alpha-۱-antitrypsin in pathogenesis of hepatocellular carcinoma
نویسندگان
چکیده
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.
منابع مشابه
Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma
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 cirrhosi...
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Forty-two cases of hepatocellular carcinoma (HCC) were examined for the presence of the inclusions of alpha-1-antitrypsin (AAT), which indicate a carrier state for the Pi Z gene. These were found in the non-neoplastic liver tissue of two cases of HCC and in one of the 98 control livers, a difference that is not statistically significant. Typical globules of AAT deficiency were not found in HCC ...
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It has been established that alpha-1-antitrypsin (AAT) deficiency due to the homozygous Pi Z state may give rise to cirrhosis and hepatic fibrosis, although the mechanism whereby this occurs is obscure. Also there are numerous reports of hepatocellular carcinoma (HCC) developing in such cases (Ganrot et al., 1967; Berg and Eriksson, 1972; Eriksson and Hagerstrand, 1974). The position of the het...
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عنوان ژورنال:
hepatitis monthlyجلد ۱۲، شماره ۱۰ HCC، صفحات ۰-۰
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