| Abstract | Unatoč pretkliničkim i kliničkim ispitivanjima, hepatotoksičnost predstavlja problem kod primjene mnogih postojećih
lijekova te ostaje najčešći uzrok povlačenja lijekova nakon stavljanja u promet.
U analiziranom razdoblju od siječnja 2019. do prosinca 2021. u KBC-u Zagreb nađen je 31 slučaj biopsijom potvrđenog
oštećenja jetrenog parenhima potencijalno uzrokovanog lijekovima; u 17 (54,84 %) žena i 14 (45,16 %) muškaraca.
Radilo se o 5 (16,13 %) pacijenata dječje dobi, 21 (67,74 %) pacijentu mlađe odrasle i odrasle dobi te o 5 (16,13 %)
pacijenata starije životne dobi. Kao najčešće kliničke manifestacije DILI-ja u ovom uzorku javljaju se nespecifična
jetrena lezija (12 pacijenata), abnormalni laboratorijski nalazi bez drugih kliničkih simptoma (8 pacijenata) te bilijarno
oštećenje, žutica i kolestaza (7 pacijenta). Laboratorijskim je pretragama najčešće nađeno miješano hepatocelularno i
bilijarno oštećenje, prisutno u 20 (64,52 %) pacijenata, slijedi hepatocelularno oštećenje u 10 (32,25 %) te bilijarno
oštećenje u jednog (3,23 %) pacijenta. U 10 (32,26 %) slučajeva radilo se o blagom, u 14 (45,16 %) o umjerenom, a u 7
(22,58 %) slučajeva o teškom oštećenju. Oštećenje se histološki najčešće manifestiralo steatozom, hemosiderozom te
steatohepatitisom, nađenima redom u 8, 7 i 6 slučajeva.
Lijekovi koji su potencijalno uzrokovali hepatotoksično oštećenje u više slučajeva su tamoksifen, prednizon,
amoksicilin-klavulanat, pembrolizumab i vinkristin, a pojedinačno nivolumab, metotreksat, azatioprin, didrogesteron,
valproat, izoniazid, aktinomicin D, ciklofosfamid, doksorubicin i paracetamol. Također su u više slučajeva nađeni
znakovi toksičnog djelovanja željeza kod pacijenata s višestrukim transfuzijama krvnih pripravaka u tijeku liječenja
hematoloških bolesti. |
| Abstract (english) | Despite strict preclinical and clinical studies, drug-induced hepatotoxicity is a common problem during administration
of many drugs, and still remains the main reason for withdrawing drugs from the market.
This study evaluated liver biopsies with potential signs of drug induced liver injury (DILI), diagnosed in University
Hospital Centre Zagreb between January 2019 and December 2021. During the analyzed period, a 31 case of suspected
DILI was found: in 17 (54,84 %) females and 14 (45,16 %) males. There were 5 (16,13 %) pediatric patients and 26
(83,87 %) adults, including 5 older patients. Non-specific liver injury was the most common clinical diagnosis seen in
12 patients, abnormal liver tests without other symptoms were the main reason for biopsy in 8 patients, and biliary injury
with jaundice and cholestasis in 7 patients.
Mixed hepatocellular and biliary injury was the most common finding during laboratory work-up, seen in 20 (64,52 %)
cases, followed by hepatocellular injury in 10 (32,25 %) cases and biliary injury in a single (3,23 %) case. In 10 (32,26
%) cases injury was mild, in 14 (45,16 %) moderate, and in 7 (22,58 %) severe. The most common histological patterns
of injury were steatosis, hemosiderosis and steatohepatitis, seen in 8, 7 and 6 cases respectively.
Drugs suspected as a cause of DILI in multiple patients were tamoxifen, prednisone, amoxicillin-clavulanate,
pembrolizumab and vincristine. Nivolumab, methotrexate, azathioprine, dydrogesterone, valproic acid, isoniazid,
actinomycin D, cyclophosphamide, doxorubicin and paracetamol were suspected as a cause of DILI in one patient each.
Moreover, several patients showed signs of iron induced liver damage due to multiple blood transfusions during
chemotherapy treatment or after bone marrow transplantation. |
