Liver disease in alpha-1 antitrypsin deficiency: Current understanding and future therapy

COPD: Journal of Chronic Obstructive Pulmonary Disease

Volumn 10, Issue S1, 2013, Pages 35-43

  Teckman, Jeffrey H ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alpha 1 antitrypsin; Apoptosis; Autophagy; Hepatocellular proliferation; Liver

Indexed keywords

CALNEXIN; FATTY ACID BINDING PROTEIN; NONSTEROID ANTIINFLAMMATORY AGENT; URSODEOXYCHOLIC ACID;

ALPHA 1 ANTITRYPSIN DEFICIENCY; CHRONIC HEPATITIS; CHRONIC LIVER DISEASE; FEEDING DISORDER; FULMINANT HEPATIC FAILURE; GENOTYPE; HEPATOMEGALY; HETEROZYGOTE; HUMAN; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER DISEASE; LIVER FIBROSIS; LIVER NECROSIS; NEWBORN HEPATITIS; OBSTRUCTIVE JAUNDICE; PATHOPHYSIOLOGY; PHENOTYPE; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PRURITUS; REVIEW; SPLENOMEGALY; STEATOSIS; WEIGHT GAIN;

ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; CARCINOMA, HEPATOCELLULAR; GENOTYPE; HEPATITIS, CHRONIC; HEPATOCYTES; HUMANS; LIVER CIRRHOSIS; LIVER NEOPLASMS; LIVER TRANSPLANTATION;

EID: 84875678375     PISSN: 15412555     EISSN: 15412563     Source Type: Journal    
DOI: 10.3109/15412555.2013.765839     Document Type: Review

References (58)

