​Mirela Pavišić Ivelja

Ime i prezime: dr. sc. MIRELA PAVIŠIĆ IVELJA, dr. med.
 
Naslov disertacije: „PROCJENA CEREBROVASKULARNE REAKTIVNOSTI I MARKERA ENDOTELNE DISFUNKCIJE U BOLESNIKA S KRONIČNIM HEPATITISOM C“
 
Mentor: izv. prof. dr. sc. IVO IVIĆ
 
Datum obrane: 9. travnja 2021.
 
Poveznica: https://library.foi.hr/lib/knjiga.php?B=419&greska=3&item=3550


Kvalifikacijski znanstveni radovi za doktorsku disertaciju:


Ivelja MP, Ivic I, Dolic, K, Mestrovic A, Perkovic N, Jankovic S. Evaluation of cerebrovascular reactivity in chronic hepatitis C patients using transcranial color Doppler. PLoS One. 2019;14(6):e0218206.
 
Ivelja MP, Dolic, K, Tandara L , Perkovic N, Mestrovic A, Ivic I. Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection. PeerJ. 2021;9:e10723.
 
 
SAŽETAK:
 
Uvod: Kronična HCV infekcija je povezana sa sistemskim upalnim odgovorom i metaboličkim komplikacijama koje mogu pogodovati razvoju ateroskleroze i većem riziku od cerebrovaskularne bolesti (CVB).
 
Cilj: Cilj ove disertacije bio je procijeniti cerebrovaskularnu reaktivnosti (CVR) u bolesnika s kroničnim hepatitisom C te odrediti serumske razine E-selektina, VCAM-1, ICAM-1 i VEGF-A i njihovu korelaciju s CVR.
 
Metode: Ispitanicima s kroničnim hepatitisom C, kao i zdravim kontrolama učinjena je procjena CVR sukladno etabliranom testu zadržavanja daha koji koristi transkranijski color Doppler (TCCD) za mjerenje brzina protoka krvi i indeksa zadržavanja daha (BHI). Uzet je uzorak krvi ispitanicima u hepatitis i kontrolnoj skupini radi analize biljega endotelne disfunkcije i njihove korelacije s CVR procijenjene kroz ultrazvučno određen BHI.
 
Rezultati: Rezultati dobiveni tijekom zadržavanja daha su otkrili značajno niže vrijednosti prosječne vršne sistoličke brzine (AvPS start, P = 0.018), krajnje dijastoličke (AvED start, P = 0.031), srednje brzine na samom početku postupka zadržavanja daha (AvmeanV start, P = 0.02), kao i niže srednje vršne sistoličke brzine na kraju zadržavanja daha (AvPS max, P = 0.02) u hepatitis skupini. Vrijednosti CVR, procijenjene kroz BHI, su bile također značajno niže (P = 0.045) u HCV ispitanika. Dobivene su značajne razlike između testiranih skupina u svim endotelnim markerima izuzev E-selektina. Dok su ICAM-1 i sVCAM-1 bili značajno viši u hepatitis skupini, VEGF-A je bio značajno niži. Nije nađena značajna povezanost između BHI i bilo kojeg od biljega endotelne disfunkcije u kontrolnoj skupini, dok u skupini s hepatitisom dijagram rasapa ICAM-1 u odnosu na BHI sugerira moguću povezanost.
 
Zaključak: Rezultati ove disertacije potvrđuju povezanost kroničnog hepatitisa C s promijenjenom CVR i povišenim biljezima endotelne aktivacije (ICAM-1, VCAM-1) kao mogućim indikatorima povećanog rizika od cerebrovaskularne bolesti u bolesnika s HCV-om.
 
SUMMARY:
 
“EVALUATION OF CEREBROVASCULAR REACTIVITY AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION”
 
Background: Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis and increased risk of ischemic cerebrovascular disease.
 
Aim: This doctoral thesis is aimed to assess cerebrovascular reactivity (CVR) in patients with chronic hepatitis C, and also to determine E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection in order to correlate them with CVR.
 
Methods: Patients with chronic hepatitis C infection, as well as healthy blood donors in the control group, were assessed for CVR according to the well-established breath-holding test that uses the transcranial color Doppler (TCCD) for measurement of blood flow velocity and breath-holding index (BHI). A blood sample was taken from examinees in both groups to assess markers of endothelial dysfunction and to correlate them with CVR that was expressed as BHI determined by TCCD.
 
Results: Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. CVR values, calculated as the BHI, were also significantly lower (P = 0.045) in the hepatitis C group. The obtained results revealed significant differences between the groups in all endothelial markers with the exception of E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group the scatter plot of ICAM-1 vs BHI suggested possible association.
 
 Conclusions: the results of this doctoral thesis confirm an association between a chronic HCV infection and altered CVR as well as higher levels of markers of endothelial activation (ICAM- 1, VCAM-1) as possible indicators of an increased cerebrovascular disease risk. Ispiši stranicu