Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection

Abstract

In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.

Keywords: COVID-19; COVID-19 drugs; COVID-19 treatment; drug-induced liver injury (DILI); liver dysfunction; liver function; liver injury.

Figure 1

Liver injury during COVID-19 infection can occur through multiple pathways. A few common examples are pictured above, and they include: direct injury through the ACE-2 receptor, uncontrolled general inflammation as a result of the cytokine storm syndrome (CSS), and drug-induced liver injury (DILI).

Figure 2

COVID-19 medications that can cause DILI, the category in which they belong, the liver contraindications that exist, and the DILI patterns that they develop. Abbreviations used: NSAIDs—non-steroidal anti-inflammatory drugs; LMWH—low molecular weight heparins; LF—liver failure; ALT—alanine aminotransferase; ULN—upper limit of normal; FRP—favipiravir; AST—aspartate aminotransferase; ALP—alkaline phosphatase; MAFLD—metabolic associated fatty liver disease; NAFLD—non-alcoholic fatty liver disease. The arrow used in this figure signifies elevation of the mentioned biomarkers.