Uloga mutanata virusa hepatitisa B u liječenju kronične HBV infekcije

master's thesis

• Title (english): Hepatitis B virus mutants influence on chronic HBV infection therapy
• Author: Ivana Fileš
• Mentor: Sandra Šupraha Goreta (mentor)
• Committee member: Sandra Šupraha Goreta
• Committee member: Olga Gornik
• Committee member: Miranda Sertić
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2015-09-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Hepatitis B je upala jetre koja nastaje infekcijom virusom hepatitisa B (HBV). Najčešće se javlja kao akutni hepatits, no kod malog postotka inficiranih osoba prelazi u kronični oblik koji predstavlja visok rizik za razvoj ciroze jetre ili hepatocelularnog karcinoma. Procjenjuje se da je trenutan broj kronično zaraženih osoba u cijelom svijetu oko 240 milijuna, što ga čini značajnim faktorom morbiditeta i mortaliteta. Virus je vrlo infektivan, a prenosi se kontaktom sa zaraženim tjelesnim tekućinama. Replikacija virusa uključuje reverznu transkripciju uz virusnu DNA polimerazu koja nema ispravljačku sposobnost. To rezultira pojavom mutantnih virusa koji se mogu izdvojiti djelovanjem imunološkog sustava ili pod utjecajem antivirotika. Brojna su istraživanjaje pokazala da genetička varijabilnost virusa utječe na brzinu progresije bolesti, pouzdanost dijagnostičkih metoda, uspjeh antivirusne terapije i imunizacije. Mutacije u površinskom antigenu HBsAg mogu dovesti do neuspješne imunizacije cijepljenjem („escape“ mutanti) te neuspješne detekcije dijagnostičkim metodama. Nemogućnost detekcije predstavlja problem jer takve osobe mogu postati donori krvi i tako širiti zarazu. Također, mutacije u YMDD motivu virusne DNA polimeraze imaju važnu ulogu u razvoju rezistencije na nukleoz(t)idne analoge. Praćenje HBV mutacija važno je u svrhu bolje prevencije, dijagnoze te stvaranja efikasne antivirusne terapije.

Abstract (english)

Hepatitis B is a liver inflammation caused by hepatitis B virus (HBV) infection. Usually it occurs as acute hepatitis, but in some cases virus remains in patient, causing a chronic infection. Consequently, it can lead to development of cirrhosis and hepatocellular carcinoma. Worldwide, there are an estimated 240 million chronically infected persons. Therefore, chronic HBV infection is a major public health issue. Hepatitis B virus is very infectious and it spreads through contact with infected body fluids. Virus replication includes reverse transcription using a viral DNA polymerase lacking proof-reading ability. This results in the emergence of mutant viruses that can be selected out by host immunity or antiviral drugs. Numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of the virus. Mutations in hepatitis B surface antigen (HBsAg) may lead to evasion of vaccine-induced immunity („vaccine escape“ mutants) and loss of HBV detection by diagnostic assays. The inability to detect HBV means that these individuals may become blood donors and continue HBV transmission. Also, mutations in YMDD motif of viral DNA polimerase are associated with resistance to nucleos(t)ide analogues. Monitoring of HBV mutations contributes to improvement of prevention, diagnosis and creating more efficient antiviral therapy.

• Keywords: hepatitis B virus; kronični hepatitis B; HBV mutacije; rezistencija na lijekove; vaccine escape mutanti
• Keywords (english): hepatitis B virus; chronic hepatatis B; HBV mutations; drug resistance; vaccine escape mutants
• Language: croatian
• URN:NBN: urn:nbn:hr:163:902946
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-02-18 16:01:39