Pathogenesis and Pathology of Liver Disease Associated With ₁-Antitrypsin Deficiency

¹ From the Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy

₁-Antitrypsin (₁-AT) accumulates in the rough endoplasmic reticulum through a mechanism of polymerization. Polymerization is favored by the incorrect tertiary structure of the ₁-AT caused by a point mutation at position 342 of the protein. Accumulation of ₁-AT in the liver cells (and in hepatocytes and colangiocytes) is not sufficient per se to explain the liver disease that is manifested in a minority of PiZ subjects and thus, a trigger factor must be hypothesized. A virus (hepatitis C virus or some other kind of virus not identified as yet) is among the most probable trigger factors. In Z subjects (among the general population), relevant liver disease is probably a more rare event than thought in the past and most of these subjects escape major liver disease. Usually, liver disease is not a significant problem in patients with COPD.

Key Words: ₁-antitrypsin deficiency • cholestasis • liver disease • lung disease