RESUMO
The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).
Assuntos
Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Mutação/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/análogos & derivados , Adolescente , Adulto , Idoso , Estudos Transversais , DNA Viral/análise , Quimioterapia Combinada/métodos , Feminino , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Organofosfonatos/administração & dosagem , Tenofovir , Carga Viral , Adulto JovemRESUMO
Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.
Assuntos
DNA Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Cirrose Hepática/virologia , Adolescente , Adulto , Idoso , Alanina Transaminase/análise , Brasil , Criança , Estudos Transversais , Feminino , Fibrose , Genótipo , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Índice de Gravidade de Doença , Adulto JovemRESUMO
The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Mutação/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/análogos & derivados , Estudos Transversais , DNA Viral/análise , Quimioterapia Combinada/métodos , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Mutação/genética , Organofosfonatos/administração & dosagem , Carga ViralRESUMO
Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.