Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% ...(55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death.
Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects.
We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation.
We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings.
Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.
Background: Liver involvement in Coronavirus disease 2019 (COVID-19) has been recognised. We aimed to investigate the correlation of non-invasive surrogates of liver steatosis, fibrosis and ...inflammation using transient elastography (TE) and FibroScan-AST (FAST) score with (a) clinical severity and (b) 30-day composite outcome of mechanical ventilation (MV) or death among patients hospitalized due to COVID-19. Method: Patients with non-critical COVID-19 at admission were included. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by TE. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) and need for high-flow nasal cannula (HFNC) oxygen supplementation. Results: 217 patients were included (66.5% males, median age 65 years, 4.6% with history of chronic liver disease). Twenty-four (11.1%) patients met the 30-day composite outcome. Median LSM, CAP and FAST score were 5.2 kPa, 274 dB/m and 0.31, respectively, and neither was associated with clinical severity of COVID-19 at admission. In multivariate analysis FAST > 0.36 (OR 3.19, p = 0.036), 4CMS (OR 1.68, p = 0.002) and HFNC (OR 7.03, p = 0.001) were independent predictors of adverse composite outcome. Conclusion: Whereas LSM and CAP failed to show correlation with COVID-19 severity and outcomes, FAST score was an independent risk factor for 30-day mortality or need for MV.
Eosinophilic esophagitis is a chronic, Th2-mediated disease characterized by the presence of predominantly eosinophilic inflammation in the esophagus. The disease is mediated by an immune or ...antigenic pathophysiological background, and the definition of the disease requires the presence of clinical symptoms and histological elements of the disease. Over the past ten years, there has been an increase in the incidence and prevalence of EoE, where the prevalence of EoE varies, and in the general population is 0.2–4 / 1000 in asymptomatic patients, while in symptomatic patients it is 5–6%. The prevalence in the general population is considered to be 43 to 52/100000. Pathophysiologically, it is a polygenic disease in which certain cytokines (IL-4, IL-5, IL-13, IL-14 and TGF-β) play a key role by activating eotaxin-3 in the esophageal mucosa. Eotaxin-3 strongly attracts eosinophils into the esophageal mucosa, and thus activated eosinophils lead to the attraction of other inflammatory cells, the release of mediators and the onset of disease. The histological criterion for the diagnosis of EoE is the presence of more than 15 eosinophils present in the visual field of esophageal mucosal biopsies. Clinically, the disease can manifest itself by a spectrum of symptoms, from acute food impaction, dysphagia, epigastric pain and heartburn, and nonspecific symptoms such as incontinence or vomiting also occur in these patients. The basis of treatment of these patients is based on drug therapy, dietary recommendations and endoscopic dilatation. Thea im of these clinical recommendations is to present the pathway of diagnosis and therapy of eosinophilic esophagitis.
Eozinofilni ezofagitis je kronična bolest posredovana putem Th2 obrasca imunosne reakcije, karakterizirana prisutnošću predominatno eozinofilnih upalnih promjena u jednjaku. Bolest je posredovana ...imuno/antigenim patofizološkim putem, a za definiciju bolesti potrebno je prisustvo kliničkih simptoma i histoloških elemenata bolesti. Unatrag desetak godina bilježi se porast incidencije i prevalencije EoE, gdje prevalencija EoE varira, te u općoj populaciji iznosi 0,2–4/1000 u asimptomatskih bolesnika, dok kod simptomatskih bolesnika ona iznosi 5–6%. Smatra se da prevalencija u općoj populaciji iznosi 43 do 52/100000. Patofiziološki riječ je o poligenskoj bolesti u kojoj određeni citokini (IL-4, IL-5,IL-13, IL-14, TGF-β) igraju ključnu ulogu aktivirajući eotaksin-3 u sluznici jednjaka. Eotaksin-3 snažno privlači eozinofile u sluznicu jednjaka, a tako aktivirani eozinofili dovode do privlačenja drugih upalnih stanica, oslobađanja medijatora i nastanka bolesti. Histološki kriterij dijagnoze EoE je prisutnost više od 15 eozinofila prisutnih u vidnom polju bioptata sluznice jednjaka. Klinički, bolest se može manifestirati spektrom simptoma, od akutne impakcije hrane, disfagije, boli u žličici i žgaravice, a i nespecifični simptomi poput inapetencije ili povraćanja također se javljaju kod ovih bolesnika. Osnova liječenja ovih bolesnika temelji se na medikamentnom liječenju, dijetalnim preporukama i endoskopskoj dilataciji. Cilj ovih kliničkih smjernica jest prikazati preporučeni algoritam dijagnostike i liječenja eozinofilnog ezofagitisa.
