Review article: drug-induced liver injury in the non-alcoholic fatty liver disease context - A physiopathological and clinical integrated view

BESSONE F.; RAZORI M.V.; DIRCHWOLF M.; ROMA M.G.; RODIL M.A.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018 vol. 48 p. 892 - 913

0269-2813

Background: Non-alcoholic fatty disease (NAFLD)is the most common liver disease, since it is strongly associated with obesity and metabolic syndrome pandemics. NAFLD may affect drug disposal and has commonpathomechanisms with drug-induced liver injury (DILI); this may predispose tohepatoxicity induced by certain drugs that share these pathomechanisms. Inaddition, drugs may trigger fatty liver and inflammation per se by mimicking NAFLDpathomechanisms.Aim: To provide a comprehensive update on (1) potential mechanisms whereby certaindrugs can be more hepatotoxic in NAFLD patients, (2) the steatogenic effects of drugs and (3) the mechanism involved in drug-induced steatohepatis.Methods: A language- and date-unrestrictedMedline literature search was conducted to identify pertinentbasic and clinical studies on the topic.Results: Drugs can induce macrovesicularsteatosis by mimicking NAFLD pathogenic factors, including insulin resistanceand unbalance between fat gain and loss. Other forms of hepatic fataccumulation exist, such as microvesicular steatosis and phospholipidosis, andare mostly associated with acute mitochondrial dysfunction and defectivelipophagy, respectively. Drug-induced mitochondrial dysfunction is alsocommonly involved in drug-induced steatohepatitis. Patients with pre-existingNAFLD may be at higher risk for DILI induced by certain drugs, and polypharmacyin obese individuals to treat their comorbidities may be a contributing factor.Conclusions: The relationship between DILI andNAFLD may be reciprocal: drugs can cause NAFLD by acting as prosteatogenicfactors, and pre-existing NAFLD could be a predisposing condition for certaindrugs to cause DILI. Polypharmacy associated with obesity might potentiate theassociation between this condition and DILI.