On April 29, 2022, this report was posted online as an MMWR Early Release.
Julia M. Baker, PhD1,2; Markus Buchfellner, MD3; William Britt, MD3; Veronica Sanchez, PhD3; Jennifer L. Potter, MPH3; L. Amanda Ingram, MPH4; Henry Shiau, MD5,6; Luz Helena Gutierrez Sanchez, MD5,6; Stephanie Saaybi, MD5; David Kelly, MD6,7; Xiaoyan Lu, MS1; Everardo M. Vega, PhD1; Stephanie Ayers-Millsap, MPH8; Wesley G. Willeford, MD8; Negar Rassaei, MD9; Hannah Bullock, PhD9,10; Sarah Reagan-Steiner, MD9; Ali Martin4; Elizabeth A. Moulton, MD, PhD11,12; Daryl M. Lamson13; Kirsten St. George, PhD13,14; Umesh D. Parashar, MD, MBBS1; Aron J. Hall, DVM1; Adam MacNeil, PhD1; Jacqueline E. Tate, PhD1; Hannah L. Kirking, MD1 (View author affiliations)
View suggested citation
Views equals page views plus PDF downloads
- PDF pdf icon[90K]
During October–November 2021, clinicians at a children’s hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.*
Clinical records from the hospital were reviewed to identify patients seen on or after October 1, 2021, with hepatitis and an adenovirus infection, detected via real-time polymerase chain reaction (PCR) testing on whole blood specimens, and no other known cause for hepatitis. An additional four children were identified, for a total of nine patients with hepatitis of unknown etiology and concomitant adenovirus infection during October 2021–February 2022. On February 1, 2022, a statewide health advisory† was disseminated to aid in the identification of cases at other facilities in Alabama; no additional patients were identified.
All nine children were patients at Children’s of Alabama. These patients were from geographically distinct parts of the state; no epidemiologic links among patients were identified. The median age at admission was 2 years, 11 months (IQR = 1 year, 8 months to 5 years, 9 months) and seven patients were female (Table). All patients were immunocompetent with no clinically significant medical comorbidities.
Before admission, among the nine patients, vomiting, diarrhea, and upper respiratory symptoms were reported by seven, six, and three patients, respectively. At admission, eight patients had scleral icterus, seven had hepatomegaly, six had jaundice, and one had encephalopathy (Table). Elevated transaminases were detected among all patients§ (alanine aminotransferase [ALT] range = 603–4,696 U/L; aspartate aminotransferase [AST] range = 447–4,000 U/L); total bilirubin ranged from normal to elevated (range = 0.23–13.5 mg/dL, elevated in eight patients). All patients received negative test results for hepatitis viruses A, B, and C, and several other causes of pediatric hepatitis and infections were ruled out including autoimmune hepatitis, Wilson disease, bacteremia, urinary tract infections, and SARS-CoV-2 infection. None of the children had documented history of previous SARS-CoV-2 infection.
Adenovirus was detected in whole blood specimens from all patients by real-time PCR testing (initial viral load range = 991–70,680 copies/mL). Hexon gene hypervariable region sequencing was performed on specimens from five patients, and adenovirus type 41 was detected in all five specimens. Low viral loads precluded sequencing among three patients, and residual specimens were not available for sequencing for one patient. Seven patients were coinfected with other viral pathogens (Table). Six received positive test results for Epstein-Barr virus (EBV) by PCR testing but negative test results for EBV immunoglobulin M (IgM) antibodies (one patient did not have IgM testing), suggesting that these were likely not acute infections but rather low-level reactivation of previous infections. Other detected viruses included enterovirus/rhinovirus, metapneumovirus, respiratory syncytial virus, and human coronavirus OC43.
Liver biopsies from six patients demonstrated various degrees of hepatitis with no viral inclusions observed, no immunohistochemical evidence of adenovirus, or no viral particles identified by electron microscopy. Three patients developed acute liver failure, two of whom were treated with cidofovir (off-label use) and steroids, and were transferred to a different medical facility where they underwent liver transplantation. Plasma specimens from these two patients were negative for adenovirus by real-time PCR testing upon arrival at the receiving medical facility, but both patients received positive test results when retested by the same real-time PCR test using a whole blood specimen. All patients have recovered or are recovering, including the two transplant recipients.