The survey is documented with suic'uie pounds as raftered in conversations with patients subsequent to attempted suicide.
In non-psychotic persons the most frequent causes are aggressivity (of the ...husband or wife), humiliation, violence, loneliness, alcoholism or divorce. This can all be ascribed, according to the author, to a lacking of spiritual values and is one of the characteristics of spiritual poverty of life under exclusion of love.
Psychotic persons chiefly state as grounds for attempted suicide: »It just came over me!«, or depression owing to their ailment. The author points out that such states can be prevented by healthy education through the mass media and suitable social conditions.
The paper analyzes the basic demographic processes in the Republic of Croatia (NUTS 1), in its statistical macro-regions (NUTS 2) and counties (NUTS 3) in the inter-census period from 2001 to 2011. ...The theoretical part discusses the optimal structure and the establishment of statistical macro-regions, as well as the impact of demographic factors on their formation. The authors are critical of the quality and content of certain demographic categories set in the last census and their incomparability with previous censuses. Medium-intensity depopulation is still continuing; however, a large part of the Croatian territory is affected by this unfavourable characteristic of the overall population trend. Namely, in the last decade of the inter-census period, only the City of Zagreb and Zagreb County in Continental Croatia recorded an increase in population, while in Adriatic Croatia such a case was found only in the Zadar and Istria Counties. Both components of the overall population trends in Croatia - natural change and net migration - bear a negative denominator. Only two of twenty-one NUTS 3 units showed natural increase (the Split-Dalmatia and Dubrovnik-Neretva Counties), while the other counties, even the immigration ones, registered natural population decrease. It is obvious from migration data that Croatia has polarized to Zagreb and its surroundings as the economic and demographic centre of the country, and to the coastal counties that, for the most part, still have an economically attractive tourism-based economic development and migration attractiveness to some extent. Most Continental Croatian counties consist of poorly developed, peripheral areas of depopulation and demographic decline in general. Adapted from the source document.
The paper analyzes the basic demographic processes in the Republic of Croatia (NUTS 1), in its statistical macro-regions (NUTS 2) and counties (NUTS 3) in the inter-census period from 2001 to 2011. ...The theoretical part discusses the optimal structure and the establishment of statistical macro-regions, as well as the impact of demographic factors on their formation. The authors are critical of the quality and content of certain demographic categories set in the last census and their incomparability with previous censuses. Medium-intensity depopulation is still continuing; however, a large part of the Croatian territory is affected by this unfavourable characteristic of the overall population trend. Namely, in the last decade of the intercensus period, only the City of Zagreb and Zagreb County in Continental Croatia recorded an increase in population, while in Adriatic Croatia such a case was found only in the Zadar and Istria Counties. Both components of the overall population trends in Croatia – natural change and net migration – bear a negative denominator. Only two of twenty-one NUTS 3 units showed natural increase (the Split-Dalmatia and Dubrovnik-Neretva Counties), while the other counties, even the immigration ones, registered natural population decrease. It is obvious from migration data that Croatia has polarized to Zagreb and its surroundings as the economic and demographic centre of the country, and to the coastal counties that, for the most part, still have an economically attractive tourism-based economic development and migration attractiveness to some extent. Most Continental Croatian counties consist of poorly developed, peripheral areas of depopulation and demographic decline in general.
