Hepatitis B – still the commonest sexually transmitted hepatitis in Croatia

Hepatitis B predstavlja značajan javnozdravstveni problem. Trećina svjetske populacije ima serološke znakove aktualne ili preboljele infekcije, a 350 milijuna ljudi je kronično inficirano. Jetrena bolest uzrokovana hepatitis B virusom uzrokuje godišnje preko milijun smrtnih ishoda kao posljedica dekompenzirane ciroze jetre i hepatocelularnog karcinoma. Predominantni načini prijenosa ovise o geografskom području i higijenskim uvjetima. U zemljama poput Hrvatske, hepatitis B se najčešće prenosi seksualnim putem i korštenjem nečistih igala kod intravenskih ovisnika o drogama. Rizik kroniciteta ovisi o dobi u času infekcije, odnosno o imunološkoj zrelosti zaražene osobe. Liječenje hepatitisa B ima za cilj eradikaciju virusa u ranoj fazi bolesti te trajnu supresiju HBV replikacije kod kronične bolesti, prevenirajući time razvoj ciroze i hepatocelularnog karcinoma. Lijekovi za hepatitis B odobreni u Europi su konvencionalni i pegilirani interferon-α, lamivudin, telbivudin, entekavir, adefovir i tenofovir. Uobičajene indikacije za terapiju su serumski HBV DNA >2000 IU/mL (>10 000 kopija/mL), povišen serumski ALT (2×) te umjerena do teška nekroinflamatorna aktivnost i/ili fibroza. Najvažnije je, međutim, provoditi profilaktičke mjere u osoba s rizikom akviriranja infekcije.Hepatitis B is a global public health problem. Approximately one third of the world population has serological evidence of past or present infection with hepatitis B virus (HBV), with more than 350 million people chronically infected, of whom roughly one million die annually from HBV-related liver disease (liver cirrhosis, hepatocellular cancer). The predominant mode of transmission of HBV varies in different areas of the world. In countries like Croatia, unprotected sexual intercourse and intravenous drug use in adults are major routes of transmission. Risk of chronicity depends on the age at infection and resultant immune maturity. Chronic carriers of HBV are at increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). The goals of therapy for hepatitis B are eradication of virus in the early stage of disease and continuous suppression of viral replication in chronic disease, thus preventing the progression of cirrhosis and HCC. Drugs approved for the treatment of HBV infection in Europe are conventional interferon alpha, pegylated interferon alpha, lamivudine, telbivudine, entecavir, adefovir and tenofovir. The usual indications for treatment are serum HBV DNA>2000 IU/mL (>10 000 copies/mL), elevated aminotransferase levels and moderate to severe necroinflammatory activity and/or fibrosis. Preventive measures are most important in persons at risk of aquiring infection

Current Therapeutic Strategy in Inflammatory Bowel Diseases: The Importance of Mucosal Healing

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.Inflammatory bowel diseases, particularly Crohn’s disease, are characterized by intermittent clinical course, where each relapse leads to additional bowel injuries with resultant complications and the need for frequent hospitalisations and surgeries. Our current therapeutic strategy is therefore to apply an accelerated step-up approach. This approach consist in an obligatory early introduction of most efficient drugs in order to achieve early control of destructive inflammatory processes and thereby prevent their complications. A key to the achievement of a long and stable remission is mucosal healing, which is defined as endoscopic remission with absence of mucosal ulcerations. Although mucosal healing is only the initial event, it is critical in the suppression of inflammation in deeper layers of the bowel wall. This paper describes the mechanisms of mucosal healing and evaluates the ability of presently available drugs to induce mucosal healing. Many questions remain open like timing of discontinuation of biological therapy and development of new drugs with alternative mechanisms of action, so important for patients who are primary non-responders to anti-TNF therapy

