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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-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. PATIENTS AND METHODS: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve 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-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.
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Bencimidazoles/uso terapéutico , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Pirrolidinas/uso terapéutico , Quinoxalinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Esquema de Medicación , Combinación de Medicamentos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND: In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES: This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS: A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS: PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS: A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.
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Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Mutación , Proteínas del Núcleo Viral/genética , Adulto , Anciano , ADN Viral , Femenino , Genotipo , Humanos , Persona de Mediana EdadRESUMEN
INTRODUCTION: Few studies have evaluated the factors involved in the spontaneous HBsAg seroclearance in patients with chronic hepatitis B (HBV) followed up on a long-term basis from areas with a low prevalence of HBV infection. We aimed to determine the rate of spontaneous HBsAg seroclearance and the factors related to it in patients with chronic HBV infection followed up at the Hepatitis Outpatient Clinic of HCFMRP from 1992-2008. MATERIALS AND METHODS: A total of 548 patients with chronic HBV infection (366 with chronic hepatitis B and 182 inactive carriers) were followed for 15 years and 9 months with an annual measurement of HBV-DNA, ALT, AST and GGT (average of 4 annual determinations) and serology (HBsAg, HBeAg, Anti-HBeAg and Anti-HBsAg). RESULTS: Spontaneous HBsAg seroclearance occurred in 40 patients (7.3%) with a mean age of 46.0 ± 14.4 years, corresponding to an annual rate of 0.7%.The factors related to spontaneous HBsAg seroclearance were inactive carrier status (67.5 vs. 32.5%, p = 0.000191) and age of more than 40 years (p = 0.0007). There was no difference in the rate of spontaneous HBsAg seroclearance when comparing males and females (p = 0.383). Patients with spontaneous HBsAg seroclearance did not progress to more severe forms of the disease during follow-up. CONCLUSION: Spontaneous HBsAg seroclearance has a favorable long-term prognosis in patients with chronic HBV infection. HBsAg seroclearance occurred at rates compatible with low prevalence areas and was associated with low serum HBV-DNA levels and an age older than 40 years.
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ADN Viral/sangre , Anticuerpos contra la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Adulto , Factores de Edad , Portador Sano , Progresión de la Enfermedad , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Adulto JovenRESUMEN
Fulminant hepatitis is a severe clinical disease characterized by a marked decline in liver function and encephalopathy. In a previous survey, using metagenomics in a group of 27 patients with this clinical condition, we observed an expressive quantity of reads of the Human pegivirus-1 (HPgV-1). Therefore, the objective of this study was to evaluate the frequency, molecular features, and HPgV-1 circulating genotypes in patients with fulminant hepatitis. After testing the collected plasma samples, we discovered twelve samples (44.4%) that were positive for HPgV-1 RNA (using both real-time and nested PCR). The positive samples presented a mean cycle threshold (Ct) of 28.5 (±7.3). Genotyping assignments revealed that all HPgV-1 positive samples belonged to the HPgV-1 genotype 2 (both subgenotypes 2A and 2B were identified). Although HPgV-1 is considered a commensal virus, little is known regarding its prevalence and genotypes in cases of fulminant hepatitis. More research is needed to understand whether HPgV-1 can be implicated in clinical disorders and infectious diseases.
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BACKGROUND Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) alpha with proven efficacy and known safety profile, is currently widely used in the treatment of inflammatory bowel diseases. Increased risk for serious infections and malignant neoplasms secondary to immunosuppression is a major concern during therapy with this medication. Histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum. Disseminated forms of the disease have immunodepression as a major risk factor. CASE REPORT A 39-years-old man had been followed with refractory fistulizing ileocolonic Crohn's disease using combination therapy (infliximab plus azathioprine) and also receiving short courses of steroids. After 2 years of this immunosuppressive therapy, the patient presented with high fever (39.5ºC) for 5 days, associated with profuse sweating, and moderate pain in the left hypochondrium. The patient was hospitalized. Diagnoses of tuberculosis, malignancy, autoimmune diseases, and bacterial and viral infections were rapidly discarded after investigation. Clinical, laboratory, and image signs of liver involvement prompted a guided percutaneous biopsy, which revealed granulomatous hepatitis, with the presence of fungal structures suggestive of Histoplasma capsulatum. Upon treatment with liposomal amphotericin followed by itraconazole, the patient showed an impressively positive clinical response. CONCLUSIONS TNF blockers, particularly when associated with other immunosuppressors, are a serious risk factor for opportunistic infections. This unusual case of disseminated histoplasmosis in a patient with Crohn's disease using infliximab in combination with azathioprine and steroids emphasizes the need for surveillance of this uncommon but potentially lethal complication before starting TNF blockers therapy.
