CLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Ability of a Combined FIB4/miRNA181a Score to Predict Significant Liver Fibrosis in NAFLD Patients(2021) LIMA, Rodrigo Vieira Costa; STEFANO, Jose Tadeu; MALTA, Fernanda de Mello; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; ARRESE, Marco; OLIVEIRA, Claudia P.Liver biopsy is the gold standard for assessing fibrosis, but there is a need to seek non-invasive biomarkers for this purpose. The aim of this study was to evaluate the correlation between the serum levels of the microRNAs miR-21, miR-29a, miR-122, miR-155 and miR-181a and the phenotypic expression of NAFLD. A cross-sectional study was carried out on 108 NAFLD patients diagnosed by liver biopsy. FIB-4 and NAFLD fibrosis scores were calculated. The comparison between the distributions of microRNA values according to the presence or absence of histological fibrosis (F2-F4) was performed. A multivariate logistic regression analysis was performed to build a score for predicting fibrosis using FIB-4 and Ln (miR-181a) as independent variables. Only miR-181a showed a statistical difference between patients with significant liver fibrosis (>F2) and those without (F0-F1) (p = 0.017). FIB-4 revealed an AUC on the ROC curve of 0.667 to predict clinically significant fibrosis (F2-F4). When assessed using the score in association with Ln (miR-181a), there was an improvement in the ROC curve, with an AUC of 0.71. miR-181a can be used as a non-invasive method of predicting fibrosis in NAFLD, and an association with FIB-4 has the potential to increase the accuracy of each method alone.
- Cardiovascular risk, atherosclerosis and metabolic syndrome after liver transplantation: a mini review(2013) OLIVEIRA, Claudia Pinto Marques Souza de; STEFANO, Jose Tadeu; ALVARES-DA-SILVA, Mario ReisLiver transplantation is the standard of care for acute and chronic end-stage liver disease. Advances in medical therapy and surgical techniques have transformed the long-term survival of liver-transplant (LT) recipients. The prevalence of post-transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. Currently, deaths related to cardiovascular complications are one of the main causes of long-term mortality in LT recipients, as cardiovascular disease is the reason of 19-42% of non-liver-related mortality after transplant. On the other hand, metabolic syndrome is common among LT recipients before and after transplantation. In fact, their components (abdominal obesity, diabetes mellitus, hypertension and dyslipidemia) are often exacerbated by transplant-specific factors, such as immunosuppression, inappropriate diet, smoking and a sedentary lifestyle, and add a significant risk of developing atherosclerosis. These aspects are discussed in this article.
- Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients Applicability of the BCLC Staging System(2016) KIKUCHI, Luciana; OLIVEIRA, Claudia P.; ALVARES-DA-SILVA, Mario R.; TANI, Claudia M.; DINIZ, Marcio A.; STEFANO, Jose T.; CHAGAS, Aline L.; ALENCAR, Regiane S. S. M.; VEZOZZO, Denise C. P.; SANTOS, Gilmar R.; CAMPOS, Priscila B.; ALVES, Venancio A. F.; RATZIU, Vlad; CARRILHO, Flair J.Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for,patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients.