Hepatitis B – still the commonest sexually transmitted hepatitis in Croatia

Hepatitis B predstavlja značajan javnozdravstveni problem. Trećina svjetske populacije ima serološke znakove aktualne ili preboljele infekcije, a 350 milijuna ljudi je kronično inficirano. Jetrena bolest uzrokovana hepatitis B virusom uzrokuje godišnje preko milijun smrtnih ishoda kao posljedica dekompenzirane ciroze jetre i hepatocelularnog karcinoma. Predominantni načini prijenosa ovise o geografskom području i higijenskim uvjetima. U zemljama poput Hrvatske, hepatitis B se najčešće prenosi seksualnim putem i korštenjem nečistih igala kod intravenskih ovisnika o drogama. Rizik kroniciteta ovisi o dobi u času infekcije, odnosno o imunološkoj zrelosti zaražene osobe. Liječenje hepatitisa B ima za cilj eradikaciju virusa u ranoj fazi bolesti te trajnu supresiju HBV replikacije kod kronične bolesti, prevenirajući time razvoj ciroze i hepatocelularnog karcinoma. Lijekovi za hepatitis B odobreni u Europi su konvencionalni i pegilirani interferon-α, lamivudin, telbivudin, entekavir, adefovir i tenofovir. Uobičajene indikacije za terapiju su serumski HBV DNA >2000 IU/mL (>10 000 kopija/mL), povišen serumski ALT (2×) te umjerena do teška nekroinflamatorna aktivnost i/ili fibroza. Najvažnije je, međutim, provoditi profilaktičke mjere u osoba s rizikom akviriranja infekcije.Hepatitis B is a global public health problem. Approximately one third of the world population has serological evidence of past or present infection with hepatitis B virus (HBV), with more than 350 million people chronically infected, of whom roughly one million die annually from HBV-related liver disease (liver cirrhosis, hepatocellular cancer). The predominant mode of transmission of HBV varies in different areas of the world. In countries like Croatia, unprotected sexual intercourse and intravenous drug use in adults are major routes of transmission. Risk of chronicity depends on the age at infection and resultant immune maturity. Chronic carriers of HBV are at increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). The goals of therapy for hepatitis B are eradication of virus in the early stage of disease and continuous suppression of viral replication in chronic disease, thus preventing the progression of cirrhosis and HCC. Drugs approved for the treatment of HBV infection in Europe are conventional interferon alpha, pegylated interferon alpha, lamivudine, telbivudine, entecavir, adefovir and tenofovir. The usual indications for treatment are serum HBV DNA>2000 IU/mL (>10 000 copies/mL), elevated aminotransferase levels and moderate to severe necroinflammatory activity and/or fibrosis. Preventive measures are most important in persons at risk of aquiring infection

Inflammatory bowel disease

Upalne bolesti crijeva su heterogena skupina upalnih bolesti karakterizirane kroničnom imunom aktivacijom i upalom gastrointestinalnog trakta praćene brojnim ekstraintestinalnim komplikacijama. Dvije najvažnije forme bolesti su Crohnova bolest i ulcerozni kolitis s brojnim fenotipovima. Patogeneza bolesti je još uvijek nejasna. Dijagnostički i terapijski pristup je vrlo kompleksan i zahtijeva dobro poznavanje tijeka i komplikacija bolesti i terapije. U ovom radu je prikazana sadašnja terapijska strategija s posebnim naglaskom na važnost procesa mukoznog cijeljenja te analiza saznanja o mjestu biološke terapije u liječenju IBD.Inflammatory bowel disease (IBD) is heterogenous group of inflammatory disorders characterized by chronic immune activation and inflammation of the gastrointestinal tract, associated with numerous extraintestinal manifestations. Two most important forms are Crohn’s disease and ulcerative colitis with several phenotypes. Etiopathogenesis of IBD is still unknown. Diagnostic and therapeutic approach of IBD is very complex and requires excellent knowledge of the clinical course and complications of the disease itself and therapy. The paper provides present therapeutic strategy with emphasis on the importance of mucosal healing and analysis of present knowledge of the role of biologics in the therapy of IBD

Inflammatory bowel disease

Upalne bolesti crijeva su heterogena skupina upalnih bolesti karakterizirane kroničnom imunom aktivacijom i upalom gastrointestinalnog trakta praćene brojnim ekstraintestinalnim komplikacijama. Dvije najvažnije forme bolesti su Crohnova bolest i ulcerozni kolitis s brojnim fenotipovima. Patogeneza bolesti je još uvijek nejasna. Dijagnostički i terapijski pristup je vrlo kompleksan i zahtijeva dobro poznavanje tijeka i komplikacija bolesti i terapije. U ovom radu je prikazana sadašnja terapijska strategija s posebnim naglaskom na važnost procesa mukoznog cijeljenja te analiza saznanja o mjestu biološke terapije u liječenju IBD.Inflammatory bowel disease (IBD) is heterogenous group of inflammatory disorders characterized by chronic immune activation and inflammation of the gastrointestinal tract, associated with numerous extraintestinal manifestations. Two most important forms are Crohn’s disease and ulcerative colitis with several phenotypes. Etiopathogenesis of IBD is still unknown. Diagnostic and therapeutic approach of IBD is very complex and requires excellent knowledge of the clinical course and complications of the disease itself and therapy. The paper provides present therapeutic strategy with emphasis on the importance of mucosal healing and analysis of present knowledge of the role of biologics in the therapy of IBD

