Liver Transplantation for Advanced Liver Disease with Alpha-1antitrypsin Deficiency

Abstract

Alpha-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson. 1 In 1969, Sharp 2 described the first cases of alpha-1-antitrypsindeficiency disease in children with cirrhosis. Since then, this inborn error has been recognized as one of the more common factors in cirrhosis of infancy and childhood, 3 including "neonatal hepatitis." 4 Alpha-1-antitrypsin is a glycoprotein that accounts for a major portion of the alpha-1 globulin fraction of the serum. 5 It is responsible for approximately 90 per cent of the antitrypsin activity 6 of the serum, and it also inhibits several other plasma enzymes, including plasmin, 7 elastase, 8 collagenase, 9 and chymotrypsin. 10 Cirrhosis develops in about 15 per cent of patients with homozygous phenotype PiZZ (Pi = protease inhibitor), 11 and there have been a few recent reports of cirrhosis in heterozygous patients. 12,13 There has been no effective, specific medical treatment for such patients. This report will examine the place of orthotopic liver transplantation in the treatment of seven white patients who had end-stage liver disease due to alpha-1-antitrypsin deficiency. After transplantation, the phenotypes of the recipients became those of the donors, and alpha-1-antitrypsin levels were restored to normal. Thus, the metabolic basis of the disease was corrected for as long as the patients survived the transplantation procedure. Three of the patients are still alive after 13, 21, and 36 months. The others died between 12 days and 28 months after transplantation. Methods Liver replacements were performed in seven patients who had alpha-1-antitrypsin deficiency disease. One of these cases has been reported previously. 14 Phenotypes for alpha-1-antitrypsin (Pi) were determined by means of acid-starch electrophoresis followed by crossed immunoelectrophoresis, as described elsewhere. 15,29 The nomenclature recommended by the International Alpha-1-antitrypsin Pi Committee was used. 14 The normal alpha-1-antitrypsin values were established by means of analysis of serum from 2213 Red Cross donors in Los Angeles, all with the phenotype MM. The range of 140 to 470 mg per 100 ml encompassed approximately two standard deviations from the mean.

Idiopathic Hemochromotosis and Alpha-1-Antitrypsin Deficiency: Coexistence in a Family with Progressive Liver Disease in the Proband

“…Liver transplantation has been shown to correct the metabolic defect in AAT deficiency, and as in our case, results in the conversion of the patients' phenotype from ZZ to MM after successful transplantation (22).…”

Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium.

“…Studies of changes in a,-AT allotypes after orthotopic liver transplantation have shown that liver is the predominant site of synthesis of blood-borne a,-AT (2,3). There is evidence for extrahepatic sites ofsynthesis, notably that in blood monocytes and tissue macrophages (4).…”

A lymphokine regulates expression of alpha-1-proteinase inhibitor in human monocytes and macrophages.

“…Liver is the predominant site of synthesis (5,6), but human monocytes and macrophages also synthesize and secrete a1PI (7). Furthermore, the cellular defect in homozygous PiZZ aPI deficiency, a selective decrease in rate of secretion of aPI, is expressed in human monocytes from PiZZ individuals (8).…”