ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
6 resultados
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conferenceObject ASSOCIATION BETWEEN PNPLA3 AND TM6SF2 GENE POLYMORPHISMS AND GENETIC ANCESTRY IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE FROM A HIGHLY ADMIXED BRAZILIAN POPULATION(2021) CAVALCANTE, Lourianne Nascimento; LYRA, Andre; STEFANO, Jose Tadeu; MAZO, Daniel; PORTO, Jun; REIS, Rui Manuel; LONGATTO FILHO, Adhemar; CARRILHO, Flair Jose; ALVES, Venancio A. F.; OLIVEIRA, Claudia P. M. S.conferenceObject Hepatocellular carcinoma in non-alchoolic steatohepatitis (NASH): Clinical, histopathological aspects and immunohistochemical of metabolic and proliferative related-markers(2017) CAMPOS, Priscila B.; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; CHAGAS, Aline; HERMAN, Paulo; D'ALBUQUERQUE, Luiz C.; ALVARES-DA-SILVA, Mario R.; LONGATTO-FILHO, Adhemar; BALTAZAR, Ftima; GRANJA, Sara; CARRILHO, Flair J.; ALVES, Venancio Avancini F.- 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.
- 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"".
- African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population(2022) CAVALCANTE, Lourianne Nascimento; PORTO, Jun; MAZO, Daniel; LONGATTO-FILHO, Adhemar; STEFANO, Jose Tadeu; LYRA, Andre Castro; CARRILHO, Flair Jose; REIS, Rui Manuel; ALVES, Venancio A. F.; SANYAL, Arun J.; OLIVEIRA, Claudia P.Introduction and objectives: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ances-try Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population.Methods: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplanta-tion. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyp-ing were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; a<0.05 was considered significant.Results: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerin-dian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 +/- 0.205 versus 0.105 +/- 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes.Conclusion: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.(c) 2022 Published by Elsevier Espana, S.L.U. on behalf of Fundacion Clinica Medica 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/)
- P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC(2023) NASSAR-REIS, Joao Pedro; UMETA, Pedro Fukui; STEFANO, Jose Tadeu; LONGATTO-FILHO, Adhemar; CARRILHO, Flair Jose; ALVES, Venancio Avancini Ferreira; COGLIATI, Bruno; OLIVEIRA, Claudia P.The efficacy of systemic therapy for hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is poorly understood. In this study we evaluated the effects of sorafenib based on the expression of molecular markers related to major hepatocarcinogenesis pathways and angiogenesis in a NASH-related HCC model. Forty male rats were submitted to NASH-HCC induction through the combination of a high-fat and choline deficient diet and diethylnitrosamine (100 mg/L) administration in the drinking water for 13 and 16 weeks. After the induction period, the rats received daily gavage administration of saline solution (control) or Sorafenib (5 mg/kg/day) for 3 weeks. Thereafter, the animals were euthanized and samples from liver nodules were collected for histopathological analysis and immunohistochemical assessment of HEP-PAR-1, glutamine-synthetase, VEGF, survivin, & beta;-catenin and p53. A semi-quantitative score was used for VEGF, survivin and & beta;-catenin analysis. For p53, the percentage of positive cells was determined. Results were processed by Wilcoxon's test or Student's t-test. Both protocols efficiently induced HCC, most of them being moderately to poorly differentiated. Sorafenib-treated animals showed a decreased expression of VEGF and p53 in HCCs generated at 13 weeks when compared to control animals (p = 0.03; p = 0.04, respectively). No significant difference in & beta;-catenin and survivin were observed. There was a significant decrease in VEGF and p53 expression when comparing the two control groups (13 vs. 16 weeks, p < 0.01). p53 and VEGF are promising biomarkers for assessment of efficacy of Sorafenib, whereas survivin and & beta;-catenin were not found useful. Decreased immunohistochemical expression of p53 and VEGF in the 16 week control group may indicate a different metabolic status of HCC.