Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of ...biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also associated with chronic liver diseases. The aim of this study was to identify semaphorins associated with NAFLD and their relationship with steatosis and fibrosis stages. In this prospective, case-control study, serum semaphorin concentrations (SEMA3A, -3C, -4A, -4D, -5A and -7A) were measured in 95 NAFLD patients and 35 healthy controls. Significantly higher concentrations of SEMA3A, -3C and -4D and lower concentrations of SEAMA5A and -7A were found in NAFLD. While there was no difference according to steatosis grades, SEMA3C and SEMA4D significantly increased and SEMA3A significantly decreased with fibrosis stages and had better accuracy in predicting fibrosis compared to the FIB-4 score. Immunohistochemistry confirmed higher expression of SEMA4D in hepatocytes, endothelial cells and lymphocytes in NAFLD livers. The SEMA5A rs1319222 TT genotype was more frequent in the NAFLD group and was associated with higher liver stiffness measurements. In conclusion, we provide the first evidence of the association of semaphorins with fibrosis in patients with NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on ...increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.
Nealkoholna bolest masne jetre (engl. nonalcoholic fatty liver disease, NAFLD) oznacava prekomjerno nakupljanje masti unutar hepatocita, a povezana je s metabolickim sindromom i inzulinskom ...rezistencijom. Ucestalost NAFLD-a je u porastu i prati rastucu ucestalost metabolickog sindroma i njegovih komponenata. Stoga su izradene hrvatske smjernice koje obuhvacaju postupnik probira bolesnika s rizicnim cimbenicima za NAFLD te preporucenu dijagnosticku obradu i lijecenje bolesnika s NAFLD-om. Probir na NAFLD potrebno je raditi bolesnicima s dijabetesom tipa 2 ili osobama s dva ili vise rizicnih cimbenika u sklopu metabolickog sindroma, a probir se izvodi neinvazivnim laboratorijskim i slikovnim metodama za otkrivanje fibroze. Obradom bolesnika potrebno je iskljuciti postojanje drugih uzroka ostecenja jetre te utvrditi stadij fibroze kao najvaznijeg cimbenika u prognozi bolesti. Bolesnici s pocetnim stadijima fibroze nastavljaju se pratiti na razini primarne zdravstvene zastite uz lijecenje metabolickih rizicnih cimbenika, dijetetske mjere i pojacanu tjelesnu aktivnost. Bolesnike sa znacajnom fibrozom preporuca se uputiti gastroenterologu/hepatologu radi daljnjeg lijecenja, pracenja te prepoznavanja i zbrinjavanja komplikacija bolesti. Kljucne rijeci: Nealkoholna bolest masnejetre (NAFLD); Nealkoholni steatohepatitis (NASH); Metabolicki sindrom; Fibroza; Ciroza; Probir; Neinvazivne metode; Dijagnostika; Lijecenje; Hepatocelularni karcinom
Posljednjih je 15 godina standardna terapija u liječenju kroničnog hepatitisa C kombinirana terapija pegiliranim interferonom (PEG-INF) i ribavirinom (RBV) u trajanju od 24 do 48 tjedana, ovisno o ...genotipu HCV-a. Standardna terapija rezultirala je održivim virološkim odgovorom (engl. sustained virological response, SVR) od 75 do 85% u pacijenata s genotipom 2 i 3, ali samo od 40 do 50% u pacijenata s genotipom 1. Trenutačno postoji brz i kontinuiran razvoj brojnih novih lijekova protiv hepatitis C-virusa (HCV), koji su u žarištu ovog pregleda. Boceprevir i telaprevir, dva inhibitora NS3/4A-proteaze prve generacije, unaprijedili su liječenje HCV-a. Nedavno su registrirani u nekoliko zemalja diljem svijeta u kombinaciji s PEGINF-om i RBV-om za liječenje bolesnika s genotipom 1. Trojna terapija s boceprevirom ili telaprevirom u usporedbi s kombinacijom PEG-INF/RBV poboljšava SVR za 25-31% u prethodno neliječenih bolesnika s genotipm 1, za 40-64% u bolesnika koji su nakon prethodne terapije imali povrat infekcije (“relapser”), za 33-45% u bolesnika koji su tijekom prethodne terapije imali djelomičan odgovor (“partial responders”) i za 34-38% kod bolesnika koji na prethodnu terapiju nisu imali odgovor (“null-responder”). U isto vrijeme primjena individualiziranog liječenja, odnosno liječenja ovisnog o virološkom odgovoru (engl. response-guided therapy, RGT), dovodi do skraćenja trajanja ukupnog liječenja na samo 24 tjedna u 45-55% prethodno neliječenih bolesnika. Postoji međutim nekoliko izazova u korištenju nove trojne kombinacije u bolesnika s genotipom 1, kao što je potreba za brzim rezultatima HCV RNA-testiranja s pomoću osjetljivih kvantitativnih testova, nove i češće nuspojave (anemija i disgeuzija za boceprevir; pruritus, osip i anemija za telaprevir), nove