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Infección por adenovirus humano como potencial causante de hepatitis en pediatría

 

Human adenovirus infection= as a potential cause of hepatitis in pediatrics

 


= 1

Geovanna Patricia Cualchi Alvarracin

 

https://orcid.org/0009-0004-5615-5498

 

 

Carrera de medicin= a, Universidad Católica de Cuenca, Cuenca, Ecuador.

geovanna.c= ualchi@est.ucacue.edu.ec

= 2

Manuel Rafael Aldás Erazo

 

https://orcid.org/0000-0003-1229-490X

 

 

 Carrera de medicina, Universidad Catól= ica de Cuenca, Cuenca, Ecuador.

rafaelalda= serazo@hotmail.com

 

 

 

 

 

 

 =

 

Artículo de Investigación Científica y Tecnológica

Enviado: 10/02/2023

Revisado: 25/03/2023

Aceptado: 12/04/2023

Publicado:15/05/2023

DOI: https://doi.org/10.33262/ap.v5i2.1.352

<= span style=3D'font-size:12.0pt;line-height:115%;font-family:"Times New Roman",= serif; mso-fareast-font-family:Calibri;color:blue'> 

 

 

Cítese:

 

 

Cualchi Alvarracin, G. P., & Aldás Erazo, M. R. (2023). Infección por adenovi= rus humano como potencial causante de hepatitis en pediatría. AlfaPublicacion= es, 5(2.1), 22–41. = https://doi.org/10.33262/ap.v5i2.1.352

 

 

 

ALFA PUBLICACIONES, es una revista multidisciplinar, trimestral, que se public= ará en soporte electrónico tiene como misión contribuir a la &nbs= p; formación de profesionales competentes con visión humanística y crítica q= ue sean capaces de exponer sus resultados investigativos y científicos en la misma medida que se promueva mediante su intervención cambios positivos e= n la sociedad. https://alfapublicaciones.= com  

La revista es editada por la Editorial Ciencia Digital (Editorial de prestigio registrada en la Cámara Ecuatoria= na de Libro con No de Afiliación 663) www.celibro.org.ec<= /a>

 

 

 

Esta revista está protegida bajo una licencia Creative Commons Attribution Non Commercial No Derivatives 4.0 International. Copia de la licencia: http://creativecommons.org= /licenses/by-nc-nd/4.0/

 

Pala= bras claves:=

Adenovirus Humanos, Brote de Enfermedad, Causalidad, Hepatitis, Pediatría

 

Resumen

Introducción: Un Reciente Brote De Enfermedad A Nivel Mundial Acerca De Casos De Hepatitis Aguda De Origen Desconocido En Pacientes Pediátricos Ha Activado Las Aler= tas Sanitarias Ya Que En La Mayoría De Países Se Ha Reportado Un Incremento Inusual De Esta Enfermedad, Que Han Captado La Atención, Debido Al Rápido Progreso Hacia Una Insuficiencia Hepática Aguda. Objetivo: Describ= ir La Relación Que Existe Entre La Infección Por Adenovirus Humano Y La Hepatit= is Aguda Severa De Origen Desconocido En Pediatría. Metodología: Se R= ealizó Una Revisión Bibliográfica Acerca De La Infección Por Adenovirus Humano C= omo Potencial Causante De Hepatitis En Pediatría Para El Cual Se Utilizaron Varios Estudios Publicados En Bases De Datos Como PubMed, SciELO, Scop= us, Web Of Science. Resultados: La Causalidad De Dicha Enfermedad Hast= a El Momento Se Mantiene Incierta, Pero Se Han Propuesto Varias Hipótesis, Ent= re Ellas La Más Aceptada Alega Que Podría Ser Una Consecuencia De La Infecci= ón Por Adenovirus Humano Y Aunque Está Bien Establecido Que Las Infecciones = Por Este Patógeno Son Frecuentes En Los Niños No Está Justificado Totalmente = La Gravedad De Los Síntomas Clínicos Como Causa Subyacente. Conclusión: <= /b>Será Un Desafío, Determinar El Papel Del Adenovirus En La Hepatitis Aguda Pediátrica, Ya Que El Comprender Su Fisiopatología Permitirá Desarrollar Estrategias De Vigilancia Y Tratamiento Eficaces Que Eviten La Exacerbaci= ón De La Enfermedad Y El Trasplante Hepático Mientras Tanto Se Sugiere Consider= ar El Adenovirus En El Diagnóstico Diferencial De La Hepatitis No A-E Aguda.= Área de estudio general: Medicina. Área de estudio específica: Hepa= titis Viral En Pediatría, Infecciones Por Adenovirus.

