key: cord-0697246-ywwe4cps
authors: Romana, Ponziani Francesca; Antonio, Nesci; Fabio, Del Zompo; Francesco, Santopaolo; Maurizio, Pompili; Antonio, Gasbarrini
title: Correlation between liver function tests abnormalities and interleukin-6 serum levels in patients with SARS-CoV-2 infection
date: 2020-12-30
journal: Gastroenterology
DOI: 10.1053/j.gastro.2020.05.103
sha: 693f7d317738343919260ae54e7b66b0089ee791
doc_id: 697246
cord_uid: ywwe4cps

nan

We have read with interest the paper by Singh et al. 1 reporting high risk for hospitalizations and mortality in patients with chronic liver disease affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 is frequently associated with elevation in liver function tests, including alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) 1, 2, 3 . Vascular endothelium, smooth muscle cells and cholangiocytes express the angiotensinconverting enzyme 2 (ACE2) receptor, which is used by SARS-CoV-2 to enter the cells, suggesting that liver involvement can due to direct viral damage 4 Our data demonstrate a correlation between liver function tests abnormalities and IL-6 serum levels, proving that liver injury can be initiated by the virus and further sustained by inflammation.

SARS-CoV-2 disease may evolve through different phases: while in the initial stage viral symptoms are predominant, a subgroup of patients progresses to pneumonia and systemic hyperinflammation, characterized by "cytokine storm syndrome" with systemic organ involvement 6 . In this stage, IL-6 is over-expressed and has been associated with adverse clinical outcomes 7 .

In our series, circulating IL-6 was elevated in patients with ALT or GGT abnormalities. Furthermore, patients in the late phase of the disease had an increased prevalence of liver tests abnormalities and higher levels of IL-6 compared to those in the early phase. We also found an increased prevalence of AST or GGT elevation and higher IL-6 serum levels in patients requiring intensive care, confirming the association between liver injury, hyper-inflammation and SARS-CoV-2 disease severity.

In conclusion, we can argue that liver function tests abnormalities are prevalently due to cytopathic viral effect in the early phase, and to liver involvement as "innocent bystander" in SARS-CoV-2-related inflammatory syndrome in the late phase. Patients with chronic liver disease could be severely affected by this cytokine storm, as supposed by Singh et al. 1 . However, the prevalence of SARS-CoV-2 infection among these patients is low and only retrospective data from electronic medical records are available; this makes difficult to conduct specific investigations and, consequently, to draw definitive conclusions.

J o u r n a l P r e -p r o o f

Clinical Characteristics and Outcomes of COVID-19 Among Patients with Pre-Existing Liver Disease in United States: A Multi-Center Research Network Study

Liver injury in COVID-19: management and challenges

Characteristics of Liver Tests in COVID-19 Patients

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal

Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis