LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental

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https://observatorio.fm.usp.br/handle/OPI/3622
O Laboratório de Gastroenterologia e Clínica Experimental é ligado ao Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).

Linhas de pesquisa: doenças inflamatórias, autoimunes e funcionais do intestino: genética, etiopatogenia, imunologia e epidemiologia, doença celíaca: imunologia e epidemiologia; quantificação do glúten em alimentos; nano partículas e micropartículas em processo inflamatório intestinal; modelos experimentais de colite; hepatites virais, cirroses e suas complicações e hepatopatias; doença hepática gordurosa; obesidade; estresse oxidativo e síndrome metabólica.

Site oficial: http://limhc.fm.usp.br/portal/lim07-laboratorio-de-gastroenterologia-clinica-e-experimental/

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article 2 Citação(ões) na Scopus
Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
(2022) GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.
article 0 Citação(ões) na Scopus
Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease
(2023) FERRARI, J. Tonin; GUERREIRO, G. Tayguara Silveira; LONGO, L.; SILVEIRA, T. R. D.; CERSKI, C. T. Schmidt; TOZAWA, E.; OLIVEIRA, C. P.; ÁLVARES-DA-SILVA, M. R.; URIBE-CRUZ, C.
Summary Aim. To evaluate the effects of rifaximin through microbiota modulation in a model of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease. Methods. Three groups of 8 adult male Sprague-Dawley rats each were divided as follows: the HCC group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine as a carcinogen, the hepatocellular carcinoma treated group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine and treated with rifaximin and the control group: animals fed standard diet and water. The rats were euthanized after 16 weeks. We performed analyses of liver pathology for non-alcoholic fatty liver disease severity and cancer grading, gene expression in intestinal and hepatic tissues and fecal microbiota. Results. All animals in the hepatocellular carcinoma group had non-alcoholic fatty liver disease and developed hepatocellular carcinoma lesions. Rifaximin animals showed less intense non-alcoholic fatty liver disease (assessed by non-alcoholic fatty liver disease activity score [NAS]) compared to the hepatocellular carcinoma group. Both the hepatocellular carcinoma and hepatocellular carcinoma + rifaximin groups showed areas of fibrosis as assessed by picrosirius red. Three animals in the rifaximin group did not develop cancerous lesions. Gut microbiota analyses revealed differences in diversity and composition in the control group vs hepatocellular carcinoma and rifaximin groups. Twelve differentially abundant genera were identified between the hepatocellular carcinoma and rifaximin groups. In the rifaximin group, gene expression of intestinal tight junctions decreased. Conclusions. In a rodent model of non-alcoholic fatty liver disease-related hepatocellular carcinoma, rifaximin reduces the histological severity of non-alcoholic fatty liver disease and the occurrence of hepatocellular carcinoma, probably by modulating the gut microbiota independently of markers of intestinal permeability.
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Lung ECM composition, its influence factors and transcriptomics in the lungs of severe COVID-19.
(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Toledo Do; BRITO, Jose Mara De; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; MONTEIRO, Renata Aparecida De Almeida; DUARTE NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz Da; DOLHNIKOFF, Marisa; MAUAD, Thais
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YSTRATEGIES TO ELIMINATE HEPATITIS C VIRUS INFECTION IN THE AMERICAS