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Enfermedad de Crohn , Histoplasmosis , Adulto , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Histoplasma , Histoplasmosis/diagnóstico , Humanos , Terapia de Inmunosupresión , Infliximab/efectos adversos , MasculinoRESUMEN
Hepatitis C virus usually produces chronic infection and liver damage. Considering that: i) the human leukocyte antigen-E (HLA-E) molecule may modulate the immune response, and ii) little is known about the role of HLA-E gene variability on chronic hepatitis C, we studied the impact of HLA-E polymorphisms on the magnitude of HLA-E liver expression and severity of hepatitis C. HLA-E variability was evaluated in terms of: i) single nucleotide polymorphism (SNP) alleles and genotypes along the gene (beginning of the promoter region, coding region and 3'UTR), and ii) ensemble of SNPs that defines the coding region alleles, considered individually or as genotypes. The comparisons of the HLA-E variation sites between patients and controls revealed no significant results. The HLA-E + 424 T > C (rs1059510), +756 G > A (rs1264457) and + 3777 G > A (rs1059655) variation sites and the HLA-E*01:01:01:01 and HLA-E*01:03:02:01 alleles, considered at single or double doses, were associated with the magnitude of HLA-E liver expression in Kupfer cell, steatosis, inflammatory activity and liver fibrosis. Although these associations were lost after corrections for multiple comparisons, these variable sites may propitiate biological clues for the understanding of the mechanisms associated with hepatitis C severity.
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Genotipo , Hepacivirus/fisiología , Hepatitis C Crónica/genética , Antígenos de Histocompatibilidad Clase I/genética , Hígado/metabolismo , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Regulación de la Expresión Génica , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto Joven , Antígenos HLA-ERESUMEN
This study was performed with the purpose of testing the hypothesis that the high prevalence of hepatitis C among former athletes is associated with their past use of injectable stimulants. The study involved the participation of 208 former professional and amateur soccer and basketball players from the region of Ribeirão Preto, Brazil, who answered a questionnaire regarding their exposure to risk factors, including the use of injectable stimulants in the time they were engaged in sporting activities. ELISA tests were used to detect infection by the hepatitis C virus, and confirmed with PCR and genotyping for the positive cases. It was observed that the former use of injectable stimulants was a practice disseminated among the participants (24.5%), reaching 50.8% in the professionals. The overall prevalence for hepatitis C was 7.2%, with values of 11% among professionals and 5.5% among amateurs. In both categories, the presence of infection was markedly higher among those who admitted past use of injectable stimulants when compared to those who denied such practice (36% and 0.8% among amateurs; 21.9% and 0% among professionals, respectively). Multivariate analysis showed that the use of those substances was the only variable associated with the risk of hepatitis C. This confirms previous observations, performed with reduced sample sizes and without comparison groups, which indicated that the use of injectable vitamins was a risk factor of hepatitis C among former athletes.
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Baloncesto/estadística & datos numéricos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Hepatitis C/transmisión , Fútbol/estadística & datos numéricos , Adulto , Anciano , Brasil/epidemiología , Ensayo de Inmunoadsorción Enzimática , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Inyecciones Intravenosas/efectos adversos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de RiesgoRESUMEN
INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.
