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Dijetoterapija i klinička prehrana zauzimaju važno mjesto u liječenju bolesnika s upalnim bolestima crijeva (UBC). Nutritivna potpora važna je komponenta liječenja pacijenata s UBC-om, a uključuje prevenciju i liječe-nje svih oblika malnutricije. Potvrđenu malnutriciju u bolesnika s upalnim bolestima crijeva treba adekvatno zbrinjavati jer pogoršava prognozu, stupanj komplikacija, mortalitet i kvalitetu života bolesnika. Enteralna je prehrana izuzetno važan dio nutritivnog liječenja u upalnim bolestima crijeva, a u pojedinim situacijama ima značenje primarne terapije. Parenteralna prehrana ima mjesto u liječenju upalnih bolesti crijeva, i u akutnim situacijama i u kroničnom liječenju bolesnika sa sindromom kratkog crijeva. U izradi ovih smjernica sudjelo-vali su predstavnici Hrvatskog društva za kliničku prehranu Hrvatskoga liječničkog zbora, Hrvatskog društva za imunologiju sluznice Hrvatskoga liječničkog zbora, Hrvatskoga gastroenterološkog društva i Hrvatskog društva nutricionista i dijetetičara. Utemeljene su na dokazima, prema sustavu GRADE (engl. Grading of Re-commendations, Assessment, Development and Evaluation), koji uz snagu dokaza opisuje i razinu preporuke. Temeljni zaključci ovih smjernica odnose se na prepoznavanje malnutricije u ovoj skupini bolesnika, određi-vanje nutritivnih potreba, nadoknadu ključnih nutrijenata i farmakonutrijenata, primjenu različitih modaliteta artificijalne prehrane te specifičnosti perioperativne prehrane., Diet therapy and clinical nutrition have a significant place in the treatment of patients with inflammatory bowel disease (IBD). Nutritional support is an important component of medical therapy in patients with IBD, and in-cludes the prevention and treatment of all forms of malnutrition. Confirmed malnutrition in patients with in-flammatory bowel disease should be treated adequately as it exacerbates prognosis, degree of complications, mortality and quality of life of a patient. Enteral nutrition is an extremely important part of nutritional therapy in inflammatory bowel diseases, and in some situations it has the meaning of primary therapy. Parenteral nutri-tion has its place in nutrition therapy of inflammatory bowel disease, both in acute and chronic treatment of patients with short bowel syndrome. Representatives of the Croatian Society of Clinical Nutrition Croatian Medical Association, Croatian Society of Mucosal Immunology Croatian Medical Association, Croatian Socie-ty of Gastroenterology and Croatian Society of Nutritionists and Dietitians participated in the development of these guidelines. They are evidence-based, according to the GRADE (Grading of Recommendations, Assess-ment, Development and Evaluation) system which, with the strength of evidence, also describes the level of recommendation. The basic conclusions of these guidelines relate to the assessment of malnutrition in this group of patients, the determination of nutritional needs, the replacement of key nutrients and pharmaconutri-ents, the application of various artificial nutrition modalities and the specificities of perioperative nutrition.

Diet therapy and clinical nutrition have a significant place in the treatment of patients with inflammatory bowel disease (IBD). Nutritional support is an important component of medical therapy in patients with IBD, and in-cludes the prevention and treatment of all forms of malnutrition. Confirmed malnutrition in patients with in-flammatory bowel disease should be treated adequately as it exacerbates prognosis, degree of complications, mortality and quality of life of a patient. Enteral nutrition is an extremely important part of nutritional therapy in inflammatory bowel diseases, and in some situations it has the meaning of primary therapy. Parenteral nutri-tion has its place in nutrition therapy of inflammatory bowel disease, both in acute and chronic treatment of patients with short bowel syndrome. Representatives of the Croatian Society of Clinical Nutrition Croatian Medical Association, Croatian Society of Mucosal Immunology Croatian Medical Association, Croatian Society of Gastroenterology and Croatian Society of Nutritionists and Dietitians participated in the development of these guidelines. They are evidence-based, according to the GRADE (Grading of Recommendations, Assess-ment, Development and Evaluation) system which, with the strength of evidence, also describes the level of recommendation. The basic conclusions of these guidelines relate to the assessment of malnutrition in this group of patients, the determination of nutritional needs, the replacement of key nutrients and pharmaconutrients, the application of various artificial nutrition modalities and the specificities of perioperative nutrition.