 

Keywords: Adenoviruses Human, Disease Outbreaks, Causality, Hepatitis, Pediat= rics

 

Ab= stract

Introduction: A recent outbreak of disease worldwide about cases of acute hepatitis of unknown origin in pediatric patients has activated health alerts since in most countries an unusual increase in this disease has been reported, which has captured the attention, due to rapid progress towards acute liver failure= . Objective: Describe the relationship between human adenovirus infection and hepatitis of unknown origin in pediatrics. Methodology: A bibliographic review was conducted on human adenovirus infection as a potential cause of hepatitis in pediatrics, for which several studies published in databases such as PubMed, SciELO, Scopus, and Web of Science were used. Results: The causality of this disease remains uncertai= n up to now, but several hypotheses have been proposed, among them the most accepted allegation that it could be a consequence of infection by human adenovirus and although it is well established that infections by this pathogen are common in children, the severity of clinical symptoms as the underlying cause is not fully justified. Conclusion: It will be a challenge to determine the role of adenovirus in acute pediatric hepatiti= s, since understanding its pathophysiology will allow developing effective surveillance and treatment strategies that prevent exacerbation of the disease and liver transplantation. Meanwhile, it is suggested to consider adenovirus as the differential diagnosis of acute non-A-E hepatitis.

 

 

 

Introducción<= /b>

Las enfermedades infecciosas han constituido desde hace mucho tiempo un problem= a de salud en el mundo que amenaza la vida del ser humano. Un reciente brote de enfermedad a nivel mundial sobre hepatitis aguda grave de origen desconocid= o en niños ha activado las alertas sanitarias ya que en algunos países se han reportado casos emergentes de hepatitis aguda grave siendo su etiología has= ta el momento desconocida. La hepatitis aguda es provocada por varios agentes = patógenos que repercuten en el hígado, pues dañan a los hepatocitos y alteran la func= ión hepática generando un cuadro clínico grave (Gong et al., 2022).<= /span>

La etiología subyacente exacta de esta enfermedad todavía= no se ha revelado, pero existe una hipótesis princip= al que refiere que un agente infeccioso es el culpable del brote. Según lo publicado = por el Centro Europeo para la Prevención y el Control de las Enfermedades (ECDC= ) se detectó un agente viral conocido como adenovirus (HAdV) en el 62,2% de las muestras analizadas tipificándose molecularmente como tipo F41 (Cates et al= ., 2022). No obstante, hasta el momento, es desconocida la causa certera de es= ta patología, por lo cual se han planteado varias hipótesis que siguen en investigación activa, descartándose hasta la fecha a los virus que comúnmen= te producen hepatitis es decir a los virus de la hepatitis A, B, C, D y E ya q= ue no se detectaron en ninguna de las muestras estudiadas, lo que impulsó a emplear el término para esta enfermedad de "hepatitis no A-E aguda&quo= t; (Namakin et al., 2022).

Los casos se presentaron inicialmente en el Reino Unido seguido a la vez de Irl= anda del Norte, notificándose posteriormente nuevos casos en países de Europa, América del Norte, América del Sur, Asia Sudoriental y países de la zona del Mediterráneo Oriental. Si bien se han repo= rtado casos entre niños de 1 a 16 años se ha determinado que la edad predominante= se encuentra entre los 3 y 5 años, afectando a niños y a niñas la mayoría de r= aza caucásica (Gao et al., 2022). 

Si bien las hepatitis agudas graves de etiología desconocida no son una novedad. Lo que más ha llamado la atención de este reciente brote ha sido el surgimiento de casos congregados= en un mismo entorno temporal y el modo en la que progresa a una insuficiencia hepática aguda en los pacientes pediátricos sin patología previa. Además de ello es necesario discutir sobre el potencial agente etiológico de esta enfermedad para que los sistemas de salud puedan refinar las acciones de control y prevención de la enfermedad (Zhang et al., 2022; Zacur, 2022).

Por lo cual la finalidad del presente es describir la relación que existe entre= la infección por adenovirus humano y la hepatitis de origen desconocido en pediatría.

Metodología

Se realizó una revisión bibliográfica que abarca un tipo = de estudio de enfoque cualitativo, de tipo narrativo y de diseño no experiment= al, en donde por medio del formato PICO se estructuró la pregunta de investigac= ión y se procedió a desarrollar la estrategia de búsqueda de la información, así como la producción de los datos, incorporando tanto los criterios de inclus= ión como de exclusión.

Estrategia de búsqueda

La ecuación de búsqueda de los datos fue elaborada a trav= és de palabras claves escogidas del tesauro Medical Subject Headings (Mesh)= y DeCS, en combinación simultánea con operadores lógicos “AND” y “OR” implementados en las bases de datos seleccionados para optimizar así la búsqueda de aquellos estudios de gran relevancia.

Los términos usados para la búsqueda fueron: “Severe acute hepatitis” AND “unknown aetiology” AND “c= hildren”, “hepatitis outbreak 2022” AND “pediatric” OR “children”, “Adenovirus” AND” hepatitis acute” AND “pediatric”, “Acute severe non-A-E-hepatitis” AND “Causality” AND “pediatric population”.

