COVID, MIS-C show evidence of liver injury, require long-term monitoring
Children with COVID-19 and multisystem inflammatory syndrome had varied outcomes and liver injuries but all should keep long-term liver monitoring to ensure return to normal levels, per a researcher at The Liver Meeting Digital Experience.
“Patients with either MIS-C or COVID-10 had liver injury. In both cohorts, patients with liver injury were statistically more likely to be older, and in COVID-19 more likely to be Hispanic and in MIS-C, more likely to be male. In patients diagnosed with COVID-19, obese and overweight patients were more likely to have more severe acute liver injury,” Amanda Cantor, MD, of Columbia University, said during her presentation.
In this retrospective study, Cantor and colleagues looked at 291 pediatric patients who tested positive for SARS-CoV-2 from March to May 2020 at two tertiary care hospitals in New York City. They categorized patients as having multisystem inflammatory syndrome in children (MIS-C; n = 71) or acute COVID-19 (n = 220).
In the COVID cohort, patients with liver injury were more likely to be Hispanic (P < .05) and older while the MIS-C cohort were more likely to be male (P < .05) and older.
When researchers looked at comorbidities in each group, they found patients with COVID-19 were more likely to have a preexisting condition but there was no difference in liver injury for those patients. In the MIS-C group, preexisting conditions were less common but when present, increased the likelihood of liver injury (P < .05). The most common comorbidity in this group was asthma.
“This injury was more severe in those patients with COVID-19 who were obese or overweight,” Cantor said.
Investigators associated the degree of liver injury with BMI in the COVID-19 group in which 61.9% of patients with overweight had acute liver injury (P < .05) as well as 53.9% of patients who had obesity (P < .05). In the MIS-C group, those BMI levels linked to 41.6% and 30.5%, respectively, having acute liver injury.
“While the degree of liver injury in MIS-C correlated with inflammatory markers, this was not wholly the case in patients with COVID-19 infection,” Cantor said.
In looking at inflammatory markers of acute liver injury, the study showed high ferritin in both groups (P < .01), high CRP in both groups (P < .05 in MIS-C; P < .01 in COVID-19) and high D-dimer in the MIS-C group (P < .05).
“More patients with MIS-C required the ICU and although MIS-C had a more severe presentation, all the deaths occurred in the COVID-19 cohort,” Cantor said.
Of the patients with MIS-C, 53.5% required ICU care vs. 24.4% in the COVID-19 cohort. There were six reported deaths and only two presented with liver injury.
“These data I have presented demonstrate variability of disease and liver injury found amongst the two clinical illnesses COVID-19 and MIS-C. Liver injury was documented in both populations of pediatric patients,” Cantor said. “The acute liver injury described here might be a transient phenomenon, but patients from both cohorts require careful monitoring during admission and long-term follow up to ensure normalization.”
Perspective
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COVID-19 is known to affect several organ systems. In addition to respiratory tract injury, there have been a plethora of publications describing the multisystemic nature of the infection that can involve neurological, gastrointestinal and hepatic injury. Abnormal liver biochemistries have been well described in COVID-19 infected patients and is most likely multifactorial, primarily from direct viral cytotoxicity. Other potentiating hepatotoxic mechanisms include the development of a systemic inflammatory response with ischemia, hypoxia and reperfusion injury to the liver, hepatotoxicity from medications, or from a “secondary hit phenomenon” due a pre-existing liver condition or pre-morbidity such as obesity or diabetes.
Since the outbreak of COVID-19 resulting in a massive pandemic, the relative incidence of serious infection in children has been low. Interestingly, children are thought to have a milder form of COVID-19 with a relatively low rate of hospitalization compared with adults. However, in May 2020, there were reports of a MIS-C with features like an atypical Kawasaki syndrome that were thought to be related to COVID-19 infection. Feldstein and colleagues reported 186 previously healthy children who presented with MIS-C with multisystem organ involvement that affected the liver and gastrointestinal tract (92%), cardiovascular (80%), hematologic (76%), mucocutaneous (74%) and respiratory (70%) systems. In this cohort, most children had laboratory evidence of an antecedent or concurrent SARS-CoV-2 infection and in general did not have prior co-morbidities present. Many of these patients were in the intensive care units requiring cardio-pulmonary support and although most were discharged home, there was a reported mortality rate of 2%.
Since this report, there have been at least 1,000 pediatric cases worldwide of MIS-C that is observed to occur 2 to 4 weeks after COVID-19 infection with a higher proportion reported in Black, Hispanic and persons from South Asia. This illness can be critical in many cases with multiorgan system involvement and although most children recover, there is a small percentage who have died. Understanding the underlying mechanism in children along with ethnic differences may help us understand this novel virus and shed light into genetic variations that may either predispose to infection with the concomitant hyperinflammatory state or may aid in prevention. In any case, these patients warrant long term follow up and to ensure that the systemic injury and organ system involvement resolves over time and normalization of laboratory values is achieved.
Reference:
Feldstein LR, et al. N Engl J Med. 2020; doi:10.1056/NEJMoa2021680.
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