MARIO GUIMARAES PESSOA

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico

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Assunto: Hepatitis C ×

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  • article 36 Citação(ões) na Scopus
    Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach
    (2019) BENZAKEN, Adele Schwartz; GIRADE, Renato; CATAPAN, Elisa; PEREIRA, Gerson Fernando Mendes; ALMEIDA, Elton Carlos de; VIVALDINI, Simone; FERNANDES, Neide; RAZAVI, Homie; SCHMELZER, Jonathan; FERRAZ, Maria Lucia; FERREIRA, Paulo Roberto Abrao; PESSOA, Mario Guimaraes; MARTINELLI, Ana; SOUTO, Francisco Jose Dutra; WALSH, Nick; MENDES-CORRE, Maria Cassia
    Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers. (C) 2019 Sociedade Brasileira de Infectologia.
  • article 3 Citação(ões) na Scopus
    Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study
    (2017) CALLEFI, Luciana Azevedo; VILLELA-NOGUEIRA, Cristiane Alves; TENORE, Simone de Barros; CARNAUBA-JUNIOR, Dimas; COELHO, Henrique Sergio Moraes; PINTO, Paulo de Tarso A.; NABUCO, Leticia Cancella; PESSOA, Mario Guimaraes; FERRAZ, Maria Lucia Cardoso Gomes; FERREIRA, Paulo Roberto Abrao; MARTINELLI, Ana de Lourdes Candolo; CHACHA, Silvana Gama Florencio; FERREIRA, Adalgisa de Souza Paiva; BISIO, Alessandra Porto de Macedo; BRANDAO-MELLO, Carlos Eduardo; ALVARES-DA-SILVA, Mario Reis; REUTER, Tania; ALEXANDRA, Claudia; IVANTES, Pontes; PEREZ, Renata de Mello; MENDES-CORREA, Maria Cassia Jacintho
    OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p < 0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p < 0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm(3), and achievement of a rapid viral response. Female gender, age > 465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.
  • article 3 Citação(ões) na Scopus
    Hepatitis E virus infection increases the risk of diabetes and severity of liver disease in patients with chronic hepatitis C virus infection
    (2021) ZITELLI, Patricia Momoyo Yoshimura; GOMES-GOUVEA, Michele; MAZO, Daniel F.; SINGER, Julio da Motta; OLIVEIRA, Claudia P. M. S.; FARIAS, Alberto Queiroz; PINHO, Joao Renato; TANIGAWA, Ryan Yukimatsu; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair Jose; PESSOA, Mario Guimaraes
    OBJECTIVES: Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection. METHODS: This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients. RESULTS: Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis >= 3 versus <= 2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of >= 1.45 (p=0.003), and Fibrosis-4 score of >= 3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups. CONCLUSIONS: This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.
  • article 2 Citação(ões) na Scopus
    National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents
    (2022) FERRAZ, Maria Lucia Gomes; PICCOLI, Leonora de Zorzi; REZENDE, Rosamar; BORBA, Luiz Augusto; PISSAIA JUNIOR, Alcindo; CHEINQUER, Hugo; SILVA, Giovanni Faria; FERREIRA, Paulo Roberto Abrao; VILLELA-NOGUEIRA, Cristiane Alves; MAZO, Daniel Ferraz; SOUZA, Fernanda Fernandes; CODES, Liana; IVANTES, Claudia Alexandra Pontes; GOMIDE, Geisa Perez Medina; PEREIRA, Gustavo Henrique Santos; PESSOA, Mario Guimaraes; FRANCA, Alex Vianey Callado; PINTO, Arlene dos Santos; TEIXEIRA, Rosangela; BITTENCOURT, Paulo Lisboa
    Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associ-ated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, fre-quently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country. (c) 2022 Sociedade Brasileira de Infectologia.
  • article 1 Citação(ões) na Scopus
    Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study
    (2021) LOURENCO, Mariana Sandoval; ZITELLI, Patricia Momoyo Y.; CUNHA-SILVA, Marlone; OLIVEIRA, Arthur Ivan N.; LIMA, Roque Gabriel Rezende de; OLIVEIRA, Souza Evandro de; OLIVEIRA, Claudia P.; SEVA-PEREIRA, Tiago; CARRILHO, Flair J.; PESSOA, Mario G.; MAZO, Daniel F.
    OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir +/- ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p.=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p.=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p.=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p.=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.
  • article 7 Citação(ões) na Scopus
    Efficacy and safety of glecaprevir/pibrentasvir in treatment-naive adults with chronic hepatitis C virus genotypes 1-6 in Brazil
