Infecção pelo vírus da hepatite E em pacientes com infecção crônica pelo vírus da hepatite C
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2017-09-25
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Tese de doutorado
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Resumo Introdução: O impacto da infecção pelo vírus da hepatite E (HEV) em pacientes com infecção crônica pelo vírus da hepatite C (HCV) é pouco conhecido. Objetivos: Avaliar a associação entre presença de anticorpos anti-HEV e cirrose hepática em pacientes com infecção crônica pelo HCV; estimar a soroprevalência do HEV nesses pacientes, assim como descrever os fatores de risco associados; e avaliar a associação entre infecção prévia pelo HEV e resistência à insulina. Métodos: Entre outubro de 2015 e dezembro de 2016, foram avaliados 618 pacientes de três centros de referência do estado de São Paulo com infecção crônica pelo HCV. Avaliou-se presença de anticorpos da classe IgG contra o vírus da hepatite E por método imunoenzimático (WANTAI HEV-IgG ELISA). Amostras com resultados reagentes e indeterminados foram testadas para presença de anticorpos anti-HEV IgM. Resultados: A soroprevalência encontrada foi de 10,2% (IC 95% 8,0 – 12,8%). Maior soroprevalência apresentou associação independente com idade superior a 60 anos (OR = 2,13; p = 0,001), história de contato prévio com porcos (OR = 2,06; p = 0,02) e hemofilia (OR = 35,69; p = 0,004). Soropositividade para hepatite E, ajustada para sexo, idade e genótipo do HCV, apresentou forte tendência de associação com presença de cirrose hepática (OR = 1,72; IC 95% 0,96 – 3,07; p = 0,06). Presença de anticorpos contra o HEV apresentou associação independente com resistência insulínica (OR: 4,24; p = 0,05). Discussão e Conclusões: Pacientes com infecção crônica pelo HCV estão sob risco de superinfecção pelo vírus da hepatite E em São Paulo. Contato com porcos é fator de risco para a infecção, indicando possível zoonose de transmissão alimentar ou por contato com os dejetos dos animais. Alta prevalência em hemofílicos sugere possibilidade de transmissão alternativa por via parenteral. A tendência de associação entre infecção prévia pelo vírus da hepatite E e cirrose sugere aceleração da progressão de fibrose hepática em pacientes com hepatite C crônica. Infecção prévia pelo vírus da hepatite E se associa à presença de resistência insulínica, podendo esta ser manifestação extra-hepática sustentada após resolução da infecção pelo vírus.
Abstract: The impact of hepatitis E virus (HEV) infection in patients with chronic hepatitis C is unknown. Aims: To evaluate the association between anti-HEV antibody and cirrhosis in patients with chronic hepatitis C; to estimate the seroprevalence of HEV in this patient population, as well as to describe the associated risk factors; and to evaluate the association between previous HEV infection and insulin resistance. Methods: From October, 2015 to December, 2016, a total of 618 chronically infected with hepatitis C virus patients were included from three reference centers of São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: Of the 618 patients tested, 10.2% turned out positive for anti-HEV IgG (IC 95% 8.0 – 12.8%). Higher seroprevalence was found independently associated with age grater than 60 years (OR = 2.13; p = 0.001), previous contact with pigs (OR = 2.06; p = 0.02) and hemophilia (OR = 35.69; p = 0.004). HEV seropositivity, adjusted for sex, age and HCV genotype, presented a clear trend to be associated with cirrhosis (OR = 1.72; p = 0.06). Presence of HEV antibodies was shown to be independently associated with insulin resistance (OR: 4.24; p = 0.05). Discussion and Conclusions: Patients with chronic hepatitis C are under risk of HEV superinfection in São Paulo. Contact with pigs is a risk factor for the infection, suggesting a possible zoonosis with oral transmission through contaminated meat or by direct contact with waste from these animals. High prevalence in haemophiliac patients suggests the possibility of parenteral transmission. The trend for the association between previous infection by HEV and cirrhosis suggests acceleration of fibrosis progression in patients chronically infected by the hepatitis C virus. Previous infection by HEV is independently associated with insulin resistance, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection.
Abstract: The impact of hepatitis E virus (HEV) infection in patients with chronic hepatitis C is unknown. Aims: To evaluate the association between anti-HEV antibody and cirrhosis in patients with chronic hepatitis C; to estimate the seroprevalence of HEV in this patient population, as well as to describe the associated risk factors; and to evaluate the association between previous HEV infection and insulin resistance. Methods: From October, 2015 to December, 2016, a total of 618 chronically infected with hepatitis C virus patients were included from three reference centers of São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: Of the 618 patients tested, 10.2% turned out positive for anti-HEV IgG (IC 95% 8.0 – 12.8%). Higher seroprevalence was found independently associated with age grater than 60 years (OR = 2.13; p = 0.001), previous contact with pigs (OR = 2.06; p = 0.02) and hemophilia (OR = 35.69; p = 0.004). HEV seropositivity, adjusted for sex, age and HCV genotype, presented a clear trend to be associated with cirrhosis (OR = 1.72; p = 0.06). Presence of HEV antibodies was shown to be independently associated with insulin resistance (OR: 4.24; p = 0.05). Discussion and Conclusions: Patients with chronic hepatitis C are under risk of HEV superinfection in São Paulo. Contact with pigs is a risk factor for the infection, suggesting a possible zoonosis with oral transmission through contaminated meat or by direct contact with waste from these animals. High prevalence in haemophiliac patients suggests the possibility of parenteral transmission. The trend for the association between previous infection by HEV and cirrhosis suggests acceleration of fibrosis progression in patients chronically infected by the hepatitis C virus. Previous infection by HEV is independently associated with insulin resistance, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection.