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U radu opisujemo mladu bolesnicu sa šećernom bolesti tipa I koja se zarazila virusom hepatitisa A (HAV) genotipa IB tijekom boravka u Burkini Faso. Prikaz bolesnice nedvojbeno potvrđuje važnost pridržavanja preporuka stručnih društava i nadležnih tijela o cijepljenju putnika., We describe a clinical case of hepatitis A in a young women with type I diabetes infected with genotype IB of hepatitis A virus (HAV) from Burkina Faso. The case confirms the importance of strict adherence to the recommendations by professional associations and institutions regarding vaccination of the travellers.

Hepatitis C vodeći je uzrok kronične bolesti jetre, hepatocelularnog karcinoma i važna indikacija za transplantaciju jetre. Glavni cilj liječenja je postizanje trajnog virološkog odgovora koji označava negativnu viremiju 12 tjedana nakon završetka liječenja (SVR, od engl. sustained virological response). Uvođenjem antivirusnih lijekova s izravnim djelovanjem, povećala se stopa SVR-a, skratilo vrijeme trajanja terapije i utjecalo se na stadij fibroze i steatoze jetre nakon liječenja. Cilj ovog rada bio je analizirati promjenu stadija fibroze (F1-F4) i steatoze (S0-S3) primjenom tranzijentne elastografije u prethodno neliječenih bolesnika s kroničnim hepatitisom C (n=205) koji su postigli trajni virološki odgovor, a bili liječeni isključivo direktno djelujućim antivirusnim lijekovima (DAA).

Polimorfizam jednog nukleotida (engl. single nucleotide polymorphism, SNP) rs12979860 u blizini promotora gena za interleukin-28B (IL-28B) tj. genotipizacija IL-28B povezana je s prirodnim tijekom infekcije virusom hepatitisa C kao i s odgovorom na antivirusno i imunomodulacijsko liječenje kombinacijom pegiliranog interferona alfa i ribavirina (tzv. dvojna terapija). U eri direktno djelujućih antivirusnih lijekova genotip IL-28B više nije značajan prediktor ishoda liječenja no i dalje je važan parametar koji određuje prirodni tijek povijesti HCV infekcije. U zemljama koje nemaju univerzalni pristup novim terapijskim opcijama genotipizacija IL-28B i dalje se primjenjuje u pred-terapijskoj obradi bolesnika koji se liječe dvojnom terapijom. Cilj ovog rada bio je analizirati rezultate genotipizacije IL-28B (udio homozigota za T i C alel te heterozigota) u 595 bolesnika s kroničnim hepatitisom C koji su bili uključeni u kliničku skrb Zavoda za virusni hepatitis Klinike za infektivne bolesti "Dr. Fran Mihaljević" u Zagrebu od siječnja 2013. do prosinca 2015. g. SNP rs12979860 detektiran je metodom lančane reakcije polimerazom u stvarnom vremenu. Analiza SNP-a rs12979860 u genu za IL-28B pokazala je da su 335 od 595 (56,3%) ispitanika bili CT heterozigoti, 173 od 595 ispitanika (29,1%) C homozigoti i 87 od 595 ispitanika (14,6%) T homozigoti. Distribucija C i T alela u SNP-u rs12979860 gena za IL-28B sukladni su literaturnim podatcima analize prevalencije ovih alela u osoba bijele rase europskog porijekla., Single nucleotide polymorphism (SNP) rs12979860 in the promotor region of the gene coding for interleukin-28B (IL-28B) is associated with the natural history of hepatitis C virus (HCV) infection and response to antiviral and immunomodulatory therapy with combination of pegylated interferon alpha and ribavirin (dual therapy). Despite the fact that the predictive role IL-28B genotyping is decreasing in the era of highly successful direct acting antiviral (DAA)-based treatment, it remains to be useful as a tool for predicting a natural course of HCV infection. In resource-limited settings with restricted access to new treatment options IL-28B polymorphism typing is still a part of pre-treatment workup before admission of dual therapy. The aim of this study was to analyse the results of IL-28B genotyping (percentages of C and T homozygotes and heterozygotes) for 595 Caucasian patients with chronic hepatitis C receiving clinical care at the Department of Viral Hepatitis of the University Hospital for Infectious Diseases, Zagreb and Croatian Reference Center for Viral Hepatitis since January 2013 till December 2015. Detection of single nucleotide polymorphism (SNP) rs12979860 was determined by using a real-time PCR test. Analysis of rs12979860 SNP in the IL-28B gene showed that 335 of 595 (56.3%) patients were CT heterozygotes, followed by C homozygotes (173 of 595 patients, 29.1%) whereas T homozygotes were the least frequent (87 of 595 patients, 14.6%). The patterns of IL-28 polymorphism in Croatian patients with chronic hepatitis C is in accordance with other results for Caucasians.

