Acute Hepatitis Children Cases 2022

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Last reviewed
June 21, 2022

Acute Hepatitis Children Cases In 2022

The World Health Organization (WHO), the U.K., Europe, Canada, and the USA have reported acute liver inflammation infections of unknown etiology among children. As of June 16, 2022, the WHO/PAHO confirmed at least 869 probable cases of acute hepatitis of unknown etiology were reported in healthy people under 16 years of age in 33 countries. Of these, the vast majority (290) are in the U.S.

The WHO says 'most researchers involved in these acute liver investigations have not formulated a hypostasis and continue questioning causality vs. coincidence.' Furthermore, investigations have not found an association between hepatitis viruses (A to E) with serum transaminases greater than 500 IU/l in these children.

However, most (54%) of these pediatric cases have found adenovirus hAd41-F, and some children (10%) were infected with the SARS-CoV-2 coronavirus. Of these pediatric cases with data regarding COVID-19 vaccination status, about 85% were unvaccinated.

Since April 5, 2022, the U.K. Heath Security Agency (UKHSA) confirmed 251 cases as of June 13, 2022. Of the confirmed cases, 180 are residents in England. Among U.K. pediatric cases (ave. 3 yrs age), twelve required liver transplantation. And there is no evidence of any link to COVID-19 vaccination in the children. On May 19, 2022, the UKHSA published Technical Briefing #3: Investigation into acute hepatitis of unknown etiology in children in England.

As of June 16, 2022, the European CDC 449 cases of acute hepatitis of unknown etiology among children aged 16 years and under have been reported from the World Health Organization European region. The majority (76.6%) of reported cases are five years old or younger. Around a third (31.2%) of cases were admitted to an intensive care unit, and 19 (8.4%) children received a liver transplant. A total of 313 cases were tested for adenovirus, of which 52.4% tested positive. A total of 292 cases were PCR tested for SARS-CoV-2, and 10.6% tested positive.

Since the initial report in October 2021, the U.S. CDC has confirmed that 290 pediatric cases of an unknown cause are under investigation in (39) states, Puerto Rico, and Washington DC as of June 15, 2022. Previously, seven liver transplants and six related fatalities were reported by CDC staff. The percentage of specimens positive for adenovirus types 40/41 among children did not appear to increase above pre-COVID-19 pandemic historical levels, although the total number of specimens submitted for testing has increased over time, stated the CDC MMWR issued on June 17, 2022.

Acute Hepatitis Cases - Country

As of June 21, 2022, the following countries have reported pediatric patients with acute hepatitis: AustriaArgentinaBelgium, Brazil, Columbia, CyrusDenmarkEngland, GreeceIreland, Italy, Japan, Latvia, the NetherlandsNorway, PolandPortugalScotland, SerbiaSingapore, Spain, Sweden, USA, and the United Kingdom.

Acute Hepatitis Children News

June 21, 2022 - The Pan American Health Organization announced new guidance for laboratories in the region to contribute to investigations into the causes of hepatitis of unknown origin in children. "While this is a severe disease in children and is a cause of concern, its occurrence remains rare," commented Ruben Mayorga at the PAHO. He stressed, however, that it is important to “continue to monitor the situation and to investigate probable cases."

June 20, 2022 - Prof Rela and his India-based team were recognized as South Asia’s largest Paediatric liver transplant program, having performed over 500+ pediatric liver transplantations. “Liver transplantation in children was unheard of and has seen many families suffer. And now, to see how this is made available to the neediest too, I must thank the Government of Tamil Nadu for their relentless support."

June 17, 2022 - Since the last ECDC surveillance bulletin, 48 new cases have been reported from eight countries (Austria (one), Greece (three), Ireland (one), Italy (two), the Netherlands (one), Spain (one), Sweden (one), and the United Kingdom (38).

June 17, 2022 - The UKHSA published - Research and analysis: Investigation into acute hepatitis of unknown etiology in children in England: case update.

June 16, 2022 - The U.S. CDC's National Center for Immunization and Respiratory Diseases published a 'Technical Report: Acute Hepatitis of Unknown Cause.'

June 14, 2022 - The U.S. CDC published an early version of an MMWR - Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children — U.S., 2017–2022.

June 14, 2022 - The U.S. CDC reported 'Analyses of four data sources did not indicate recent increases in hepatitis-associated emergency department visits or hospitalizations, liver transplants, or adenovirus types 40/41 percent positivity among U.S. children compared with pre–COVID-19 pandemic levels.' The findings in this CDC report are subject to at least seven limitations.

June 11, 2022 - Portugal's Directorate-General for Health (DGS) recently issued advice for children with symptoms suggestive of acute hepatitis should attend a hospital urgently.

June 10, 2022 - Study: Long COVID-19 Liver Manifestation in Children. We report five pediatric patients who recovered from COVID-19 and later presented with liver injury. We report two distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup that excluded other known etiologies.

June 7, 2022 - The World Hepatitis Summit 2022 urges action to eliminate viral hepatitis as unexplained hepatitis cases in children increases globally.

