Utjecaj nealkoholne masne bolesti jetre na serumske koncentracije transformirajućeg čimbenika rasta beta u COVID-19

master's thesis

• Title (english): The influence of non-alcoholic fatty liver disease on serum concentrations of transforming growth factor-beta in COVID-19
• Author: Frano Šušak
• Mentor: Neven Papić (mentor)
• Committee member: Adriana Vince (predsjednik povjerenstva)
• Committee member: Goran Tešović (član povjerenstva)
• Committee member: Neven Papić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Infectious Diseases); Zagreb
• Defense date and country: 2023-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Infectology

Abstract

Nealkoholna masna bolest jetre (NAFLD) vodeći je uzrok kronične jetrene bolesti u razvijenom svijetu i prepoznata je kao rizični faktor za razvoj težih oblika COVID-19. Unatoč tome, imunološki mehanizmi kojima NAFLD pogoršava COVID-19 su i dalje nepoznati. Transformirajući čimbenik rasta beta 1 (TGF-β1) sa svojim imunomodulatornim i profibrotičkim djelovanjem ima važnu ulogu u NAFLD-u. Njegova uloga u COVID-19 je manje jasna, ali bi mogla biti patofiziološka poveznica između te dvije bolesti. Cilj ovog istraživanja parova bio je analizirati serumske koncentracije TGF-β1 u COVID-19 pacijenata ovisno o prisustvu NAFLD-a i težine bolesti. U istraživanje je uključeno 60 hospitaliziranih COVID-19 pacijenata (od kojih 30 je dijagnosticiran NAFLD) i 20 zdravih kontrola (od kojih 10 je dijagnosticiran NAFLD) koji se nisu razlikovali ovisno o dobi i spolu. Izmjerene su im serumske koncentracije TGF-β1 te su hospitalizirani pacijenti dodatno podijeljeni u podskupine ovisno o težini COVID-19 (srednje teški, teški i kritični). Oboljeli od COVID-19 imali su niže vrijednosti TGF-β1 u odnosu na zdrave kontrole. Prisustvo NAFLD-a bilo je povezano s višim koncentracijama TGF-β1 i u COVID-19 oboljelih i u zdravih kontrola. Nadalje, serumske razine TGF-β1 korelirale su s težinom COVID-19, a najviše su bile u kritično bolesnih. Iako su teži oblici bolesti bili praćeni višim koncentracijama TGF-β1, u non-NAFLD skupini, za razliku od NAFLD skupine, nije postojala statistički značajna razlika u razini TGF-β1 ovisno o težini COVID-19. Osim toga, koncentracije TGF-β1 pokazale su dobru diskriminativnu vrijednost u predikciji razvoja komplikacija i loših ishoda COVID-19 poput potrebe za naprednim mjerama respiratorne potpore, vremena oporavka, primitka u jedinicu intenzivnog liječenja (JIL), razvoja nozokomijalnih infekcija i smrtnosti. Zaključno, TGF-β1 bi mogao biti dobar prognostički biomarker za težinu bolesti i loše ishode COVID-19 u pacijenata s NAFLD-om.

Abstract (english)

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in Western countries, was identified as a possible risk factor for COVID-19 severity. However, immunological mechanisms by which NAFLD exacerbates COVID-19 remain unknown. Transforming growth factor-beta1 (TGF-β1) has an important immunomodulatory and profibrotic role, which has already been well described in NAFLD. However, the role of TGF-β1 in COVID-19 remains unclear but could also be the pathophysiology link between these two conditions. The aim of this case-control study was to analyze the expression of TGF-β1 in COVID-19 patients depending on the presence of NAFLD and disease severity. Serum TGF-β1 concentrations were measured in 60 hospitalized COVID-19 patients (30 subsequently diagnosed with NAFLD) and 20 healthy controls (10 subsequently diagnosed with NAFLD). There were no differences in age and sex between the groups and the COVID-19 group was further divided into subgroups depending on disease severity (moderate, severe, and critical). The COVID-19 group had lower levels of TGF-β1 compared to healthy controls. NAFLD was associated with higher serum TGF-β1 concentrations in both the COVID-19 group and healthy controls. TGF-β1 concentrations also correlated with COVID-19 severity. However, unlike in the NAFLD group, there was no significant correlation between TGF-β1 concentrations and disease severity in the non-NAFLD group. Furthermore, admission TGF-β1 concentrations showed good discriminative accuracy in predicting the development of critical disease and COVID-19 complications (need for advanced respiratory support, ICU admission, time to recovery, development of nosocomial infections, and mortality). In conclusion, TGF-β1 could be an efficient biomarker for predicting disease severity and adverse outcomes in patients with NAFLD.

• Keywords: COVID-19; SARS-CoV-2; NAFLD; TGF-β1; citokini
• Keywords (english): COVID-19; SARS-CoV2; NAFLD; TGF-β1; cytokines
• Language: croatian
• URN:NBN: urn:nbn:hr:105:428032
• 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: 2023-11-02 10:40:54