Trajni virusološki odgovor nakon 48 tjedana liječenja kombinacijom pegiliranog interferona alfa-2 i ribavirina u bolesnika s kroničnim hepatitisom C inficiranih genotipom 1 postiže se u oko 55% bolesnika. Prethodne studije pokazale su da je kraća, 24-tjedna terapija u bolesnika s niskom početnom viremijom (, About 55% of patients with genotype 1 chronic hepatitis C infection have sustained response to 48-week therapy with pegylated interferon alfa-2 and ribavirin. Previous studies have shown that patients with low pretreatment viremia (< 600 000 IU/mL) can be treated for 24 weeks with similar efficacy as with 48-week therapy, when early viral kinetic is measured. Our study showed that patients with low pretreatment viral load (< 600 000 IU/mL) are very heterogenous group and sustained viral response to pegylated interferon alfa-2 and ribavirin therapy is not better than in high viral load group (low viremia patients SVR 53.2% (n = 94), high viremia patients SVR 50.8% (n = 122)). Pretreatment low viral load patients that did not achieve SVR (n = 44) had a significantly higher fibrosis stage (non-SVR fibrosis stage 3.47 Ishak score vs. SVR+ fibrosis stage 2.94; p = 0,004), and they were significantly older (non-SVR patients 46.4 years, SVR+ patients 39.6 years, p = 0.008). Low initial viremia patients with cirrhosis (n = 6) did not achieve SVR at all, while among patients with fibrosis stage 4/6, 52 % achieved SVR. Our results suggest that apart from viral load at the beginning of treatment, fibrosis stage is also a predicting factor for therapy outcome, particularly in older patients and patients with cirrhosis.

Cilj ovog istraživanja bio je odrediti heterogenost podtipova HIV-a te analizirati primarnu rezistenciju virusa na antiretrovirusne lijekove u 30 prethodno neliječenih osoba koje su uključene u kliničku skrb Referentnog centra za dijagnostiku i liječenje HIV/AIDS-a tijekom 2013. g. Sekvenciranjem pol gena HIV-a te primjenom bioinformatičkih algoritama određeni su podtipovi virusa te detektirane mutacije povezane s primarnom rezistencijom na antiretrovirusne lijekove. Većina ispitanika (86,7%) bila je zaražena podtipom B. Otkriveno je 12 mutacija povezanih s primarnom rezistencijom HIV-a na antiretrovirusne lijekove, tj. 9 mutacija povezanih s primarnom rezistencijom na nukleozidne analoge inhibitore reverzne transkriptaze (NRTI) te 3 mutacije povezane s rezistencijom na nenukleozidne inihibitore reverzne transkriptaze (NNRTI). Primarna rezistencija na dvije klase antiretrovirusnih lijekova (NRTI i NNRTI) otkrivena je u jednog ispitanika. Najzastupljenija mutacija povezana s primarnom rezistencijom virusa na lijekove bila je T215S (rezistencija na NRTI). Mutacije značajne za nastanak primarne rezistencije detektirane su u 4 osobe zaražene podtipom B, jedne osobe zaražene podtipom A1 te jedne osobe zaražene rekombinantom podtipova A1 i B. U ovom je istraživanju po prvi puta dokazana pojava primarne rezistencije HIV-a na antiretrovirusne lijekove u osoba zaraženih non-B podtipovima virusa iz Hrvatske., The aim of this study was to analyse HIV subtype diversity as well as primary resistance to antiretroviral drugs in 30 treatment-naive individuals entering clinical care at the National Refence Center for HIV/AIDS during 2013. Sequencing the pol region of the viral genome and bioinformatic algorithms were used to determine HIV subtypes and to analyse transmitted drug resistance mutations. The majority of individuals (86,7 %) were infected with HIV-1 subtype B. Twelve mutations associated with primary resistance to antiretroviral drugs were detected in the study: 9 mutations conferring resistance to NRTI (nucleotide reverse-transcriptase inhibitors) and 3 mutations associated with resistance to NNRTI (non-nucleotide reverse-transcriptase inhibitors). Primary resistance to two antiretroviral drug classes (NRTI and NNRTI) were detected in one individual. The most frequent mutation was T1215S associated with primary resistance to NRTI. Drug resistance mutations were detected in 4 subtype B and 2 non-B HIV-infected individuals. This study showed, for the first time, the presence of mutations associated with primary resistance of HIV to antiretroviral drugs in individuals infected with non-B subtypes in Croatia.

