LIVER DISEASE IN CHILDREN CAUSED BY Α1-ANTITRYPSIN DEFICIENCY
Abstract
Alpha-1 antitrypsin deficiency is a frequent metabolic, genetically-associated disease in which the liver is affected, primarily in patients with a ZZ phenotype. However, according to the literature to 20 years of life, only 10-15% of patients retain or develop clinical signs of the disease. We observed 7 children with the ZZ phenotype of α₁-antitrypsin, who had a severe neonatal cholestasis, a neonatal liver syndrome, and asymptomatic moderate hyperfermentemia in young children at the initial examination. In the course of further follow-up, a tendency toward weakening of the manifestations of the disease or normalization of liver laboratory tests was observed in all, no one showed signs of progression of liver fibrosis for a period of up to 3 years. However, in children among genetic diseases in this disease, most often there is a need for a liver transplant. Diagnosis of α₁-antitrypsin deficiency is to determine its level in the blood and phenotyping. Genetic diagnosis is possible. Treatment of liver damage with α₁-AT deficiency is an unresolved problem, but in recent years new strategies have been applied when it is possible to influence individual pathological mechanisms that cause liver damage.
About the Authors
N. N. Vlasov
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
E. A. Kornienko
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
S. I. Melnik
Saint-Petersburg State Research Institute of Phthisiopulmonology; North-Western State Medical University n. a. I. I. Mechnikov
Russian Federation
Russian Federation
References
1. Perlmutter D. H.: “Alpha-1-antitrypsin” // In book Schiff E. R., Sorrell M. F., Maddrey W. C. (eds.) Schiff’s Diseases of the Liver, 11th edn. Oxford, Wiley-Blackwell, 2011, p. 835-867.
2. Silverman E. K., Sandhaus R. A.: “Clinical practice. Alpha1-antitrypsin deficience” // N. Engl. J. Med., 2009, 360, p. 2749-2757.
3. Sherlock S., Dooley J.: «Diseases of the Liver and Biliary System» // Oxford, UK: Blackwell Science Ltd a Blackwell Publishing, 11 Edition, 2002-706 p.
4. Teckman J. H., Qu D., Perlmutter D. H.: “Molecular pathogenesis of liver disease in α₁-antitrypsin deficiency” // Hepatology, 1996, 24, p. 1504-1516.
5. Carlson J. A., Rogers B. B., Sifers R. N. et al.”Accumulation of PiZ antitrypsin causes liver damage in transgenic mice” // Clin. Invest. 1988, 83, p. 1183-1190.
6. Eriksson S.: “α₁-antitrypsin deficiency” // J. Hepatol., 1999, 30, suppl. 1, p. 34-39.
7. Perlmutter D. H.: “Alpha-1-antitrypsin deficiency” // Semin. Liver Dis., 1998, 18, p. 217-222.
8. Crystal R. G.: “α₁-Antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy” // J. Clin. Invest, 1990, 85, p. 1343-1352.
9. Lomas D. A.: Loop sheet polymerization: the structural basis of Z α₁-antitrypsin accumulation in the liver” // Clin. Sci., 1994, 86, p. 489.
10. Lomas D. A., Evans D. L.I., Finch J. T. et al.: “The mechanism of Z α₁-antitrypsin accumulation in the liver” // Nature, 1992, 357, p. 605-607.
11. Qu D., Teckman J. H., Perlmutter D. H.: “α₁-Antitrypsin deficiency associated liver disease” // J. Gasroenterol., Hepatol., 1997, 12, p. 404-416.
12. Teckman J. H., Perlmutter D. H.: “Conceptual advances in the pathogenesis and treatment of childhood liver disease” // Gasroenterology, 1995, 108, p. 1263-1279.
13. Wu G., Whitman F., Mobments E. et al.: “A lag in intracellular degradation of mutant α₁-antitrypsin correlated with the liver disease phenotype in homozygous PiZZ α₁-antitrypsin deficiency” // Proc. Natl. Acad. Sci. USA, 1995, 91, p. 9014-9018.
14. Geller S., Hichols W. S., Dycacio M. J. et al.; ‘Histopathology of α₁-antitrypsin liver disease in a transgenic mouse model” // Hepatology, 1990, 12, 40, p. 40-47.
