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dc.creatorTopić, Aleksandra
dc.creatorLjujić, Mila
dc.creatorRadojković, Dragica
dc.date.accessioned2019-09-02T11:27:56Z
dc.date.available2019-09-02T11:27:56Z
dc.date.issued2012
dc.identifier.issn1735-143X
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/1659
dc.description.abstractContext: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the clinical manifestations of A1ATD is liver disease in childhood and cirrhosis and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and pathophysiology of liver failure in early childhood caused by A1ATD are well known, but the association with hepatocellular carcinoma is not clarified. The aim of this article is to review different aspects of association between A1AT variants and hepatocellular carcinoma, with emphasis on the epidemiology and molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis of HCC is also discussed. Evidence Acquisitions: Search for relevant articles were performed through Pub Med, HighWire, and Science Direct using the keywords "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1". Articles published until 2011 were reviewed. Results: Epidemiology studies revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC unrelated to the presence of HBV or HCV infections. However, predisposition to HCC in moderate A1ATD is rare, and probably happens in combination with HBV and/or HCV infections or other unknown risk factors. It is assumed that accumulation of polymers of A1ATD variants in endoplasmic reticulum of hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also, increased level of A1AT was recognized as diagnostic and prognostic marker of HCC. Conclusions: Clarification of a carcinogenic role for A1ATD and identification of pro-inflammatory or some still unknown factors that lead to increased susceptibility to HCC associated with A1ATD may contribute to a better understanding of hepatic carcinogenesis and to the development of new drugs.en
dc.publisherKowsar Publ, Hoensbroek
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173008/RS//
dc.rightsopenAccess
dc.sourceHepatitis Monthly
dc.subjectAlpha 1-Antitrypsin Deficiencyen
dc.subjectCarcinoma, Hepatocellularen
dc.subjectAutophagyen
dc.subjectFucoseen
dc.titleAlpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinomaen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractТопиц, Aлександра; Љујић, Мила; Радојковић, Драгица;
dc.citation.volume12
dc.citation.issue10
dc.citation.other12(10): -
dc.citation.rankM23
dc.identifier.wos000314117000009
dc.identifier.doi10.5812/hepatmon.7042
dc.identifier.pmid23162602
dc.identifier.scopus2-s2.0-84871476851
dc.identifier.fulltexthttps://farfar.pharmacy.bg.ac.rs//bitstream/id/492/1657.pdf
dc.identifier.rcubconv_2764
dc.type.versionpublishedVersion


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