Fabio Farinati

Liver injury during SARS-CoV-2 infection: clinical, immunologic and pathologic molecular interactions (LIVER-COV)

Required budget: 10.000 euro

Liver injury is frequently reported in patients with COVID-19 (14-53%), particularly in cases with a severe disease, with an elevation in ALT, AST and bilirubin.

The main hypotheses on the mechanisms of liver damage are: direct SARS-CoV-2 cytopathic effect; drug hepatotoxicity and immuno-mediated inflammation. The literature suggests that cytokine release syndrome (CRS), an uncontrolled release of proinflammatory mediators by an overly activated immune system, might play a major role in severe COVID-19 disease. Despite the possibility of a direct liver involvement, data on liver histopathologic features, among which those we published (Trevenzoli M, J Gastrointest Liver Dis, 2020) do not demonstrate any specific damage. The role of CRS in the pathogenesis of liver injury is far from being elucidated, and its characterization would allow a better understanding of the multiorgan involvement. Moreover, little is known about the role of pre-existing liver disease on the severity of COVID-19.

With this study, we aim to evaluate the frequency and the clinical relevance of liver injury in hospitalized COVID-19 patients, the disease course in patients with liver disease and the medium-term impact of the infection on liver function, but also to study the histologic characteristics of patients with liver damage and CRS as the main mechanism of injury.

Patients hospitalized for COVID-19 at Padova Hospital from February 2020 will be retrospectively and prospectively evaluated. Cytokine profiling will be performed in prospectively recruited patients with liver injury and mild to severe pulmonary disease, and in all patients undergoing liver biopsy. Biopsies will be also analyzed in order to characterize the specific features associated with liver injury. The possibility of utilizing animal models of COVID-19 infection, for instance mice, where the infection induces lung disease and mortality (Leist SR, Cell 2020), to assess extent and mechanism of liver damage will be also explored.