COVID ‐19 and Liver Injury, Beyond the First Pandemic Waves: Clinical and Immune‐Virological Features

A liver involvement in Coronavirus disease 19 (COVID-19) has been frequently observed in patients hospitalised for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection during 2020; in such cases, the clinical and prognostic relevance of hepatocellular damage has been widely acknowledged. On the other hand, there is less extensive evidence of liver injury (LI) in the subsequent waves of the COVID-19 pandemic. The aim of this study was to assess the prevalence of LI and to determine the clinical, biochemical, and immune-virologic characteristics associated with its development in SARS-CoV-2-positive patients hospitalised in 2021–2022. This single-centre retrospective study included 455 patients with confirmed SARS-CoV-2 infection and respiratory failure. LI was defined by the detection of transaminase levels exceeding three times the upper limit of normality (ULN) and was further classified as early or late liver injury based on whether the peak transaminase value occurred within or after 7 days from hospital admission. LI was found in 17.6% (80/455) of the overall cohort, while early liver injury (ELI) and late liver injury (LLI) were detected in 10.4% and 11.5%, respectively. LI was associated with younger age, elevated inflammatory and tissue damage markers, with the presence of chronic liver disease (CLD), and with the use of interleukin-6 (IL-6) inhibitors. Patients with LI had a higher probability of severe COVID-19, transfer to intensive care unit, and in-hospital death than those without. In multivariable analysis, younger age, administration of IL-6 inhibitors, and the presence of higher gammaglutamyl transferase (GGT) levels were independently related to the development of overall LI, whereas in-hospital mortality was independently correlated with the occurrence of LLI. The occurrence of hepatocellular damage therefore has been associated with a pro-inflammatory profile and with worse overall outcomes but not with increased likelihood of liver failure or liver-related mortality.