Diagnosis, treatment, and prevention of severe acute hepatitis of unknown etiology in children

Abstract

Background Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital’s previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. Data sources Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. Results As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%–10% of cases require liver transplant). Conclusions The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.

Severe acute hepatitis of unknown etiology in children in 2022: A Narrative Review

“…As the next step, to prevent severe complications such as hepatic encephalopathy and hepatorenal syndrome, symptoms such as hypovolemia, hypoproteinemia, gastrointestinal bleeding, infection, and hypoglycemia must be taken seriously [ 25 ].…”

“…Adenoviruses have been detected in almost half of the known cases of this disease through PCR tests. For these cases, supportive treatment is still at the top of the order, although cidofovir has shown promise [ 25 , 26 ].…”

“…Therefore, it is not advised to use fresh frozen plasma or platelets to treat coagulation problems on a preventative basis [ 29 ]. In case of vitamin K deficiency, it should be prescribed; the dosage of cryoprecipitate can be changed following the TEG value to keep fibrinogen within the normal range [ 25 ].…”

Updated information regarding acute severe hepatitis of unknown origin in children: Viewpoints of and insights from pediatricians

“…In the report by the WHO, children ages 0-5 accounted for 75.9% of cases (4). All of the children presented with manifestations of acute hepatitis, i.e., significantly elevated (over 500 U/L) serum levels of aspartate transaminase (AST) and/or alanine transaminase (ALT) (6). The symptoms were nonspecific and included jaundice, vomiting, pale stools, fever, and gastrointestinal symptoms.…”

“…The etiology of SHIC remains unclear, so all the available diagnostic protocols seem to be oriented toward an "exclusionary" or "exploratory" diagnosis (6). A diagnosis of exclusion means two steps: 1) Confirmation of hepatitis: usually using indices like ALT and/or AST and 2) Exclusion of hepatitis with known causes, such as an infection with hepatitis virus A, B, C, D, or E; medication/vaccine or toxinrelated hepatitis; autoimmune-related hepatitis; and secondary hepatitis related to a disease in some other system.…”