Aim To analyze the distribution of SLC6A4 gene polymorphisms in Crohn’s disease (CD) patients and their association with the disease. Methods We evaluated the presence/absence of promoter (5- HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis. Results CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively ; P = 0.154) and age (41.3 ± 12.8 years vs 41.7 ± 8.8 years, respectively, P = 0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P = 0.003 and P = 0.002, respectively) and between the corresponding female subgroups (P = 0.004 and P = 0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P = 0.013, age- and sexadjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29- 0.86 ; women: P = 0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S- STin2.12 (5-HTTLPR/ rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P = 0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. Conclusion STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis.

Želučani je karcinom četvrti po učestalosti karcinom u svijetu i drugi po učestalosti razlog mortaliteta uzrokovanog malignim bolestima. Iako je etiologija tog karcinoma multifaktorijalna, Helicobactor pylori infekcija izrazito je povezana sa želučanom karcinogenezom. Na karcinogenezu utječu i neko čimbenici okoliša, kao i genetska raznolikost, koji mogu dovesti do različitih upalnih odgovora te time utjecati na klinički ishod bolesti. Kronični gastritis izazvan Helicobacter pylori infekcijom najjači je poznati čimbenik rizika razvoja adenokarcinoma distalnog dijela želuca, mada učinak bakterijske eradikacije na samu karcinogenezu ostaje zasada nedovoljno istražen. Iako izgleda da eradikacija Helicobacter pylori infekcije smanjuje rizik nastanka želučanog karcinoma, više novijih terapijskih pokušaja prevencije nastanka tog tumora eradikacijom Helikobacter pylori infekcije polučile su razočaravajuće rezultate. U pokušaju razjašnjenja tog problema u populacijama s visokim rizikom, istraživači su započeli provođenje prospektivnih randomiziranih, dvostruko slijepih populacijskih studija. Rezultati prethodnih studija ukazali su na važnost dugotrajnog i pomnog praćenja bolesnika nakon provedene eradikacijske terapije. Izgleda da je eradikacija infekcije u svrhu prevencije želučanog karcinoma djelotvorna samo onda kada se provede prije razvoja premalignih promjena/lezija: atrofije, metaplazije i displazije želučane sluznice. Osim toga, značajna učinkovitost izliječenja uočena u mlađih bolesnika, sugerira potrebu provođenja eradikacije Helicobacter pylori infekcije što je to moguće ranije.

Hrvatske konsenzus konferencije o virusnim hepatitisima održane su 2005. i 2009. g. (1). S obzirom na brojne nove spoznaje o epidemiologiji, dijagnostici i liječenju virusnih hepatitisa (poglavito kroničnog hepatitisa C genotipa 1) u protekle četiri godine, 28. veljače 2013. g. održana je nova Hrvatska konsensus konferencija o virusnim hepatitisima u Zagrebu. Sažeti tekst ove Hrvatske konsenzus konferencije o virusnim hepatitisima sadrži prikaz novih spoznaja o epidemiologiji virusnih hepatitisa, serološkoj i molekularnoj dijagnostici virusnih hepatitisa, određivanju polimorfizma promotora gena za IL-28, procjeni stadija fibroze, algoritmu dijagnostičkog praćenja bolesnika, liječenju kroničnog hepatitisa C (genotipovi 1-6) i hepatitisa B, liječenju specijalnih populacija (djeca, bolesnici na dijalizi, bolesnici liječeni transplantacijom, osobe s HIV/HCV koinfekcijom) i nuspojavama liječenja.

