COVID-19 and liver injury: An ongoing challenge

Table 1 Evidence of hepatotoxicity of most studied and used drugs in coronavirus disease 2019

Drug	Mechanism of action	Characteristics of LI	Risk of DILI	DILI pattern
Corticosteroids[126]	Anti-inflammatory	Hepatomegaly, steatosis; triggering/worsening NAFLD; reactivation HBV (prolonged administration)	Low	Hepatocellular or mixed
Remdesivir[70]	Antiviral; active inhibitor of viral RNA-dependent RNA polymerases	Mild-to-moderate ALT and AST elevations; Elevation > 5 times ULN in 9% (resolved with discontinuation)	Moderate	Hepatocellular
Tocilizumab[72]	Anti-IL-6 receptor monoclonal antibody	Elevation of ALT and AST; no reports of severe LI or HBV reactivation (in COVID-19 trials)	Moderate	Hepatocellular
Anakinra[73]	IL-1 inhibitor	ALT elevation in < 1%; No association with HBV reactivation	Low	Hepatocellular
Nirmatrelvir/ritonavir[74]	Antiviral; Inhibitor of the main protease of SARS-CoV-2/protease inhibitor and potent inhibitor of the enzyme CYP 3A4	Mild ALT and AST elevation; no reports of clinical apparent LI; limited data	Low	Hepatocellular
Molnupiravir[127]	Antiviral; prodrug of the ribonucleoside analogue N-hydroxycytidine	Mild ALT and AST elevation; no reports of clinical apparent LI; limited data	Low	Hepatocellular
Low-molecular-weight heparins[128]	Anticoagulant	Mild ALT and AST elevation; LI with rapid onset and rapid recovery, without clinical symptoms	Low	Hepatocellular
NSAIDs[129]	Anti-inflammatory	Mild, transient and asymptomatic elevation of liver enzymes; more common in obese patients with comorbidities; reports of acute hepatitis (idiosyngratic, prolonged administration)	Moderate	Hepatocellular, cholestatic or mixed
Acetaminophen[130]	Analgesic and antipyretic	Dose-dependent; transient and asymptomatic elevation of ALT and AST; acute hepatitis and/or acute liver failure in overdose	High	Hepatocellular

DILI: Drug-induced liver injury; ALT: Alanine aminotransaminase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus; IL-6: Interleukin-6; IL-1: Interleukin-1; LI: Liver injury; NAFLD: Non-alcoholic fatty liver disease; ULN: Upper limit of normal; NSAID: Nonsteroidal antiinflammatory drugs.