Could Herpesviridae be the cause of severe acute hepatitis of unknown origin in children?

INTRODUCTION: Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED: Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION: Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.

Deteção de citomegalovirus, herpesvirus humano 6 e herpesvirus humano 7 em amostras de lesões em glândula salivar parafinadas / Detection of cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 in paraffin salivary gland lesion samples

Guimarães Os vírus têm sido considerados como importantes patógenos no desenvolvimento de neoplasias em glândulas salivares, dentre estes, destacam-se os Betaherpesvirus humano como o Citomegalovirus humano (HCMV), Herpesvirus humano 6 (HHV-6) e Herpesvirus humano 7 (HHV-7). Os betaherpesvírus são característicos por apresentarem alta prevalência na população mundial, sem apresentar sazonalidade, capazes de causar infecção latente e reativação viral em seus hospedeiros. Devido a detecção destes vírus em amostras de saliva, tem sido proposto em alguns estudos a ação de betaherpesvírus em algumas patogenias de glândulas salivares, como a formação de patogenias nestes órgãos. Neoplasias em glândulas salivares representam cerca de 3-6% de todas as neoplasias de cabeça e pescoço, com incidência mundial anual de aproximadamente 0,4-13,5% por 100.000 indivíduos. Apesar de haver dados de detecção de betaherpesvírus em neoplasias salivares e em amostras de saliva, ainda existem estudos insuficientes que explorem o papel destes vírus nestas patogenias salivares. O objetivo deste estudo foi investigar a presença dos Betaherpesvirus humano (HCMV, HHV-6 e HHV-7) em neoplasias de glândula salivar parafinadas. Um ensaio de qPCR foi realizado para amplificação das regiões U54, U56 e U37 do HCMV, HHV-6 e HHV-7, respectivamente para quantificar a carga viral em 68 amostras parafinadas de lesões salivares. Dentre as 68 amostras processadas, 51,4% eram de mucocele (35/68), 39,7% de adenoma pleomórfico (27/68) e 8,8% de carcinoma mucoepidermoóide (6/68). A detecção de betaherpesvírus nestas lesões foi alta, apresentando maior detecção para HCMV com 52,9%, 47,05% para HHV-6 e 39,7% para HHV-7, possuindo predominância de detecção de betaherpesvírus na lesão do tipo adenoma pleomórfico. Foi observado que 50,0% das amostras apresentaram tripla-infecção por HCMV/HHV-6/HHV-7, sendo detectado 20,0% de coinfecções por HCMV/HHV-6, 20,0% de HCMV/HHV-7 e 10,0% de HHV-6/HHV-7, com coinfecções ocorrendo na lesão do tipo adenoma pleomórfico em maior taxa. A alta detecção de HCMV, HHV-6 e HHV-7 em glândulas salivares, indica que este órgão pode ser possível de sítio de replicação destes vírus

The viruses have been considered as important pathogens in the development of neoplasms in salivary glands, between these, Human betaherpesvirus such as Human cytomegalovirus (HCMV), Human herpesvirus 6 (HHV-6) and Human herpesvirus 7 (HHV-7) stand out. Betaherpesvirus is characteristic because they have a high prevalence in the world population, without presenting seasonality, capable of causing latent infection and viral reactivation in their hosts. Due to the detection of these viruses in saliva samples, the action of betaherpesvirus in some pathogenesis of salivary glands, such as the formation of pathogenesis in these organs, has been proposed in some studies. Salivary gland neoplasms account for about 3-6% of all head and neck neoplasms, with an annual worldwide incidence of approximately 0,4-13,5% per 100,000 individuals. Although there are data for the detection of betaherpesvirus in salivary neoplasms and saliva samples, thereare still insufficient studies exploring the role of these viruses in these salivary pathogeneses. The aim of this study was to investigate the presence of human Betaherpesvirus (HCMV, HHV-6 and HHV-7) in paraffin salivary gland neoplasms. A qPCR assay was performed to amplify the U54, U56 and U37 regions of HCMV, HHV-6 and HHV-7, respectively to quantify the viral load in 68 paraffin samples of salivary lesions. Among the 68 samples processed,51,4%were mucocele (35/68), 39.7% pleomorphic adenoma (27/68) and 8,8% mucoepidermoid carcinoma (6/68). The detection of betaherpesvirus in these lesions was high, presenting higher detection for HCMV with 52,9%, 47,05% for HHV6 and 39,7% for HHV-7, with predominance of detection of betaherpesvirus in the lesion of the pleomorphic adenoma type. It was observed that 50.0% of the samples presented triple-infection by HCMV/HHV-6/HHV-7, and 20.0% of co-infections by HCMV/HHV-6, 20.0% of HCMV/HHV-7 and 10.0% of HHV-6/HHV-7 were detected, with co-infections occurring with higher predominance of pleomorphic adenoma lesion. The high detection of HCMV, HHV-6 and HHV-7 in salivary glands indicates that this organ may be possible from replication site.