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Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma

AUTHORS

Aleksandra Topic 1 , * , Mila Ljujic 2 , Dragica Radojkovic 2

1 University of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, aleksandra.topic1@gmail.com, Serbia

2 University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Serbia

How to Cite: Topic A, Ljujic M, Radojkovic D. Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma, Hepat Mon. 2012 ; 12(10):7042. doi: 10.5812/hepatmon.7042.

ARTICLE INFORMATION

Hepatitis Monthly: 12 (10); 7042
Published Online: October 30, 2012
Article Type: Review Article
Received: February 16, 2012
Accepted: June 30, 2012
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Abstract

Context: 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 proinflammatory 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.

Keywords

Alpha 1-Antitrypsin Deficiency Carcinoma, Hepatocellular Autophagy Fucose

© 2012, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

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