Uvođenje biološke terapije u kliničku praksu je značajan napredak u liječenju kroničnih upalnih bolesti crijeva, prije svega zbog njihove dokazane djelotvornosti te činjenice da su to prvi lijekovi kojima se uspjelo promijeniti prirodni tijek tih bolesti. Radi se, međutim, o vrlo skupim lijekovima s vrlo kompleksnim mehanizmima djelovanja i mogućim nuspojavama, te njihovo korištenje u vrlo kompliciranim bolestima kakve su upalne bolesti crijeva zahtijeva smjernice bazirane na rezultatima dobro kontroliranih studija. Referentni centar Ministarstva zdravlja i Sekcija za upalne bolesti crijeva Hrvatskog gastroenterološkog društva organizirali su stoga konsenzus konferenciju tijekom koje su definirane hrvatske smjernice za liječenje upalnih bolesti crijeva anti-TNF lijekovima. Tekst sa smjernicama uključuje definicije upalnih bolesti crijeva, opće principe liječenja upalnih bolesti crijeva, važnost mukoznog cijeljenja, analizu razloga dedjelotvornosti i gubitka djelotvornosti anti-TNF terapije, daje preporuke o dužini terapije, daje smjernice za probir na oportunističke infekcije prije početka anti-TNF terapije, osvrće se na probleme reprodukcije vezane za anti-TNF terapiju te konačno daje smjernice za liječenje raznih fenotipova upalnih bolesti crijeva i ekstraintestinalnih manifestacija upalnih bolesti crijeva.

Hrvatske konsenzus konferencije o virusnim hepatitisima održane su 2005. i 2009. g. (1). S obzirom na brojne nove spoznaje o epidemiologiji, dijagnostici i liječenju virusnih hepatitisa (poglavito kroničnog hepatitisa C genotipa 1) u protekle četiri godine, 28. veljače 2013. g. održana je nova Hrvatska konsensus konferencija o virusnim hepatitisima u Zagrebu. Sažeti tekst ove Hrvatske konsenzus konferencije o virusnim hepatitisima sadrži prikaz novih spoznaja o epidemiologiji virusnih hepatitisa, serološkoj i mo¬lekularnoj dijagnostici virusnih hepatitisa, određivanju polimorfizma promotora gena za IL-28, procjeni stadija fibroze, algoritmu dijagnostičkog praćenja bolesnika, liječenju kroničnog hepatitisa C (genotipovi 1-6) i hepatitisa B, liječenju specijalnih populacija (djeca, bolesnici na dijalizi, bolesnici liječeni transplantacijom, osobe s HIV/HCV koinfekcijom) i nuspojavama liječenja.

S obzirom na činjenicu da TNF ima važnu ulogu u patogenezi upalnih bolesti crijeva, u liječenju ulceroznog kolitisa upotrebljavaju se anti-TNF lijekovi. Iako su ovi lijekovi značajno unaprijedili liječenje bolesnika, imunogeničnost ograničava njihove mogućnosti u kliničkoj primjeni. Infliksimab i adalimumab su učinkoviti u postizanju i održavanju remisije u ambulantnih bolesnika s umjereno teškim i teškim ulceroznim kolitisom. Biološki lijekovi mogu biti i lijek izbora za liječenje bolesnika s refraktornim proktitisom i refraktornim pouchitis-om. U hospitaliziranih bolesnika s teškim akutnim kolitisom refraktornih na intravensku primjenu kortikosteroida može se primijeniti infliksimab kao druga linija terapije, ali je adekvatna dugotrajna terapija održavanja s anti-TNF lijekom potrebna za dugoročni učinak. S obzirom na poznate rizike i nuspojave anti-TNF lijekova nužna su buduća istraživanja, osobito o problemu konkomitantne terapije tiopurinskim lijekovima.

Anticardiolipin antibodies as potential serologic markers of thrombosis risk in IBD patients

Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6- mercaptopurine (6-MP) are not effective in one- third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. Among them, of recognized importance are thiopurine S- methyltransferase (TPMT), xanthine oxidase (XO) and inosine triphosphate pyrophosphatase (ITPA). While genetic variability in TPMT has been translated into practical guidelines the importance of XO and ITPA is not still fully understood. ITPA catalyzes the pyrophosphohydrolysis of inosine triphosphate (6- TITP) to inosine monophosphate (6-TIMP), thereby preventing an abnormal accumulation of 6-TITP nucleotides in cells and their incorporation into RNA and DNA. ITPA deficiency has been related with non-myelosuppression adverse effects such as pancreatitis, nausea, flu-like symptoms and skin rashes in patients treated with AZA/6-MP. XO catalyzes the catabolism of 6-MP to 6-thiouric acid. 6-MP induced adverse effects may increase in poor XO metabolizers. Since genetic variability shows marked interindividual and interethnic differences, the aim of this study was to examine the allelic variations of of ITPA and XO in Croatian IBD patients. PATIENTS and METHODS. DNA of 235 patients with IBD was genotyped for ITPA 94C>T, ITPA124+21A>C, XO 837C>T, XO 2211C>T by methods based on RealTime Polymerase Chain Reaction. RESULTS. Concerning the 94C>A variant of the ITPA gene, 198 (86.1%) individuals were homozygous for the wild-type allele (C/C), 30(13%) were heterozygous (A/C), and 2 (0.9%) were homozygous for the mutant allele (A/A). For ITPA 124+21A>C, 143 (60.8%) individuals were homozygous for the wild-type (A/A), 89 (37.9%) were heterozygous (A/C) and 3(1.3%) were homozygous for the mutated allele (C/C). Concerning the 837C>T variant of the XO gene, 203 (90.2%) individuals were homozygous for the wild- type allele (C/C) and 22(9.8%) were heterozygous (A/C). For XO 2211C>T 98 (43.6%) individuals were homozygous for the wild-type (C/C), 89 (42.6%) were heterozygous (C /T) and 31(13.8%) were homozygous for the mutated allele (T/T). CONCLUSION. ITPA and XO exhibit considerable variability in Croatian population which could be, besides TPMT polymorphism, additional risk factors for thiopurine drug adverse reactions.

The risk of relapse after discontinuation of biological therapy in crohn's disease patients – inital experience in a tertiary centre.

Najbolji pokazatelj težine oštećenja jetre i prognoze bolesti u kroničnom virusnom hepatitisu je uznapredovalost jetrene fibroze. Ona se može utvrditi biopsijom jetre ali i neinvazivnim fizikalnim ili biološkim metodama. Biopsiju jetre koristimo za etiološku dijagnozu bolesti jetre, utvrđivanje težine bolesti (stadija fibroze) i za definiranje prognoze. U kroničnom virusnom hepatitisu navedene informacije pomažu i u procjeni omjera koristi i rizika te modaliteta antivirusne terapije. Serološkim testovima i elastografijom moguće je razlikovati značajnu fibrozu (F ≥2) od početne fibroze (AUROC 0, 77-0, 83 za serologiju i 0, 84 za elastografiju) i cirozu od necirotičnih stadija fibroze (AUROC 0, 77-0, 86 za serologiju i 0, 9-0, 94 prosječne vrijednosti AUROC u meta- analizama za elastografiju). U pojedinačnoj izvedbi metoda izbora za razlikovanje ciroze od necirotičnih stadija jetrene fibroze je elastografija. Kombinacijom seroloških testova i elastografije moguće je u slučaju podudarnih vrijednosti s točnosti od 93-95 % utvrditi postojanje ciroze i izbjeći biopsije u 77-80 % bolesnika. U slučaju da se vrijednosti testova ne podudaraju ili ukazuju na intermedijarne stadije fibroze treba učiniti biopsiju jetre, jer su u tom kontekstu neinvazivni testovi manje pouzdani. Istraživanja su pokazala kako nalaz tranzijentne elastografije ima visoku prediktivnu vrijednost za razvoj dekompenzacije ciroze i nastanak portohipertenzivnih komplikacija te diskriminira bolesnike u odnosu na prognozu 5-godišnjeg preživljenja.

Upalne bolesti crijeva, osobito Crohnova bolest, karakterizirane su intermitentnim tijekom bolesti, gdje svaki relaps bolesti dovodi do dodatnog oštećenja crijeva s rezultirajućim komplikacijama i potrebom za čestim hospitalizacijama i kirurškim zahvatima. Stoga se današnja terapija bazira na akceleriranom “step-up” pristupu gdje se što ranije nastoje uključiti najdjelotvorniji lijekovi kako bi rano zaustavili destruktivni upalni proces i prevenirali komplikacije. Ključni uvjet za postizanje duge stabilne remisije jest mukozno cijeljenje koje se definira kao endoskopska remisija, odnosno odsutnost mukoznih ulceracija. Mukozno cijeljenje samo je inicijalni, ali bitan događaj u supresiji upale u dubljim slojevima stijenke crijeva. U radu se opisuju mehanizmi procesa mukoznog cijeljenja te djelotvornost danas dostupnih lijekova u postizanju mukoznog cijeljenja. Ostaju mnoga otvorena pitanja poput izbora trenutka prekida biološke terapije te razvoja lijekova s alternativnim mehanizmima djelovanja važnih za bolesnike koji ne reagiraju na anti-TNF-terapiju.

