VENANCIO AVANCINI FERREIRA ALVES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis(2021) PINYOL, Roser; TORRECILLA, Sara; WANG, Huan; MONTIRONI, Carla; PIQUE-GILI, Marta; TORRES-MARTIN, Miguel; WEI-QIANG, Leow; WILLOUGHBY, Catherine E.; RAMADORI, Pierluigi; ANDREU-OLLER, Carmen; TAIK, Patricia; LEE, Youngmin A.; MOEINI, Agrin; PEIX, Judit; FAURE-DUPUY, Suzanne; RIEDL, Tobias; SCHUEHLE, Svenja; OLIVEIRA, Claudia P.; ALVES, Venancio A.; BOFFETTA, Paolo; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; DUFOUR, Jean-Francois; THUNG, Swan N.; REEVES, Helen L.; CARRILHO, Flair J.; CHANG, Charissa; V, Andrew Uzilov; HEIKENWALDER, Mathias; SANYAL, Arun; FRIEDMAN, Scott L.; SIA, Daniela; LLOVET, Josep M.Background and Aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. Results: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/ TGF-beta proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. Conclusions: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. Lay summary: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC.
- Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis (vol 75, pg 865, 2021)(2021) PINYOL, Roser; TORRECILLA, Sara; WANG, Huan; MONTIRONI, Carla; PIQUE-GILI, Marta; TORRES-MARTIN, Miguel; WEI-QIANG, Leow; WILLOUGHBY, Catherine E.; RAMADORI, Pierluigi; ANDREU-OLLER, Carmen; TAIK, Patricia; LEE, Youngmin A.; MOEINI, Agrin; PEIX, Judit; FAURE-DUPUY, Suzanne; RIEDL, Tobias; SCHUEHLE, Svenja; OLIVEIRA, Claudia P.; ALVES, Venancio A.; BOFFETTA, Paolo; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; DUFOUR, Jean-Francois; THUNG, Swan N.; REEVES, Helen L.; CARRILHO, Flair J.; CHANG, Charissa; UZILOV, Andrew V.; HEIKENWALDER, Mathias; SANYAL, Arun; FRIEDMAN, Scott L.; SIA, Daniela; LLOVET, Josep M.
conferenceObject Hepatic epithelioid hemangioendotelioma: An international multicenter study(2019) ZAMPARELLI, Marco Sanduzzi; RIMOLA, Jordi; MONTIRONI, Carla; NUNES, Vinicius; ALVES, Venancio Avancini Ferreira; SAPENA, Victor; FORNER, Alejandro; CARRILHO, Flair Jose; DIAZ, Alba; FUSTER, Carla; FERRER, Joana; FUSTER, Josep; AYUSO, Carmen; SOLE, Manel; BRUIX, Jordi; REIG, Maria- Noninvasive mapping of fibrosis and inflammation in nonalcoholic fatty liver disease: isolating fibrogenesis in the Space of Disse with MRI R2 multicomponent relaxometry(2018) CLARK, P.; CHUA-ANUSORN, W.; OLIVEIRA, C.; ROCHA, M.; CARRILHO, F. J.; LIMA, F.; ALVES, V.; OLIVEIRA, B.; FILHO, H. L.
- Molecular fingerprint of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis(2019) TORRECILLA, Sara; PINYOL, Roser; WANG, Huan; MONTIRONI, Carla; ANDREU-OLLER, Carmen; LEOW, Wei Qiang; MOEINI, Agrin; OLIVEIRA, Claudia; ALVES, Venancio Avancini Ferreira; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa; SIA, Daniela; LLOVET, Josep M.
conferenceObject Combination of long term N-Acetylcysteine and Ursodeoxycolic Acid in NASH: a multicenter randomized control trial(2017) OLIVEIRA, C. P.; COTRIM, H. P.; CRISTINA, A.; SIQUEIRA, G.; SALGADO, A. L. A.; STEFANO, J. T.; BRIZOLLA, P.; MATTOS, L.; MARTINS, A. H. B.; ANDRADE, A. R.; SCIUTO, R.; FREITAS, L. A.; ALVES, V. A. F.; CARRILHO, F. J.; PARISE, E. R.conferenceObject HEPATOCELLULAR CARCINOMA IN NON-ALCHOOLIC STEATOHEPATITIS - HISTOPATHOLOGICAL ASPECTS(2016) CAMPOS, P. B. de; OLIVEIRA, C. P.; KIKUCHI, L.; STEFANO, J. T.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; SILVA, M. R. Alvares da; CARRILHO, F. J.; ALVES, V. A. F.conferenceObject EFFECTS OF omega-3 POLYUNSATURATED FATTY ACIDS (PUFA) FROM FISH AND FLAXSEED OILS ON NONALCOHOLIC STEATOHEPATITIS (NASH)(2013) NOGUEIRA, M. A.; ALVES, V. A. F.; STEFANO, J. T.; RODRIGUES, L.; CARRILHO, F. J.; WAITZBERG, D.; OLIVEIRA, C. P.Introduction: There are very few intervention strategies that have been proven in non-alcoholic fatty liver disease (NAFLD). Omega-3 polyunsaturated fatty acids (PUFA) seem to be efficacious on NAFLD treatment from experimental models, but few randomized trails have been realized. The aim of this study was to evaluate prospectively the efficacy of Omega-3 PUFA derived from fish and flaxseed in non-alcoholic steatohepatitis (NASH) patients. Methods: Sixty patients with biopsy proven NASH were included in the randomized placebo controlled trial. The patients were randomized into two groups. Omega-3 group (n=30) received capsules containing 945mg of Omega-3 PUFA [α linolenic acid/64%, eicosapentaenoic acid (EPA)/16% and docosahexaenoic acid (DHA)/21%], in 3 capsules/day. Placebo Group (n=30), received 3 placebo capsules containing mineral oil. The intervention was carried out for 6 months, when patients were re-submitted for new liver biopsy. Primary endpoint was liver histology according to the NASH activity score (NAS) at baseline and 6 months. Second endpoints were evaluated by analysis of serum aminotransferases, fasting lipid profile, serum glucose, anthropometric parameters and serum levels of cytokines at 0, 3 and 6 months. Results: These 60 patients enrolled, 10 were not finished the study (5 in Omega-3 group and 5 in the Placebo group). Concerning the primary endpoint, the NAS activity improved by 57% in the placebo group and 67% in the omega-3 group, however, no significant difference was seen (p=0.33), the hepatocellular ballooning reduced 22% in the placebo group and 33% in the omega-3 group, also with no difference between groups (p=0.28). Omega-3 did not reduce steatosis, lobular inflammation and fibrosis. Serum aminotransferases, fasting lipid profile, serum glucose, anthropometric parameters and serum levels of IL-6 and TNF-α were not altered with the treatment. Conclusion: Our results indicate that Omega-3 PUFA from fish and flaxseed oil compound cannot improve, after 6 months, the liver histology, biochemical parameters and serum levels of IL-6 and TNF-α. The limitations of this study were the small number of patients enrolled and the composition of Omega-3 compound that was enriched with linolenic acid (64%) than EPA/DHA. Further study is needed to confirm these results.conferenceObject Novel mapping of fibrosis and hepatic inflammation in NASH patients with dual R2 MRI relaxometry(2017) FILHO, H. M. L.; CHUA-ANUSORN, W.; OLIVEIRA, C. P.; CARRILHO, F. J.; LIMA, F.; ALVES, V.; CLARK, P.; ROCHA, M.