Humani papilomavirusi (HPV) su heterogena skupina virusa koja se tijekom evolucije izvrsno prilagodila replikaciji u stanicama epitela. Perzistentna infekcija humanim papilomavirusima obvezan je etiološki kofaktor u nastanku benignih i malignih novotvorina pločastog epitela. Prepoznavanje različitosti onokogenog potencijala pojedinih genotipova HPV-a potaknulo je brojna istraživanja kliničke značajnosti molekularne heterogenosti ove skupine virusa. Molekularna analiza HPV-a značajna je ne samo u temeljnim virusološkim istraživanjima već i u humanoj medicini s posebnim naglaskom na problematiku povezanosti HPV-a s određenim tipovima tumora, razvoj klinički vrijednih dijagnostičkih testova, procjenu rizika od nastanka malignih lezija, sastavljanje kliničkih postupnika za probir, praćenje i liječenje zaraženih, razvoj cjepiva, analizu "pre-cjepne" distribucije genotipova, procjenu obuhvatnosti i učinkovitosti cjepiva i praćenje distribucije genotipova nakon uvođenja univerzalnog cijepljenja., Human papillomaviruses (HPV) are a heterogeneous group of viruses that have throughout their evolution adapted to replication in epithelial cells. Persistent infection with human papillomaviruses represents a necessary co-factor for the development of benign and malignant epithelial neoplasia. Different oncogenic potential of individual HPV genotypes encouraged numerous studies on clinical significance of the observed molecular heterogeneity of HPV. Molecular analysis of HPV is relevant not only for basic virological research but for human medicine as well with particular emphasis on association between HPV and various types of human tumors, development of clinically validated diagnostic assays, assessment of risk for progression of cervical lesions, vaccine design and development, analysis of pre-vaccination distribution of HPV genotypes, analysis of vaccine coverage and efficacy as well as monitoring of possible genotype replacement following introduction of universal HPV vaccination.

Toxoplasma gondii jedan je od glavnih oportunistički patogena u bolesnika zaraženih HIV-om. Prevalencija zaraze parazitom T. gondii u HIV-bolesnika u Hrvatskoj do sada nije poznata. Cilj rada bio je utvrditi seroprevalenciju toksoplazmoze u HIV-bolesnika u Hrvatskoj. Uključeno je 166 HIV-bolesnika i 219 dobrovoljnih davatelja krvi (DDK) kao zdrava kontrola. Enzimskim imunotestom određena su protutijela IgM, IgG i IgA na T. gondii. Seroprevalencija toksoplazmoze u HIV-bolesnika iznosi 51,8 %, a u DDK 52,5 %. Protutijela IgM bila su reaktivna samo u 2 HIV-bolesnika i 2 DDK, a IgA u 2 HIV-bolesnika i 1 DDK. Prema rizičnom ponašanju za HIV-infekciju utvrđeno je da muškarci koji imaju spolne odnose s drugim muškarcima imaju statistički značajno višu prevalenciju (66,7 %) i 2,4 puta veću šansu za toksoplazmozu nego drugi HIV-bolesnici (OR 2,37; 95 % IP 1,12–5,13). Rezultati su analizirani prema dobi, spolu, geografskom podrijetlu i za HIV-bolesnike broju CD4+ limfocita T i nisu nađene statistički značajne razlike ni za jedan parametar. Ovo je prvo istraživanje u kojem je utvrđena seroprevalencija toksoplazmoze u HIV-bolesnika u Hrvatskoj., Toxoplasma gondii is one of the main opportunistic agents in HIV-infected patients. The prevalence of T. gondii infection in HIV-infected patients in Croatia is unknown. The aim of the study was to determine the seroprevalence of toxoplasmosis in HIV-infected patients in Croatia. Included in the study were 166 HIV-infected patients and 219 blood donors (BD) as healthy control. Anti-toxoplasma IgM, IgG and IgA antibodies were determined with enzyme immunoassay respectively. Seroprevalence of toxoplasmosis in HIV-patients was 51.8 % and in BD 52.5 %. IgM antibodies were found in 2 HIV-patients and 2 BD, and IgA in 2 HIV-patients and 1 BD. According to HIV risk behaviour men who have sex with other men had significantly higher prevalence rate (66.7 %) and 2.4 higher risk for toxoplasma infection than other HIV-infected patients (OR 2.37; 95 % CI 1.12–5.13). Results were analyzed according to age, gender, geographic origin and for HIV-infected patients also according to CD4+ T-cell count number, and no statistically significant differences were found. This is the first study that presents seroprevalence of toxoplasmosis in HIV-infected patients in Croatia.

