Sars-Cov2 and Liver Damage in Pediatric Population

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2) initially was perceived as a lower respiratory tract infection. However, with time coronavirus disease (COVID-19) presented with a wide variability of symptoms, including gastrointestinal and hepatic. This because the viral tropism to the angiotensin-converting enzyme 2 (ACE2) receptor found in liver and bile-duct epithelial cells. The ACE2 expression is mainly in cholangiocytes (60% of cells), minimally expressed in hepatocytes (3% of cells) and absent in Kupffer cells. Hepatic involvement can be evidenced with elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), these alterations have been evidenced in up to 43% of patients. The aim of this study is to evaluate liver damage in pediatric patients with COVID-19. Material(s) and Method(s) A retrospective cohort was carried out between March 2020 to October 2021 at the Instituto Nacional de Pediatria in Mexico City. We include all patients between 0 to 18 years with positive COVID-19 PCR test or antigen rapid test. Result(s) We had a total population of 161 subjects of which 83 had liver function tests (inflammation, excretion, or synthesis) during SARS-CoV2 infection;82 had ALT value. Mean age was 5.3 years and 56% were men (n 47). Fifty-four patients (65%) had previous comorbidity, with oncological diseases being the most frequent (33%). Of the 54 patients with previous comorbidity, 3 had liver disease (Graft-versus-host disease, nonalcoholic fatty liver disease and autoimmune hepatitis). Regarding treatment, 32 patients did not require oxygen support, 32 patients had non-invasive devices and 19 patients required mechanical ventilation. Fifty-four percent (n = 45) were using steroid management. In relation to the outcome of the patients, 11 die and the rest were discharged. Liver function tests were submitted 2 days after admission, 51 patients (62%) presented elevation of ALT (according to age and sex). Second liver function tests were taken around day 23 53 patients. Table 1 shows the average of each of the parameters. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators like C-reactive protein (CRP) and ferritin. Therefore, levels of this inflammatory mediators were evaluated, the average of this parameters was 1601 ng/mL and 8.19 mg/L respectively in the first test. Analysis: We evaluated the difference that existed in liver function tests by comparing the first and second determination. Regarding AST, INR and PT, a significant difference was found (p = <0.05) with improvement compared to baseline. While the ALT did not show a significant difference, there was an improvement compared to baseline. Secondary to the association described between elevation of inflammatory mediators and severity of the disease, a Pearson Correlation test was performed between liver inflammatory tests and ferritin/prealbumin. A significant correlation was obtained when comparing ALT with ferritin (r = 0.301, p = 0.033) and AST with ferritin (r = 0.311, p= 0.028), which demonstrate a weak correlation probably associated with the amount of population. The correlation between ALT/AST and prealbumin was carried out without being significant. In search of associated factors, it was found that the alteration of liver function tests is a risk factor for needing support with supplemental oxygen with an Odds Ratio of 2.007 (CI 0.77-5.31). From 19 patients who required mechanical ventilation, 73.7% had altered liver function tests. Conclusion(s) SARS-CoV2 is a virus that has been shown to have liver involvement which can be demonstrated with elevation of liver function test. In our series, 62% had elevated ALT, being the most sensitive parameter of liver inflammation. With respect to factors associated with liver impairment, we found that higher ferritin levels are associated with greater liver involvement, as well as that having hepatic impairment is a risk factor for the use of supplemental oxygen. Therefore, it is important to consider in patients with COVID-19 liver function tests and thus make a timely detection of alterations at this level. Studies with more population are required to have external validity.