Oštećenje jetre ksenobioticima

master's thesis

• Title (english): Liver damage due to xenobiotics
• Author: Irena Tomić
• Mentor: Lucija Virović Jukić (mentor)
• Committee member: Davor Hrabar (predsjednik povjerenstva)
• Committee member: Ivančica Delaš (član povjerenstva)
• Committee member: Lucija Virović Jukić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2018-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology

Abstract

Poznato je preko 1000 lijekova i biljnih pripravaka koji mogu uzrokovati oštećenje jetre (DILI, engl. drug-induced liver injury).
Oštećenje jetre može nastati na dva različita načina: izravnim oštećenjem jetre koje je ovisno o dozi, ili idiosinkratski, nepredvidljivo i neovisno o dozi, pri čemu podležeći patofiziološki mehanizam može biti imunološki ili metabolički. Lijekovi koji najčešće uzrokuju DILI su antibiotici, analgetici, lijekovi koji djeluju na živčani sustav i statini. Oštećenje jetre lijekovima jedan je od dva najčešća razloga za povlačenje lijekova s tržišta. DILI se najčešće klasificira prema obrascu povišenja jetrenih enzima u tri skupine, hepatocelularno oštećenje, kolestatsko oštećenje ili miješano oštećenje. Kliničke manifestacije DILI-ja su različite pa se tako bolesnici prezentiraju samo s prolaznim povišenjem aminotransferaza, preko kolestaze sa svrbežom, akutnog hepatitisa praćenog žuticom pa sve do akutnog zatajenja jetre koje zahtjeva hitnu transplantaciju jetre. Simptomatski bolesnici mogu se žaliti na slabost, mučninu, povraćanje, svrbež, umjereno povišenu tjelesnu temperaturu, bol u desnom gornjem kvadrantu abdomena, žuticu, taman urin i svijetlu stolicu. Ne postoje specifični dijagnostički testovi, nego se dijagnoza DILI-ja postavlja isključivanjem jetrenih bolesti druge etiologije koje imaju sličnu kliničku ili laboratorijsku prezentaciju, uz detaljne podatke o svim lijekovima koje pacijent uzima. Liječenje DILI-ja najčešće se svodi na isključivanje inkriminiranog lijeka iz daljnje upotrebe uz primjenu potpornih mjera, a specifična farmakoterapija uključuje primjenu N-acetilcisteina u slučaju oštećenja jetre paracetamolom i L-karnitina u slučaju predoziranja valproatom.

Abstract (english)

Over 1,000 drugs and herbal substances are known to cause drug-induced liver injury (DILI). Liver injury occurs through two different mechanisms: the liver can be affected directly in a dose-dependent manner, or idiosyncratically in an unpredictable manner through immunological or metabolic underlying pathophysiological mechanism and independently of the dose. Antimicrobial agents, analgesics, statins and drugs that affect the nervous system are most commonly associated with the development of DILI. DILI is one of the two leading indications for drug withdrawal from the pharmaceutical market. DILI is often categorized by the type of hepatic injury into hepatocellular, cholestatic, or mixed, each with its characteristic enzyme elevation pattern. The diagnosis of DILI unites a wide spectrum of clinical manifestations, from mild liver test abnormalities, cholestasis with pruritus and acute hepatitis with jaundice to acute liver failure which requires emergent liver transplantation. Symptomatic patients may report malaise, nausea, vomiting, pruritus, low-grade fever, right upper quadrant pain, jaundice, pale stools and dark urine. There is no specific diagnostic test for DILI. The diagnosis depends on obtaining a careful drug use history and ruling out other potential causes of liver injury. The primary treatment for DILI is withdrawal of the offending drug, followed by supportive care. Specific therapies include use of N-acetylcysteine for intoxication with acetaminophen, and of L-carnitine for overdosing with valproic acid.

• Keywords: DILI; oštećenje jetre ksenobioticima; izravno oštećenje; idiosinkratsko oštećenje; hepatocelularni kolestatski i miješani tip oštećenja
• Keywords (english): DILI (Drug-Induced Liver Injury); direct mechanism; idiosyncratic mechanism; hepatocellular cholestatic or mixed injury
• Language: croatian
• URN:NBN: urn:nbn:hr:105:000505
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-01-25 10:37:17