A hepatite B na região de São José do Rio Preto: estudo de genótipos e subgenótipos circulantes / Hepatitis B in the region of São José do Rio Preto: study of circulating genotypes and subgenotypes

RESUMO

As Hepatites virais representam um grave problema de sa úde pública no mundo, pelo número de indivíduos atingidos , pela s formas graves e mortalidade. Aproximadamente um terç o da população mundial atual já se expôs ao vírus da hepatite B, e estima se que 248 milhões de pessoas estejam infectadas cronicamente. No Brasil, a região Sudeste apresenta o maior número de casos no tificados para essa enfermidade, com maiores taxas de n otificação no Estado de São Paulo. São José do Rio Preto, localizada no noroeste Paulista, está entre as três regiões com maiores taxas migratórias do estado com intensa circulação e flutuação da população, e possui muitos pacientes em tratamento da Hepati te B, de diversas localidades Considerando que nesta Região nenhum estudo sobre os aspectos epidemiológicos e moleculares dessa infecção viral foi realizado este estudo teve o objetivo de investigar os genótipos e subgenótipos do vírus da hepatite B circ ul antes , a l ém de avaliar a presença de mutações de resistência aos análogos de núcleos(t)ídeos, e as características epidemiológicas dos pacientes. Foram incluídas no estudo 127 amostras de soro ou plasma de portadores do HBV , de diferentes Unidades de Saú de da Região Administrativa de São José do Rio Preto, coletadas no período de setembro de 2015 a janeiro de 2018. O DNA do HBV foi extra ído das amostras, amplificado por nested PCR (regiões S/ Pol), e o s fragmentos obtidos na amplificação foram sequenciados em sequenciador automático. A identificação dos genótipos/subgenótipos e a pesquisa de mutações foram realizadas com sucesso em 126 amostras, após análise das sequ ências obtidas. Os genótipos encontrados foram A (51,6%; 65/126), B (0,8%; 1/126), C (0,8%; 1/126), D (37,3%; 47/126), E (0 ,8%; 1/126), e F (8,7%; 11/126); com relação aos subgenótipos, uma grande diversidade foi observada A1 (40,5%), A2 (11,1%), B1 (0,8%), C1 (0,8%), D1 (1,6%), D2 (5,6%), D3 (28,6%), D4 (1,6%), F2a (7,1%) e F4 ( Os genóti pos A e D foram predominantes, sendo os subgenótipos A1 e D3 os mais prevalentes...(AU)

ABSTRACT

Viral Hepatitis represents a serious public health problem in the world, due to the number of individuals affected, serious forms and mortality. Approximately one-third of the world's population has already been exposed to the hepatitis B virus, and it is estimated that 248 million people are chronically infected. In Brazil, the Southeast region has the highest number of cases reported for this disease, with the highest reporting rates in the State of São Paulo. São José do Rio Preto, located in northwest State, is among the three regions with the highest migratory rates of the state with intense circulation and population fluctuation, and has many patients under treatment of Hepatitis B, from several locations. Considering that in this Region no study on the epidemiological and molecular aspects of this viral infection was carried out, this study aimed to investigate circulating genotypes and subgenotypes of the hepatitis B virus, in addition to evaluating the presence of resistance mutations to nucleos(t)ides analogues, and the epidemiological characteristics of the patients. The study included 127 serum or plasma samples from HBV carriers from different Health Units of the Administrative Region of São José do Rio Preto collected from September 2015 to January 2018. HBV DNA was extracted from samples, amplified by nested PCR (S/Pol regions), and the fragments obtained in the amplification were sequenced in an automated sequencer. Identification of genotypes and subgenotypes and mutation screening were performed successfully in 126 samples after analysis of the sequences obtained. The genotypes were A (51.6%, 65/126), B (0.8%, 1/126), C (0.8%, 1/126), D (37.3%, 47/126 ), E (0.8%, 1/126), and F (8.7%, 11/126); with respect to the subgenotypes, a great diversity was observed A1 (40.5%), A2 (11.1%), B1 (0.8%), C1 (0.8%), D1 (1.6%) , D2 (5.6%), D3 (28.6%), D4 (1.6%), F2a (7.1%) and F4 (1.6%). Genotypes A and D were predominant, with subgenotypes A1 and D3 being the most prevalent. Among the patients undergoing treatment, strains of HBV with resistance mutations (rtM204V/I/S) associated or not to compensatory mutations (rtL180M, rtV173L) were identified in 13.9% (5/36) of the analyzed samples; mutations of partial resistance to Entecavir (rtM204V / I / S) or potentially associated with Adefovir resistance (rtV214A, rtL217R, rtQ215S, rtN238T and rtP237H) in 13.9% (5/36) and 19.4% (7/36) of the patients, respectively. Already in the group of non-treated patients, 1.1% (1/90) of the samples presented resistance mutation (rtM204V) and partial resistance to Entecavir, in addition to a mutation (rtA181T) conferring partial resistance in vitro, but not implies in vivo resistance to Tenofovir; one sample (1.1%) presented compensatory mutation (rtV/F/L/M207I), which usually appears after other primary variants of resistance to Lamivudine; and 26.7% (24/90) of the samples showed mutations of potential resistance to Adefovir (rtV214A, rtL217R, rtP237H, rtN238T, rtQ215S, rtI233V). All the samples analyzed were chronic carriers of HBV, with cirrhosis present in 4.7% (6/127), and HIV and/or HCV coinfections in 12.6% (16/127). The great diversity of genotypes/subgenotypes observed reflects the intense migration that occurs in the studied region, due to its importance as a reference center in health. Among strains of HBV, with mutations of resistance to nucleos(t)ide analogs, the profile of mutations conferring potential resistance to adefovir seems to be the most widespread in this population, but total resistance to lamivudine and emtricitabine and partial resistance to entecavir were observed in half of the patients under treatment with resistance profile. All these data demonstrate the importance of Hepatitis B in the region of São José do Rio Preto and demonstrate the need for an active surveillance for the effective management of chronic HBV patients in order to reduce the mortality and morbidity associated with this viral infection. (AU)