Citokini u serumu bolesnika s kroničnim hepatititsom C na hemodijalizi [Cytokine serum levels in patients with chronic hepatitis C infection of regular hemodialysis]

Slaviček, Jasna (2012) Citokini u serumu bolesnika s kroničnim hepatititsom C na hemodijalizi [Cytokine serum levels in patients with chronic hepatitis C infection of regular hemodialysis]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Serum cytokine concentrations were determined in this study in hepatitis C virus infected patients on chronic hemodialysis. Aims of the study. To determine differences in serum cytokine concentrations between hepatitis C virus (HCV) positive and HCV-negative patients on chronic hemodialysis, and differences in serum cytokine levels between HCV-RNA positive and HCV-RNA negative patients. To investigate the relation between circulating cytokines and liver enzymes in HCV-positive patients and their role in pathogenesis of chronic HCV infection. To study the relation between viral load and cytokines in patients with chronic hepatitis C. Patients and methods. The study included 31 patients on chronic hemodialysis with chronic hepatitis C, and 28 HCV negative patients on chronic hemodialysis. 113 healthy subjects participated as controls. In the sera of patients and healthy controls, the concentrations of the following cytokines were determined on a microchip: IL-2, IL-4, IL-6, IL-8, IL-1, IL-1β, IL-10, INF-, VEGF, EGF, MCP-1 and TNF-  Results. The concentrations of proinflammatory cytokines IL-1β, TNF- , IL-8, IL-6, MCP-1 and VEGF were higher in subjects on hemodialysis than in healthy subjects. There was no significant difference in INF-, IL-10 and IL-1 levels. HCV positive patients had significantly higher concentrations of IL- 6, TNF-  and IL-1β proinflammatory cytokines and lower IL-4 and EGF levels than healthy subjects. In comparison to HCV negative patients, HCV positive patients had higher IL-2 concentration. Hepatitis C genotype had no significant effect on the serum level of cytokines except on TNF-  which was significantly reduced in patients with genotype 1a infection. The consequence of HCV infection is increased concentration of ALT and GGT transaminases, particularly in patients with confirmed viral RNA. CRP levels do not significantly differ between HCV positive and HCV negative patients. Different hepatitis C genotypes do not show selective effect on serum concentrations of transaminases, CRP and ferritin. Conclusion. Increased formation of Th2 cytokines was not observed in this study in HCV infected patients on chronic hemodialysis. The study did not confirm the hypothesis that the inability to eradicate chronic HCV infection in dialysis patients was the consequence of increased formation of Th2 cytokine.

Abstract in Croatian

U ovom istraživanju mjerili smo serumske koncentracije citokina u bolesnika na kroničnoj hemodijalizi zaraženih hepatitisom C. Cilj istraživanja: utvrditi razlike u serumskim koncentracijama citokina izmedju HCV pozitivnih i HCV negativnih bolesnika na kroničnoj hemodijalizi te razlike u serumskim koncentracijama citokina između HCV-RNA pozitivnih i HCV-RNA negativnih bolesnika. Istražiti odnos između cirkulirajućih citokina i jetrenih enzima u HCV pozitivnih bolesnika te njihovu ulogu u patogenezi kronične HCV infekcije. Istražiti odnos virusnog opterećenja i citokina u bolesnika s kroničnim C hepatitisom. Bolesnici i metode: u istraživanje je uključeno 31 bolesnika na kroničnoj hemodijalizi s kroničnim hepatitisom C te 28 hepatitis C negativnih bolesnika na kroničnoj hemodijalizi. Kao kontrola poslužilo je 113 zdravih ispitanika. U serumu bolesnika i zdravih ispitanika određena je koncentracija slijedećih citokina na citokinskom mikročipu: IL-2, IL-4, IL-6, IL-8, IL-1, IL-1β, IL-10, INF-, VEGF, EGF, MCP-1 i TNF- . Rezultati: U ispitanika na hemodijalizi povišena je koncentracija proupalnih citokina IL-1β, TNF-, IL-8, IL-6 i MCP-1 i VEGF u odnosu na zdrave ispitanike. Nije bilo značajne razlike u INF-, IL-10 i IL-1. Hepatitis C pozitivni bolesnici imaju značajno povišenu koncentraciju proupalnih citokina: IL- 6, TNF-  i IL-1β a sniženu koncentraciju IL-4 i EGF u odnosu na zdrave ispitanike. U usporedbi s hepatitis C negativnim bolesnicima, hepatitis C pozitivni bolesnici imaju povišenu koncentraciju IL-2. Genotip hepatitisa C nema značajan učinak na serumske koncentracije citokina osim na TNF- , koji je značajno snižen u bolesnika zaraženih genotipom 1a. Zaraženost virusom hepatitisa C ima za posljedicu povišene koncentracije transaminaza ALT i GGT, naročito u bolesnika s dokazanom virusnom RNA. Razine CRP značajno se ne razlikuju između hepatitis C pozitivnih i hepatitis C negativnih bolesnika. Razni genotipovi hepatitisa C ne pokazuju selektivan učinak na serumske koncentracije transaminaza, CRP i feritina. Zaključak: U ovom istraživanju nije nađeno povećano stvaranje Th2 citokina u bolesnika zaraženih hepatitisom C na kroničnoj hemodijalizi. Istraživanje nije potvrdilo hipotezu da je nemogućnost iskorjenjivanja kronične HCV infekcije u bolesnika na dijalizi posljedica povećanog stvaranja citokina tipa Th2.

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