15. Geller S., Hichols W. S., Kim S. S. et al.; “Hepatocarcinogenesis is the sequel to hepatitis in Z#2 α₁-antotrypsin transgenic mice: histopatholgical and DNA ploidy studies” // Hepatology, 1994, 19, p. 389-397.
16. Perlmutter D. H.: “Alpha-1-antitrypsin deficiency: Importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates” // Annu Rev. Med., 2011, 62, 4.1-4.13.
17. Hadzic N., Quaglia A., Mieli-Vergani G.: “Hepatocellular carcinoma in a 12-year-old child with PiZZ α₁-antitrypsin deficiency” // Hepatology, 2006, 43, p. 194.
18. Zhou H., Ortiz-Pallardo M.E., Ko Y., Fischer H-P.: “Is heterozygous alpha-1-antitrypsin deficiency type PiZ a risk factor for primary liver cancer” // Cancer, 2000, 88, p. 2668-2676.
19. Perlmutter D.: “α₁-Antitrypsin deficiency” // In book Suchy F. J., Sokol R. J., Balistreri W. F. Liver Disease in Children. Fourth Edition. Cambridge University Press 2014, p. 400-418.
20. Propst T., Propst A., Dietze O. et al.: “Prevalence of hepatocellular carcinoma in α₁-antitrypsin deficiency” // J. Hepatol., 1994, 21, p. 1006.
21. Glasgow J. F.T., Lynch, Hercz A. et al.: “α₁-antitrypsin deficiency in association with both cirrhosis and chronic obstructive lung disease in two sibs” // Am. J. Med., 1973, 54, p. 181.
22. Bakula A., Socha P., Adamowich M. et al.: “Early and late clinical presentation of α-1 antitrypcin deficiency in children” // Gut, 2005, suppl. N VII, vol. 54 - Endoscopy, 2005, suppl. N1, vol. 34, p. A 193.
23. Francavilla R., Castellaneta S. P., Hadzic N. et al.: “α-1 antitrypsin deficiency: a 29 years experience in 241 children”. // J. Hepatol., 1999, vol. 30, suppl. № 1, p. 51.
24. Francavilla R., Castellaneta S. P., Hadzic N. et al.: “Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation”. // J. Hepatol., 2000, 32, р. 986-989.
25. Sveger T., Eriksson S.: “The liver in adolescents with α₁-anritrypsin deficiency” // Hepatology, 1995, 22, р. 514-517.
26. Roberts E. A.: “ The Acutely Ill Baby” // In book “Diseases of the Liver and Biliary System in Children Edited By Deirdre Kelly, 2008, Blackwell Publishing, p. 57-105.
27. Nord K. S., Saad S., Joshi V.V, McLoughlin L.C.: “Concurrence of a1-antitrypsin deficiency and biliary atresia” // J. Pediatr., 1987, 111, p. 416-418.
28. Cottrall K., Cook P. J.L., Mowat A. P.: “Neonatal hepatitis syndrome and alpha-1-antitrypsin deficiency: An epidemiological study in south-east England” // Postgrad. Med. J., 1974, 50, p. 376-380.
29. Roberts E. A.: “The Jaundiced Baby” // In book: Kelly D.: Diseases of the Liver and Biliary System in Children. Third Edition. Blackwell Publishing, 2008, p. 57-106.
30. Sharp H. I.: “Alpha 1-antitrypsin deficiency” // Hosp. Pract., 1971, 6(5), p. 83-96.
31. Sveger T.: “The natural history of liver disease in α₁-antitrypsin deficient children” // Acta Paediatr. Scand., 1988, p. 847-851.
32. Ybarguen E., Gross C. R., Savik S. K. et al.: “Liver disease in α₁-antitrypsin deficiency: prognostic indicators” // J. Pediatr., 1990, 117, p. 864-870.
33. Sveger T.: “Liver disease in α₁-antitrypsin deficiency detected by screening of 200 000 infants” // N. Engl. J. Med., 1976, 294, 1216-1221.
34. Brantly M.: “Laboratory diagnosis of α₁-АТ deficiency”. // In Crystal R. G. editor. Alpha 1-Antitrypsin Deficiency: Biology, Pathogenesis, Clinical Manifestations, Therapy. New York: Marcel Dekker, 1996, p. 221-226.
