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

Table 2 Hepatotoxicity of the most common drugs used to treat coronavirus disease 2019

Drug	Evidence of hepatotoxicity	Probability
Azithromycin	Liver damage is usually self-limited cholestatic hepatitis, which appears 1 wk to 3 wk after starting treatment. It may also appear after some time following medicine discontinuance. Cholestasis and elevated transaminases can persist for up to 6 mo. Despite presenting the hepatocellular and cholestatic forms of injury, cholestatic is more often related to acute liver failure, death, or liver transplantation	A
Lopinavir/ritonavir	Clinically apparent liver disease occurs in 3% to 10% of patients. The onset of symptoms or jaundice is usually 1 wk to 8 wk, and the pattern of elevations in serum enzymes varies from hepatocellular to cholestatic or mixed. The injury is usually self-limiting; however, fatal cases have been reported	D
Hydroxy-chloroquine	It has not been associated with significant elevations in serum enzymes during therapy for rheumatic diseases. When used in relatively high doses, it can trigger an acute liver injury with a sudden onset of fever and marked elevation of serum enzymes. Post COVID-19 data have not been assessed	C
Tocilizumab	It has been associated with several cases of clinically apparent liver injury with jaundice. Although the liver injury was severe, it was usually self-limiting, with complete recovery within 2 mo to 3 mo. In at least one case, however, the affected patient died of liver failure. Current recommendations are patient monitoring by routine liver tests before medication. In registration trials, serum aminotransferase elevations occurred in a high proportion (10% to 50%) of patients	C
Remdesivir	Between 10% and 50% of patients treated developed transient, mild-to-moderate serum ALT and AST elevations within 1 d to 5 d of starting therapy without changes in serum bilirubin or alkaline phosphatase levels. Elevations above 5 times ULN were reported in up to 9% of patients in several clinical trials, but the abnormalities resolved with discontinuance and were not associated with a clinically apparent injury	D
Nevirapine	Associated with significant elevations in ALT (above 5 times the ULN) in 4% to 20% of patients and symptomatic elevations in 1% to 5%	A
Ivermectin	Associated with minor, self-limiting elevations in serum aminotransferase and sporadic cases of clinically apparent liver damage. Post COVID-19 data have not been assessed	D

Adapted from LiverTox^© database[27]. A: Well know hepatotoxicity; B: Highly likely hepatotoxicity; C: Probably hepatotoxicity; D: Possible hepatotoxicity; COVID-19: Coronavirus disease 2019; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ULN: Upper limit of normal.