- Pro-atherosclerotic markers and cardiovascular risk factors one year after liver transplantation(2014) ALVARES-DA-SILVA, Mario Reis; OLIVEIRA, Claudia Pinto Marques Souza de; STEFANO, Jose Tadeu; BARBEIRO, Hermes V.; BARBEIRO, Denise; SORIANO, Francisco G.; FARIAS, Alberto Queiroz; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz Augusto CarneiroAIM: To investigate pro-atherosclerotic markers (endothelial dysfunction and inflammation) in patients one year after liver transplantation. METHODS: Forty-four consecutive liver transplant (LT) outpatients who were admitted between August 2009 and July 2010, were followed-up by for 1 year, exhibited no evidences of infection or rejection, all of them underwent tacrolimus-based immunosuppressive regimens were consecutively enrolled. Inflammatory cytokines (TNF alpha, IFN gamma, IL-8, and IL-10), endothelial biomarkers (sVCAM-1, sICAM-1, MPO, adiponectin, PAI-1, SAP, SAA, E-selectin, and MMP-9), high sensitive C-reactive protein, and Framingham risk score (FRS) were assessed. The anthropometric data, aminotransferases, metabolic syndrome features, glucose and lipid profiles, and insulin resistance data were also collected. The LT recipients were compared to 22 biopsy-proven non-alcoholic steatohepatitis (NASH) patients and 20 healthy controls (non-obese, non-diabetics, and non-dyslipidemic). RESULTS: The LT recipients had significantly younger ages and lower body mass indices, aminotransferases, fasting glucose and insulin levels, glucose homeostasis model and metabolic syndrome features than the NASH patients. Classic cardiovascular risk markers, such as Hs-CRP and FRS [2.0 (1.0-8.75)], were lower in the LT patients compared to those observed in the NASH patients (P = 0.009). In contrast, the LT recipients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls (pg/mL): lower IL-10 levels (32.3 and 32.3 vs 62.5, respectively, P = 0.019) and higher IFN gamma (626.1 and 411.9 vs 67.9, respectively, P < 0.001), E-selectin (48.5 and 90.03 vs 35.7, respectively, P < 0.001), sVCAM-1 (1820.6 and 1692.4 vs 1167.2, respectively, P < 0.001), and sICAM-1 (230.3 and 259.7 vs 152.9, respectively, P = 0.015) levels. CONCLUSION: Non-obese LT recipients have similar pro-atherosclerotic serum profiles after a short 1-year follow-up period compared to NASH patients, suggesting a high risk of atherosclerosis in this population.
- Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey(2016) COTRIM, Helma P.; OLIVEIRA, Claudia P.; COELHO, Henrique Sergio M.; ALVARES-DA-SILVA, Mario R.; NABUCO, Leticia; PARISE, Edison Roberto; IVANTES, Claudia; MARTINELLI, Ana L. C.; GALIZZI-FILHO, Joao; CARRILHO, Flair J.OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (420 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases' 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, Sao Paulo, Parana and Rio Grande do Sul). The mean age was 67 +/- 11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, >= 3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.
- Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype(2020) CAMPOS, Priscila B. de; OLIVEIRA, Claudia P.; STEFANO, Jose T.; MARTINS-FILHO, Sebastiao N.; CHAGAS, Aline L.; HERMAN, Paulo; D'ALBUQUERQUE, Luiz C.; ALVARES-DA-SILVA, Mario R.; LONGATTO-FILHO, Adhemar; CARRILHO, Flair J.; ALVES, Venancio A. F.Objectives. This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. Methods. We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohistochemical reactivity for K19 and Ki-67. Results. Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m(2). Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as ""steatohepatitic HCC"". Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. Conclusion. NAFLD-related HCC was found in non-cirrhotic patients in 42% of cases, alpha-fetoprotcin level was normal in 63% and ""steatohepatitic HCC"" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially ""an inflammatory, non-proliferative subtype of HCC"".
- NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features(2022) RECUERO, Amanda Medeiros; GOMES, Larissa Garcia; MACIEL, Gustavo Arantes Rosa; MALTA, Fernanda de Mello; SALLES, Ana Paula Moreira; VEZOZZO, Denise Cerqueira Paranagua; BARACAT, Edmund Chada; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; STEFANO, Jose Tadeu; OLIVEIRA, Claudia P.Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance >= 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values >= 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.
