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Severe hepatitis of unknown cause in 15 nations: Does pathology offer a clue?

Daniel R. Lucey, MD, MPH, FIDSA
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This month, WHO, the U.K. Health Security Agency, the U.S. CDC, the European CDC and others have reported on acute, severe hepatitis of unknown etiology in children ages 1 month to 16 years. Most of the 15 nations investigating cases are in Europe (led by the U.K., which first reported their outbreak to WHO in early April). Other nations with ongoing investigations include the USA, Israel, Canada and Japan. The initial cases in the USA were in Alabama last October-November. This month, Illinois, North Carolina and other states are pursuing investigations, and the U.S. CDC posted a Health Advisory via its Health Alert Network on April 21.

Of the approximately 170 cases, 17 have required liver transplantation (e.g., in the U.K., U.S. and Israel). One child has died. No diagnostic test is available given that no infectious or noninfectious causes have been identified, despite intensive searching. Thus, it is impossible to know how many more nonsevere cases there have been.

One potential important clue that has not been reported yet is the pathology of the liver. The 17 liver transplant cases across several countries means that a detailed analysis of the microscopic histopathology of the liver in these cases is available. Liver biopsies on some of these 17 cases and additional cases likely occurred. It is likely these data have been shared with WHO, CDC, and others and have been submitted to one or more medical journals for publication.

A fundamental question is whether there is a characteristic pattern in the pathology of the liver in these patients. Such a pattern might be seen at the advanced stage when liver transplantation was performed, or earlier before the severe liver damage of the unknown process had perhaps obscured an earlier characteristic pattern.

If such a liver pathology pattern has been found, then it could be used to help identify the etiology of the hepatitis or at least serve to provide a unifying clinical-pathologic syndrome as soon as possible.

More data can be anticipated week by week throughout May 2022.


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