(2023) DIAZ, Luis Antonio; GARCIA, Sergio; AYARES, Gustavo; URIBE, Javier; IDALSOAGA, Francisco; FUENTEALBA, Jose Miguel; FUENTES-LOPEZ, Eduardo; MEDEL, Maria Paz; RAMIREZ-CADIZ, Carolina A.; KHAN, Rayan; LAZO, Mariana; FERRECCIO, Catterina; MENDIZABAL, Manuel; DIRCHWOLF, Melisa Melisa; SALAZAR, Patricia Guerra; OLIVEIRA, Claudia P. M. S.; PESSOA, Mario G.; ALVARES-DA-SILVA, Mario R.; SEBASTIANI, Giada; BRAHMANIA, Mayur; RAMJI, Alnoor; NIAZI, Mina; KO, Hin Hin; FELD, Jordan J.; RESTREPO, Juan Carlos; QUESADA, Wagner Enrique Ramirez; ALFARO, Omar; FERNANDEZ, Marlen Ivon Castellanos; ESTUPINAN, Enrique Carrera; AGUIRRE, Jose Roberto; MALDONADO, Katherine; SANCHEZ, Abel; SANCHEZ, Marco; SR., Teresa Andara; CASTRO-NARRO, Graciela Elia; CHAVEZ-TAPIA, Norberto Carlos; MENDEZ-SANCHEZ, Nahum; ADAMES-ALMENGOR, Enrique; LOMBARDO, Julissa; SR., Marcos Girala; MORAN, Elias; PADILLA-MACHACA, Martin; FERRER, Javier Diaz; TAGLE, Martin; MAINARDI, Vitoria; HERNANDEZ, Nelia; MARTINEZ, Edmundo; ALVARADO-TAPIAS, Edilmar; LEON, Roberto; TALAL, Andrew; THOMAS, Emmanuel; SPRINGER, Sandra; SICILIA, Mauricio Garcia Saenz de; ZHANG, Wei; BAJAJ, Jasmohan S.; TAPPER, Elliot B.; IZZY, Manhal; GISH, Robert G.; ATTAR, Bashar M.; COTTER, Thomas G.; LUCEY, Michael R.; KAMATH, Patrick S.; SINGAL, Ashwani K.; BATALLER, Ramon; MEZZANO, Gabriel; SOZA, Alejandro; LAZARUS, Jeffrey V.; ARRESE, Marco; ARAB, Juan Pablo
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SITOSTEROLEMIA AND PREMATURE CORONARY ATHEROSCLEROSIS IN A YOUNG WOMAN: A CASE REPORT.
(2023) CORSO, Mariana P. Xerfan; MARTINHAGO, Gustavo; BORGES, Kartagena; BECERE, Matheus AndraDe lazzari; CHACRA, Ana Paula Marte; MIZUTA, Marjorie Hayashida; MINAME, Marcio Hiroshi; SANTOS, Raul; ROCHA, Viviane Zorzanelli
article 0 Citação(ões) na Scopus
Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of Sao Paulo City, Brazil
(2023) JOELSONS, Daniel; ALENCAR, Cecilia Salete; PINHO, Joao Renato Rebello; HO, Yeh-Li
Background: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. Methods: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. Results: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. Conclusion: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics. (c) 2023 Sociedade Brasileira de Infectologia.
article 0 Citação(ões) na Scopus
Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D
(2023) REUTER, Tania; GOMES-GOUVEA, Michele Soares; CHUFFI, Samira; DUQUE, Ulisses Horst; PERINI, Waltesia; AZEVEDO, Raymundo Soares; PINHO, Joao Renato Rebello; LEWIS-XIMENEZ, Lia L.; VILLAR, Livia Melo; ESPUL, Carlos Alberto; PUJOL, Flor H.; ROMAN, Sonia
In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espirito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espirito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.
article 0 Citação(ões) na Scopus
Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure
(2023) LUGLIO, Michele; MARQUES, Tatiana de Carvalho Silva; PEREIRA, Maria Fernanda Badue; DELGADO, Artur Figueiredo; CARVALHO, Werther Brunow de; TANNURI, Ana Cristina Aoun; SANDY, Natascha Silva; LITVINOV, Nadia; PAULA, Camila Sanson Yoshino de; SANTOS, Ariane Guissi dos; LAZARI, Carolina dos Santos; GOUVEA, Michele Soares Gomes; PAULA, Anderson Vicente de; MENDOZA, Tania Regina Tozetto; TANIGAWAH, Ryan Yukimatsu; LIMAH, Fabiana Roberto; HIRAYAMAH, Andre Bubna; SANTOS, Isabela Gusson Galdino dos; PINHOG, Joao Renato Rebello; SABINOG, Ester Cerdeira; MENDES-CORREAHG, Maria Cassia; ALVESH, Venancio Avancini Ferreira; MARQUESC, Heloisa Helena de Sousa
A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.
article 0 Citação(ões) na Scopus
Lysosomal Acid Lipase Deficiency in the Etiological Investigation of Cryptogenic Liver Disease in Adults: A Multicenter Brazilian Study
(2023) CANDOLO, Aline Coelho Rocha; CANCADO, Guilherme Grossi Lopes; ZITELLI, Patricia Momoyo; MAZO, Daniel Ferraz de Campos; OLIVEIRA, Claudia Pinto Marques; CUNHA-SILVA, Marlone; GRECA, Raquel Dias; ARAUJO, Roberta Chaves; ALUSTAU, Amanda Sacha Paulino Tolentino; COUTO, Claudia Alves; NARDELLI, Mateus Jorge; LIMA, Roque Gabriel Rezende de; FARIAS, Alberto Queiroz; CARRILHO, Flair Jose; PESSOA, Mario Guimaraes
Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 +/- 10.1 years and a mean body-mass index (BMI) of 23.1 +/- 1.7 kg/m2. The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 +/- 3.2, 21.7 +/- 3.2, and 206.7 +/- 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival.
article 0 Citação(ões) na Scopus
Liver transplantation in Latin America: reality and challenges
(2023) AGUIRRE-VILLARREAL, David; SERVIN-ROJAS, Maximiliano; SANCHEZ-CEDILLO, Aczel; CHAVEZ-VILLA, Mariana; HERNANDEZ-ALEJANDRO, Roberto; ARAB, Juan Pablo; RUIZ, Isaac; AVENDANO-CASTRO, Karla P.; MATAMOROS, Maria A.; ADAMES-ALMENGOR, Enrique; DIAZ-FERRER, Javier; RODRIGUEZ-AGUILAR, Erika Faride; PAEZ-ZAYAS, Victor Manuel; CONTRERAS, Alan G.; ALVARES-DA-SILVA, Mario R.; MENDIZABAL, Manuel; OLIVEIRA, Claudia P.; NAVASA, Miquel; GARCIA-JUAREZ, Ignacio
Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant pro-grams and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.