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Clinicopathologic Features of Severe Acute Hepatitis Associated With Adenovirus Infection in Children
Jiancong Liang1, David R Kelly2, Anita Pai3
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center.
Insights
Severe acute hepatitis in children linked to adenovirus infection shows liver injury resembling autoimmune hepatitis. This suggests a potential immune response to the virus, with most patients recovering with supportive care.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Virology
Background:
- Reports of severe acute hepatitis in children of unknown cause have increased.
- Adenovirus detection in these cases is frequent, but its etiological role is uncertain.
- Systematic histopathologic analysis of liver biopsies is lacking.
Purpose of the Study:
- To investigate the histopathologic features of liver injury in children with unexplained acute hepatitis and adenovirus infection.
- To compare these features with cases of unexplained acute severe hepatitis without adenovirus.
- To explore the potential immune-mediated mechanisms involved.
Main Methods:
- Retrospective study of 11 children hospitalized with unexplained acute hepatitis and adenovirus infection (October 2021-May 2022).
- Analysis of liver biopsies using histopathology, immunohistochemistry, and polymerase chain reaction (PCR).
- Comparison with a control group of children with unexplained acute severe hepatitis without adenovirus.
Main Results:
- Liver biopsies showed moderately to severely active hepatitis in 73% of cases, with features mimicking autoimmune hepatitis.
- PCR confirmed enteric adenovirus serotype 41 in 91% of cases; immunohistochemistry was negative for adenovirus.
- Histologic features like portal inflammation, interface activity, and bile duct injury were more common compared to controls.
Conclusions:
- Liver injury in children with severe acute hepatitis and adenovirus infection presents a hepatitic pattern resembling severe autoimmune hepatitis.
- The findings suggest a possible immune-mediated process associated with adenovirus infection.
- Most children recovered with supportive treatment, avoiding liver transplantation.
Abstract:
A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.
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