Alpha-1-antitrypsin in Pathogenesis of Hepatocellular Carcinoma

Overview

Journal Hepat Mon

Publisher Brieflands

Specialty Gastroenterology

Date 2012 Nov 20

PMID 23162602

Citations 23

Authors

Aleksandra Topic

Mila Ljujic

Dragica Radojkovic

Affiliations

Soon will be listed here.

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.

Citing Articles

A Review of Incidence and Related Risk Factors in the Development of Hepatocellular Carcinoma.

Lampimukhi M, Qassim T, Venu R, Pakhala N, Mylavarapu S, Perera T Cureus. 2023; 15(11):e49429.

PMID: 38149129 PMC: 10750138. DOI: 10.7759/cureus.49429.

A pilot study on some critical immune elements in HBV infection: evidence of Alpha-1 Antitrypsin as an immunological biomarker.

Sarkar N, Chakravarty R, Ganguli S, Singh S, Narayan J, Banerjee A Gastroenterol Hepatol Bed Bench. 2023; 15(4):377-386.

PMID: 36762226 PMC: 9876771. DOI: 10.22037/ghfbb.v15i4.2587.

Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study.

Demirtas C, Tolu T, Keklikkiran C, Ozdogan O, Gunduz F Turk J Gastroenterol. 2021; 32(8):685-693.

PMID: 34528882 PMC: 8975315. DOI: 10.5152/tjg.2021.20677.

Liver disease with unknown etiology - have you ruled out alpha-1 antitrypsin deficiency?.

Patel D, Teckman J Ther Adv Chronic Dis. 2021; 12_suppl:2040622321995684.

PMID: 34408828 PMC: 8367207. DOI: 10.1177/2040622321995684.

Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements.

Perisetti A, Goyal H, Yendala R, Thandassery R, Giorgakis E World J Gastroenterol. 2021; 27(24):3466-3482.

PMID: 34239263 PMC: 8240056. DOI: 10.3748/wjg.v27.i24.3466.

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