The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study

INTRODUCTION. Elevated liver enzyme levels are common in patients with COVID-19. Personalised prescribing to reduce the risk of hepatotoxicity requires studying the role of pharmacotherapy in the development of liver dysfunction in COVID-19 patients.

AIM. This study aimed to identify the presence and strength of the relationship between an increase in alanine transaminase (ALT) levels and the use of potentially hepatotoxic medicinal products in hospitalised patients with COVID-19 to provide practising clinicians with a case-specific approach for selecting medicinal products with a lower risk of hepatotoxicity.

MATERIALS AND METHODS. The authors analysed 1,296 medical records of COVID-19 patients who had been admitted to a Volgograd Region hospital for infectious diseases in 2020–2022. A case-control study was performed using the pair-matched case–control method, with pairs of patients matched by their sex, age, and COVID-19 severity and outcomes. The authors identified the medical records of COVID-19 patients with baseline alanine transaminase (ALT) levels <1 or 2 times the upper limit of the normal range (ULN) and selected the medical records of the patients who had been having elevated ALT levels ≥2, 3, and 5 ULN (cases) or ALT levels <2 ULN (controls) throughout their hospital stay.

RESULTS. There was a significantly higher likelihood of detecting the use of ≥3 medicinal products associated with a high risk of drug-induced liver injury (DILI) in the medical records of all case groups than in those of the controls (odds ratio (OR)=2.38 (1.54–3.67), p<0.001, for detecting the use of ≥3 high-risk medicinal products and an increase in ALT levels from <1 ULN at baseline to >2 ULN, 195 pairs; OR=2.59 (1.48–4.53), p<0.001, for detecting the use of ≥3 high-risk medicinal products and an increase in ALT levels from <1 ULN at baseline to >3 ULN, 115 pairs). Certain medicinal products were associated with a significant increase in the risk of ALT rising to levels >2 ULN in patients with baseline levels <1 ULN (remdesivir: OR=4.38 (2.98–6.42), p<0.001; olokizumab: OR=7.83 (3.35–18.32), p<0.001; and levilimab: OR=3.0 (1.19–7.56), p=0.014) and levels >3 ULN in patients with baseline levels <2 ULN (remdesivir: OR=2.0 (1.21–3.30), p=0.006; olokizumab: OR=3.94 (2.35–6.62), p<0.001; and levilimab: OR=2.67 (1.24–5.74), p=0.009).

CONCLUSIONS. According to this study, there is a statistically significant association between elevated ALT levels in hospitalised COVID-19 patients and the use of several hepatotoxic medicines. Further studies are required to assess the safety of medicines used to treat COVID-19. It is also necessary to develop methods for the early detection and prevention of DILI.

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