Adenovirus type 41 is primarily spread via the fecal-oral route and predominantly affects the gut. It is a common cause of pediatric acute gastroenteritis typically with diarrhea, vomiting and fever, often accompanied by respiratory symptoms (1). Adenovirus is recognized as a cause of hepatitis among immunocompromised children (2). It might be an underrecognized contributor to liver injury among healthy children (3); however, the magnitude of this relationship remains under investigation.
This cluster, along with recently identified possible cases in Europe (4–6), suggests that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology among children. Clinicians and laboratorians should be aware of possible differences in adenovirus test sensitivity for different specimen types; tests using whole blood might be more sensitive than those using plasma. CDC is monitoring the situation closely to understand the possible cause of illness and identify potential efforts to prevent or mitigate illness. Enhanced surveillance is underway in coordination with jurisdictional public health partners. Clinicians are encouraged to report possible cases of pediatric hepatitis with unknown etiology occurring on or after October 1, 2021, to public health authorities for further investigation.¶
Paige A. Armstrong, Julu Bhatnagar, Neil Gupta, Senad Handanagic, Megan Hofmeister, Philip Spradling, CDC; James J. Dunn, Texas Children’s Hospital, Houston, Texas; Advanced Technology and Genomics Core, Wadsworth Center, New York Department of Health, Albany New York.
Corresponding author: Julia M. Baker, email@example.com.
1Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC; 2Epidemic Intelligence Service, CDC; 3Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama; 4Alabama Department of Public Health; 5Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Alabama at Birmingham, Birmingham, Alabama; 6Children’s of Alabama, Birmingham, Alabama; 7Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama; 8Jefferson County Department of Health, Birmingham, Alabama; 9Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC; 10Synergy America, Inc., Duluth, Georgia; 11Department of Pediatrics, Division of Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas; 12Texas Children’s Hospital, Houston, Texas; 13Wadsworth Center, New York State Department of Health; 14Department of Biomedical Sciences, University at Albany, Albany, New York.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. William Britt reports consulting fees from Hookipa Pharma and stocks from Kroger Care, First Energy Corporation, MDU Resources Group, and PG&E Corporation. Elizabeth A. Moulton serves as a coinvestigator for Pfizer SARS-CoV-2 vaccine trials in healthy and immunocompromised pediatric patients with payment made to her institution. Kirsten St. George reports receipt of research support for her institution through equipment and materials from Thermo Fisher, and royalties from ZeptoMetrix Corporation paid to her institution. No other potential conflicts of interest were disclosed.
* 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
§ Normal ranges are ALT = 9–25 U/L; AST = 21–44 U/L; total bilirubin = 0.1–1.0 mg/dL.
- Kang G. Viral diarrhea. In: Quah SR, ed. International encyclopedia of public health. 2nd ed. Cambridge, MA: Elsevier; 2017:360–7. https://www.sciencedirect.com/referencework/9780128037089/international-encyclopedia-of-public-healthexternal icon
- Hierholzer JC. Adenoviruses in the immunocompromised host. Clin Microbiol Rev 1992;5:262–74. https://doi.org/10.1128/CMR.5.3.262external icon PMID:1323383external icon
- Munoz FM, Piedra PA, Demmler GJ. Disseminated adenovirus disease in immunocompromised and immunocompetent children. Clin Infect Dis 1998;27:1194–200. https://doi.org/10.1086/514978external icon PMID:9827268external icon
- UK Health Security Agency. Increase in acute hepatitis cases of unknown aetiology in children. London, United Kingdom: Department of Health and Social Care, UK Health Security Agency; 2022. https://www.gov.uk/government/publications/hepatitis-increase-in-acute-cases-of-unknown-aetiology-in-children/increase-in-acute-hepatitis-cases-of-unknown-aetiology-in-childrenexternal icon
- Marsh K, Tayler R, Pollock L, et al. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022. Euro Surveill 2022;27. https://doi.org/10.2807/1560-7917.ES.2022.27.15.2200318external icon PMID:35426362external icon
- World Health Organization. Multi-Country – acute, severe hepatitis of unknown origin in children. Geneva, Switzerland: World Health Organization; 2022. Accessed April 23, 2022. https://www.who.int/emergencies/disease-outbreak-news/item/multi-country-acute-severe-hepatitis-of-unknown-origin-in-childrenexternal icon
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; EBV = Epstein-Barr virus; IgM = immunoglobulin M; PCR = polymerase chain reaction.