Background: Inflammatory bowel disease (IBD) patients (pts) frequently suffer one or more extraintestinal manifestations (EIMs) during their course of disease. EIMs are important because they can produce greater morbidity than the underlying intestinal disease. The aim of the study was to evaluate the prevalence of EIMs in IBD patients hospitalized in tertiary referral center and to assess the relationship between disease phenotype and EIM. Methods: The clinical backgrounds of 324 IBD patients, 212 with Crohn’s disease (CD) and 112 with ulcerative colitis (UC), were analyzed respectively. Patients were phenotyped according to Montreal classification. Musculosceletal (arthritis, arthralgia, sacroileitis), skin (erythema nodosum, pyoderma gangrenosum), hepatic (primary sclerosing cholangitis (PSC), chronic hepatitis) and ocular manifestations (episcleritis, uveitis) were assessed. The relationship between disease phenotype and EIM was analyzed statistically. Results: In our cohort regarding to behaviour there were 94 CD pts (44.5%) with inflammatory type (B1), 71 pts (33.5%) with stricturing (B2) and 47 pts (22.1%) with penetrating behaviour (B3). Perianal disease (p) had 74 pts (35.07%). Regarding localization 71 CD pts (33.65%) had ileal disease (L1), colonic localization (L2) had 34 CD pts (16.11%), ileocolonic localization (L3) had 104 pts (49.29%) and isolated upper gastrointestinal tract (L4) involvement had 3 pts (1.41%). There were 11 UC patients (9.9%) with proctitis, 23 pts (20.7%) with left-sided colitis and 78 pts (69.4%) with extensive colitis. Overall prevalence of EIMs in IBD pts was 22.2%. EIMs were confirmed in 48 pts (22.6%) with CD and 24 pts (21.4%) in UC (p = 0.889, Fisher). There was no significant difference in the prevalence of musculosceletal, ocular and skin manifestations between CD and UC pts. PSC was significantly more discovered in UC than in CD group (p = 0.008, Fisher). Extension of UC disease did not influence the prevalence of EIMs. Ileal localization (L1) in CD patients influenced the presence of skin manifestations (p = 0.038). There was also noticed an association between inflammatory behaviour (B1) and skin manifestations (p = 0.05). Conclusions: The reported frequency of EIMs in our IBD cohort is in accordance with previously published results. The significant association between UC and PSC was also confirmed. Two recognized associations between inflammatory CD phenotype and ileal disease with skin manifestations needs to be clarifyed in a larger cohort of patients.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare clinical entity with a main characteristic being mucus production. Extension of IPMN along pancretic ducts and mucus production lead to ductal obstruction and dilatation, resulting in recurrent episodes of acute pancreatitis. Molecular background of IPMN-a comprises several aberrations, with the K-ras gene mutation being the likely trigger that initiates further genetic changes. Due to its indolent nature, IPMN is most commonly diagnosed in the 7th decade of life. Depending on the histology type, IPMN has a malignant potential. Therefore, surgical therapy remains a "gold standard" of treatment. Insidious, slow progression of the disease and absence of symptoms in a certain number of patients makes diagnostic approach to this entity difficult. In this paper we present a patient with IPMN of the pancreas, in whom the episodes of acute pancreatitis had been present for 22 years.

Cjelovitost I multidisciplinarnost u nastanku venske tromboze kao I specificnosti rizika u bolesnika s upalnom bolesti crijeva. Prevencija I rana dijagnostika tromboembolijske bolesti u populaciji IBD bolesnika.

The authors discuss allelic variants in MDR1/ABCB1 gene and response to corticosteroid therapy.