BIOLOGICAL PROPERTIES OF HEPATITIS C VIRUS

SAŽETAK Mehanizam infekcije, umnažanje virusa u ciljnim stanicama, tvrdokornost infekcije, te posljedično patogeneza kronične jetrene bolesti, nedovoljno su poznati. Hepatitis C virus (HCV) tvori malena jednolančana pozitivna RNA koja se svrstava u rod Hepacivirus u porodici Flaviviridae. Genom virusa sadrži 9600 nukleotida koji – u ovisnosti o genotipu – sintetiziraju poliprotein od približno 3000 aminokiselina. Razlikuje se 6 glavnih HCV genotipova (1 – 6), te više podtipova (a – c). Tijekom godina infekcije, virus u domaćinu postoji u obliku genetski različitih čestica nazvanih kvazivrstama. Virus hepatitisa C jest hepatotropni virus, stoga se glavnina njegova umnažanja zbiva u hepatocitu. No, u manjim količinama može se naći i u mononuklearnim stanicama periferne krvi, te u limfnim čvorovima, stoga su i to prirodne ciljne stanice virusa. Poznavanje životnoga ciklusa virusa uglavnom je hipotetsko, s obzirom na nedostupnost učinkovite kulture stanica za istraživanja in vitro.ABSTRACT The mechanisms of hepatitis C virus infection (HCV) and replication in targeted cells, the mechanism of persistent viral infection and the pathogenesis of HCV hepatic disease are poorly understood. HCV is a smallenveloped virus containing a positive-sense, singlestrained (RNA). It is classified in the separate genus Hepacivirus in the Flaviviridae family. HCV genome contains approximately 9600 nucleotides that encode a polyprotein of around 3000 amino acids depending on the genotype. The various genotypes are distributed into 6 main types (1-6) with various subtypes (a-c). Within its hosts HCV exists as a pool of genetically distinct but closely related variants called quasispecies. Hepatocytes appear to be the major site of HCV replication, but peripheral blood mononuclear cells and lymph nodes are also natural target cells. Because of the lack of convenient in vitro tissue culture systems for efficient virus propagation the current understanding of the molecular mechanisms of HCV replication is mainly hypothetic

Hepatitis B

Infekcija čovjeka virusom hepatitisa B može se manifestirati kao asimptomatska infekcija ili kao akutna bolest s različitim kliničkim oblicima, od blagog do fulminantnog hepatitisa. Ishod bolesti također može biti različit, od izlječenja s normalizacijom svih laboratorijskih nalaza i eliminacijom virusa, preko inaktivnog nosilaštva HBsAg bez znakova kliničke bolesti do perzistentne infekcije sa znakovima kronične bolesti jetre. Posljedice perzistentne infekcije mogu biti pogubne, kao što su ciroza i hepatocelularni karcinom jetre. Danas postoje mogućnosti brze dijagnostike svih navedenih oblika bolesti, efi kasne i sigurne zaštite svih rizičnih populacija i liječenja teških oblika bolesti kao što su akutni fulminantni hepatitis i kronični hepatitis. Cilj ovog rada je prikazati najnovije spoznaje o patogenezi, dijagnostici, profi laksi i terapiji B hepatitisa, koje će nam pomoći da bolje razumijemo bolest, da upoznamo svoje bolesnike sa zaštitom od ove bolesti, o mogućim posljedicama infekcije i današnjim mogućnostima liječenja akutnih i kroničnih oblika bolesti.Infection with hepatitis B virus can be manifested either as asymptomatic infection or as acute disease with various clinical manifestations, from mild to fulminant hepatitis. The outcome of the infection is also complex, from normalization of all laboratory tests, elimination of the virus, inactive carrier state of HBsAg without signs of clinical disease, to persistent infection with signs of chronic liver disease. The sequelae of persistent infection may be serious such as liver cirrhosis or hepatocellular carcinoma. At present time, the accurate diagnosis of all forms of the disease, effi cient protection of risk population and antiviral treatment for severe forms of the disease, such as acute fulminant hepatitis and chronic hepatitis, are available. The aim of this paper is to present new knowledge about the pathogenesis, diagnostic procedures, prophylaxis and treatment of hepatitis B in order to better understand the disease, inform our patients about protection from this disease, analyze possible consequences of the infection, and review present status of available therapies of acute and chronic forms of the disease