U članku se analiziraju osnovni demografski procesi u Republici Hrvatskoj (NUTS 1), u njenim statističkim makroregijama (NUTS 2) i županijama (NUTS 3) u međupopisnom razdoblju 2001. – 2011. U ...teorijskom dijelu raspravlja se o optimalnom ustroju i uspostavi statističkih makroregija te o utjecaju demografskih čimbenika na njihovo formiranje. Autori se kritički postavljaju prema kvaliteti i sadržaju pojedinih demografskih kategorija u posljednjem popisu stanovništva te njegovoj neusporedivosti s prethodnim popisima. I nadalje je prisutna depopulacija srednjeg intenziteta, međutim teritorijalno veliki dio hrvatskog prostora zahvaćen je tim nepovoljnim obilježjem općega kretanja. Naime samo su Grad Zagreb i Zagrebačka županija u Kontinentalnoj Hrvatskoj u posljednjemu desetljetnome međupopisnom razdoblju zabilježili porast broja stanovnika, dok je u Jadranskoj Hrvatskoj takav slučaj samo u Zadarskoj i Istarskoj županiji. Obje sastavnice općega kretanja stanovništva Hrvatske, prirodno kretanje i migracijski saldo, imaju negativni predznak. Od 21 NUTS 3 jedinice samo su dvije imale prirodni prirast (Splitsko-dalmatinska i Dubrovačko-neretvanska), dok su ostale županije, pa čak i imigracijske, registrirale prirodni pad stanovništva. Iz migracijskih podataka očito je da se Hrvatska demografski polarizirala na Zagreb i okolicu kao gospodarsko i demografsko središte države te na priobalne županije, koje gospodarski razvoj i donekle migracijsku atraktivnost uglavnom temelje na još uvijek ekonomski atraktivnom turizmu. Većina županija Kontinentalne Hrvatske čini slabo razvijena, periferna područja depopulacije i općenito demografskog nazadovanja.
The paper analyzes the basic demographic processes in the Republic of Croatia (NUTS 1), in its statistical macro-regions (NUTS 2) and counties (NUTS 3) in the inter-census period from 2001 to 2011. ...The theoretical part discusses the optimal structure and the establishment of statistical macro-regions, as well as the impact of demographic factors on their formation. The authors are critical of the quality and content of certain demographic categories set in the last census and their incomparability with previous censuses. Medium-intensity depopulation is still continuing; however, a large part of the Croatian territory is affected by this unfavourable characteristic of the overall population trend. Namely, in the last decade of the intercensus period, only the City of Zagreb and Zagreb County in Continental Croatia recorded an increase in population, while in Adriatic Croatia such a case was found only in the Zadar and Istria Counties. Both components of the overall population trends in Croatia - natural change and net migration - bear a negative denominator. Only two of twenty-one NUTS 3 units showed natural increase (the Split-Dalmatia and Dubrovnik-Neretva Counties), while the other counties, even the immigration ones, registered natural population decrease. It is obvious from migration data that Croatia has polarized to Zagreb and its surroundings as the economic and demographic centre of the country, and to the coastal counties that, for the most part, still have an economically attractive tourism-based economic development and migration attractiveness to some extent. Most Continental Croatian counties consist of poorly developed, peripheral areas of depopulation and demographic decline in general. Reprinted by permission of the Institute for Migration and Ethnic Studies, Zagreb
The significance of migration in the contemporary demographic development of Rijeka and its coastal area is discussed in the paper. The analysis has shown that the City of Rijeka presents a ...demographically regressive area from which the deconcentration of population, mainly to suburban areas, is taking place. At the same time, the Littoral is the area of demographic growth as a result of high immigration rates, while natural demographic trends are negative; however, this does not have such intensity as in the case of the urban population of Rijeka. The comparison of vital index and migration data indicates a high degree of correlation between immigration and natural change in population so that settlements in the nearer gravitation area, being the space of strong in-migration between the 1990s and 2000s, shows distinct demographic growth and positive population bio-dynamics. Compared with them, settlements in the broader gravitational area have weaker intensity of permanent population resettlement as well as considerably unfavourable total and natural population trends. Based on the established demographic situation, population forecasts have been made for the years 2021 and 2031 indicating continued depopulation processes in the macro-regional centre of Rijeka and further demographic progression in the coastal area. Reprinted by permission of the Institute for Migration and Ethnic Studies, Zagreb
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