35. Pitulainen E., Carlson J., Ohlsson K. et al.: “Alpha-1-antitrypsin deficiency in 26-year-old subjects: lung, liver and protease/protease inhibitor studies” // Chest 2005, 128, 2076-2081.
36. Volpert D, Molleston JP, Perlmutter DH. Alpha1-antitrypsin deficiency-associated liver disease progresses slowly in some children. // J. Pediatr. Gastroenterol. Nutr., 2000б 31б, р. 258-263.
37. Graziadi I. W., Joseph J. J., Wiesner R. H. et al: “Increased risk of chronic liver failure in adults with heterozygous α₁-antitrypsin deficiency” // Hepatology, 1998, 28, p. 1058.
38. Pittschieler K.: “Heterozygotes and liver involvement”. // Acta Paediatr., 1994, 83 (suppl. 393), p. 21-23.
39. Francavilla R., Castellaneta S. P., Hadzic N. et al.: “Liver disease in PiSS/PiSZ phenotype of α-1 antitrypsin deficiency”. // J. Hepatol., 1999, vol. 30, suppl. № 1, p. 164.
40. Psacharopoulos H. T., Mowat A. P., Cook P. J. et al.: “Outcome of liver disease associated with alpha 1 antitrypsin deficiency (PiZ). Implications for genetic counselling and antenatal diagnosis” // Arch. Dis. Child., 1983, 58, p. 882-887.
41. Nebbia G., Hadchouel M., Odievre M. et al.: “Early assessment of evolution of liver disease associated with alpha 1-antitrypsin deficiency in childhood” // J. Pediatr., 1983, 102, p. 661-665.
42. Ibarguen E, Gross CR, Savik SK, Sharp HL. Liver disease in alpha-1-antitrypsin deficiency: prognostic indicators. // J. Pediatr., 1990, 117, 864-870.
43. Prachalias A. A., Kalife M., Francavilla R. et al.: “Liver transplantation for alpha-1-antitrypsin deficiency in children” // Transpl. Int., 2000, 13, 207-210.
44. Teckman J. H., Perlmutter D. H.: “Retention of mutant α₁-antitrypsin Z in endoplasmatic reticulum is associated with an autophagic response” // Am. J. Physiol., 2000, 279, G961-G974.
45. Lang T., Mühlbauer M., Strobelt M. et al.: “Alpha-1-antitrypsin deficiency in children: liver disease is not reflected by low serum levels of alpha-1-antitrypsin a study on 48 pediatric patients” // Eur. J. Med. Res., 2005, 10, p. 509-514.
46. Teckman J. H.: “Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: preliminary study” // J. Pediatr. Gastroenterol. Nutr., 2004, 39, 34-37.
47. Burrows J. A., Willis L. K., Perlmutter D. H.: “Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: a potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency” // Proc. Natl. Acad. Sci. U S A 2000, 97, 1796-1801.
48. Marcus N. Y., Perlmutter D. H.: “Glucosidase and mannosidase inhibitor mediate increased secretion of mutant α₁-antitrypsin Z” // Z. J. Biol. Chem., 2000, 275, 1987-1992.
49. Hidvegi T., Ewing M., Hale P. Et al.: “An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis” // Science, 2010, 329, p. 229-232.
50. Kemmer N., Kaiser T., Zacharias V. et al.: “Alpha-1-antitrypsin deficiency: outcomes after liver transplantation” // Transplant. Proc., 2008, 40, 1492-1494.
51. Vennarecci G., Gunson B. K., Ismail T. et al.: “Transplantation for end stage liver disease related to alpha 1 antitrypsin” // Transplantation, 1996, 61, p. 1488-1495.
52. Van Furth r., Kramps J. A., van der Putten A. B. et al.: “Change in alpha-1-antitrypsin phenotype after orthotopic liver transplant” // Clin. Exp. Immunol., 1986, 66, p. 669.).
Review
For citations:
Vlasov N.N., Kornienko E.A., Melnik S.I. LIVER DISEASE IN CHILDREN CAUSED BY Α1-ANTITRYPSIN DEFICIENCY. Experimental and Clinical Gastroenterology. 2018;(2):89-99. (In Russ.)
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