Antibiotic‑associated drug‑induced liver damage with cholestasis: actualization of problem in COVID‑19 era

Abstract

Drug-induced liver injury (DILI) is a fairly frequent adverse drug reaction, which accounts for about half (40–50 %) of cases of acute liver damage. The cholestatic variant of DILI is characterized by an increase in the activity of alkaline phosphatase (ALP) above the two upper limits of the norm (ULN) or the ratio of alanine aminotransferase (ALT) / ALP ≤ 2 in chronic course. A common cause of the cholestatic variant of DILI is a use of drugs for the treatment of infectious diseases, such as beta-lactam antibiotics, Aminoglycosides, Amphenicol, Lincosamides, macrolides, fluoroquinolones, antituberculosis drugs, etc. This problem has acquired particular urgency during the COVID-19 pandemic. The widespread use of azithromycin, hydroxychloroquine, interferons, lopinavir, and other drugs for the treatment of COVID-19 also contributed to an increase in the incidence of DILI. In accordance with clinical guidelines in case of suspicion of a drug-induced liver damage, one should stop use of suspected drug and, if necessary, prescribe hepatoprotectors, for example, ursodeoxycholic acid (UDCA). The effectiveness of the use of UDCA in patients with DILI, including those caused by the intake of antibacterial drugs, has been confirmed by randomized placebo-controlled clinical trials. The effectiveness of UDCA -drug Ursosan® has been confirmed in real life clinical practice. This drug can be used for long-term (up to several months), or lifelong treatment with hepatotoxic drugs like antituberculosis and antirheumatic drugs. The daily dose of Ursosan® is 12–15 mg/kg, if necessary – 20 mg / kg (with a weight of a patient about 75–100 kg, daily dose will be equal to two tablets of Ursosan Forte®, 500 mg).