Abstract
Many drugs (now it’s known more than 1200) are associated with hepatic side effects. Children (especially newborns and infants) are unique population with specific characteristics of absorption, metabolism and elimination of drugs that can predispose to hepatotoxicity. Aim of this review is to estimate risk factors of hepatotoxicity related to the patients’ peculiarities and drug itself, also to describe some mechanisms and types of drug-induced liver disease (DILD) and beside this to offer some methods of the treatment and prevention of hepatotoxicity. In children the most often mentioned drugs caused DILD are antibiotics, psychotropics and NSAIDs and the main type of DILD is acute hepatitis with mortality of 10%. To conclude it’s highly important to monitor activity of hepatic enzymes (ALT, AST, AP) during treatment by potentially hepatotoxic drugs in patients from risk groups (early age, any liver disease, diabetes mellitus, obesity, poor nutritional status) in order to timely withdraw offending drug and prescribe hepatoprotectors or even perform liver transplantation.
Highlights
The essential role in development of Drug-induced liver diseases (DILD) in children belongs to age-dependent maturation of cytochrome P450 system and in particular its isoenzyme 3A4 that participates in metabolism of 50% of all drugs [4] including those that have evident hepatototoxic effect - erythromycin, co-trimoxazol
Drug-induced liver disorders (DILD) are the diverse group of clinicomorphological types of liver injury caused by drug intake. during last 10-15 years the number of DILD increased in 30 times
In children the leading positions are placed by antibiotics, antipsychotics, non-steroidal anti-inflammatory drugs (NSAID) as a reason for DILD
Summary
Drug-induced liver diseases (DILD) – heterogeneous group of clinical and morphological liver changes caused by pharmacological treatment. Actuality of this problem: Frequency of the drug-induced liver diseases is up to 25% of all adverse reactions related to pharmacological treatment and is on the third place following viral and alcohol related liver diseases. In children the most often mentioned drugs caused DILD are antibiotics (AB) contributing to nearly 50% of all cases of liver toxicity [2]. The frequency of hospitalizations caused by different signs of drug-induced hepatotoxicity are 1,9-6,2% and even 20% in some centers, and the frequency of fatal outcome in DILD achieve 7,4-11,9% [9,10,11,12]. The real number of patients with DILD are not specified due to different reasons: 1) wide over-the-counter availability; 2) seasonal fluctuation of drugs intake – more intensive use of antipyretic drugs and antibiotics (AB) in autumn and winter; 3) absence of evident clinical signs of DILD in some cases; 4) underreporting (“even though know but keep silent”); 5) absence of similar reports in literature; 6) present liver injury does not correlate with chemical and pharmacological characteristics of the drug; 7) unidentified cases of DILD or wrong interpretation of causality of liver injury mainly due to underestimation of possibility of drug-induced pathology in general
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