IBD is associated with thromboembolic disease. We investigated prevalence of thromboembolic complications in tertiary referral Centre.

Is it possible to predict lamivudine resistance in chronic hepatitis B patients treated with lamivudine?

Clinically significant disease of the pancreas in association with inflammatory bowel disease (IBD) is unusual but reported. IBD patients have a risk of developing pancreatitis as well as pancreatic insufficiency (PI). Pancreatic elastase-1 is a human and pancreas specific enzyme that is not degraded during intestinal transport and correlates with exocrine pancreatic function test. The aim of this study was to evaluate the relationship between ulcerative colitis pancreatic insufficiency as an extraintestinal manifestation of IBD

Aim The high incidence of bone disease and increasing evidence for Crohn´s disease (CD) affecting bone status in corticosteroid users and non-users suggest that bone metabolism is affected by inflammatory process per se. The immunomodulatory effects of vitamin D by down- regulating Th1-driven immune response, suggest plausible role in autoimmune disease such as IBD. In patients with CD, we investigated an association of 25- hydroxyvitamin D3 with TNF- family pathway, known as RANK-RANKL-OPG pathway, driven in osteoclastogenesis. Methods Precursor metabolite, 25-hydroxyvitamin D3 was measured in 120 subjects with either long-standing (n=80) and naïve (n=15) Crohn disease, and ulcerative colitis (n=25). The spine and hip bone mineral density (BMD) was measured by DXA. All patients sera were analyzed for free sRANKL, OPG, TNF-α, IL-1β, IL-6, osteocalcin and C-telopeptide. Body mass index was calculated. Results CD patients with low BMD (n=68) have 25(OH)-D3 median, 31 nmol/l (quartile 20-44) in the range of serious deficient to insufficiency, whereas in patients with normal bone status (n=27) it was higher, 39 nmol/l (31- 72), but still in the range of inadequate supply (ANOVA p=0.004). In addition, 75% of naïve CD patients, at diagnosis, showed serious deficiency of 25(OH)-D3: 29 nmol/l (23- 33). In the univariate analysis age, disease duration, body mass index, lumbal and hip BMD, osteocalcin and C- telopeptide were not associated 25(OH)-D3 level. After performing multivariate analysis, proinflammatory cytokines and regulatory molecules of osteoclastogenesis have shown significant correlation. Multiple stepwise regression analysis revealed that free sRANKL (β=- 0.29, inversely) and IL-6 (β=-0.3 inversely) were independent predictors of 25(OH)-D3 level (p=0.018). Conclusion Low serum level of vitamin D is an indicator of bone disease in Crohn´s disease. Presented findings show that 25-hydroxyvitamin D3 level was significantly decreased in either long- standing and naïve patients, and its level is independently but inversely, associated with markers of underlying inflammatory process.

A majority of patients with primary sclerosing cholangitis has ulcerative colitis. Underlying cause is believed to be autoimmunity. We investigated differences in demographic data and disease extension in patients with UC and PSC.

Background. Wilson disease (WD) is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of copper transporting P-type ATPase (ATP7B). More than 400 disease causing mutations of the ATP7B gene have been identified to date. Methods. Genomic DNA was used to amplify 21 exons of the ATP7B gene. Sequencing analysis was performed by PCR and capillary electrophoresis with BigDye Terminator v3.1 kit on AB Genetic analyzer 3130xl. Results. Here we report results of sequencing analysis of the ATP7B gene. We have analyzed coding region of the ATP7B gene of clinically diagnosed WD patients from Croatia, already screened for the most common His1069Gln mutation. It accounts for 54, 4% of Wilson disease alleles in croatian population. Out of the total number of 71 tested patients with WD, molecular analysis has confirmed the clinical diagnosis in 44 patients (61, 9%) so far. 17 (23, 9%) patients are homozygous for the most common His1069Gln mutation. In 13 patients (18, 4%) only one mutation has been identified. Mutations in croatian population are mostly distributed in exons 5, 8, 13, 14, 15 and 21 of the ATP7B gene. Conclusions. Sequencing analysis of the ATP7B gene is the best method to establish the frequency of mutations in specific population so the screening test panel for most common mutations can be developed for this population.

