ABSTRACT
RESUMEN El virus de la hepatitis E tiene una amplia distribución a nivel mundial. Se presentaron dos casos clínicos en la provincia de Matanzas, con diagnóstico confirmado de hepatitis E mediante la determinación del ARN viral en heces fecales congeladas; a pesar de proceder de áreas de salud distantes, coincidieron en el mismo período de tiempo. El primero de ellos, una gestante asintomática diagnosticada fortuitamente a partir de elevación de enzimas hepáticas de citolisis. Evolucionó satisfactoriamente sin repercusión en su bienestar materno, trasmisión fetal, ni complicaciones perinatales. El segundo, una paciente portadora de síndrome metabólico, con evolución tórpida de su cuadro infeccioso viral, que la llevó a la insuficiencia hepática y a la muerte. Con estos casos se reflejó el amplio espectro de esta enfermedad en cuanto a formas clínicas de presentación y evolución. Se demostró que pueden ocurrir complicaciones en cualquier grupo poblacional, de ahí la importancia de considerarla en el diagnóstico diferencial de las enfermedades infecciosas hepáticas (AU).
ABSTRACT Hepatitis E virus is widely distributed around the world. Two clinical cases occurring in the province of Matanzas were presented, both with diagnosis of E hepatitis confirmed through viral RNA determination in frozen stool; although patients came from faraway health areas, they coincided in the same time period. The first patient, a pregnant asymptomatic woman, was incidentally diagnosed due to an increase of cytolysis liver enzymes. Her evolution was satisfactory without repercussion on maternal wellbeing, fetal transmission, nor perinatal complications. The second patient, a metabolic syndrome carrier, had torpid evolution of a viral infectious disease leading her to liver failure and death. These cases highlighted the wide range of this disease according to its clinical forms of presentation and evolution. It was showed that complications may occur in any population group, in consequence it is important to consider this disease when making the differential diagnosis of liver infectious diseases (AU).
Subject(s)
Humans , Male , Female , Clinical Evolution/classification , Hepatitis E/therapy , Hepatitis E/rehabilitation , Hepatitis E/epidemiology , Metabolic Syndrome/complications , Pregnant Women , Hepatic Insufficiency/diagnosis , Hepatic Insufficiency/therapyABSTRACT
BACKGROUND & AIMS: HEV is a significant cause of acute hepatitis globally. Some genotypes establish persistent infection when immunity is impaired. Adaptive immune mechanisms that mediate resolution of infection have not been identified. Herein, the requirement for CD8+ T cells to control HEV infection was assessed in rhesus macaques, a model of acute and persistent HEV infection in humans. METHODS: Rhesus macaques were untreated or treated with depleting anti-CD8α monoclonal antibodies before challenge with an HEV genotype (gt)3 isolate derived from a chronically infected human patient. HEV replication, alanine aminotransferase, anti-capsid antibody and HEV-specific CD4+ and CD8+ T cell responses were assessed after infection. RESULTS: HEV control in untreated macaques coincided with the onset of a neutralizing IgG response against the ORF2 capsid and liver infiltration of functional HEV-specific CD4+ and CD8+ T cells. Virus control was delayed by 1 week in CD8+ T cell-depleted macaques. Infection resolved with onset of a neutralizing IgG antibody response and a much more robust expansion of CD4+ T cells with antiviral effector function. CONCLUSIONS: Liver infiltration of functional CD8+ T cells coincident with HEV clearance in untreated rhesus macaques, and a 1-week delay in HEV clearance in CD8+ T cell-depleted rhesus macaques, support a role for this subset in timely control of virus replication. Resolution of infection in the absence of CD8+ T cells nonetheless indicates that neutralizing antibodies and/or CD4+ T cells may act autonomously to inhibit HEV replication. HEV susceptibility to multiple adaptive effector mechanisms may explain why persistence occurs only with generalized immune suppression. The findings also suggest that neutralizing antibodies and/or CD4+ T cells should be considered as a component of immunotherapy for chronic infection. LAY SUMMARY: The hepatitis E virus (HEV) is a major cause of liver disease globally. Some genetic types (genotypes) of HEV persist in the body if immunity is impaired. Our objective was to identify immune responses that promote clearance of HEV. Findings indicate that HEV may be susceptible to multiple arms of the immune response that can act independently to terminate infection. They also provide a pathway to assess immune therapies for chronic HEV infection.