1. Nelson DR, Teckman J, Di Bisceglie AM, Brenner DA. Diagnosis and management of patients with a(1)-Antitrypsin (A1AT) Deficiency. Clin Gastroenterol Hepatol. 2011. Epub 2011/12/28.
2. Rudnick DA, Liao Y, An JK, Muglia LJ, Perlmutter DH, Teckman JH. Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency. Hepatology 2004; 39(4):1048-1055.
3. American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency. Am J Respir Crit Care Med 2003; 168(7):818-900.
4. Eriksson S. Alpha-1-antitrypsin deficiency: natural course and therapeutic strategies. In: Boyer JL, Blum, H.E., Maier, K.-P., Sauerbruch, T., Stalder, G.A., editor. Falk Symposium 115: Liver Cirrhosis and its Development. Dordrecht: Kluwer Academic Publishers; 2001. p. 307-315.
5. Qu D, Teckman JH, Perlmutter DH. Review: Alpha 1-antitrypsin deficiency associated liver disease. J Gastroenterol Hepatol 1997; 12(5):404-416.
6. Lindblad D, Blomenkamp K, Teckman J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 2007; 46(4):1228- 1235. Epub 2007/09/22.
7. Eriksson S. Discovery of alpha 1-antitrypsin deficiency. Lung 1990; 168 Suppl:523-529.
8. Perlmutter DH. Alpha-1-antitrypsin deficiency: diagnosis and treatment. Clin Liver Dis 2004; 8(4):839-859, viii-ix.
9. Sveger T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med 1976; 294(24):1316-1321.
10. Sveger T. alpha 1-antitrypsin deficiency in early childhood. Pediatrics 1978; 62(1):22-25.
11. Eriksson S. Alpha 1-antitrypsin deficiency. J Hepatol 1999; 30 Suppl 1:34-39.
12. An JK, Blomenkamp K, Lindblad D, Teckman JH. Quantitative isolation of alphalAT mutant Z protein polymers from human and mouse livers and the effect of heat. Hepatology 2005; 41(1):160-167.
13. Sveger T, Eriksson S. The liver in adolescents with alpha 1-antitrypsin deficiency. Hepatology 1995; 22(2):514-517.
14. Cruz PE, Mueller C, Cossette TL, Golant A, Tang Q, Beattie SG, et al. In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA. Lab Invest 2007; 87(9):893-902. Epub 2007/06/27.
15. Sveger T. The natural history of liver disease in alpha 1-antitrypsin deficient children. Acta Paediatr Scand 1988; 77(6):847-851.
16. Mowat AP. Alpha 1-antitrypsin deficiency (PiZZ): features of liver involvement in childhood. Acta Paediatr Suppl 1994; 393:13-17.
17. Pittschieler K, Massi G. Alpha 1 antitrypsin deficiency in two population groups in north Italy. Paediatr Padol 1988; 23(4):307-311.
18. Eriksson S. A 30-year perspective on alpha 1-antitrypsin deficiency. Chest 1996; 110(6 Suppl):237S-42S.
19. Eriksson S, Lindmark B, Olsson S. Lack of association between hemochromatosis and alpha-antitrypsin deficiency. Acta Med Scand 1986; 219(3):291-294.
20. Mahadeva R, Chang WS, Dafforn TR, Oakley DJ, Foreman RC, Calvin J, et al. Heteropolymerization of S, I, and Z alpha1- antitrypsin and liver cirrhosis. J Clin Invest 1999; 103(7):999- 1006.
21. Teckman JH, Perlmutter DH. The endoplasmic reticulum degradation pathway for mutant secretory proteins alpha1- antitrypsin Z and S is distinct from that for an unassembled membrane protein. J Biol Chem 1996; 271(22):13215-13220.
22. Lomas DA, Elliott PR, Sidhar SK, Foreman RC, Finch JT, Cox DW, et al. alpha 1-Antitrypsin Mmalton (Phe52- deleted) forms loop-sheet polymers in vivo. Evidence for the C sheet mechanism of polymerization. J Biol Chem 1995; 270(28):16864-16870.
23. Lomas DA, Finch JT, Seyama K, Nukiwa T, Carrell RW. Alpha 1-antitrypsin Siiyama (Ser53→Phe). Further evidence for intracellular loop-sheet polymerization. J Biol Chem 1993; 268(21):15333-15335.
24. Pittschieler K. Liver disease and heterozygous alpha-1-antitrypsin deficiency. Acta Paediatr Scand 1991; 80(3):323-327.
25. Kaserbacher R, Propst T, Propst A, Graziadei I, Judmaier G, Vogel W. Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. Hepatology 1993; 18(3):707-708.
26. Propst T, Propst A, Dietze O, Judmaier G, Braunsteiner H, Vogel W. High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease. Ann Intern Med 1992; 117(8):641-645.
27. Lykavieris P, Ducot B, Lachaux A, Dabadie A, Broue P, Sarles J, et al. Liver disease associated with ZZ alpha1-antitrypsin deficiency and ursodeoxycholic acid therapy in children. J Pediatr Gastroenterol Nutr 2008; 47(5):623-629. Epub 2008/10/29.
28. Rudnick DA, Shikapwashya O, Blomenkamp K, Teckman JH. Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency. Hepatology 2006; 44(4):976-982. Epub 2006/09/29.
29. Piitulainen E, Sveger T. Respiratory symptoms and lung function in young adults with severe alpha(1)-antitrypsin deficiency (PiZZ). Thorax 2002; 57(8):705-708.
30. Sveger T, Thelin T, McNeil TF. Young adults with alpha 1-antitrypsin deficiency identified neonatally: their health, knowledge about and adaptation to the high-risk condition. Acta Paediatr 1997; 86(1):37-40.
