativo (10,2 por cento) (p < 0,001). CONCLUSÕES: Observaram-se elevadas proporções de indivíduos com infecção pelo HBV com padrão sorológico HBeAg negativo, entre os quais houve maior risco para a transmissão vertical/intrafamiliar. O uso abusivo de álcool esteve associado a indivíduos do sexo masculino e, neste grupo, à cirrose hepática. Observou-se tendência ao aumento no número de casos HBeAg negativo ao longo do tempo.

Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon

BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.

Clinical, endoscopic and prognostic aspects of primary gastric non-hodgkin's lymphoma associated with acquired immunodeficiency syndrome

Primary gastric non-Hodgkin's lymphoma (NHL) is a co-morbidity that can be observed during the clinical course of acquired immunodeficiency syndrome (AIDS). We evaluated the prevalence, clinical-evolutive aspects and form of endoscopic presentation of primary gastric NHL associated with AIDS. Two hundred and forty-three HIV patients were submitted to upper digestive endoscopy, with evaluation of clinical, endoscopic and histological data. A CD4 count was made by flow cytometry and viral load was determined in a branched-DNA assay. Six cases (five men; mean age: 37 years; range: 29-46 years) of primary gastric NHL were detected. The median CD4 count was 140 cells/mm³ and the median viral load was 40,313 copies/mL. Upper digestive endoscopy revealed polypoid (in four patients) ulcero-infiltrative (two patients) and ulcerated (two patients) lesions and combined polypoid and ulcerated lesions (two patients). Histology of the gastric lesions demonstrated B cell NHL (four patients) and T cell NHL (two patients). Five of the six patients died of complications related to gastric NHL. We concluded that primary gastric NHL is an important cause of mortality associated with AIDS.