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    Testing for AAT Deficiency
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    Alpha One International Registry
    provides AAT Deficiency Testing. This AAT Deficiency Testing is a
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    This testing will include measuring the CONCENTRATION of AAT in your blood, determining the TYPE of ATT in your blood and (where appropriate) determining your AAT genotype by testing the DNA in your blood; State of the art, full-spectrum Alpha-1 Testing .

    Please read the detail at: AAT Deficiency Detection Center
    Report on the Relationship of
    Alpha 1 and Liver Disease in Older Patients

    The following article discusses a small study on the incidence of liver disease/injury and its relationship to Alpha 1 deficient patients.

    Late manifestations of a1-antitrypsin deficiency
    Prof. Dr. med. J. Reichen

    For the molecular basis of liver injury in a1antitrypsin deficiency the reader is referred to a recent review (1) and my pathophysiology syllabus (in German). The natural story in affected neonates and adolescents has been described by Sveger's landmark papers (2-4). In the pre-hepatitis C era, a small series from the Mayo clinic showed chronic liver disease to occur at age 58, 66 and 72 years in ZZ, SZ and MZ phenotypes; liver disease was advanced in most of them (5). In autopsy series of identified cases, cirrhosis and HCC were frequent, but these patients actually lived longer than patients with a1-antitrypsin deficiency without liver disease (6). The risk of liver disease in PiZZ appears particularly high in men over age 50 (7). In a cohort of transplant candidates, heterozygotes PiZ carriers were overrepresented (9.2 % vs 2-4 % in the normal population (8). Similar data were found in a Swedish cohort of patients with chronic liver disease (7.6 vs 4. 8 %); of note was that in this study - where screening was performed with a monoclonal antibody specific for Z - only 50 % of affected patients had lowered a1-antitrypsin levels (9). A similar conclusion was reached by Iezzoni et al. in a study on explants: PAS positive globules were found in 10 % of patients, but a1-antitrypsin deficiency had been recognized pre-OLT in only 3/17 (10). Also, cryptogenic liver disease is overrepresented in heterozygotes (8;9;11). Non-cirrhotic portal hypertension has been described in an adult with MZ (19). PiZZ leading to cirrhosis is clearly at increased risk to develop hepatocellular carcinoma (6;11;12) with hepatitis viruses playing no role (12). In the 19 patients from the Mayo clinic, two presented with hepatocellular cancer, both in patients with ZZ (5). Six cases of hepatoma in heterozygotes were found as opposed to only 1 in control patients (9). The risk of HCC is attributable to cirrhosis, not the metabolic defect (13). Interestingly, large cell dysplasia occurs in patients with inclusion globules (14). The significance of an old study reporting copper storage and Mallory bodies in patients with HCC associated with a1-antitrypsin deficiency remains unclear (15). Immunohistochemistry is reported to be superior to PAS/diastase staining (16, 17). The degree of fibrosis increases with increasing age in heterozygotes (17); in this series, one case of HCC and three of cholangiocarcinoma were found. In a series of hepatic tumors, heterozygosity for Z was also markedly overrepresented (18); this was particularly true for cholangiocarcinoma and combined cholangia- and hepatocellular cancers.


    Reference List
      1. Teckman JH, Qu DF, Perlmutter DH. Molecular pathogenesis of liver disease in ?1-antitrypsin deficiency. Hepatology 1996; 24(6):1504-1516.
      2. Sveger T. Liver disease in alpha-1-antitrypsin deficiency detected by screening of 200-000 infants. N Engl J Med 1976; 294:1316-1321.
      3. Sveger T. The natural history of liver disease in alpha1-antitrypsin deficient children. Acta Paed Scand 1988; 77:847-851.
      4. Sveger T, Eriksson S. The liver in adolescents with ?1-antitrypsin deficiency. Hepatology 1995; 22:514-517.
      5. Rakela J, Goldschmiedt M, Ludwig J. Late manifestation of chronic liver disease in adults with alpha- 1-antitrypsin deficiency. Dig Dis Sci 1987; 32:1358-1362.
      6. Eriksson S. Alpha-1-antitrypsin deficiency and liver cirrhosis in adults. An analysis of 35 Swedish autopsied cases. Acta Med Scand 1987; 221:461-467.
      7. Cox DW, Smyth S. Risk for liver disease in adults with alpha 1-antitrypsin deficiency. Am J Med 1983; 74:221-227.
      8. Graziadei IW, Joseph JJ, Wiesner RH, Therneau TM, Batts KP, Porayko MK. Increased risk of chronic liver failure in adults with heterozygous ?1-antitrypsin deficiency. Hepatology 1998; 28(4):1058-1063.
      9. Carlson J, Eriksson S. Chronic 'cryptogenic' liver disease and malignant hepatoma in intermediate alpha-1-antitrypsin deficiency identified by a Pi Z- specific monoclonal antibody. Scand J Gastroenterol 1985; 20:835-842.
      10. Iezzoni JC, Gaffey MJ, Stacy EK, Normansell DE. Hepatocytic globules in end-stage hepatic disease - Relationship to alpha1-antitrypsin phenotype. Am J Clin Pathol 1997; 107(6):692-697.
      11. Bell H, Schrumpf E, Fagerhol MK. Heterozygous MZ alpha-1-antitrypsin deficiency in adults with chronic liver disease. Scand J Gastroenterol 1990; 25:788-792.
      12. Elzouki ANY, Eriksson S. Risk of hepatobiliary disease in adults with severe ?1-antitrypsin deficiency (PiZZ): Is chronic viral hepatitis B or C an additional risk factor for cirrhosis and hepatocellular carcinoma? Eur J Gastroenterol Hepatol 1996; 8:989-994.
      13. Propst T, Propst A, Dietze O, Judmaier G, Braunsteiner H, Vogel W. Prevalence of hepatocellular carcinoma in alpha-1- antitrypsin deficiency. J Hepatol 1994; 21(6):1006-1011.
      14. Cohen C, Derose PB. Liver cell dysplasia in alpha-1-antitrypsin deficiency. Modern Pathol 1994; 7:31-36.
      15. Rubel LR, Ishak KG, Benjamin SB, Knuff TE. Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Association with cirrhosis- copper storage- and Mallory bodies. Arch Pathol Lab Med 1982; 106:768-681.
      16. Callea F, Fevery J, De Groote J, Desmet VJ. Detection of Pi Z phenotype individuals by alpha-1-antitrypsin immunohistochemistry in paraffin-embedded liver tissue specimens. J Hepatol 1986; 2:389-401.
      17. Fischer HP, Ortiz-Pallardo ME, Ko Y et al. Chronic liver disease in heterozygous a1-antitrypsin deficiency PiZ. J. Hepatol. 2000; 33: 883-892.
      18. Zhou H, Ortiz-Pallardo ME, Ko Y, Fischer HP (2000). Is heterzygous alpha-1-antitrypsin deficiency type PiZ a risk factor for primary liver carcinoma? Cancer 88:2668-2676.
      19. Lee FI, Kelly JK, Vasudev KS (1983). Hepatic changes in a patient with alpha-1-antitrypsin deficiency (MZ phenotype. Portal tract elastosis and noncirrhotic portal hypertension. Arch Pathol Lab Med 107: 453-455.


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