Aim To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS‐CoV‐2 infection. Methods This self‐controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory‐confirmed COVID‐19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non‐exposure period were estimated using the conditional Poisson regression models. Results Of 860 COVID‐19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre‐exposure period (ALI: IRR = 6.169, 95% CI = 4.549–8.365; AKI: IRR = 7.074, 95% CI = 3.763–13.298) and remained elevated during remdesivir treatment. Compared to the pre‐exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915–1.737; AKI: IRR = 1.261, 95% CI = 0.889–1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793–1.489; AKI: IRR = 1.152, 95% CI = 0.821–1.616). Conclusion The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID‐19 may be due to the underlying SARS‐CoV‐2 infection. The risks of AKI and ALI were elevated in the pre‐exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre‐exposure period.
BackgroundElevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reported as adverse events of nirmatrelvir/ritonavir users in the EPIC‐HR trial.AimTo quantify the risk and severity of acute liver injury (ALI) associated with nirmatrelvir/ritonavir use.MethodsThis 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.ResultsAmong 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.ConclusionThe 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.
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