31. Mayer AS, Stoller JK, Vedal S, Ruttenber AJ, Strand M, Sandhaus RA, et al. Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency. Inter J Chron Obstruct Pulmon Dis 2006; 1(4):485-492. Epub 2007/11/30.
32. Sveger T, Piitulainen E, Arborelius M, Jr. Lung function in adolescents with alpha 1-antitrypsin deficiency. Acta Paediatr 1994; 83(11):1170-1173.
33. Eden E, Hammel J, Rouhani FN, Brantly ML, Barker AF, Buist AS, et al. Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry. Chest 2003;123(3):765-771.
34. Wu Y, Whitman I, Molmenti E, Moore K, Hippenmeyer P, Perlmutter DH. A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency. Proc Natl Acad Sci USA 1994; 91(19):9014-9018.
35. Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992; 357(6379):605-607.
36. Teckman JH, Perlmutter DH. Retention of mutant alpha(1)- antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Am J Physiol Gastrointest Liver Physiol 2000; 279(5):G961-974.
37. Hidvegi T, Mirnics K, Hale P, Ewing M, Beckett C, Perlmutter DH. Regulator of G Signaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1-antitrypsin Z in the classical form of alpha1- antitrypsin deficiency. J Biol Chem 2007; 282(38):27769-80. Epub 2007/07/20.
38. Lomas DA, Mahadeva R. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest 2002; 110(11):1585-1590.
39. Qu D, Teckman JH, Omura S, Perlmutter DH. Degradation of a mutant secretory protein, alpha1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem 1996; 271(37):22791-22795.
40. James EL, Bottomley SP. The mechanism of alpha 1-antitrypsin polymerization probed by fluorescence spectroscopy. Arch Biochem Biophys 1998; 356(2):296-300.
41. Cabral CM, Choudhury P, Liu Y, Sifers RN. Processing by endoplasmic reticulum mannosidases partitions a secretionimpaired glycoprotein into distinct disposal pathways. J Biol Chem 2000; 275(32):25015-25022.
42. Teckman JH, Burrows J, Hidvegi T, Schmidt B, Hale PD, Perlmutter DH. The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes. J Biol Chem 2001; 276(48):44865-44872.
43. Sifers RN. Cell biology. Protein degradation unlocked. Science 2003; 299(5611):1330-1331.
44. Dafforn TR, Mahadeva R, Elliott PR, Sivasothy P, Lomas DA. A kinetic mechanism for the polymerization of alpha1- antitrypsin. J Biol Chem 1999; 274(14):9548-9555.
45. Kaushal S, Annamali M, Blomenkamp K, Rudnick D, Halloran D, Brunt EM, et al. Rapamycin reduces intrahepatic alpha-1- antitrypsin mutant Z protein polymers and liver injury in a mouse model. Exp Biol Med (Maywood) 2010; 235(6):700-709 Epub 2010/06/01.
46. Hidvegi T, Ewing M, Hale P, Dippold C, Beckett C, Kemp C, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science 2010; 329(5988):229-232. Epub 2010/06/05.
47. Teckman JH, An JK, Blomenkamp K, Schmidt B, Perlmutter D. Mitochondrial autophagy and injury in the liver in alpha 1-antitrypsin deficiency. Am J Physiol Gastrointest Liver Physiol 2004; 286(5):G851-G862.
48. Wu Y, Swulius MT, Moremen KW, Sifers RN. Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation. Proc Natl Acad Sci USA 2003; 100(14):8229-8234.
49. Teckman JH, Gilmore R, Perlmutter DH. Role of ubiquitin in proteasomal degradation of mutant alpha(1)-antitrypsin Z in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol 2000; 278(1):G39-G48.
50. Cabral CM, Liu Y, Moremen KW, Sifers RN. Organizational diversity among distinct glycoprotein endoplasmic reticulumassociated degradation programs. Mol Biol Cell 2002; 13(8):2639-2650.
51. Chappell S, Hadzic N, Stockley R, Guetta-Baranes T, Morgan K, Kalsheker N. A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease. Hepatology 2008; 47(1):127-132. Epub 2007/11/01.
52. Pan S, Huang L, McPherson J, Muzny D, Rouhani F, Brantly M, et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology 2009; 50(1):275-281. Epub 2009/05/16.
53. Lawless MW, Greene CM, Mulgrew A, Taggart CC, O'Neill SJ, McElvaney NG. Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. J Immunol 2004; 172(9):5722- 5726.
54. Miller SD, Greene CM, McLean C, Lawless MW, Taggart CC, O'Neill SJ, et al. Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad. Hepatology 2007; 46(2):496-503. Epub 2007/06/15.
55. Rudnick DA, Perlmutter DH. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005; 42(3):514-521.
56. Schmidt BZ, Perlmutter DH. Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol 2005; 289(3):G444-G455.
57. Mueller C, Tang Q, Gruntman A, Blomenkamp K, Teckman J, Song L, et al. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles. Mol Ther 2012. Epub 2012/01/19.
58. Teckman JH. Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study. J Pediatr Gastroenterol Nutr 2004; 39(1):34-37.