Base de datos

Durante el proceso de búsqueda se incluyeron estudios publicados en bases de datos = de información científica como PubMed, SciELO, Scopus, Web of Science, a las cuales se les aplicó la pertinente ecuación de búsqueda documental en el idioma respectivo de cada una de las bases de datos.

Posteriormente se utilizaron en cada base de datos los filtros correspondientes con el fin= de reducir la cantidad de estudios a revisar e identificar estudios significat= ivos realizándose dicha búsqueda desde el mes de noviembre del 2022 hasta abril = del 2023.

Extracción de los datos

Para la extracción de la información se tomaron en cuenta varios aspectos que nos permitan capturar de una mejor manera los hallazgos relevantes de cada uno de los estudios científicos incluidos. Entre dichos aspectos se refieren al año y país del estudio, la población o muestra estudiada, los tipos de análisis realizados, brote de hepatitis, los hallaz= gos y resultados, las limitaciones y conclusiones de cada artículo. 

Criterios de inclusión

Los criterios de selección de búsqueda se limitaron a artículos científicos o g= uías clínicas en cualquier idioma de contenido posterior al año 2018. Se incluye= ron investigaciones realizadas en pacientes en edad pediátrica (desde el nacimi= ento - 18 años) con hepatitis no A-E aguda grave desde el año 2021 hasta el año 2023.

Criterios de exclusión

Se excluyeron los estudios de tesis de pregrado, grado y posgrado, capítulos de libros, artículos incompletos, reseñas, páginas web comerciales, artículos repetidos, estudios de pacientes pediátricos con enfermedades no relacionad= as a la hepatitis no A-E aguda grave, así como todos los artículos científicos c= on más de 5 años de antigüedad.

Desarrollo

Hepatitis no a-e aguda severa

La hepatitis es un término general que se emplea para describir a la inflamaci= ón que sucede en el hígado que por lo general está causada por virus hepatotrópicos (VHA, VHB, VHC, VHD, VHE) que afectan primordialmente a los hepatocitos (Razavi, 2020; Jefferies et al., 2018). Sin embargo, se acuño e= l término “hepatitis no A-E aguda” después de que los análisis de laboratorio para= estos virus hepatotrópicos arrojaran resu= ltados negativos. La etiología subyacente precisa aún no ha sido identificada= ; no obstante, la idea principal que se mantiene hasta el momento es que un agen= te infeccioso sea el culpable de esta reciente incidencia (Tahir et al., 2022)

Desde enero del año 2022 se ha iniciado una investigación= en curso con el fin de evaluar la hepatitis en niños ya que el número de casos= de esta enfermedad últimamente ha resultado ser superior al habitual, de los cuales la mayoría tuvieron lugar en el Reino Unido (UK). Aunque aún no se define un caso confirmado, la “Organización Mundial de la Salud (OMS)” establece como definición de un caso probable de hepatitis no A-E aguda, a cualquier sujeto de 16 años o menos que presente hepatitis aguda desde el 1= de octubre de 2021 y valores de laboratorio de AST o ALT superior a 500 UI/L (Sallam et al., 2022). Tal definición puede ser restructurada= en función del progreso de la enfermedad, así como de la información disponible sobre nuevos hallazgos (Zhu & Chen, 2022). La OMS analizó el riesgo par= a la salud pública a nivel mundial catalogándolo como moderado (Khader et al., 2= 022).

Actualmente se están llevando a cabo investigaciones para determinar el agente o agentes causantes, no obstante, se ha convertido el foco principal de estas la infección por adenovirus puesto que ha presentado el mayor porcentaje de positividad de anticuerpos (Kelgeri et al., 2022).<= o:p>

Etiología

Es conocido que entre los agentes etiológicos de las hepatitis incluyen causas= no infecciosas entre las cuales destacan las condiciones inmunológicas, enfermedades metabólicas y exposición tanto a fármacos como a toxinas y den= tro de las causas infecciosas se encuentran principalmente los virus hepatotrop= os siendo los agentes de hepatitis virales más comunes los virus de la hepatit= is A, B, C, D y E. Existen otras infecciones virales que afectan de forma ocasional al hígado siendo los más conocidos los citomegalovirus (CMV), vir= us Coxsackie, Virus del Herpes Simple, el adenovirus, Rotavirus, Parvovirus B1= 9 y el Echovirus (Gong et al., 2022; Zhu & Chen, 2022; Dunn et al., 2022; Y= ao et al., 2022).

Sin embargo, la causa subyacente de la hepatitis aguda grave de origen desconoc= ido en los pacientes pediátricos no está definida aún, es esquiva incluso con la aplicación de modernos métodos de diagnóstico que se basan en la detección = de antígenos y genes. Por lo que se especula que podría ser causada o por una infección con patógenos o por factores no infecciosos, tales como factores químicos, físicos y del huésped (Hu et al., 2022).

Entre los gérmenes infecciosos, los virus son aquellos que están más estrechamente asociados con la hepatitis que las bacterias y los hongos, además se presume como causa subyacente a los virus cuando los pacientes manifiestan un pródr= omo respiratorio o gastrointestinal típico con fiebre (Hu et al., 2022; Karpen, 2022).

