GASPAR LISBOA NETO
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Evaluation of inflammatory activity on liver biopsy of patients with chronic hepatitis C who have recovered from HBV infection: a case series study(2012) LISBOA NETO, G.; CAVALHEIRO, N.; BARONE, A.- 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.
- Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in Sao Paulo state(2018) MOREIRA, Regina Celia; SANTOS, Ana Paula de Torres; LISBOA-NETO, Gaspar; MENDES-CORREA, Maria Cassia Jacintho; LEMOS, Marcilio Figueiredo; MALTA, Fernanda Mello; SANTANA, RAbia Anita Ferraz; DASTOLI, Gregorio Tadeu Fernando; CASTRO, Vanessa Fusco Duarte de; PINHO, Joao Renato RebelloHepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naive patients, living in Sao Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype la and lb, respectively. HCV-RNA was extracted, amplified, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV la infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no difference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These findings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C.
conferenceObject HEPATITIS C TREATMENT AMONG HCV-HIV CO-INFECTED PATIENTS IN BRAZIL: A MULTICENTER STUDY ON BASELINE RESISTANCE ANALYSES AND SUSTAINED VIROLOGIC RESPONSE RATE(2019) CORREA, Maria Cassia Mendes; MACHADO, Soraia Mafra; LEITE, Andrea Gurgel Batista; VIGANI, Aline; DIAZ, Ana Claudia Marques Barbosa; FERREIRA, Paulo; CARNAUBA JUNIOR, Dimas; TENORE, Simone; SR., Carlos Eduardo Brandao-Mello; GONZALEZ, Mario; SIROMA, Fabiana; PRADO, Kleber D.; GONGORA, Delzi Vigna Nunes; NETO, Gaspar Lisboa; PINHO, Joao Renato R.; MALTA, FernandaconferenceObject 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.- Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil(2017) MALTA, Fernanda; GASPARETO, Karine Vieira; LISBOA-NETO, Gaspar; CARRILHO, Flair Jose; MENDES-CORREA, Maria Cassia; PINHO, Joao Renato RebelloBackground: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Methods: Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naive patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). Results: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Conclusions: Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naive patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.
- Characterization of clinical predictors of naturally occurring NS3/NS4A protease polymorphism in genotype 1 hepatitis C virus mono and HIV co-infected patients(2017) NETO, Gaspar Lisboa; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; NOBLE, Caroline F.; ROMANO, Camila M.; PINHO, Joao R. Rebello; SILVA, Mariliza H.; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.
- Serological and molecular markers of hepatitis E virus infection in HIV-infected patients in Brazil(2018) FERREIRA, A. C.; GOMES-GOUVEA, Michele Soares; LISBOA-NETO, G.; MENDES-CORREA, M. C. J.; PICONE, C. M.; SALLES, N. A.; MENDRONE-JUNIOR, A.; CARRILHO, F. J.; PINHO, J. R. R.In Brazil, the circulation of hepatitis E virus (HEV) has been demonstrated in distinct groups of individuals and some animals, but its prevalence among individuals with human immunodeficiency virus (HIV) infection is unknown. This study aimed to assess the frequency of serological and molecular HEV markers in individuals infected with HIV from So Paulo, Brazil. Serum and plasma samples of 354 HIV-infected patients collected between 2007 and 2013 were included. All samples were tested for anti-HEV IgG and IgM antibodies and HEV RNA. Anti-HEV IgG and IgM antibodies were detected in 10.7% (38/354) and 1.4% (5/354) of the samples, respectively. Both antibodies were detected simultaneously in only two samples. HEV RNA was not detected in any sample. There was no significant correlation of anti-HEV serological status (positivity to anti-HEV IgG and/or IgM) with sex, age, CD4(+) T cell count, HIV viral load, antiretroviral therapy, liver enzyme levels, or coinfection with hepatitis B virus and/or hepatitis C virus. Our study provides serological evidence of past and recent HEV infections in HIV-infected patients from So Paulo, Brazil. However, the occurrence of ongoing HEV infection appears be a rare event in this population.
- Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources(2019) MATOS, Maria Laura Mariano de; FERRUFINO, Rosario Quiroga; NASTRI, Ana Catharina de Seixas Santos; ODONGO, Fatuma Catherine Atieno; CAMPOS, Aleia Faustina; LUIZ, Andre Machado; LISBOA-NETO, Gaspar; WITKIN, Steven S.; MENDES-CORREA, Maria CassiaOBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clinicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.
- Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV(2017) NOBLE, Caroline Furtado; MALTA, Fernanda; LISBOA-NETO, Gaspar; GOMES-GOUVEA, Michele Soares; LEITE, Andrea Gurgel Batista; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; CARRILHO, Flair Jose; MENDES-CORREA, Maria Cassia; PINHO, Joao Renato RebelloResistance-associated variants (RAVs) represent a challenge to the success of new HCV therapies. The aim of this study was to describe the prevalence of naturally occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-na < ve patients infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and sample collection were performed between 2011 and 2013. Using Sanger-based sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3 %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V (3.2-6.3 %). Understanding the real RAVs scenario in patients is fundamental to establishing the most effective therapeutic strategy and in minimizing the risks for their selection.