June 2, 2022 - The journal Nature published: A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. Our approach to integrating cALT, histology, and imaging reveals new insights into a genetic liability to NAFLD.

May 31, 2022 - Revive Therapeutics Ltd. announced that in light of the growing cases of acute hepatitis in children, the Company would advance its drug pipeline for inflammatory liver disorders, including Bucillamine in the prevention of ischemia-reperfusion injury during liver transplantation and Cannabidiol for autoimmune hepatitis.

May 27, 2022 - Japan's Ministry of health, labor, and welfare announced the 31st case of acute hepatitis in children of unknown etiology.

May 20, 2022 - Public Health Scotland confirmed that 26 cases of sudden onset hepatitis (liver inflammation) in children aged ten and under had been identified in Scotland since January 2022.

May 20, 2022 - The UKHSA published Technical Briefing document #3 on investigating acute hepatitis cases of unknown etiology in children in England.

May 17, 2022 - The BMJ published an Editorial: Acute hepatitis of unknown origin in children: 'Many leads but few clear answers.'

May 16, 2022 - NanoViricides, Inc. has initiated a program to screen its library of broad-spectrum antiviral nanoviricides against human Adenovirus 41 Type F (hAd41-F), believed to be strongly associated with the occurrence of severe hepatitis syndrome in some children, causing liver transplants as well as fatalities in large percentages of cases.

May 16, 2022 - Isabella Eckerle, co-Head of the Centre for Emerging Viral Diseases at the Geneva University Hospitals, said the possibility of acute hepatitis in children following COVID-19 infection could not be ruled out.

May 13, 2022 - The Lancet published: Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens. 'We suggest that children with acute hepatitis be investigated for SARS-CoV-2 persistence in stool, T-cell receptor skewing, and IFN-γ upregulation because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitised host. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis.'

May 12, 2022 - The Lancet published: Explaining unexplained hepatitis in children.

May 11, 2022 - The U.S. CDC issued Health Alert Network Health Update CDCHAN-00465 with information about an epidemiologic investigation of pediatric cases of hepatitis of unknown etiology in the U.S. Where possible, clinical specimens should be tested locally to ensure timely results for patient care. Nucleic acid amplification testing, such as polymerase chain reaction, is preferred for adenovirus detection (currently unavailable for FFPE liver biopsy or native liver explant). Testing whole blood by PCR is more sensitive and preferred over testing plasma by PCR.

May 9, 2022 - Indonesia identified 15 cases of acute hepatitis of unknown origin after reporting three pediatric fatalities.

May 6, 2022 - Staff from the U.S. CDC conducted a telebriefing where Dr. Jay Butler, the deputy director of infectious diseases, commented 'these pediatric cases have been reported since October 2021, with initial cases confirmed in Alabama. Of the 109 diagnosed children, 90% were hospitalized, 14% required liver transplants, five children have died, with some children are still hospitalized.

April 29, 2022 - The CDC reported: The Alabama cluster review: cases began Oct. 1, 2021, no geographical or epidemiological links between the children who were <= age 5; adenovirus was detected in all children, with type 41 detected in five specimens; three patients developed acute liver failure, two of whom were treated with cidofovir (off-label use) and steroids, and underwent liver transplantation; at admission, eight patients had scleral icterus, seven had hepatomegaly, six had jaundice, and one had encephalopathy.

April 29, 2022 - Garcetin Madrid reported that in Spain, between January 2022 and April 29, 2022, twenty-two acute hepatitis-like cases have been detected with no epidemiological link. A total of 8 have been in the Community of Madrid. In one case, it has been possible to determine through genomic sequencing that the Adenovirus is type 2.

April 26, 2022 - The Romanian Ministry of Health announced a 5-year-old child from the Bucharest-Ilfov area was admitted to a specialized hospital on April 4, 2022, for severe acute hepatitis.

April 20, 2022 - The Journal of Virology published: SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. In this case report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within these liver infiltrating T cells, we observed an enrichment of T cells reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to liver inflammation. Autoimmune-hepatitis-like disease after vaccination against SARS-CoV-2 is now recognized as a rare adverse event not identified in early trials. The widespread use of the vaccine with the administration of hundreds of million doses worldwide also raises questions of causality vs. coincidence.

April 21, 2022 - The U.S. CDC published Health Advisory #CDCHAN-00462 - Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology. A possible association between pediatric hepatitis and adenovirus 41 infection is currently under investigation.

April 20, 2022 - A peer-reviewed Research Article by the Journal of Hepatology: SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. Conclusions - COVID-19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination-induced antigen-specific tissue-resident immunity requiring systemic immunosuppression.

April 18, 2022 - The Alabama Department of Public Health recently announced it is investigating an increase in hepatitis in nine young children in Alabama, with a potential association with Adenovirus 41.

December 27, 2022 - The journal Immunology published: New-onset autoimmune phenomena post-COVID-19 vaccination which summarized the emerging evidence about autoimmune manifestations occurring in response to certain COVID-19 vaccines. 