Hipótesis etiológicas del brote de hepatitis no a-e aguda infantil<= /i>

En base a los hallazg= os disponibles, los investigadores han postulado hipótesis temporales acerca d= e las posibles etiologías, las cuales pueden modificarse a medida que avanza la investigación (Sallam et al., 2022; Pérez-Gracia et al., 2022).

Estas posibles etiolo= gías propuestas son:

·&nb= sp;          Un cofactor que afecte a los niños pequeños y hace que las infecciones leves normales por adenovirus sean más graves o induzca una inmunopatología (Sallam et al., 2022; Pérez-Gracia et al., 2022).

·&nb= sp;          Una nueva vari= ante de adenovirus, ya sea con o sin la participación de un cofactor (Sallam et al., 2022; Pérez-Gracia et al., 2022).

·&nb= sp;          Alguna exposic= ión a una toxina, droga o exposición medioambiental (Pérez-Gracia et al., 2022; Ma et al., 2022).

·&nb= sp;          Un agente pató= geno nuevo que actúe solo o como factor de coinfección, o que se detecta algún v= irus adenoasociado serotipo 2 acompañado de una coinfección por algún virus auxi= liar (Gong et al., 2022; Sallam et al., 2022; Pérez-Gracia et al., 2022).

·&nb= sp;          Infección prev= ia con SARS-CoV-2, incluida la variante Ómicron (Pérez-Gracia et al., 2022; Ma et al., 2022).=

·      =      Una variante n= ueva del virus SARS-CoV-2 (Sallam et al., 2022; Ma et al., 2022).

Sin embargo, según investigaciones realizadas en Reino Unido, la principal hipótesis causante de esta patología descrita podría ser la infección por el adenovirus F41 asociada conjuntamente a cofactores que potencien su efecto,= no obstante, se indica la necesidad de seguir investigando (Pérez-Gracia et al= ., 2022; Yao et al., 2022).

Cuadro clínico=

El síndrome clínico de los niños afectados con hepatitis no A-E aguda grave se caracter= iza por presentar los niveles de las transaminasas significativamente elevadas,= ALT o AST>500 U/L, acompañados de ictericia y letargo además pueden tener hepatomegalia. La mayoría de síntomas gastrointestinales reportados fueron dolor abdominal, vómitos, heces pálidas y diarrea antes del inicio de la hepatitis aguda grave, en otros casos también se reportaron fiebre, coluria, equimosis sin una causa atribuible y en menor medida rash cutáneo y síntomas respiratorios (Khader et al., 2022; Li et al., 2022; Elsheikh et al., 2022;= Uwishema et al., 2022). 

Diagnóstico

Ante la presencia de un paciente con sospecha clínica de hepatitis de etología desconocida, se debe profundizar en las pruebas diagnósticas para lograr identificar su origen ya sea este de carácter infeccioso, tóxico o metabóli= co. Es necesario realizar las pruebas de daño hepático (AST, ALT, fosfatasa alcalina, GGT), así como las pruebas de función hepática (bilirrubina total= y conjugada, albúmina, INR). Parte de las pruebas deben incluir la valoración= de hepatitis virales agudas (serología para hepatitis A, B, C, D, y E), además= de otros virus como EBV, CMV y VIH (Zhaori, 2022).

También de acuerdo con el contexto epidemiológico de hoy en día, se deben tener en consideración los virus respiratorios (adenovirus, influenza A y B, SARS-Co= V-2) y patógenos específicos del sistema gastrointestinal (identificación de adenovirus y rotavirus en heces, coprocultivo). El gold standard para determinar los cambios patológicos y patógenos en el tejido hepático es la biopsia además brinda información del proceso disruptivo en el hígado (Uwis= hema et al., 2022; Zhaori, 2022; Gao et al., 2022).

Tratamiento

El tratamiento de la hepatitis depende de la etiología subyacente. Como todaví= a no se encuentra esclarecida la etiología de la hepatitis no A-E aguda severa, = no se dispone de un tratamiento específico para esta patología. No obstante, es fundamental administrar un tratamiento integral, monitorear de forma contin= ua y evaluar de forma dinámica los indicadores de laboratorio, es importante est= ar siempre alerta a la insuficiencia hepática y a la prevención de sus complicaciones. Aunque la mayoría de los niños se recuperan por completo co= n la atención adecuada, el curso clínico puede ser dinámico y rara vez puede progresar a insuficiencia hepática aguda (Gong et al., 2022; Feld et al., 2= 022; Secretaría de Salud D. G., 2022).  =

Hasta la fecha no se ha verificado la eficacia de ningún agente antivírico, sin embargo, en pacientes inmunocomprometidos puesto que las tasas de mortalidad son altas, se ha visto la necesidad de usar medicamentos como la ribavirina= y cidofovir, además se ha visto que el uso de este último ha sido exitoso en niños inmunocomprometidos (Vargas-Mosso et al., 2022). 

