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Hepatitis C virus (HCV) je, globalno posmatrano, najčešći uzročnik hroničnog virusnog hepatitisa sa dugogodišnjim progresivnim tokom, varijabilnom kliničkom slikom i često nepredvidivim ishodom. Naša drţava spada u grupu zemalja sa intermedijernom zastupljenošću HCV infekcije, tj. prevalencijom od 0,19% meĎu dobrovoljnim davaocima krvi i procenjenom prevalencijom od 1,13% na nivou Srbije. U našoj zemlji postoji višedecenijsko iskustvo u dijagnostici i lečenju pacijenata sa HCV infekcijom, ali osim kliničkih opservacija, nema objavljenih podataka o dugoročnom ishodu kod ovih pacijenata. U terapijskom i prognostičkom smislu najzahtevniju grupu predstavljaju pacijenti kod kojih se HCV infekcija otkrije u fazi uznapredovalog oštećenja jetre (fibroze ili ciroze), najčešće zbog višedecenijskog asimptomatskog toka bolesti, ali i zbog neadekvatnih mera skrininga, posebno u populacijama pod povećanim rizikom. U ovoj grupi pacijenata, čak i nakon terapijskog uspeha i postizanja nedetektibilne viremije (bez obzira na vrstu korišćenog terapijskog protokola), postoji rizik od nastanka nepovoljnih ishoda-uključujući virusološki i biohemijski relaps, dekompenzaciju jetre i pojave hepatocelularnog karcinoma (HCC). Višedecenijsko iskustvo u primeni kombinovane antivirusne terapije pegilovanim interferonom (PEG-IFN) i ribavirinom je pokazalo da postizanje stabilnog virusološkog odgovora (SVR) značajno redukuje morbiditet i mortalitet u grupi pacijenata sa teškim preterapijskim oštećenjem jetre. Pored toga, kliničke opservacije i literaturni podaci stranih autora govore u prilog potrebi za nastavkom praćenja ove grupe pacijenata i redovnim skriningom na HCC, čak i u slučaju odrţavanja nedetektibilne viremije i/ili regresije fibroze. Multikauzalna priroda, individualan tok bolesti i često nepredvidiv dugoročni ishod u ovoj grupi pacijenata, čak i nakon trajne supresije viremije, a u odsustvu preporuka o duţini praćenja i bilo kakvih publikovanih podataka u našoj zemlji, predmet su pose, Hepatitis C virus (HCV) is the most common worldwide cause of chronic viral hepatitis with a long-term progression, variable clinical presentation and outcome. Serbia is a country with an intermediary prevalence of HCV infection, estimated around 0,19% among blood donors and aproximately 1,13% in the general population of Serbia. In spite of two decades of diagnostic and therapeutic experiences with clinical observances, there are no published data concerning long-term prognosis and outcome in these patients. Patients with baseline liver fibrosis and cirrhosis present the most challenging group of patients, and are mostly underdiagnosed due to the asymptomatic nature of the disease and insufficient screening, especially in certain groups of patients. In this particular group, even after treatment success and HCV supression, remains a risk of unfavourable outcomes including virological and biochemical relapse, adverse clinical outcomes and hepatocellular carcinoma (HCC). Although sustained virological response (SVR) undoubtedly reduces liver-related morbidity and mortality in patients with severe baseline liver damage, clinical observance and published data show that these patients need continuous monitoring and HCC screening in spite of HCV supression and/or fibrosis regression. AIM: Main purpose of this study was to examine reliability and durability of SVR, as a predictor of treatment success and long-term outcome in patients with HCV related severe baseline liver injury. PATIENTS AND METHODS: A cohort study included 325 patients with HCV related severe baseline liver injury, who completed treatment protocol with pegylated interferon and ribavirin from January 2003. until November 2011. at the Hepatology department of the Clinic for Infectious And Tropical Diseases, Clinical Center of Serbia. After treatment completion, patients were followed and endpoints were December 2015, death outcome or the date of the last checkup. Inclusion criteria included: chronic hepat

Introduction: Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection. Methodology: Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes. Results: The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GT(rs)(8099917) in 78.6% and GG(rs)(12980275) in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes. Conclusions: Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.

Uvod: Hronični hepatitis C (HHC) je značajan uzročnik morbiditeta i mortaliteta u svetu. Značaj genetskih faktora u patogenezi HHC još uvek nije u potpunosti razjašnjen. Varijacije UGT1A1 gena su najčeša uzrok nasledne nekonjugovane hiperbilirubinemije - Zilberovog sindroma. Ovo je prva studija koja se bavi ispitivanjem učesta I osti TA ponavljanja u promotorskoj regiji UGT1A1 gena i analizom povezanosti UGT1A1*28 genotipa sa stepenom fibroze, viremijom i biohemijskim markerima kod pacijenata sa teškim oštećenjem jetre izazvanim HHC i virusološkim relapsom. Metode: Analizirana su TA ponavljanja u promotorskoj regiji UGT1A1 gena, kod 42 pacijenta sa teškom fibrozom i cirozom izazvanom HHC, koji postigli stabilan virusološki odgovor i 42 ispitanika u kontrolnoj grupi zdravih dobro - voljnih davalaca krvi. Pacijenti sa HHC su dodatno analizirani kliničkim pregledima, laboratorijskim analizama (hematološki, biohemijski i virusološki) i fibroskenom jetre. Rezultati: UGT1A1*28 genotip (7/7 TA ponavljanja) je bio prisutan kod 23.8% pacijenata sa HHC i 16,7% zdravih ispitanika, ali bez statistički značajne razlike (p= 0,49). Nivoi feritina i ukupnog bilirubina su bili u korelaciji sa prisustvom UGT1A1*28 pre primene antivirusne terapije, što sugeriše prediktivnu ulogu ovog genotipa. U ovoj studiji nije bilo korelacije UGT1A1*28 genotipa sa stepenom fibroze i viremijom. Prisustvo UGT1A1*28 genotipa nije uticalo na terapijske prekide i redukcije doze antivirusnih lekova, ishod lečenja niti pojavu kasnog virusološkog res lapsa kod pacijenata sa HHC i teškim oštećenjem jetre. Zaključak: Učestalost UGT1A1*28 genotipa je visoka među srpskim zdravim ispitanicima i pacijentima sa HHC infekcijom. Ispitivani genotip se ne dovodi u vezu sa nes željenim efektima ribavirina niti ima uticaj na ishod lečenja i dugoročnu prognozu pacijenata sa HHC., Background: Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in UGT1A1 gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of UGT1A1 TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse. Methods: Genetic testing of UGT1A1 TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging. Results: UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p= 0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of U G T1A1*28 genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of U G T1A 1*28 genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of U G T1A 1*28 genotype in CHC patients with severe liver injury. Conclusions: Frequencies of U G T1A 1*28 genotype are high in both Serbian CHC patients and healthy subjects. The presence of U G T1A 1*28 genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

Hepatitis C virusna (HCV) infekcija predstavlja globalni zdravstveni problem..., Hepatitis C virus (HCV) infection represents global health issue...