March 12, 2019 - Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of PracticeProspective randomized clinical trials do not support the use of antiviral therapy. However, most transplant centers consider intravenous cidofovir the standard practice for treating severe, progressive, or disseminated adenovirus disease. In addition, intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia.

October 6, 2017 - U.S. CDC MMWR: Human Adenovirus (41) Surveillance — the United States, 2003–2016.

August 4, 2017 - Epidemic Keratoconjunctivitis Outbreak Associated with Human Adenovirus Type 8 — U.S. Virgin Islands, June–November 2016.

June 2017 - The American Journal of Surgical Pathology: Adenovirus Hepatitis - Clinicopathologic Analysis of 12 Consecutive Cases From a Single Institution. 

January 2007 - Treatment of Adenovirus Disease in Stem Cell Transplant Recipients with Cidofovir. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.

August 1996 - U.S. NIH - Adenovirus 41 replication: cell-related differences in viral gene transcription.

August 1994 - This paper used various approaches to characterize the two proteins and determine whether both fibers were expressed in infected cells and viral particles. DNA sequencing of the subgroup F human adenovirus serotype 41 (TAK, Ad41) fiber gene revealed the presence of two adjacent open reading frames encoding information for proteins with molecular weights of 60.6 kDa and 41.4 kDa (Pieniazek et al.; Nucleic Acids Res. 18: p. 1901, 1990).

Adenovirus Vaccines

There is an adenovector vaccine available for most U.S. military personnel. In addition, the U.S. Department of Defense recommends it for military recruits entering basic training. It may also be recommended for other military personnel at high risk for adenovirus infection. Initially approved by the U.S. FDA in 2011, the Johnson & Johnson (Barr Labs, Inc.) adenovirus vaccine contains live adenovirus Type 4 and Type 7. The vaccine (BL 125296) comes as two tablets, taken orally, and should be swallowed whole, not chewed or crushed. The safety and effectiveness of Adenovirus Type 4 and Type 7 Vaccine in immunocompromised individuals have not been evaluated. In Canada, the Adenovirus Vaccine (W6369-19A009/A) was approved in 2018.

Autoimmune Hepatitis

Autoimmune hepatitis (AIH) can occur in individuals where environmental factors trigger an immune-mediated reaction against hepatocytes. Vaccines are a very rare cause of AIH. There are two clinically relevant types of AIH, including type 1 and type 2. Type 1 AIH, also referred to as the classic type, is typically diagnosed in adulthood, whereas type 2 is diagnosed during childhood. Both types are treated similarly; however, type 2 AIH can be more severe and difficult to control. 

Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in your liver. The more severe form of NAFLD is called nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. NAFLD is one of the most common forms of chronic liver disease in children and adolescents, which may be related to environmental and genetic reasons.

Hepatitis B Vaccination

The U.S. Advisory Committee on Immunization Practices recommends universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series and vaccination of children and adolescents aged <19 years who have not been vaccinated previously.

CHA Vaccine Institute is developing CVI-HBV-002, a therapeutic vaccine to cure hepatitis B. The institute is conducting a phase 2b trial in Korea and plans to release the outcome in 2023. The institute is also testing CVI-HBV-002 as a preventive vaccine for people who did not respond to an existing hepatitis B vaccine in a phase 1 study.

Hepatitis Vaccines

The U.S. CDC published the updated pediatric vaccination schedule, including hepatitis, in February 2022. In addition, breaking hepatitis vaccine news is posted at this link.

EU/EEA Acute Hepatitis Case Definitions

Probable: A person presenting with acute hepatitis (non-hepatitis viruses A, B, C, D, and E) with aspartate transaminase or alanine transaminase over 500 IU/L, who is 16 years old or younger, since 1 October 2021. Epi-linked: A person presenting with acute hepatitis (non-hepatitis viruses A, B, C, D, and E) of any age who is close contact with a probable case since 1 October 2021.

Liver Tests

On May 9, 2022, additional guidance from AAP: Red Book Online Outbreaks: Hepatitis Cases Possibly Associated with Adenoviral Infection. The following summary recommends adenovirus testing in children with acute hepatitis of unknown etiology. On May 6, 2022, the U.S. CDC stated, 'a possible association between pediatric hepatitis and adenovirus infection is currently under investigation after subsequent laboratory testing identified adenovirus type 41 infection in several cases.' Please consider the collection and submission of the following specimen types (if available) for adenovirus detection.

Elevated liver enzymes are a common scenario encountered by physicians in clinical practice. The term "liver function tests" (LFTs) is used commonly to check the overall health of a person's liver. LFTs have been found to be imprecise and potentially misleading since many of the tests are not direct measures of their function. Furthermore, the commonly used liver biochemical tests may be abnormal even in patients with a healthy liver. As an example, a population-based survey in the U.S. conducted between 1999 and 2002 estimated that abnormal alanine aminotransferase was present in 8.9% of respondents.

Note: This page's content was fact-checked, medically reviewed for clarity, and was curated for mobile readership.