Cidofovir for Adenovirus-Related Hepatitis in Kids Clears Viremia

NEW YORK (Reuters Health) – Off-label use of cidofovir in children with acute liver failure and confirmed adenovirus infection cleared the virus or substantially reduced viremia in a small case series from Kings College Hospital, London.

Dr. Avita Verma and colleagues report on nine children who presented with jaundice, gastrointestinal symptoms, and blood tests positive for adenovirus. The median age was 3.2 years. Two children were infected with SARS-CoV-2 four to six weeks before presentation; the others were positive for SARS-CoV-2 spike-RBD total antibody. Six of the nine required a liver transplantation.

All patients received the standard dose of 5 mg/kg weekly for 2 weeks, then every other week, unless they required continuous renal replacement therapy (CRRT), in which case a reduced dose of 2 mg/kg was used. Three of the six patients requiring liver transplantation received cidofovir before transplantation. There was no recurrence of hepatitis for at least two weeks posttransplant.

Eight patients had complete viral clearance. One patient had substantial reduction from 5.6 log10 copies per mL to 2.5 log10 copies per mL after the third dose of cidofovir but did not fully clear the viremia, possibly, according to the authors, due to the short follow-up.

All patients initially presented with normal renal function. Five received CRRT as part of management of encephalopathy and hyperammonemia. Four of the patients who had been transplanted had elevated creatinine levels, including three who developed acute kidney injury with creatinine three times normal. In two cases, creatinine elevations were associated with the initiation of tacrolimus, in the other two, it was felt to be a combination of cidofovir and tacrolimus. All except one had normalized creatinine at discharge; one patient had persistently raised creatinine two weeks after treatment and at discharge.

The other five patients had transient renal dysfunction (up to double baseline creatinine), but still with the normal range. However, the authors note, increases in creatinine could have been masked in patients who required CRRT.

“Our limited experience showed transient nephrotoxicity with reduction in viral load and nonrecurrence of hepatitis in the allograft,” the authors concluded. “While we continue to understand the precise cause and pathophysiology of this condition, interim use of cidofovir in children with acute liver failure and adenoviremia seems to be relatively safe and well tolerated in the short-term, and effective in reducing adenoviremia.”

SOURCE: The Lancet Gastroenterology and Hepatology, online June 16, 2022.

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