    (2021) PERIBANEZ-GONZALEZA, Mario; CHEINQUER, Hugo; RODRIGUES, Lino; LIMA, Maria Patelli; ALVARES-DA-SILVA, Mario Reis; MADRUGA, Jose; PARISE, Edison Roberto; PESSOA, Mario Guimaraes; FURTADO, Juvencio; VILLANOVA, Marcia; FERREIRA, Adalgisa; MAZZOLENI, Felipe; NASCIMENTO, Ecio; SILVA, Giovanni Faria; FREDRICK, Linda; KRISHNAN, Preethi; BURROUGHS, Margaret; REUTER, Tania
    Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naive Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naive Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported >= 1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-nave Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. (C) 2020 Published by Elsevier Espafia, 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.
  • article 4 Citação(ões) na Scopus
    Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin +/- amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial
    (2012) PESSOA, Mario G.; CHEINQUER, Hugo; ALMEIDA, Paulo R. L.; SILVA, Giovanni F.; LIMA, Maria Patelli J. S.; PARANA, Raymundo; LACERDA, Marco A.; PARISE, Edison R.; PERNAMBUCO, Jose R. B.; PEDROSA, Suelene S.; TEIXEIRA, Rosangela; SETTE JR., Hoel; TATSCH, Fernando
    Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.
  • article 2 Citação(ões) na Scopus
    The impact of hepatitis E infection on hepatic fibrosis in liver transplanted patients for hepatitis C infection
    (2021) MORAES, Adriano Claudio Pereira de; GOUVEA, Michele Gomes; FERREIRA, Ariana Carolina; PINHO, Joao Renato Rebello; MELLO, Evandro Sobroza de; D'ALBUQUERQUE, Luiz Augusto Carneiro; TERRABUIO, Debora; ABDALA, Edson; CARRILHO, Flair Jose; PESSOA, Mario Guimaraes
    Hepatitis E Virus (HEV) is an infection known worldwide for its asymptomatic and self-limited course in most cases. Some cases progressing to chronicity have been described in immunosuppressed patients, especially in recipients of solid organ transplants. We evaluated laboratory parameters of HEV infection (HEV RNA, anti-HEV IgM and anti-HEV IgG) through enzyme-linked immunosorbent assay (Elisa), confirmed by immunoblotting, in a cohort of 294 patients who received liver transplants at the HCFMUSP (Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo). Laboratory and demographic data were collected from the entirety of the transplanted population. Hepatic biopsies of 122 patients transplanted due liver failure secondary to hepatitis C (HCV), with or without serological or molecular markers of HEV, were analyzed according to METAVIR score. Out of 24 (8.2%) patients tested positive for anti-HEV IgG, six (2%) were positive for anti-HEV IgM and 17 (5.8%) for HEV RNA. Of the patients transplanted because of HCV infection, 95 (77.8%) had received treatment including ribavirin for at least six months before blood sample collection. Among patients transplanted due to HCV cirrhosis who tested positive for anti-HEV IgG, only three (37.5%) showed fibrosis beyond stage 2, while five (41.7%) of the HEV RNA-positive patients had liver fibrosis beyond stage 2. Overall, the prevalence of HEV in the post-hepatic transplant scenario appears to be low, and, at least histologically, seemingly not harmful. We conclude that, although some studies reported a risk of HEV chronification, patients who had their livers transplanted due to HCV and showed serological or molecular markers of HEV did not have higher levels of fibrosis compared to patients who showed no indications of HEV infection at the time of the analysis. (C) 2021 Sociedade Brasileira de Infectologia.
  • article 2 Citação(ões) na Scopus
    Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus
    (2017) GRANDO, Aline Vitali; FERREIRA, Paulo Roberto Abrao; PESSOA, Mario Guimaraes; MAZO, Daniel Ferraz de Campos; BRANDAO-MELLO, Carlos Eduardo; REUTER, Tania; MARTINELLI, Ana de Lourdes Candolo; GONZALEZ, Mario Peribanez; NASTRI, Ana Catharina Seixas-Santos; CAMPOS, Aleia Faustina; LOPES, Max Igor Banks Ferreira; BRITO, Jose David Urbaez; MENDES-CORREA, Maria Cassia
    Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.
  • article 18 Citação(ões) na Scopus
    Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin
    (2017) BARBOSA, Mary Ellen Dias; ZANINOTTO, Ana Luiza; MAZO, Daniel Ferraz de Campos; PESSOA, Mario Guimaraes; OLIVEIRA, Claudia Pinto Marques Souza de; CARRILHO, Flair Jose; FARIAS, Alberto Queiroz
    Background: Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. Method: A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. Results: Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719). Conclusions: Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.