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. 2023 Dec;43(12):2657-2667.
doi: 10.1111/liv.15673. Epub 2023 Jul 13.

Risk of acute liver injury following the nirmatrelvir/ritonavir use

Carlos King Ho Wong  1   2   3 , Lung Yi Mak  4   5 , Ivan Chi Ho Au  1 , Wing Yiu Cheng  6 , Ching Hei So  1 , Kristy Tsz Kwan Lau  1 , Eric Ho Yin Lau  3   7 , Benjamin J Cowling  3   7 , Gabriel M Leung  3   7 , Man Fung Yuen  4   5
Affiliations

Risk of acute liver injury following the nirmatrelvir/ritonavir use

Carlos King Ho Wong et al. Liver Int. 2023 Dec.

Abstract

Background: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reported as adverse events of nirmatrelvir/ritonavir users in the EPIC-HR trial.

Aim: To quantify the risk and severity of acute liver injury (ALI) associated with nirmatrelvir/ritonavir use.

Methods: This self-controlled case-series study was conducted using electronic medical records of patients with confirmed diagnosis of SARS-CoV-2 infection between 26th February 2022 and 12th February 2023 in Hong Kong.

Results: Among 2 409 848 patients with SARS-CoV-2 infection during the study period, 153 853 were prescribed with nirmatrelvir/ritonavir, of whom 834 (.5%) had incident ALI (moderate: 30.5%; moderate to severe: 18.9%; severe or fatal: 5.8%). Compared with the non-exposure period, risk of ALI increased significantly during the pre-exposure period (IRR = 38.13, 95% CI = 29.29-49.62) and remained elevated during the five-day nirmatrelvir/ritonavir treatment (IRR = 20.75, 95% CI = 17.06-25.25) and during wash-out period (IRR = 16.27, 95% CI = 13.23-20.01). Compared to the pre-exposure period, risk of ALI was not increased during the five-day nirmatrelvir/ritonavir treatment period (IRR = .54, 95% CI = .43-.70). Compared to 5469 non-nirmatrelvir/ritonavir users with incident ALI, nirmatrelvir/ritonavir users had less severe ALI by the severity index (p < .001) and peak INR (1.7 vs. 2.3; p < .001). ALI cases with nirmatrelvir/ritonavir use had lower risk of all-cause death (29.1% vs. 39.1%; OR = .64; p < .001) and no increase in risk of liver decompensation (1.0% vs. 1.3%; OR = .62; p = .230) compared to non-users.

Conclusion: The risk of ALI associated with nirmatrelvir/ritonavir treatment for COVID-19 was elevated in the pre-exposure period, but not following nirmatrelvir/ritonavir initiation. ALI following nirmatrelvir/ritonavir treatment were mostly mild and less severe than ALI events in non-nirmatrelvir/ritonavir users.

Keywords: COVID-19; acute liver injury; case series; nirmatrelvir/ritonavir.

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References

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