Para los niños en los que la enfermedad ha progresado a una insuficiencia hepáti= ca, se requiere de inmediato un trasplante de hígado para salvar sus vidas. Si = los niños afectados presentan un síndrome inflamatorio sistémico, se puede iniciar la terapia con glucocorticoides, pero si los niños afectados son inmunodeficientes, se debe evitar la terapia con glucocorticoides, en estos casos la inmunoglobulina intravenosa puede ser beneficiosa. Es necesario recalcar que, para desarrollar regímenes terapéuticos eficaces, se deben aclarar en primer lugar los agentes etiológicos y los mecanismos patológico= s de la hepatitis aguda de etiología desconocida (Mücke & Zeuzem, 2022).

Pronóstico

El pronóstico para los pacientes con infección por adenovirus por lo general es bueno en personas inmunocompetentes, pero al contrario para los huéspedes inmunocomprometidos las tasas de mortalidad pueden alcanzar el 70%. En aque= llos niños sanos pero que lleguen a tal punto de requerir el trasplante de hígad= o el pronóstico para ellos dependerá solamente de la respuesta que manifieste al estado postquirúrgico, aunque se han notificado en pocos casos muertes en e= ste escenario (Vargas-Mosso et al., 2022; Mücke & Zeuzem, 2022).

Resultados

En esta revisión de la literatura se compiló un total de 10 artículos para eva= luar la proporción de personas en edad pediátrica que portan la enfermedad hepát= ica aguda grave de etiología desconocida, en la tabla 1 se describen los autore= s, año en el que se publicó el artículo, tipo de artículo o de estudio, lugar = en donde se presentaron los casos de esta enfermedad, número de la población estudiada, edad promedio de los pacientes afectados, porcentaje según cada autor de los test positivos para adenovirus humano y SARS-CoV-2, así como también se indica el porcentaje de pacientes que han requerido de un traspl= ante hepático como resultado de la progresión de la enfermedad, además se detall= a el número de pacientes fallecidos antes o después del trasplante de hígado.

Tab= la 1

Tamaño de la muestra de = los pacientes pediátricos con hepatitis no A-E aguda infectados por adenovirus o con SARS-CoV-2 y el nivel de sobrevivencia

Autor=

Tipo<= /o:p>

Título

País<= /o:p>

Población<= o:p>

(n)

Edad prome= dio

Test de HA= dV* positivo

Test de SARS-CoV-2* positivo

Sobreviven= cia

Trasplante hepático

Fallecidos=

Cates et al.

(2022)

Estudio retrospectivo

Interim analysis of acute hepatitis of unknown etiology in children aged <10 years — United States, October 2021–June 2022.

Estados Un= idos

296

2 años 2 m= eses

48/97=

(49,5%)

10/98=

(10,2 %)

6,1 %=

3,7%<= /o:p>

Rabaan et al. (2022)

Estudio retrospectivo

Hepatitis of unknown aetiology in children – epidemiological overvi= ew of cases reported in Europe, 1 January to 16 June 2022<= /p>

20 países = de la región Europea de la OMS*

427

5 años o m= enos

53,5%=

10,3 %

18/208 (8,= 7%)

Ninguno

Kelgeri et al. (2022)

Articulo Original

Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause=

Inglaterra= -UK*

44

4 años

27/30 (90%= )

11/39=

(28%)=

14%

Ninguno

Van Beek et al. (2022)

Estudio retrospectivo

Case numbers of acute hepatitis of unknown aetiology among children= in 24 countries up to 18 April 2022 compared to the previous 5 years

17 países = europeos y 7 no europeos

160

-

91/126

(72%)=

-

-

-

Tab= la 1

Tamaño de la muestra de = los pacientes pediátricos con hepatitis no A-E aguda infectados por adenovirus o con SARS-CoV-2 y el nivel de sobrevivencia (continuación)

Autor

Tipo<= /o:p>

Título

País<= /o:p>

Población<= o:p>

(n)

Edad prome= dio

Test de HA= dV* positivo

Test de SARS-CoV-2* positivo

Sobreviven= cia

Trasplante hepático

Fallecidos=

Marsh et al. (2022)

Estudio retrospectivo

Investigation into cases of hepatitis of unknown aetiology among yo= ung children, Scotland, 1 January 2022 to 12 April 2022

Escocia

13

3,9 años

5/11 (45,4= %)

5/13<= /o:p>

(38,46%)

2/9

(22,2%)

Ninguno

Gutierrez et al. (2022)

Artículo Original

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection

Alabama-Es= tados Unidos

9

2 años 11 meses

8/9

(89%)=

0/9

0%

2/9

(22,2%)

Ninguno

Li et al. (2022)

Artículo de revisión

Pediatric Acute Severe Hepatitis of Unknown Origin:

What is New?