- The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease(2021) MENDEZ-SANCHEZ, Nahum; ARRESE, Marco; GADANO, Adrian; OLIVEIRA, Claudia P.; FASSIO, Eduardo; ARAB, Juan Pablo; CHAVEZ-TAPIA, Norberto C.; DIRCHWOLF, Melisa; TORRE, Aldo; RIDRUEJO, Ezequiel; PINCHEMEL-COTRIM, Helma; FERNANDEZ, Marlen Ivon Castellanos; URIBE, Misael; GIRALA, Marcos; DIAZ-FERRER, Javier; RESTREPO, Juan C.; PADILLA-MACHACA, Martin; DAGHER, Lucy; GATICA, Manuel; OLAECHEA, Blanca; PESSOA, Mario G.; SILVA, MarceloThe Latin American Association for the Study of the Liver (Asociacion latinoamericana para el Estudio del Higado; ALEH) represents liver professionals in Latin America with the mission of promoting liver health and quality patient care by advancing the science and practice of hepatology and contributing to the development of a regional health policy framework. Fatty liver disease associated with metabolic dysfunction is of specific concern in the ALEH region, where its prevalence is one of the highest globally, second only to the Middle East. A recent consensus from an international panel recommended a new definition of fatty liver disease associated with metabolic dysfunction, including a shift in name from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), and adoption of a set of positive criteria to diagnose the disease, independent of alcohol intake or other liver diseases. Given, the importance of this proposal, ALEH invited leading members of regional nations to come to a consensus on it from a local perspective. We reached a consensus to endorse the proposal that the disease should be renamed as MAFLD and that the disease should be diagnosed by the proposed simple and easily applicable criteria. We expect that this change in nosology will result in improvements in disease awareness and in advances in scientific, economic, public health, political, and regulatory aspects of the disease.
- NAFLD: Challenges and opportunities to address the public health problem in Latin America(2021) PABLO, Arab Juan; ANTONIO, Diaz Luis; MELISA, Dirchwolf; MARK, Henry E.; LAZARUS, Jeffrey V.; VAUGHAN, Elly; MENDEZ-SANCHEZ, Nahum; OLIVEIRA, Claudia P.; GADANO, Adrian; ARRESE, MarcoNon-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Collectively, Latin American countries have some of the highest obesity rates in the world and the fastest-growing prevalence of type 2 diabetes mellitus (T2DM). Since obesity and T2DM are intrinsically linked with NAFLD, epidemiological projections are worrisome. In addition to this adverse epidemiological setting, the region of Latin America faces unique challenges and obstacles to addressing the growing burden of NAFLD. In this article, on the occasion of the International NASH Day on June 10, 2021, we describe the main challenges and opportunities to improve care of people living with NAFLD in Latin America. Among the major challenges to be tackled are: lack of disease awareness, limited educational opportunities for healthcare personnel and general public, health system fragmentation, and lack of effective strategies for the prevention and effective treatment of NAFLD and common comorbidities, namely obesity and T2DM. Wide dissemination of current concepts on NAFLD, and extensive collaboration between scientific societies, governments, non-governmental organizations, pharmaceutical industry, and other stakeholders is urgently needed to advance the NAFLD public health policies agenda that allows us to address this disease with a whole of society approach. (c) 2021 Published by Elsevier Espa?a, S.L.U. on behalf of Fundaci?n Cl?nica M?dica Sur, A.C. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/
- Impact of Endoscopic Sleeve Gastroplasty in Non-alcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis(2023) NUNES, Beanie Conceicao Medeiros; MOURA, Diogo Turiani Hourneaux de; KUM, Angelo So Taa; OLIVEIRA, Guilherme Henrique Peixoto de; HIRSCH, Bruno Salomao; RIBEIRO, Igor Braga; GOMES, Igor Logetto Caetite; OLIVEIRA, Claudia Pinto Marques de; MAHMOOD, Sultan; BERNARDO, Wanderley Marques; MOURA, Eduardo Guimaraes Hourneaux deNon-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Endoscopic sleeve gastroplasty (ESG) has proven to be feasible, safe, and effective in the management of obesity. We performed the first systematic review and meta-analysis evaluating NAFLD and other metabolic parameters 12 months post-ESG. Four observational studies with a total of 175 patients were included. The results showed a significant (p < 0.05) reduction of 4.85 in hepatic steatosis index (95% CI - 6.02, - 3.67), 0.5 in NAFLD fibrosis score (95% CI - 0.80, - 0.19), 6.32 U/l in ALT (95% CI - 9.52, - 3.11), 17.28% in TWL (95% CI - 18.24, - 16.31), 6.31 kg/m(2) in BMI (95% CI - 8.11, - 4.52), 47.97% in EWL (95% CI - 49.10, - 46.84), and 0.51% in HbA1c (95% CI - 0.90, - 0.12). ESG improves liver parameters, provides weight loss, and reduces HbA1c levels in patients suffering from NAFLD.