MARIANA PINHEIRO XERFAN
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series(2022) ALENCAR, Regiane Saraiva de Souza Melo; OLIVEIRA, Claudia P.; CHAGAS, Aline Lopes; FONSECA, Leonardo Gomes da; MACCALI, Claudia; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; STEFANO, Jose Tadeu; HERMAN, Paulo; D'ALBUQUERQUE, Luiz Augusto Carneiro; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseObjective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de Sao Paulo, at the Faculdade de Medicina da Universidade de Sao Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C-D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.
conferenceObject Sorafenib improves liver mitochondrial dysfunction attenuating liver fibrosis in non-alcoholic steatohepatitis (NASH) model(2012) STEFANO, Jose Tadeu; PEREIRA, Isabel V.; COELHO, Ana Maria M.; XERFAN, Mariana P.; BARBEIRO, Denise F.; TORRES, Mariana Maciel; BIDA, Patricia Martins; MAZO, Daniel F.; COGLIATI, Bruno; SOUZA, Heraldo Possolo; D'ALBUQUERQUE, Luiz C.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Background/Aim: Mitochondria dysfunction in liver may play an important role in the induction of NASH and fibrosis. Recent evidences have shown that kinase inhibitors are able to inhibit angiogenesis, a key mechanism in fibrosis development. We investigated the role of sorafenib as an antifibrotic agent in a rodent model of NASH. Methods: Adult Sprague-Dawley rats, weighing 250-300g, were fed a choline-deficient high fat diet (CDHFD)(35% total fat, 54% trans fatty acid enriched) and simultaneously exposed to diethylnitrosamine (DEN)(100 mg/Kg) in drinking water during 6 weeks to induce NASH and fibrosis. Sorafenib group (n=10) received sorafenib 2.5 mg/kg/day; NASH group (n=10) received CDHFD plus DEN by daily gavage. Control group (n=4) was fed a standard diet. After this period the animals were sacrificed and liver tissues were collected for histologic examination, mRNA isolation and analysis of mitochondrial function. Genes related to fibrosis [matrix metalloproteinases-9 (MMP-9), tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP-1 and 2)], oxidative stress [Heat Shock Protein 60 and 90 (HSP-60 and 90)] and mitochondrial biogenesis [peroxisome proliferator-activated receptorgamma co-activator 1 α (PGC-1 α )] were evaluated by RT-qPCR method. Liver mitochondrial oxidation and phosphorylation activities were measured by polarographic method. Results: Sorafenib treatment restored the liver mitochondrial function almost similar with control group, and increased RCR and state 3 respiration in comparison to NASH group (Table 1). Besides, sorafenib upregulated PGC-1 α (p<0,001), a gene related to mitochondrial biogenesis. In the other side, TIMP-2 gene expression also was upregulated (p=0,026). There was no difference in expression of HSP-60 (p=0,447), HSP-90 (p=0,141), TIMP-1 (p=0,623) and MMP-9 (p=0,623) between both groups. All of the animals treated with sorafenib showed a significant lost weight and a decreased of fibrosis score in comparison to control (p<0.05). Conclusions: 1) Treatment with sorafenib reduced fibrosis in a rodent model of NASH; 2)Sorafenib increased mRNA expression of PGC-1α and TIMP-2. 3) Sorafenib treatment improves liver mitochondrial dysfunction. Considering that PGC1 α coordinates gene expression that stimulates mitochondrial biogenesis and the TIMP-2 abrogates endothelial cell proliferation and blocks angiogenesis, sorafenib could be used in the treatment of liver fibrosis and prevent fibrosis in this model.