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Antivirales/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de Proteasas/administración & dosificación , Adulto , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Prolina/administración & dosificación , Prolina/efectos adversos , Prolina/análogos & derivados , Inhibidores de Proteasas/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Estudios Retrospectivos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) can escape from innate and adaptive immunity, making the immune response ineffective. Human leukocyte antigen E (HLA-E) might regulate the antiviral function of immune response and contribute to the persistence of HCV and the severity of liver disease. This study aimed to evaluate the expression of HLA-E in the liver and its association with the severity of liver disease in HCV patients. We performed a retrospective analysis of liver biopsies from 125 HCV patients and from 20 control subjects without liver disease. Liver biopsies were reviewed and classified according to severity of fibrosis and inflammatory activity. The pathologist assessed the magnitude of HLA-E expression in a semiquantitative way, attributing scores from 0 to 3. Immunohistochemistry showed positive for HLA-E in hepatocyte and Kupffer cells. The rate of HLA-E positivity in hepatocytes and Kupffer cells was significantly higher in HCV patients compared to controls. The liver samples classified as severe fibrosis and necroinflammatory activity presented greater expression of HLA-E on Kupffer cells and hepatocytes, with a significant linear association. It indicates that HLA-E expression may have an immunomodulatory effect and a possible role in the severity of liver disease in chronic hepatitis C.
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Expresión Génica , Hepatitis C Crónica/genética , Antígenos de Histocompatibilidad Clase I/genética , Adulto , Anciano , Biopsia , Femenino , Hepacivirus/inmunología , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Hepatocitos/metabolismo , Hepatocitos/patología , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Inmunohistoquímica , Macrófagos del Hígado/metabolismo , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Hígado/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Antígenos HLA-ERESUMEN
Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.
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Emigrantes e Inmigrantes , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Adulto , Anciano , Brasil , ADN Viral/genética , Emigración e Inmigración , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Adulto JovenAsunto(s)
Albendazol/uso terapéutico , Anticestodos/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Equinococosis/tratamiento farmacológico , Quiste Mediastínico/tratamiento farmacológico , Pericardio/efectos de los fármacos , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/parasitología , Equinococosis/diagnóstico por imagen , Equinococosis/parasitología , Humanos , Masculino , Quiste Mediastínico/diagnóstico por imagen , Quiste Mediastínico/parasitología , Persona de Mediana Edad , Pericardio/diagnóstico por imagen , Pericardio/parasitología , Resultado del TratamientoRESUMEN
Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.
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Humanos , Masculino , Femenino , Adulto , Anciano , Antivirales/administración & dosificación , Inhibidores de Proteasas/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Antivirales/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Inhibidores de Proteasas/efectos adversos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Prolina/administración & dosificación , Prolina/análogos & derivados , Prolina/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Interferón alfa-2 , Genotipo , Persona de Mediana EdadRESUMEN
BACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Proteínas del Núcleo Viral/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Genotipo , MutaciónRESUMEN
Abstract Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Emigrantes e Inmigrantes , Filogenia , Brasil , ADN Viral/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Emigración e Inmigración , GenotipoRESUMEN
INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60% of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4% of the patients, among whom the risk of vertical/intrafamily transmission was 43.2% (p = 0.02). The consumption of alcohol in amounts exceeding 20 g a day was observed in 21.3% of the subjects and was more frequent among men (33%) (p < 0.001). Among patients with cirrhosis, 54.1% were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4%) than in the HBeAg-negative group (10.2%) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.
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Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/epidemiología , Adolescente , Adulto , Anciano , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Brasil/epidemiología , Niño , ADN Viral/análisis , Femenino , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/transmisión , Hospitales Universitarios , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. AIM: To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. METHODS: Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. RESULTS: Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. CONCLUSION THE: H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits.