* Upper respiratory symptoms were identified when taking the patient’s history and conducting an initial physical exam. Upper respiratory symptoms can include nasal congestion, nasal discharge, cough, sore throat, wheezing, and dyspnea, among other symptoms.
† Normal ranges are ALT = 9–25 U/L; AST = 21–44 U/L; total bilirubin = 0.1–1.0 mg/dL.
§ The respiratory viral panels (ePlex Respiratory Pathogen Panel [GenMark] or BioFire Respiratory Panel [Biomérieux]) were used to test for adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza A, influenza A/H1, influenza A/H1–2009, influenza A/H3, influenza B, parainfluenza 1, parainfluenza 2, parainfluenza 3, parainfluenza 4, respiratory syncytial virus A, respiratory syncytial virus B, Chlamydia pneumoniae, Mycoplasma pneumoniae, Bordetella parapertussis (BioFire only), and Bordetella pertussis (BioFire only).
¶ Positive EBV test results were based on PCR testing, but all patients received negative test results for EBV IgM antibodies (except one patient who did not have IgM testing) suggesting that infections were likely not acute but rather potential low-level reactivation of previous infections.
** All patients received testing for SARS-CoV-2 using nucleic acid amplification tests.
Suggested citation for this article: Baker JM, Buchfellner M, Britt W, et al. Acute Hepatitis and Adenovirus Infection Among Children — Alabama, October 2021–February 2022. MMWR Morb Mortal Wkly Rep 2022;71:638–640. DOI: http://dx.doi.org/10.15585/mmwr.mm7118e1external icon.
MMWR and Morbidity and Mortality Weekly Report are service marks of the U.S. Department of Health and Human Services.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication.
All HTML versions of MMWR articles are generated from final proofs through an automated process. This conversion might result in character translation or format errors in the HTML version. Users are referred to the electronic PDF version (https://www.cdc.gov/mmwr) and/or the original MMWR paper copy for printable versions of official text, figures, and tables.
Questions or messages regarding errors in formatting should be addressed to firstname.lastname@example.org.
Adenoviruses are common viral pathogens in childhood; however, they can cause serious disease in an immunocompromised host. Fulminant hepatitis is a rare complication of adenoviral infection.What is acute hepatitis infection? ›
Acute viral hepatitis is inflammation of the liver, generally meaning inflammation caused by infection with one of the five hepatitis viruses. In most people, the inflammation begins suddenly and lasts only a few weeks. Symptoms range from none to very severe.Can adults get hepatitis from adenovirus? ›
Respiratory-viral-panel came positive for adenovirus. With supportive treatment, symptoms and LFT trended down, thus, liver biopsy decision was deferred. We believe this is the first reported case of adenovirus hepatitis in an immunocompetent adult.Is adenovirus linked to hepatitis? ›
In immunocompetent patients with human adenovirus infection, liver involvement is typically limited to subclinical acute hepatitis, although severe hepatitis or acute liver failure is sometimes seen in immunocompromised patients.How is adenovirus hepatitis spread? ›
Some adenoviruses can spread through an infected person's stool, for example, during diaper changing. Adenovirus can also spread through the water, such as swimming pools, but this is less common.How is adenovirus hepatitis treated? ›
Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression.Can acute hepatitis Be cured? ›
There is no cure for hepatitis once it occurs. Treatment focuses on preventing further damage to the liver, reversing existing damage if possible and symptom relief. Most cases of acute hepatitis will resolve over time.How do u get acute hepatitis? ›
You're most likely to get hepatitis A from contaminated food or water or from close contact with a person or object that's infected. Mild cases of hepatitis A don't require treatment.How do you treat acute hepatitis? ›
Hepatitis A Treatment
There is no specific therapy for acute hepatitis A infection. Therefore, prevention is the key. An effective vaccine is available and recommended for anyone with liver disease. It also is recommended for people planning to travel to areas of the world where sanitation may be less than optimal.
If you're sick you can help protect others:
- Stay home when you are sick.
- Cough and sneeze into a tissue or your upper shirt sleeve, not your hands.
- Avoid sharing cups and eating utensils with others.
- Refrain from kissing others.
