The REFHEPS group has reviewed and briefly summarized currently known data on drugs used as COVID-19 treatment below:

• Hydroxychloroquine can serve as a possible but rare cause of idiosyncratic DILI.
• Azithromycin may induce idiosyncratic acute liver injury, with clinical presentation of cholestatic hepatitis arising within 1–3 weeks after starting treatment. Azithromycin can also have a hepatocellular injury, with a short latency (a few days).
• All forms of interferon-beta may cause hepatic injury, with most cases being asymptomatic and mild. Mostly its presentation is transient with mild elevations in serum aminotransferase levels and serum alkaline phosphatase levels usually normal or minimally elevated.
• Lopinavir administration may cause moderate-to-severe elevations in serum aminotransferase levels (> 5 × ULN) in 3% to 10%, with the pattern of serum enzyme elevations varying from hepatocellular to cholestatic or mixed.
• Ritonavir, used at low ‘booster’ doses, may not increase the frequency or severity of serum enzyme elevations, and if occur, are usually asymptomatic and self-limited, resolving even with continuation of ritonavir. However, due to its enzymatic inhibitor properties, ritonavir can increase the plasmatic level of co-administered drugs which then boosts the risk of their hepatotoxicity.
• Currently, very less is known about the potential hepatotoxicity of remdesivir. It has not been reported to cause liver injury in LiverTox. Viewing its gracious use in patients with COVID-19 infection and the frequency of liver dysfunction with this disease, the attribution of hepatotoxicity to remdesivir is challenging.
• Baricitinib is currently being evaluated as an inhibitor of JAK-1 and 2 for the treatment of rheumatoid polyarthritis and has shown to be associated with mild and transient transaminases elevation. Large clinical trials have shown transaminase values > 5 × ULN occurred in < 1% of patients on baricitinib.
• Imatinib, used in several blood cancers, is associated with common elevations in serum aminotransferase levels, but ALT levels > 5 × ULN range occur in only 2–4% of patients treated for 6 months or more. Additionally, mild elevations in serum bilirubin can occur, which are usually mild, asymptomatic and resolve despite continuing therapy. Imatinib has also been related to rare instances of clinically evident acute liver injury with jaundice.
• Darunavir is associated with moderate-to-severe elevations in serum aminotransferase levels (> 5 × ULN) in 3–10% of patients overall.
• Data on Favipiravir regarding liver effects are very limited.

The acute liver injury involves

• Increase of ALT ≥ 5 × ULN

or

• Increase of ALP ≥ 2 ULN (in the absence of known bone pathology)

or

• A mixture of an elevation of ALT ≥ 3 ULN with a simultaneous elevation of total bilirubin concentration exceeding 2 × ULN.

Variations of these parameters below the limits do not describe DILI and the withdrawal of the drug should be carried out only after all confounding factors have been excluded, especially if the expected benefit/risk ratio is positive.

Source: Drug Saf, 2020;43: 615–617. https://doi.org/10.1007/s40264-020-00954-z