title: [Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?].
abstract: Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.
authors.affiliation: Universitätsklinik Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn. steffen.manekeller@ukb.unibonn.de
authors.forename: S
authors.initials: S
authors.lastname: Manekeller
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: H-P
authors.initials: HP
authors.lastname: Fischer
authors.forename: P
authors.initials: P
authors.lastname: Propping
authors.forename: A
authors.initials: A
authors.lastname: Hirner
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin