To the Editors:
Among the wide spectrum of manifestations of COVID-19, liver injury is garnering increasing attention.
Liver test abnormalities are estimated to occur in ~15% of adult patients1 and those with severe COVID-19 seem to have higher rates of liver dysfunction.2
Information on the prevalence of liver injury and the associated clinical features in children with SARs-CoV-2 infection are currently scarce.
So far, no pediatric cases of acute hepatitis occurring during the course of COVID-19 have been reported.
We describe a previously healthy 10-month-old boy who presented to Emergency Department with a two-day history of mild fever, rhinitis and cough. His mother had been diagnosed with SARs-CoV-2 infection a week earlier.
On physical examination, he was alert and responsive, normotensive and eupneic. His body temperature was 37.3°C with oxygen saturation in room air of 99%. There were no cutaneous manifestations, his lung and heart auscultation were normal. The abdomen was soft, and there was no jaundice, hepatomegaly or splenomegaly. Initial laboratory study revealed marked elevation of liver transaminases and ferritin. Serum bilirubin and albumin were in the normal range (Table 1). C-reactive protein was negative.
TABLE 1. -
Laboratory Parameters on Presentation
|White blood cell, ×103/μL
||Alkaline phosphatase, UI/L
||Total bilirubin, mg/dL
|Aspartate aminotransferase, U/L
||Prothrombin time, ratio
|Alanine aminotransferase, U/L
||C-reactive protein, mg/dL
||Creatin kinase, U/L
|Lactic dehydrogenase U/L
His parents denied any use of paracetamol. Abdominal ultrasonography and full cardiological assessment did not point out any anomalies. Nasopharyngeal swab turned positive for SARs-CoV-2 RNA. Blood cultures were negative and no coinfection was demonstrated.
The following day the fever disappeared and liver enzymes began to decrease. Only supportive therapy was administered. He was discharged after 6 days without any complications and with no need for respiratory support.
At the follow-up visit, 2 weeks later, the child was asymptomatic, and all blood tests had returned to normal range.
Our case suggests an unreported association between acute SARs-CoV-2 infection and acute hepatitis in children, thus supporting the notion that evaluation of liver enzymes during hospitalization for SARs-CoV-2 infection is also indicated in pediatric age.
In the last months, there have been increasing reports describing children with COVID-19-associated multisystem inflammatory conditions (MIS-C),3 which may present with prominent gastrointestinal and hepatic involvement.4
This syndrome seems to develop after the infection rather than during the acute stage of COVID-19 and the majority of reported patients are negative for SARs-CoV-2 RT-PCR but positive for SARs-CoV-2 antibodies.4 This observation supports the idea that in MIS-C the mechanism of liver involvement may be secondary to an immune-mediated response.
Conversely, in our patient, the concomitance of SARs-CoV-2 infection with respiratory symptoms suggests a viral-induced cytopathogenic effect in the liver supported by the proven viral tropism for the liver.5
Therefore, clinicians should consider SARs-CoV-2 as a possible etiology of acute nonicteric hepatitis even in children with mild respiratory symptoms.
Despite the benign outcome reported here, we recommend close follow-up in children with COVID-19 and liver abnormalities given the limited knowledge of the long-term impact of SARs-CoV-2 on the liver.
1. Sultan S, Altayar O, Siddique SM, et al. AGA institute rapid review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology. 2020; 159:320–334.e27.
2. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020; 5:428–430.
3. Cheung EW, Zachariah P, Gorelik M, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York city. JAMA. 2020; 324:294–296.
4. Cantor A, Miller J, Zachariah P, et al. Acute hepatitis is a prominent presentation of the multisystem inflammatory syndrome in children: a single-center report. Hepatology. 2020; 72:1522–1527.
5. Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver dam-age after 2019-nCoV infection. bioRxiv. Posted online February 4, 2020. https://doi.org/10.1101/2020.02.03.931766