Virusološka dijagnostika HCV infekcije temelji se na primjeni standardiziranih seroloških i molekularnih testova. U molekularnoj dijagnostici HCV infekcije koriste se vrlo osjetljivi testovi za kvantifikaciju HCV RNK i genotipizaciju HCV-a. Genotip HCV-a važan je čimbenik pred-terapijske obrade bolesnika koji određuje trajanje liječenja, dozu ribavirina a omogućuje i procjenu vjerojatnosti uspjeha liječenja. Međutim, detekcija i/ili kvantifikacija HCV RNK u serumu preporučuje se za dokazivanje aktivne virusne replikacije u sklopu pred-terapijske obrade bolesnika kao i za praćenje virusološkog odgovora tijekom liječenja. Rezultati praćenja distribucije genotipova HCV-a u Referentnom centru za virusni hepatitis Ministarstva zdravstva R. Hrvatske pokazuju da je oko 60 % bolesnika s kroničnim hepatitisom C zaraženo genotipom 1 HCV-a, 36 % genotipom 3a, a svega 4 % bolesnika genotipovima 2 i 4. Zlatni standard liječenja kroničnog hepatitisa C (KHC) posljednjih sedam godina je kombinacija pegiliranog interferona alfa (PEG IFN) i ribavirina. Međutim, standardna terapija ne dovodi do izliječenja u 50 % bolesnika s genotipom 1, te oko 30 % bolesnika s genotipom 3a. Stoga se suvremeno liječenje bolesnika s kroničnim hepatitisom C temelji se na individualnom pristupu koji uključuje prilagodbu algoritma liječenja genotipu virusa, viremiji, stadiju fibroze te praćenju virusne kinetike. Modifikacija algoritma liječenja u bolesnika s genotipom 1 i sporim virusološkim odgovorom uključuje produljenje liječenja na 72 tjedna dok se liječenje bolesnika zaraženih genotipom 3a koji imaju nisku viremiju, a postignu brzi virusološki odgovor, liječenje može skratiti na 16 tjedana. Bolesnike s visokim stadijem fibroze (obilna vezivna septa) nije uputno liječiti prema visini viremije, jer u toj skupini bolesnika niska viremija ne predstavlja prediktor trajnog virusološkog odgovora. Bolesnike s akutnim hepatitisom C treba liječiti monoterapijom pegiliranim interferonom alfa u trajanju od 24 tjedna., Virological diagnostics of HCV infection is based on standardized serological and molecular assays. Molecular diagnostics of HCV infection includes assays for HCV RNK detection and/or quantification as well as genotyping assays. HCV genotype is an important parameter in the pre-treatment diagnostic workup that determines treatment duration, ribavirin dosage and represents an excellent predictor of treatment success. Detection and/or quantification of HCV RNK in the serum provides direct evidence of active viral replication in patients with chronic hepatitis C and enables determination of virological response during treatment. According to the Croatian Reference Center for Viral Hepatitis, 60 % of patients with chronic hepatitis C in Croatia are infected with genotype 1, 36 % of patients with genotype 3a and only 4 % of patients with genotypes 2 and 4. Standard treatment regimen for chronic hepatitis C over the past seven years is a combination of pegylated interferon alpha (PEG IFN) and ribavirin (guanosine analogue). However, standard treatment regimen based on the combination of PEG IFN and ribavirin for 48 weeks fails to achieve sustained viral response in 50 % of patients with genotype 1. Furthermore, 25 % of patients infected with genotype 3a will fail to respond to a standard 24 week regiment. Up-to date treatment of chronic hepatitis C should be individualized (treatment guided) according to the genotype, liver fibrosis, early viral kinetics and viremia. Modification of treatment algorithm in patients with genotype 1 who are late responders to treatment should include prolonged treatment (72 weeks). In patients infected with genotypes 2 and 3 and low viremia who are rapid responders, therapy can be shortened to 16 weeks. Patients with higher fibrosis rates (fibrotic septa) should not be treated according to viremia because in those patients viremia does not correlate with the ability to achieve sustained viral response. Meta-analysis of recent clinical trials on the treatment of acute hepatitis C showed that monotherapy with PEG IFN for 24 weeks is the suggested treatment regimen for this group of patients.