interakcije lijekova i teškoće u suradljivosti bolesnika. Štoviše, učestalost SVR-a još je niska u teško izlječivih podgrupa s genotipom 1, kao null-responderi s cirozom, a od nove terapije nemaju nikakve koristi bolesnici koji ne toleriraju PEG-INF/ RBV ili koji nisu zaraženi genotipom 1. Trenutačno se u liječenju infekcije HCV-om procjenjuje učinkovitost mnogih novih anti- HCV-lijekova, različitih klasa i kombinacija, a rezultati ohrabruju. U nadolazećim godinama očekuju nas novi antivirusni lijekovi s direktnim djelovanjem (engl. direct-acting agent, DAA) s pojednostavnjenim doziranjem i/ili minimalnom toksičnošću, koji će u kombinaciji s drugim lijekovima dovesti do eradikacije virusa u gotovo većine bolesnika s kroničnom infekcijom HCV-om. Novi će agensi omogućiti protokole bez interferona.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease associated with systemic changes in immune response that drives the progression to non-alcoholic steatohepatitis ...(NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). Major risk factors of NAFLD include obesity and type 2 diabetes mellitus which are associated with infections. However, there is growing evidence that NAFLD is linked with bacterial infections independently of other components of metabolic syndrome. Patients with NAFLD have been described to have more common recurrent bacterial infections, urinary tract infections, bacteriemia of gastrointestinal origin, Clostridoides difficile enterocolitis, and more severe pneumonia. The rapidly increasing prevalence of NAFLD and NASH require novel therapeutic and prophylactic approaches based on a better understanding of immunopathogenesis of bacterial infections in these patients.
Background
Budd-Chiari syndrome is defined as a hepatic venous outflow track obstruction of various etiology, which appears at different levels. The inferior vena cava outflow membrane is an unusual, ...but a potentially treatable cause. The percutaneous treatment has emerged as a very promising management mode for such patients. Follow-up results are favorable for balloon angioplasty and/or stenting, with minimal re-stenosis rates.
Case presentation
We report a case of a young woman, earlier operated on congenital heart defect and with previous pulmonary embolic incident after childbirth, with no evidence of thrombophilia. She was admitted to our institution for a suspected right atrial tumor. After the diagnosis of Budd-Chiari syndrome caused by membranous inferior vena cava obstruction, a percutaneous treatment of a thick membrane was successfully performed, using an unusual technique.
Conclusion
Balloon angioplasty should be considered in cases of membranous obstruction of vena cava, where a focal obstruction is causing the symptoms. In our patient, the anatomy was not suitable for stenting, and balloon dilatation was successful just after the membrane was pulled apart with a big balloon in a “Rashkind-like” procedure.
Purpose
For patients at high-risk of developing hepatocellular carcinoma (HCC), biannual ultrasound surveillance has long been recommended, in order to detect the tumor in the early, potentially ...curative stages. However, globally reported HCC surveillance rates vary greatly, ranging from as low as 1.7 to as high as 80%. Our aim was to assess the utilization of surveillance with biannual ultrasound in high-risk Croatian patients and to identify the factors that impact the implementation of the recommended protocol.
Methods
This retrospective study included 145 newly diagnosed HCC patients in the period from January 2010 to September 2015. We identified low-risk and high-risk patients. The latter were further subdivided into the regular biannual ultrasound surveillance group and the non-surveillance group. The groups were compared according to demographic characteristics and BCLC stage at the time of HCC diagnosis.
Results
Among 145 patients, 80 patients were classified as high-risk according to EASL criteria. During the relevant period, 28.7% underwent regular surveillance, while 71.25% did not. Younger patients were more likely to undergo surveillance (OR 0.935 CI 0.874–0.999;
p
= 0.05). The patients who underwent regular surveillance had a higher chance of being diagnosed at a curative stage (BCLC 0 or A) (OR 3.701 CI 1.279–10.710;
p
< 0.05).Gender was not a predictor of participation in the regular surveillance protocol. Among the high-risk patients who did not undergo regular surveillance, 56.1% were not aware of the chronic liver disease prior to the HCC diagnosis.
