JOAO RENATO REBELLO PINHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Serum Lipidomic Profiling for Screening Potential Biomarkers of Liver Cirrhosis among Patients with Chronic Hepatitis C(2015) PASSOS-CASTILHO, Ana Maria; FERRAZ, Maria Lucia; CARVALHO, Valdemir M.; CARDOZO, Karina H.; KIKUCHI, Luciana; CHAGAS, Aline; PINHO, Joao Renato R.; GOMES-GOUVEA, Michele S.; MALTA, Fernanda; CARRILHO, Flair J.; GRANATO, Celso- High Prevalence of Hepatitis B Subgenotype D4 in Northeast Brazil: an Ancient Relic from African Continent?(2018) CRUZ-SANTOS, Max D.; GOMES-GOUVEA, Michele S.; COSTA-NUNES, Jomar D.; MALTA-ROMANO, Camila; TELES-SOUSA, Marinilde; FONSECA-BARROS, Lena M.; CARRILHO, Flair J.; PAIVA-FERREIRA, Adalgisa de S.; REBELLO-PINHO, Joao R.Introduction. Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world. Material and methods. We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhao, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods. Results. Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhao, particularly in populations that do not have frequent contact with populations from other regions of the world. Conclusion. Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhao. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures.
- The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C(2021) OLIVEIRA, Arthur Ivan N.; MALTA, Fernanda M.; ZITELLI, Patricia Momoyo Y.; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.; MENDES-CORREA, Maria Cassia; PESSOA, Mario G.; MAZO, Daniel F.BackgroundDespite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies.MethodsThis cross-sectional study enrolled 365 treatment-naive patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C>T) and PNPLA3 (rs738409 c.444C>G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome.ResultsIn HCV subjects, the frequencies of TM6SF2 CC and CT+TT were 89% and 11%, while PNPLA3 frequencies of CC and CG+GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT+TT genotype in HCV was associated with significant liver fibrosis (p=0.047; OR 1.953; 95% CI 1.009-3.788). In comparison to the CT+TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p=0.002), higher frequency of arterial hypertension (p=0.032), obesity (p=0.030), metabolic syndrome (p=0.014) and lower total cholesterol levels (p=0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p=0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis.ConclusionIn this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.
conferenceObject HBV resistance frequency in nucleos(t)ide analogue-untreated patients from different Brazilian regions(2012) GOMES-GOUVEA, Michele S.; MENDES-CORREA, Maria Cassia; FERREIRA, Ariana C.; TEIXEIRA, Rosangela; ANDRADE, Jose R.; BARROS, Lena Maria F.; FERREIRA, Adalgisa S.; REZENDE, Rosamar F.; NASTRI, Ana Catharina S.; LEITE, Andrea G.; PICCOLI, Leonora Z.; GALVAN, Josiane; CONDE, Simone Regina S.; SOARES, Manoel C.; CARRILHO, Flair J.; PINHO, Joao R.Background - Presence of viral variants with drug-resistance mutations in drug-naïve hepatitis B virus (HBV) infected patients can seriously compromise response to antiviral treatment. Therefore, our study aimed to determine the prevalence of HBV with drug-resistance in 557 untreated chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NA) from five different geographic regions of Brazil. Methods – HBV reverse-tran-scriptase (RT) region was sequenced and mutations associated with resistance to NA inhibitors were analyzed. Amino acid changes potentially associated with resistance were also investigated. Furthermore, HBV genotypes and subgenotypes were determined by phylogenetic analysis of the sequences. Results – HBV genotypes A [A1 (66.8%), A2 (2.3%)] and D [D1 (0.5%), D2 (4.3%), D3 (11.8%), D4 (6.6%)] were the most prevalent in Brazil, but genotypes B1 (0.2%), B2 (0.2%), C2 (0.7%), E (0.7%), F2a (4.5%), F4 (0.4%) and G (0.5%) were also found. Overall, 1.8% (10/557) of the patients carried HBV variants with primary drug-resistance mutations [rtM204V/I (0.4%); rtM204V + rtS202G (0.4%); rtA181S/T (0.4%); rtM250I (0.2%); rtA194T (0.4%)]. The four strains with mutation at position 204 also had compensatory mutations [rtL180M (3/4); rtL180M + rtV207I (1/4). One patient was infected with HBV variant only with compensatory mutations (rtV173L + rtL180M). Thirty (5%) patients were infected with strain harboring some of that mutation potentially associated with Adefovir resistance [rtS85A (n=1), rtV214A (n=6), rtQ215S (n=14), rtI233V (n=6), rtN238T (n=4), rtN238D (n=5)]. Additionally, we observed in 18 (3.2%) patients the presence of variants with novel amino acid substitutions at positions reported to be potentially associated with Adefovir resistance: rtV214G (n=2), V214E (n=1), Q215H (n=6), Q215P (n=1), E218D (n=2), I233L (n=1), T237A (n=1), N238H (n=3), N238A (n=1). Conclusions – HBV variability is high in Brazil, thirteen HBV subgenotypes were found. The rate of important drug resistance mutations was low (1.8%) among the drug-naïve HBV infected patients studied, indicating the high potential to full efficacy of nucleos(t)ide analogue therapy in these patients. The high frequency of mutations potentially associated with Adefovir resistance among untreated patients suggests that these mutations are not really associated to resistance.- Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population(2019) MAZO, Daniel F.; MALTA, Fernanda M.; STEFANO, Jose Tadeu; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; ALMEIDA, Jazon R.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Introduction and aim: Studies have shown that two polymorphisms were associated with steatosis and progression of non-alcoholic fatty liver disease (NAFLD) in different populations: the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2). However, the frequency and significance of these polymorphisms in an admixed population, i.e., Brazilian, is unknown. Therefore, we aimed to evaluate them in healthy subjects in comparison to patients with NAFLD. Material and methods: This was a multicenter cross-sectional study in 248 patients with biopsy-proven NAFLD and in 134 healthy controls from two tertiary centers in Brazil. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated. Results: In controls, the frequencies of PNPLA3 CC and CG + GG were 49.25% and 50.74%, respectively; in NAFLD patients, this was 31.05% and 68.88% (p = 0.0044, 95% CI 1.037-2.977). PNPLA3 GG subjects had an increased risk (3.29-fold) of having NAFLD when compared to CC subjects (p = 0.0044,95% CI 1.504-7.225). In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4 +/- 25.3 versus 36.7 +/- 40.1 IU/L, p= 0.0395)] and with the presence of liver fibrosis (>= F2 fibrosis, p = 0.0272). TM6SF2 polymorphisms were not in Hardy-Weinberg equilibrium in our NAFLD group precluding further analysis. Conclusion: We demonstrated for the first time that PNPLA3 CG + GG increase the risk of NAFLD among Brazilian subjects. Moreover, PNPLA3 GG was associated with liver enzyme elevation and fibrosis in NASH patients. (C) 2019 Fundacion Clinica Medica Sur, A.C.
conferenceObject Evidence of Hepatitis E Virus Infection in Liver Transplant Recipients from Brazil(2013) GOMES-GOUVEA, Michele S.; FERREIRA, Ariana C.; FEITOZA, Bruna; PESSOA, Mario G.; ABDALA, Edson; TERRABUIO, Deborah R.; MORAES, Adriano C.; BONAZZI, Patricia R.; D'ALBUQUERQUE, Luiz C.; CARRILHO, Flair J.; PINHO, Joao R.conferenceObject PNPLA3 but not TM6SF2 polymorphisms were associated with higher degrees of steatosis and liver fibrosis among Brazilian NAFLD patients(2017) MAZO, Daniel F.; MALTA, Fernanda; STEFANO, Jose Tadeu; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; ALMEIDA, Jazon Romilson S.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.