Asunto(s)
Farmacorresistencia Viral/genética , Hepatitis C Crónica , Antígenos de Histocompatibilidad Clase I/genética , Interferón-alfa/uso terapéutico , Proteínas de la Membrana/genética , Ribavirina/uso terapéutico , Adulto , Antivirales/uso terapéutico , Femenino , Variación Genética , Genotipo , Proteína de la Hemocromatosis , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/genética , Humanos , Interferón alfa-2 , Hierro/metabolismo , Hígado/metabolismo , Masculino , Prevalencia , Proteínas Recombinantes , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73%) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1% of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0%) received one treatment course, 29 (16.7%) received two courses, and 11 (6.3%) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2%), genotype 3 (40.8%) and genotype 2 (10.3%). Genotype was undetermined in 8.7% of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferones/administración & dosificación , Cirrosis Hepática/virología , ARN Viral/sangre , Ribavirina/administración & dosificación , Adulto , Antivirales/uso terapéutico , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/virología , Humanos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Ribavirina/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60 percent of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4 percent of the patients, among whom the risk of vertical/intrafamily transmission was 43.2 percent (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3 percent of the subjects and was more frequent among men (33 percent) (p < 0.001). Among patients with cirrhosis, 54.1 percent were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4 percent) than in the HBeAg-negative group (10.2 percent) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.
INTRODUÇÃO: No Brasil, a hepatite B é comum. No entanto, há diferenças regionais no que diz respeito ao grau de endemicidade, as formas de transmissão mais encontradas e a presença dos diferentes estágios evolutivos da doença crônica. O objetivo deste trabalho foi o de conhecer características clínicas, demográficas e epidemiológicas de pacientes cronicamente infectados pelo vírus da hepatite B (HBV), residentes na região de Ribeirão Preto, no sudeste do Brasil. MÉTODOS: Foi realizada a análise retrospectiva de 529 prontuários de indivíduos com monoinfecção pelo HBV. RESULTADOS: Mais de 60 por cento eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4 por cento dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2 por cento (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3 por cento dos indivíduos, sendo mais frequente entre os homens (33 por cento) (p < 0,001). Entre os pacientes com cirrose, 54,1 por cento faziam uso abusivo de bebidas alcoólicas (p = 0,04), sendo todos estes do gênero masculino. A presença de cirrose foi maior no grupo HBeAg positivo (24,4 por cento) que no grupo HBeAg negativo (10,2 por cento) (p < 0,001). CONCLUSÕES: Observaram-se elevadas proporções de indivíduos com infecção pelo HBV com padrão sorológico HBeAg negativo, entre os quais houve maior risco para a transmissão vertical/intrafamiliar. O uso abusivo de álcool esteve associado a indivíduos do sexo masculino e, neste grupo, à cirrose hepática. Observou-se tendência ao aumento no número de casos HBeAg negativo ao longo do tempo.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/epidemiología , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Brasil/epidemiología , ADN Viral/análisis , Hospitales Universitarios , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/transmisión , Cirrosis Hepática/epidemiología , Cirrosis Hepática/virología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferones/administración & dosificación , Cirrosis Hepática/virología , ARN Viral/sangre , Ribavirina/administración & dosificación , Antivirales/uso terapéutico , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/virología , Interferones/uso terapéutico , Reacción en Cadena de la Polimerasa , Ribavirina/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
This study was performed with the purpose of testing the hypothesis that the high prevalence of hepatitis C among former athletes is associated with their past use of injectable stimulants. The study involved the participation of 208 former professional and amateur soccer and basketball players from the region of Ribeirão Preto, Brazil, who answered a questionnaire regarding their exposure to risk factors, including the use of injectable stimulants in the time they were engaged in sporting activities. ELISA tests were used to detect infection by the hepatitis C virus, and confirmed with PCR and genotyping for the positive cases. It was observed that the former use of injectable stimulants was a practice disseminated among the participants (24.5 percent), reaching 50.8 percent in the professionals. The overall prevalence for hepatitis C was 7.2 percent, with values of 11 percent among professionals and 5.5 percent among amateurs. In both categories, the presence of infection was markedly higher among those who admitted past use of injectable stimulants when compared to those who denied such practice (36 percent and 0.8 percent among amateurs; 21.9 percent and 0 percent among professionals, respectively). Multivariate analysis showed that the use of those substances was the only variable associated with the risk of hepatitis C. This confirms previous observations, performed with reduced sample sizes and without comparison groups, which indicated that the use of injectable vitamins was a risk factor of hepatitis C among former athletes.