Drug-induced liver injury and COVID-19: A review for clinical practice

Table 3 Hepatoxicity of adjuvant therapy medications for coronavirus disease 2019 treatment

Drug	Evidence of hepatotoxicity	Probability
Heparin	Associated with a transient elevation of 10% to 60%, but the values ​​are generally less than 5 times the upper limit of normal and are rarely associated with symptoms or jaundice. Values ​​above 5 times the upper limit of normal occur around 2% of those receiving high heparin doses	NR
Enoxaparin	Associated with elevations in serum aminotransferases in 4% to 13% of patients, but values ​​greater than 5 times the upper limit of normal are not common and occur in higher doses. The typical liver injury in patients receiving low molecular weight heparins occurred with rapid onset (within 3 d to 5 d of onset), rapid recovery (from 1 wk to 4 wk), and the absence of symptoms and jaundice. Some patients have mild increases in serum bilirubin and alkaline phosphatase but generally remain within the normal range	E
Cortico-steroids	The use of glucocorticoids can result in hepatomegaly and steatosis. They can trigger or worsen non-alcoholic steatohepatitis. Long-term use can also exacerbate chronic viral hepatitis. High doses of intravenous corticosteroids, mainly methylprednisolone, have been associated with acute liver damage resulting in acute liver failure and death. Symptoms and jaundice develop 2 wk to 6 wk after discontinuance. Some cases have progressed to acute liver failure, resulting in death or the need for emergency liver transplantation	A
Voriconazole	Transient elevations in serum aminotransferase levels occur in 11% to 19% of patients on voriconazole. These elevations are generally asymptomatic and self-limited, but approximately 1% of patients require voriconazole discontinuance due to ALT elevations. Cases of acute liver failure have been described. Testing for serum bilirubin and aminotransferase levels is recommended at the time of initiation and weekly during the first month of therapy and monthly thereafter	B
Anidulafungin	Transient elevation of transaminases from 2% to 15%. There are rarely serious cases. Monitoring of liver tests during therapy is recommended, especially in patients with previous liver disease	D
Colchicine	It is rarely associated with elevations in serum aminotransferase or alkaline phosphatase. The cases of acute liver injury attributed to the overdose of colchicine were self-limiting, and the other toxicities of this agent, such as rhabdomyolysis, generally overshadowed the liver injury. No convincing cases of liver failure have been reported	C

Adapted from LiverTox^© database[27]. A: Well know hepatotoxicity; B: Highly likely hepatotoxicity; C: Probably hepatotoxicity; D: Possible hepatotoxicity; E: Unlikely hepatotoxicity; NR: Not reported; ALT: Alanine aminotransferase.