Hunting causes of acute hepatitis in children

After the first cases of acute hepatitis in childrenOriginally found in the United Kingdom (UK), reports of new cases are rapidly increasing around the world.

According to what has been reported The Lancet, the UK Health Organization (UKHSA) is conducting several investigations to investigate the causes. At present, laboratory tests have ruled out viral hepatitis type A, B, C, D and E, as well as other known causes of acute hepatitis. In-depth epidemiological and laboratory investigations are still ongoing, and recent reports have highlighted that the most commonly identified pathogen wasadenovirus (approximately 75% of cases). In cases where molecular typingit turned out widespread adenovirus typeF41.

Adenoviruses are very common and usually non-dangerous viruses. In the past, they have only in some cases been the cause of severe viral hepatitis, but mainly in immunocompromised children; However, in all recently reported cases, the children were otherwise healthy and not immunocompromised, suggesting a change in virus or host (resulting in a modified response to the virus).

Şahin and colleagues pointed out the urgency of rapidly identifying the etiology of severe acute hepatitis of unknown origin, all states They were encouraged to conduct comprehensive epidemiological, microbiological, toxicological and environmental studies, although no exposure or common risk factor has been identified at present. Furthermore, no association with the COVID-19 vaccine (most of the young patients did not receive a COVID-19 vaccine) has been identified with international travel, and so far no exposure to toxins or drugs has been demonstrated.

Hepatologists Müche and Zeuzem on Journal of Hepatologyin fact, they pointed out that adenoviruses are double-stranded DNA viruses without sheath, they are common pathogens that usually cause self-limiting infections in the healthy population. More than 5-10% of all febrile illnesses in infants and young children are caused by human adenoviruses, as a result of which almost all adults have serological signs of a previous infection with one or more human adenoviruses. This type of virus is typically transmitted through inhalation of aerosol droplets, fecal-oral diffusion, or conjunctival inoculation. Since the virus can survive for long periods on environmental surfaces, acquisition from exogenous sources (e.g., pillows, sheets) has been described. In addition, reactivation of human adenovirus may occur in immunocompromised patients. The most common method of diagnosis is by performing the polymerase chain reaction on samples of respiratory material, feces, blood or urine. Clinical manifestations (serotype-specific) are determined in part by differences in cell tropism and occur after an incubation period of 2 to 14 days. Symptoms that are frequently reported include, but are not limited to, respiratory infections such as pharyngitis and pneumonia (especially serotypes 1-5, 7, 14 and 21), kerato-conjunctivitis (especially serotypes 8, 19 and 37), gastrointestinal symptoms such as f .ex. diarrhea, abdominal pain, vomiting (especially from serotypes 40 and 41, but possible as concomitant symptoms for all serotypes, especially in young children) or infections of the genitals (especially for serotypes 11, 34 and 35). L ‘hepatitis was observed in immunocompromised patientsincluding neonates, especially with serotypes 1,3,5 and 7. To date, infections causing acute hepatitis have been reported in pediatric patients undergoing liver transplantation, while only a few cases of acute hepatitis have been reported with severe or even liver failure in immunocompetent children due to human adenovirus infection.

That treatment options for this type of adenovirus is limited and mostly supportive, there is no evidence to support antiviral therapy, but there are reports of immunocompromised patients who have been treated with cidofovir (antiviral). Intravenous immunoglobulin administration is currently used in people with severe hypogammaglobulinemia.

In the leader with the title Acute hepatitis of unknown origin in childrenPublished on ThatBritish Medical Journal, Cevik and colleagues briefly summarized the data reported by the European Center for Disease Prevention and Control and the World Health Organization: 450 probable cases of acute hepatitis of unknown etiology until 11 May 2022 globally, including 163 in the UK until 3 May. Affected children ranged in age from 1 month to 16 years, but more than three quarters of them in the UK were under 5 years of age and those in the US had an average age of 2. 11 deaths were reported and 31 children underwent liver transplantation (11 in the UK , 5 in Europe and 15 in the United States). As pointed out by the authors, tests for hepatitis AE viruses were evaluated globally and found negative. A detailed laboratory study conducted by the UK Health Safety Agency found that out of 126 children tested for adenovirus, 91 (72%) tested positive. On the blood samples from 18 children, it was also possible to test the subtype, which in all 18 cases was identified as type adenovirus 41F. Histological examination of explanted liver (n = 6) or liver biopsy samples (n = 8) from children in the UK showed varying degrees of severity, including hepatocellular necrosis. However, in general, the disease did not show a specific pattern and no cause was identified. Although adenovirus alone is rarely associated with fulminant liver failure in healthy children, other factors may increase its vulnerability, such as abnormal host sensitivity (due to lack of previous exposure, higher prevalence of adenovirus in the community, concomitant infection with SARS-CoV-2 or other pathogens, exposure to toxins, drugs or environmental factors). Other main hypotheses include a post-Covid-19 syndrome, a new adenovirus variant, non-infectious causes, a new pathogen, or a new variant of SARS-CoV-2. It should be noted, however, that the children in a recent series of Alabama cases did not have a history of SARS-CoV-2 infection while all tested positive for adenovirus.

In conclusion, given that currently this apparently rare but serious pathological condition has a’unknown etiopathogenesisgeneral infection control strategies, the use of standardized case definitions, the presence of diagnostic algorithms, information sharing and international cooperation aimed at an effective global response remain of fundamental importance.

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