Adenovirus can spread through droplets when someone with an infection coughs or sneezes. Fecal material (poop) can spread the infection via contaminated water, dirty diapers, and poor hand washing. Outbreaks of adenovirus at summer camps are linked to contaminated water in swimming pools and lakes.Is acute hepatitis contagious? ›
Hepatitis A can be spread from close, personal contact with an infected person, such as through certain types of sexual contact (like oral-anal sex), caring for someone who is ill, or using drugs with others. Hepatitis A is very contagious, and people can even spread the virus before they feel sick.How is acute hepatitis spread? ›
Hepatitis A and hepatitis E typically spread through contact with food or water that has been contaminated by an infected person's stool. People may also get hepatitis E by eating undercooked pork, deer, or shellfish. Hepatitis B, hepatitis C, and hepatitis D spread through contact with an infected person's blood.What is adenovirus infection? ›
Adenoviruses are common viruses that typically cause mild cold- or flu-like illness. Adenoviruses can cause illness in people of all ages any time of year.What are the symptoms of acute hepatitis? ›
Symptoms of hepatitis can include: fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, joint pain, and jaundice.What are symptoms of adenovirus? ›
- common cold or flu-like symptoms.
- sore throat.
- acute bronchitis (inflammation of the airways of the lungs, sometimes called a “chest cold”)
- pneumonia (infection of the lungs)
- pink eye (conjunctivitis)
What are adenoviruses? Adenoviruses are a group of viruses that typically cause respiratory illnesses, such as a common cold, conjunctivitis (an infection in the eye that is sometimes called pink eye), croup, bronchitis, or pneumonia.What type of virus is adenovirus? ›
Adenoviruses are medium-sized (90-100 nm), non-enveloped icosohedral viruses with double-stranded DNA. More than 50 types of immunologically distinct adenoviruses can cause infections in humans.How long does it take for adenovirus to go away? ›
Adenoviruses most often infect the airways leading to cold-like symptoms, including sore throat, sneezing, runny nose, cough, headache, chills, or symptoms of croup or bronchitis. Some people might also get a fever. Illness usually lasts three to five days, but serious infections can last for weeks.Why is it called adenovirus? ›
The adenoviruses are named after the human adenoids, from which they were first isolated. Several adenoviruses can cause respiratory and conjunctival diseases.
They could show up, though, anywhere from 6 weeks to 6 months later. Sometimes the symptoms are mild and last just a few weeks. For some people, the hep B virus stays in the body and leads to long-term liver problems.How long does acute hepatitis last? ›
An acute hepatitis B infection may last up to six months (with or without symptoms) and infected persons are able to pass the virus to others during this time.How long can symptoms of acute hepatitis last? ›
Acute hepatitis B infection lasts less than six months. Your immune system likely can clear acute hepatitis B from your body, and you should recover completely within a few months. Most people who get hepatitis B as adults have an acute infection, but it can lead to chronic infection.What kind of food is good for hepatitis patient? ›
Eat a healthy diet of fruit, whole grains, fish and lean meats, and lot of vegetables.What medications cause hepatitis? ›
- Pain and fever medicines that have acetaminophen.
- Aspirin and over-the-counter pain and fever medicines (NSAIDs or nonsteroidal anti-inflammatory medicines)
- Anabolic steroids, man-made medicines that are like the male sex hormone testosterone.
Acute viral hepatitis usually goes away on its own. Hepatitis A causes only acute infection, but hepatitis B and C often cause chronic or lifelong infection. If you have acute hepatitis A, B, or C, you may feel sick for a few months before you get better.Is hepatitis an STD or a virus? ›
Sexually transmitted diseases (STDs) are often discussed in the context of herpes, gonorrhea, chlamydia, and AIDS. Viral hepatitis, specifically hepatitis B, is also an STD often omitted from these discussions.Can you recover from hepatitis? ›
The virus does not remain in the body after the infection is gone. Most people with hepatitis A recover within 3 months. Nearly all people get better within 6 months. There is no lasting damage once you've recovered.What virus causes hepatitis? ›
In the United States, viral hepatitis is most commonly caused by hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). These three viruses can all result in acute disease with symptoms of nausea, abdominal pain, fatigue, malaise, and jaundice.How do you treat adenovirus infection? ›
There is no specific treatment for people with adenovirus infection. Most adenovirus infections are mild and don't require any medical care; clinical care of adenovirus infections includes treatment of symptoms and complications.
Use an EPA-registered disinfectant on surfaces that is effective at killing adenoviruses,* such as a bleach-based solution (2,000–5,000 ppm chlorine or 10 to 25 tablespoons of bleach per gallon of water). Ensure the disinfectants remain on all surfaces for the recommended contact time.How can you prevent adenovirus infection? ›
- Clean your hands often with soap and water.