Predictors of treatment failure in the patients with chronic hepatitis C treated with gold standard therapy

Options for treatment difficult to treat patients with chronic hepatitis C in countries with limited access to pegylated inetrefron

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The authors discuss on disturbance in immune regulation, caused by cancer.

The authors discuss on the topic of gastric pathology and patients with Crohn's disease

INTRODUCTION/OBJECTIVES: There are dilemmas in the field of gastric pathology in patients (pts) with inflammatory bowel disease (IBD) but recent reports indicate that gastric involvement in IBD pts is not as rare as previously thought. Since the azathioprine is one of the most important immunosupressives in the therapy of Crohn's disease (CD) the aim of the study was to evaluate the potential association of gastric pathology and treatment with azathioprine. AIMS & Methods: We evaluated histologically the presence of chronic gastritis, mucosal dysplasia, H. pylori infection and epitheloid granulomas in 29 azathioprine treated pts (AZA group) and 20 non-azathioprine treated pts (non-AZA group), treated with other non-immunosupressive drugs (mesalamine, corticosteroid). Patients were hospitalized in tertiary IBD center and underwent upper endoscopy with multiple biopsies during their hospital evaluation. RESULTS: 49 pts with CD with no previously registered upper gastrointestinal (GI) lesions were included in the study. AZA CD group included 29 pts (mean age 33, 3 yrs) and non-AZA group 20 pts (mean age 41.43 yrs). The characteristics of AZA group according to Vienna classification were as followed: non-penetrating non-stricturing (B1) 18 pts (62.1%), stricturing (B2) 8 pts (27.6%), penetrating (B3) 3 pts (10.3%). Ileocolonic localization (L3) had 15 pts (51.7%), colonic localization (L2) 5 pts (17.2%) and 9 pts (31%) ileal disease (L1). There was no statistical difference regarding phenotype and disease localization characteristics in non-AZA group. Chronic gastritis was detected in 20 AZA pts (69%) and in 14 (70%) non-AZA pts (p=1.00 Fischer). H. pylori infection was found in 1 AZA (3.4%) and 2 (10%) non-AZA pts (p=0.559). Epithelial dysplasia was not found iz AZA group, meanwhile 1 patient in non-AZA group (5%) had histologically confirmed dysplasia (p=0.408). Epithelial granulomas of upper GI tract was found in 2 AZA pts (6.9%), meanwhile non-AZA pts did not have epitheloid granulomas (p=0.508). CONCLUSION: We concluded that azathioprine treatment in CD patients did not increase the prevalence of chronic gastritis, H. pylori infection, dysplasia and epitheloid granulomas in gastric mucosa. For a more detailed analysis regarding the causes of this observation it is necessary to conduct a research in a larger cohort of patients.

Prehrana ima važnu višeznačnu ulogu u liječenju upalnih bolesti crijeva, poglavito u bolesnika koji boluju od Crohnove bolesti. U prvom redu adekvatna nutritivna potpora nužna je u prevenciji i liječenju malnutricije, kao i u prevenciji osteoporoze te u promicanju dobi primjerenog rasta u pedijatrijskih bolesnika. S druge strane, u aktivnoj fazi Crohnove bolesti u pedijatrijskih bolesnika enteralna je prehrana terapija izbora za uvođenje bolesnika u remisiju. Glede vrste enteralnih pripravaka istraživanja upućuju na jednaku učinkovitost elementarnih, oligomernih i polimernih enteralnih pripravaka. Uporaba standardnih polimernih enteralnih pripravaka danas se preporučuje i zbog boljeg okusa, lakšeg prihvaćanja od bolesnika, manje komplikacija te značajno nižih troškova u usporedbi s troškovima primjene ostalih enteralnih pripravaka. Najnovije spoznaje upućuju i na to da neki nutrijenti poput transformirajućeg čimbenika rasta beta (TGF-2), koji se nalaze u modificiranim polimernim enteralnim pripravcima, imaju farmakološki terapijski potencijal u liječenju upalnih bolesti crijeva, potvrđen u nekoliko kliničkih ispitivanja. Radna skupina koju su činili internisti gastroenterolozi i pedijatrijski gastroenterolozi, posebno upućeni u liječenje bolesnika s kroničnim upalnim bolestima crijeva izradila je Hrvatske smjernice za primjenu enteralne prehrane u Crohnovoj bolesti. Izrada smjernica temeljena je na dokazima iz relevantne medicinske literature te kliničkim iskustvima članova radne skupine., Nutrition has an important role in the management of inflammatory bowel disease (IBD), especially in patients with Crohn’s disease (CD). This role includes the prevention and correction of malnutrition, the prevention of osteoporosis and the promotion of optimal growth and development in children. In active Crohn’s disease, nutritional therapy (in the form of enteral feeding) is an effective primary therapy for pediatric patients. Studies have shown that there is no difference in the efficacy of elemental, oligomeric and polymeric enteral formulas. Therefore, the use of polymeric formula is recommended because of higher palatability, better acceptance by patients, lower rate of complications and lower cost when compared with other enteral formulas. Today we have knowledge that some nutrients which are added to modified special enteral formulas have almost pharmacological terapeutic potential in the management of inflammatory bowel disease. Novel nutritional therapeutic strategies for inflammatory bowel disease, such as transforming growth factor-beta-enriched (TGF-2) enteral feeding, showed beneficial effects in several clinical studies. Croatian guidelines for enteral nutrition in Crohn’s disease have been developed by interdisciplinary expert group of Croatian clinicians involved with inflammatory bowel disease. The guidelines are based on evidence from relevant medical literature and clinical experience of working group.

