Liver morphology in heterozygous alpha-1-antitrypsin deficiency PiZ

Whether heterozygotes with alpha-1-antitrypsin (AAT) deficiency type PiZ be ar an increased risk for chronic liver disease is controversial. On the bas is of liver tissue from 1,030 autopsies (autopsy series), 1,847 biopsies (b iopsy series) and 317 primary liver carcinomas (tumor series),we analysed t he effect of heterozygous state PiZ for the development of liver diseases. The PiZ status was screened immunohistochemically and verified in selected cases by SSCP analysis and by sequencing DNA extracted from paraffin embedd ed tissue. The PiZ frequency in the biopsy series (3.4%) and tumor series (5.99%) was significantly higher than in the autopsy series (1.8%). Hepatic PiZ deposit s in heterozygotes sometimes were as extensive as in homozygotes. The amoun t of PiZ deposits correlated positively with the inflammatory activity and stage of fibrosis, as well as with the age of patients. Patients with concu rrent liver disease such as hepatitis and alcoholic liver disease showed si gnificantly higher scores of inflammatory activity, stage of fibrosis and a mount of PiZ deposits than those without additional liver disease. Cholangi ocarcinomas and combined hepato-cholangiocarcinomas were seen significantly more frequently in patients with PiZ-associated liver carcinoma than in ge netic healthy individuals (p=0.004). Three out of 19 PiZ-associated liver c arcinomas had developed in cirrhotic liver tissue. Heterozygotes of type PiZ have an enhanced risk for chronic liver disease i ncluding primary liver carcinoma. PiZ-associated liver diseases will become clinically manifest in middle or old aged adults. Rarely this genetic defe ct causes liver cirrhosis even without concurrent liver disease. PiZ-associ ated liver carcinomas are frequently characterized by cholangiocellular dif ferentiation and may develop often in non-cirrhotic liver tissue. Immunohis tochemistry is a specific method to detect hepatic PiZ deposits.