- Avoid touching your eyes, nose, or mouth with unwashed hands.
- Avoid close contact with people who are sick.
Adenoviruses are a group of common viruses that infect the lining of your eyes, airways and lungs, intestines, urinary tract, and nervous system. They're common causes of fever, coughs, sore throats, diarrhea, and pink eye. Infections happen in children more often than in adults, but anyone can get them.Is adenovirus life threatening? ›
Adenovirus can be a serious, life-threatening disease, even in previously healthy children.Does adenovirus cause high fever? ›
Most often, an adenovirus infection develops in the respiratory tract. When this happens, symptoms of infection are usually similar to the common cold. Children will commonly have a high fever, which may last for several days.Which hepatitis is curable? ›
Hepatitis A usually resolves itself within a few months; hepatitis B can be suppressed with antiviral drugs until it leaves the body; and hepatitis C can be cured outright with medication.How can hepatitis be prevented? ›
- Always wash your hands thoroughly after using the restroom and when you come in contact with an infected person's blood, stools, or other bodily fluid.
- Avoid unclean food and water.
Adenoviruses are a group of viruses that typically cause respiratory illnesses, such as a common cold, conjunctivitis (an infection in the eye that is sometimes called pink eye), croup, bronchitis, or pneumonia. In children, adenoviruses usually cause infections in the respiratory tract and intestinal tract.Is adenovirus the same as hepatitis in dogs? ›
Hepatitis is defined as inflammation of the liver. As a specific disease, infectious canine hepatitis (ICH) is a viral infection caused by a member of the adenovirus family. Other members of the dog family (e.g., foxes), as well as otters and bears, can be infected, but the ICH virus is harmless to people. "...What virus is similar to adenovirus? ›
Adenoviruses and coronaviruses cause infections that share many common symptoms, so it can be hard to tell the two apart. Both can be transmitted through respiratory droplets or direct contact. Both can cause severe respiratory tract infections.
Fulminant hepatitis, or fulminant hepatic failure, is defined as a clinical syndrome of severe liver function impairment, which causes hepatic coma and the decrease in synthesizing capacity of liver, and develops within eight weeks of the onset of hepatitis.Where is adenovirus found in the body? ›
Adenoviruses are a group of common viruses that infect the lining of your eyes, airways and lungs, intestines, urinary tract, and nervous system. They're common causes of fever, coughs, sore throats, diarrhea, and pink eye. Infections happen in children more often than in adults, but anyone can get them.How common is adenovirus infection? ›
Severe disease is rare in people who are usually healthy. Around 10% of respiratory infections in children are caused by adenoviruses. Most are mild and by the age of 10-years, most children have had at least one adenovirus infection. Adenoviruses are the most common viruses causing an inflamed throat.Why is it called adenovirus? ›
The adenoviruses are named after the human adenoids, from which they were first isolated. Several adenoviruses can cause respiratory and conjunctival diseases.What is hepatitis caused from? ›
Heavy alcohol use, toxins, some medications, and certain medical conditions can cause hepatitis. However, hepatitis is often caused by a virus. In the United States, the most common types of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C.How long does the adenovirus last? ›
Adenoviruses most often infect the airways leading to cold-like symptoms, including sore throat, sneezing, runny nose, cough, headache, chills, or symptoms of croup or bronchitis. Some people might also get a fever. Illness usually lasts three to five days, but serious infections can last for weeks.What are the symptoms of adenovirus? ›
- common cold or flu-like symptoms.
- sore throat.
- acute bronchitis (inflammation of the airways of the lungs, sometimes called a “chest cold”)
- pneumonia (infection of the lungs)
- pink eye (conjunctivitis)
There is no specific treatment for people with adenovirus infection. Most adenovirus infections are mild and may require only care to help relieve symptoms, such as over-the-counter pain medicines or fever reducers.What does adenovirus do to humans? ›
Adenoviruses most commonly cause respiratory illness. The illnesses can range from the common cold to pneumonia, croup, and bronchitis. Depending on the type, adenoviruses can cause other illnesses such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease.What is the most common adenovirus? ›
Adenovirus types 3, 4 and 7 are most commonly associated with acute respiratory illness. Adenovirus type 7 has been associated with more severe outcomes than other adenovirus types, particularly in people with weakened immune systems.