Inglaterra= - UK

81

3 años

40/53 (75,= 5%)

10/61=

(16,4%)

31/81 (38,= 3%)

Ninguno

Lexmond et al. (2022a)

Estudio retrospectivo

Severe acute hepatitis and acute liver failure of unknown origin in children

22 países europeos e Israel

64

7,7 años

4/64 (6,3%= )

3/64<= /o:p>

(5 %)=

4

(6,6%)

4

(6,6%)

Gong et al.

(2022)

Artículo de revisión

Acute hepatitis of unknown origin in children: A combination of fac= tors

37 países entre América Europa y Asia

1296<= /o:p>

< 5 año= s

372/797 (46,7%)

80/660 (12= ,1%)

55

(4,2%)

29

(2,23%)

UK Health Security Agency (2022)

 

Marsh et al. (2022)

Estudio de casos y controles

Investigation into acute hepatitis of unknown etiology in children = in England

UK*

274

3 años

170/258 (65,9%)

36/237 (15= ,2%)

15/274

(5,4%)

Ninguno

*HAdV: Adenov= irus humanos

*SARS-CoV-2: Síndrome respiratorio agudo severo coronavirus 2.

*OMS: Organi= zación Mundial de la Salud

*UK: Reino Unido

Discusión

Recientemente se ha notificado a nivel mundial un brote de hepati= tis aguda severa de etiología desconocida denominada actualmente como hepatitis = no A-E aguda severa que afecta a la población pediátrica, reportándose según G= ong et al. (2022), hasta el 14 de septiembre del 2022 en todo el mundo alrededo= r de 1296 casos, no obstante Gao et al. (2022), señala que el número total real de casos puede estar subestimado, y esto en gran p= arte se debe a los limitados sistemas mejorados de vigilancia epidemiológica de = cada región incluso Vidal et al. (2022), señala que tanto la hepatitis aguda gra= ve como la insuficiencia hepática aguda de causa desconocida no están bajo vigilancia en la mayoría de los países del mundo por lo que determinar la incidencia real de esta patología es un gran desafío.

Desde enero del año 2022, los reportes= de casos de esta enfermedad han ido en aumento, aunque se han notificado casos= en distintos continentes, la mayoría de ellos fueron reportados según Kelgeri = et al. (2022), en el Reino Unido mientras que Gong et al. (2022), en su estudio menciona que la incidencia más alta se registró en los Estados Unidos pero seguido de este se encuentra Reino Unido por lo que este país constituye se= gún varios estudios el sitio de origen y con más altos casos de la hepatitis no= A-E en niños ya que fue el primer país en alertar a la OMS la ocurrencia de los casos de esta afección. Teniendo en cuenta= que gran parte de los casos estudiados hasta el momento tienen lugar en el Reino Unido, se van notificando más casos alrededor del mundo, entre los cuales se incluye América Latina que según Jorquera et al. (2022), los países que han reportado ca= sos son México, Argentina, Brasil y Panamá, la mayoría de casos en esta comunid= ad se encuentran en México y Brasil.  =

Con respecto a la eda= d se han reportado la gran mayoría de casos de esta enfermedad en niños previamente sanos que según Hu et al. (2022= ), principalmente afecta a niños y niñas caucásicos menores de 5 años de edad siendo la edad promedio los 3 años, además indica que no se encuentra una diferencia significativa en el género lo cual concuerda con Zhang et al. (2= 022), en que no se encuentra una diferencia de género y con respecto a la edad au= nque si bien se reportaron casos de niños que tenían entre 1 mes y 16 años la ed= ad predominante fueron los 5 años de edad lo cual tiene cierta relación a lo mencionado en el estudio de Vargas et al. (2022), en que el grupo etario en donde generalmente se aíslan los adenovirus es en bebés y niños, más del 80% de las infecciones por adenovir= us se ha evidenciado en niños con una edad menor a cuatro años proponiendo que esto probablemente se deba a que en esta edad su respuesta inmune humoral es inmadura y además porque pasan una parte importante de sus días en ambientes cerrados.

Siguen existiendo muchas dudas y especulaciones con respecto a la patogenia de la hepatitis no A-E sin embar= go ha tomado mucha relevancia el papel del adenovirus como factor causante de = esta patología y según Sallam et al. (2022), el argumento a favor del papel del adenovirus= se basa en la observación de que la mayoría de los casos informados fueron pos= itivos para dicho patógeno no así en el estudio de Vargas et al. (2022), se mencio= na que la presencia de los adenovirus puede ser más un hallazgo coincidente an= tes que un factor causante al no haber sido identificado inclusiones vir= ales en muestras de tejido hepático a más de ello las cargas virales han sido muy bajas. Esto hace pensar en que tan especifico puede ser el adenovirus como causa potencial de la enfermedad y que otros factores podrían estar involucrados.

Aunque el virus del SARS-CoV-2 no está vinculado de manera directa con los casos evaluados, es incuestionable pensar que, ya sea de forma indirecta o directa, por las med= idas establecidas durante la pandemia de COVID-19 y sus posteriores efectos, ten= ga rol alguno en la etiología de esta enfermedad. La relación entre el COVID-19 sigue sin aclararse y continúa atrayendo la atención de los investigadores puesto que no hay que olvidar la asociación entre la infección por el virus SARS-CoV-2 y la lesión hepática (Matthews et al., 2022). =

También otros estudios mencionan que p= uede existir una asociación entre la infección por adenovirus y la pandemia Covid-19, con respecto a ello se explica que curiosamente, debido a las med= idas preventivas y al control estricto de los brotes durante la pandemia, ocurrió una reducción de la exposición de los niños más pequeños a gérmenes comunes= , lo que condujo al desarrollo de sistemas inmunológicos diferentes a los de sus pares antes de la pandemia. Por ende, cuando estos niños posteriormente al infectarse con patógenos comunes como el adenovirus, su respuesta inmunitar= ia fue diferente que a la de sus compañeros, incrementando así su vulnerabilid= ad siendo esta la consecuencia de una menor exposición al adenovirus durante la pandemia lo cual resultó en una respues= ta inmune más vigorosa que provocó un daño hepático grave (Gong et al., 2022; Sallam = et al., 2022; Jorquera et al., 2022; Zhong et al., 2022; Rabaan et al., 2022; = Patel et al., 2023).

Si bien el HAdV-F41 está detrás de las gastroenteritis pediátricas estudios previos no han demostrado que este patógeno pueda inducir hepatitis, por lo que tras el brote de hepatitis agu= da de etiología desconocida infantil y la pandemia de COVID-19 se ha generado = una hipótesis que explica según Hu et al. (2022), que el adenovirus F41 si se recombina con otros virus es capaz de convertirse en una variante hepatotró= fica que pueda inducir hepatitis, no obstante, es necesario que se realicen investigaciones por ello Uwishema et al. (2022), sugiere que se  investigue si el genoma del virus ha cambiado.

Se han planteado otras teorías como la hipótesis del superantígeno que según Brodin et al. (2022), consiste en que una nueva infección por coronavirus puede inducir la formac= ión de reservorios virales que seguido de una infección por adenovirus puede conducir a una hepatitis. Coincidiendo a lo planteado por Li et al. (2022), en que quizás, en ciertos niños susceptibles que albergan estos reservorios virales en el intestino luego de ser sensibilizados por el adenovirus F41 y la subsiguiente viremia podrían desencadenar una tormenta de citocinas y provocar la hepatitis subsiguiente= e incluso llegar a una insuficiencia hepática aguda, por lo tanto, se recomie= nda fuertemente el monitoreo continuo del superantígeno SARS-CoV-2 en aquellos niños para aclarar si este conjuntamente con la infección por adenovirus u otros virus, causaron la enfermedad (Zhong et al., 2022).

Con respecto a la vacuna de ARNm del SARS-CoV-2 existen sugerencias de que la vacunación puede producir una hepatitis autoinmune de células T dominantes. Sin embargo, hasta el momento varios estudios mencionan que no existen pruebas que justifiquen que esta enfermedad esté relacionada con los efectos secundarios de las vacunas cont= ra el SARS-CoV-2 (Gong et al., 2022; Matthews et al., 2022; Zhong et al., 2022; Van Beek et al., 2022; Marsh et al., 2022). Según la OMS, la hipótesis de q= ue estos casos se desencadenan por los efectos secundarios de las vacunas cont= ra el SARS-CoV-2 no se sustenta, debido a que gran parte de los niños afectado= s no fueron vacunados también entre las otras de las causas descartadas fue la hepatitis autoinmune (Gong et al., 2022).

De acuerdo con lo mencionado por la OMS aquellos agentes habituales que provocan la hepatitis, como los virus de las hepatitis A, B, C, D y E, no fueron detectaron en los casos analizados. Sin embargo, no se puede descartar que otros virus de hepatitis no identificados estén provocando la enfermedad de hepatitis no A-E. En varios estudios se observaron que en ciertos casos se hallaron virus como el Epstein-Barr, citomegalovirus y el rinovirus, los cuales también pueden provocar hepatiti= s, no obstante, la tasa de infectados con estos patógenos no fue significante (Kelgeri et al., 2022; Hu et al., 2022; Chen et al., 2022; Vidal et al., 20= 22; Jorquera et al., 2022; UK Health Security Agency, 2022).<= /p>

Otros estudios mencionan que esta enfermedad en lugar de ser causada por factores individuales como la infecc= ión por adenovirus o su asociación con el SARS-CoV-2, se piensa que lo más prob= able es que se deba a una combinación de varios factores. Cabe mencionar que en = todo proceso infeccioso existen tres elementos vinculados: el hospedero, el agen= te y por último el ambiente. Estos pueden involucrarse de manera singular o bien pueden interrelacionarse entre ellos para desencadenar una enfermedad. Es importante sostener una amplia visión de estas interacciones, especialmente cuando estamos frente a una patología que está en pleno desarrollo y de la = cual todavía no existe una etiología definida (Gong et al., 2022; Jorquera et al= ., 2022).

En el estudio de Kelg= eri et al. (2022), se evidenció = que los niños con hepatitis aguda que cumplían con la definición de caso probab= le acudieron en la mayoría de los casos a atención médica con una presentación clínica predominantemente por ictericia en un 93% de los casos, otras características clínicas comunes incluyeron vómitos, diarrea, dolor abdomin= al y letargo las cuales se presentaron 3 días antes a la aparición de la icteric= ia. Así también varios estudios concuerdan que la presentación clínica más común reportada sigue siendo la ictericia, los vómitos, fatiga, dolor abdominal diarrea y heces pálidas. En la mayoría de los casos no presentaron fiebre y= en ciertos casos aparecieron síntomas de infección del tracto respiratorio superior y en otros casos encefalopatía (Cates et al., 2022; Zhang et al., 2022; Sallam et al., 2022; Kelgeri et al., 2022; Vidal et al., 2022; Patel = et al., 2023; Marsh et al., 2022; UK Health Security Agency, 2022; Gutiérrez et al., 2022). Además Sallam et al.CITATION Sal221 \n  \t  <= /span>\l 12298  (2022), indica que se encontraron niveles muy elevados de las enzimas hepáticas (ALT y AST) junto= con la ictericia además recalca que la característica llamativa fueron los nive= les altos de las aminotransferasas que superaron los 500 UI/L. 

El manejo clínico y el tratamiento es por el momento totalmente sintomático hasta conocer a ciencia cierta el origen de la enfermedad (Secretaría de Salud D. G., 2022). Varios estudios señalaron que una fracción de los= casos afectados por la hepatitis no A-E aguda se sometieron a trasplante de hígado como una opción de tratamiento para la insuficiencia hepática aguda pediátr= ica con el fin de evitar el progreso hacia una insuficiencia multiorgánica (Cat= es et al., 2022; Zhang et al., 2022; Kelgeri et al., 2022; Vidal et al., 2022; Marsh et al., 2022; Lexmond et al., 2022b). De los casos reportados hasta el momento, según la OMS el 5% de niños requirieron trasplante de híg= ado (Gao et al., 2022). De acuerdo con este contexto Alexander Deep (2022), menciona que aquellos pacientes que desarrollan una insuficiencia hepática aguda indeterminada tienen un peor pronóstico y por ende una menor probabilidad de lograr la supervivencia del hígado nativo.=

Según la OMS hasta el momento a nivel mundial se han registrado el 2% de muertes, por lo tanto, a= nte esta consecuencia se requieren de más investigaciones que continúen con la búsqueda de las causas específica= s de esta enfermedad pediátrica (Gao et al., 2022). Como la evidencia actual es limitada se requiere de una investigación rigurosa que aclare especialmente= el rol que desempeña el adenovirus en la etiopatogenia de la enfermedad. Aún n= o está establecido si la infección por adenovirus humano, sola o en combinación con un cofactor adicional, puede provocar el desarrollo de hepatitis en los niños o si lo que estamos observando simplem= ente representan hallazgos coincidentes o no relacionados (Gong et al., 2022; Hu= et al., 2022; Zhong et al., 2022; Deep, 2022).

Conclusiones

·   &nb= sp;    La infección por adenovirus es actualm= ente la hipótesis más aceptada con respecto a la hepatitis no A-E aguda en niños y aunque está bien establecido que las infecciones por este patógeno son frecuentes en los niñ= os no puede justificar por completo la gravedad de los síntomas clínicos como causa subyacente, puesto que no está del todo claro si esta cepa adenoviral= sea nueva, de incidencia creciente o pueda haber estado previamente por debajo = del nivel de detección, ya que tales datos no se han recopilado prospectivament= e.

·      =   Será un desafío, aunque necesario, el determinar el papel del adenovirus en la hepatitis aguda pediátrica, ya que= el comprender la fisiopatología de este reciente brote permitirá desarrollar estrategias de vigilancia y tratamiento eficace= s que eviten la exacerbación de la enfermedad y el trasplante hepático mientras t= anto se sugiere considerar el adenovirus en el diagnóstico diferencial de la hepatitis no A-E agud= a.

·      =    Se alienta a los médi= cos a notificar a las autoridades de salud pública sobre posibles casos de hepatitis no A-E aguda para una mayor investigación. Además, como su incide= ncia continúa aumentando es importante que los médicos estén capacitados para ab= ordar este problema de una manera eficaz en el entorno clínico.=

Conflicto de intereses

Los autores declaran que no existe conflicto de intereses en relación con el artículo presentado.

 =

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ISSN: 2773-7330

Vol. 5 No. 2.1.  pp. 22 – 41.  mayo - junio 2023=

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www= .alfapublicaciones.com

 

 

                                      Ciencia & Medicina               Página 22 | 41          

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