Conclusion
HCC surveillance is still underutilized in high-risk Croatian patients despite its obvious benefits possibly due to the untimely diagnosis of the chronic liver disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background. Ursodeoxycholic acid response score (URS) is a prognostic model that estimates the baseline probability of treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy in ...patients with primary biliary cholangitis (PBC). Aim. To independently evaluate the predictive performance of the URS model. Methods. We used a cohort of Slovak and Croatian treatment-naïve PBC patients to quantify the discrimination ability using the area under receiver operating characteristic curve (AUROC) and its 95% confidence interval (CI). Furthermore, we evaluated the calibration using calibration belts. The primary outcome was treatment response after 12 months of UDCA therapy defined as values of alkaline phosphatase ≤1.67 × upper limit of normal. Results. One hundred and ninety-four patients were included. Median pretreatment age was 56 years (interquartile range 49–62). Treatment response was achieved in 79.38% of patients. AUROC of the URS was 0.81 (95% CI 0.73–0.88) and the calibration belt revealed that response rates were correctly estimated by predicted probabilities. Conclusion. Our results confirm that the URS can be used in treatment-naïve PBC patients for estimating the treatment response probability after 12 months of UDCA therapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Nealkoholna masna bolest jetre (engl. non-alcoholic fatty liver disease, NAFLD) najčešća je kronična bolest jetre, a povezana je sa sustavnim promjenama imunosnog odgovora koje potiču progresiju u ...nealkoholni steatohepatitis (NASH), cirozu jetre i razvoj hepatocelularnog karcinoma. Glavni rizični čimbenici za razvoj NAFLD-a jesu komponente metaboličkog sindroma, pretilost i šećerna bolest, koje su poznati rizični čimbenici za razvoj infekcija. Međutim, sve je više podataka o povezanosti NAFLD-a s bakterijskim infekcijama, neovisno o ostalim komponentama metaboličkog sindroma. Kod bolesnika s NAFLD-om opisane su češće rekurirajuće bakterijske infekcije, uroinfekcije, bakterijemije gastrointestinalnog ishodišta, enterokolitis Clostridoides difficile, kao i teža klinička slika i nepovoljni ishod pneumonije. Rastuća prevalencija NAFLD-a i NASH-a zahtjeva nove terapijske i profilaktičke pristupe bazirane na boljem razumijevanju imunopatogeneze bakterijskih infekcija u ovoj skupini bolesnika.
Do početka 90-ih godina prevladavalo je uvriježeno mišljenje da su bolesnici s uznapredovalom jetrenom bolesti prirodno autoantikoagulirani i time zaštićeni od tromboembolijskih zbivanja. Međutim, ...novim saznanjima dugogodišnja je paradigma srušena. U bolesnika s cirozom jetre paralelno je reducirana sinteza prokoagulansa i endogenih antikoagulansa, dok je produkcija ekstrahepatalno sintetiziranih faktora, važnih za proces zgrušavanja i fibrinolize, očuvana. U stabilnoj jetrenoj bolesti sustav je „rebalansiran”, ali funkcionira u uskom rasponu homeostaze, što ga čini izuzetno fragilnim te ga i minimalni stres može uvesti u neželjeni ekstrem, trombozu ili krvarenje. Uz navedeno niz je drugih čimbenika koji prate jetrenu bolest, kao što su hemodinamske promjene, oštećenja drugih organa, ponajprije bubrega, te sklonost infekcijama, a koji pomiču ravnotežu prema sklonosti krvarenju ili pojačanom zgrušavanju. Konvencionalni laboratorijski testovi nisu prikladni za procjenu rizika od krvarenja u cirozi, rizični čimbenici za razvoj tromboze nisu nedvojbeno dokazani, a sigurnosni profil antitrombotskih lijekova u cirozi nije precizno utvrđen jer su ti bolesnici uglavnom isključeni iz velikih kliničkih studija. Zbog svega navedenoga dijagnostički i terapijski pristup u ovom je kontekstu kompleksan te nalaže timski rad hematologa, hepatologa i u fazi operativnog liječenja anesteziologa. U ovome preglednom radu osvrnut ćemo se na mehanizme poremećaja hemostaze i fibrinolize u bolesnika s cirozom jetre, incidenciju tromboembolijskih zbivanja, laboratorijsku dijagnostiku te profilaktičke i terapijske opcije u okviru internističke skrbi.
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