MARIA CASSIA JACINTHO MENDES CORREA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection(2015) LISBOA-NETO, Gaspar; NOBLE, Caroline F.; PINHO, Joao R. Rebello; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; ALVARADO-MORA, Monica V.; SILVA, Mariliza H. da; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; RODRIGUES, Flaviane K.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.Background: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.
bookPart Tratamento da hepatite C(2015) FOCACCIA, Roberto; MENDES-CORRêA, Maria Cássia Jacintho; BUTI, Maria; DIAGO, Moisés; ESTEBAN, Rafael; CASTRO, Rui Sarmento e; TAVARES, Ana PaulaconferenceObject CHARACTERIZATION OF CLINICAL PREDICTORS OF NATURALLY OCCURRING NS3/NS4A PROTEASE POLYMORPHISM IN GENOTYPE 1 HEPATITIS C VIRUS INFECTED PATIENTS(2015) LISBOA NETO, G.; NOBLE, C.; PINHO, J. R. R.; MALTA, F. M.; GOMES-GOUVEA, M. S.; ALVARADO-MORA, M. V.; SILVA, M. H.; LEITE, A. G.; PICCOLI, L. Z.; CARRILHO, F. J.; MENDES-CORREA, M. C.- Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity(2015) SHORES, Nathan J.; MENDES-CORREA, Maria Cassia; MAIDA, Ivana; TURNER, JoLyn; HIGH, Kevin P.; BABUDIERI, Sergio; NUNEZ, MarinaOBJECTIVE: To determine peroxisome proliferator activated receptor alpha and gamma mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor alpha and gamma mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor alpha and gamma mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor gamma mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor a mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.
- Disease burden of chronic hepatitis C in Brazil(2015) FERREIRA, Paulo Roberto Abrao; BRANDAO-MELLO, Carlos Eduardo; ESTES, Chris; GONCALES JUNIOR, Fernando Lopes; COELHO, Henrique Sergio Moraes; RAZAVI, Homie; CHEINQUER, Hugo; WOLFF, Fernando Herz; FERRAZ, Maria Lucia Gomes; PESSOA, Mario Guimardes; MENDES-CORREA, Maria CassiaBackground: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective. Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2). Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n =325,900) and decompensated (n=45,000) cirrhosis; hepatocellular carcinoma (n=19,100); and liver-related deaths (n=16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively. Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.
- The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study(2015) FERREIRA, Paulo Roberto Abrao; SILVA, Mariliza Henrique da; BRANDAO-MELO, Carlos Eduardo; REZENDE, Rosamar Eulira; GONZALEZ, Mario; REUTER, Tania; URBAEZ, Jose David; GIANINI, Reinaldo Jose; MARTINELLI, Ana; MENDES-CORREA, Maria CassiaIntroduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and REV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with Peg-IFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: in our Brazilian case series, the SVR rate under current clinical practice conditions was similar to that reported in other studies. There was a correlation between an SVR and being infected by genotypes 2 and 3, low viral load, high ALT levels at the onset of treatment, and absence of an AIDS-defining illness. Cytopenia and psychiatric disorders were the major causes of treatment interruption. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment. (C) 2014 Elsevier Editors Ltda. Este e um artigo Open Access sob a licenca de CC BY-NC-ND
- Drug-induced liver injury in hospitalized HIV patients: high incidence and association with drugs for tuberculosis(2015) TOMICH, Lisia Gomes Martins de Moura; NUNEZ, Marina; MENDES-CORREA, Maria CassiaBackground. The evaluation of liver disease in HIV patients is cumbersome because may result from a number of different causes. The aim of this retrospective study was to estimate the incidence of severe drug induced liver injury (DILI) in a group of HIV inpatients and investigate potential risk factors. Material and methods. We performed a retrospective analysis of data from HIV-infected patients hospitalized between August 2010 and August 2011 in a tertiary hospital in Sao Paulo, Brazil. Severe hepatotoxicity was defined as grade 3 (5.1 to 10 x ULN) or 4 (> 10 x ULN) of ALT and AST levels. Factors analyzed included demographics, infection with hepatitis viruses, alcohol history and use of hepatotoxic drugs prior to or during hospital admission. Results. A total of 149 patients with HIV were hospitalized during the study period. The majority were male over 42 years of age and 82 (55%) were taking HAART initiated prior to admission. Mean CD4 counts were 164 cells/mm(3). Thirty three patients (22.1%) developed severe DILI during hospital stay, which had a mean duration of 26 days. Factors associated with severe DILI in the multivariate analysis were abnormal baseline ALT levels [OR 2.02 (95%CI 1.13-3.59); p = 0.017] and tuberculosis therapy [OR 2.31 (95% CI 1.27-4.19); p = 0.006]. In conclusion, in this group of HIV patients admitted to a tertiary hospital in Brazil, we found a high incidence (22.1%) of severe DILI. The use of anti-tuberculosis drugs and baseline liver injury were independent factors associated with severe DILI during hospital stay.
- HBV carrying drug-resistance mutations in chronically infected treatment-naive patients(2015) GOMES-GOUVEA, Michele S.; FERREIRA, Ariana C.; TEIXEIRA, Rosangela; ANDRADE, Jose R.; FERREIRA, Adalgisa S. P.; BARROS, Lena M. F.; REZENDE, Rosamar E. F.; NASTRI, Ana C. S. Santos; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; GALVAN, Josiane; CONDE, Simone R. S. S.; SOARES, Manoel C. P.; KLIEMANN, Dimas A.; BERTOLINI, Dennis A.; KUNYOSHI, Aline S. O.; LYRA, Andre C.; OIKAWA, Marcio K.; ARAUJO, Luciano V. de; CARRILHO, Flair J.; MENDES-CORREA, Maria C. J.; PINHO, Joao R. RebelloBackground: Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. Methods: HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. Results: There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified sub-genotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. Conclusions: HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.