HCV exists in an individual as pool of closely related but genetically distinct variants. Development of resistant variants can be the reason of treatment failure. Aim of this study was to determine the changes in HCV quasispecies in region susceptible for mutations. Quasispecies were detected by new method, highresolution DNA melting analysis, in hypervariable region-1 at two points: 1. forty untreated patients: at baseline and after 6 months ; 2. sixty-nine treated patients: at baseline and at the end of treatment. Second sample was collected for all untreated and for 24 treated patients (45 had ETVR). For each sample result was shown as melting curve with 4 parameters: Tm (melting temperature), H (high), W (wide) and A (area). The most common genotype was 1 in both groups (57.5% in untreated and 83.3% in treated). Obtained baseline Tm was statistically significantly correlated with genotype obtained with commercial kits (p = 0.05). No significance was found for other baseline parameters. No statistical significances have been found in Tm, H, W and A for untreated and treated patients between paired samples but medians have changed in both groups (table 1 and 2).Trend of changes differed between groups, in untreated patients W and H raised while in treated declined. Without treatment, quasispecies become more heterogeneous while therapy makes them more homogeneous, towards resistant variants. Since no significant changes have been found in Tm it might be concluded that all observed changesdeveloped between same genotype at baseline.

UGT1A1 promoter gene polymorphism increases risk of gallstone formation in patients with Wilson’s disease

The research in the fielsd of HCV quasispecies is important due to the impact of HCV quasispecies on disease persistence, progression and nonresponsiveness to treatment.The goal of this study was to evaluate DNA melting curve analysis for detection of genetic variants of HCV quasispecies in HVR-1 region and their possible impact in predicting the treatment response to antiviral therapy.

High-resolution DNA melting analysis is done on treated and non-treated hepatits C patients, in order to detect quasispecies changes in hypervariable region 1 of hepatitis C genome.

The role of transrectal endoscopic ultrasound is investigated in inflammatory bowel disease

Elevated CA 19-9 is not usefull as screening test for pancreatobiliary malignancies in patients with chronic liver disease

Epidemiologija celijakije.

The authors discuss the role of strain ratio of transrectal endoscopic ultrasound elastography in selected patients who suffer of IBD

Infection and inflammation are common causes of reactive thrombocytosis. We investigated thrombocytosis in selected patients with inflammatory bowel disease.

Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens-Johnson syndrome is a hypersensitivity disorder that may also be caused by medications. We present a case of a 62-year-old male patient who developed vanishing bile duct syndrome a month after Stevens-Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens-Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens-Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens-Johnson syndrome co-occurrence.

When IBD is confined to the colon, there is lack of diagnostic tolls for distinction between Crohn's colitis and ulcerative clitis.

Učinak reterapije kroničnog hepatitisa C s dva različita protokola