PDF herunterladen
Klin Padiatr 2013; 225(05): 257-262
DOI: 10.1055/s-0033-1347196
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Prognostic Marker for Liver Disease due to Alpha1-Antitrypsin Deficiency

Prognosefaktoren bei Lebererkrankungen durch Alpha1-Antitrypsin-Mangel
D. C. Pferdmenges
1   Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
,
U. Baumann
1   Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
,
A. Müller-Heine
2   Institute for Biometry, Hannover Medical School, Hannover, Germany
,
T. Framke
2   Institute for Biometry, Hannover Medical School, Hannover, Germany
,
E.-D. Pfister
1   Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
23. August 2013 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Background:

Only some Alpha1-antitrypsin deficiency (A1ATD) PiZZ patients develop liver cirrhosis and portal hypertension. Aim of the study was to investigate the course of liver disease associated with PiZZ A1ATD and to determine prognostic factors.

Patients:

We retrospectively reviewed the clinical and laboratory data of all PiZZ children up to 18 years of age admitted to our centre since 1978. 53 patients (age at first visit 2 days to 12 years) met our criteria.

Methods:

The children were divided into 2 groups: group 1 ‘bad prognosis’, meaning the patients which were on the waiting list for liver transplantation (LTx), had a liver transplantation or had died, and group 2 ‘good prognosis’, containing the patients they were living with their own liver. We analysed family history including smoking, gestational age, maternal age at delivery, date of birth, sex, neonatal history, breast-feeding, symptoms at presentation, clinical and laboratory data and date of LTx and/or death.

Results:

Various anamnesis parameters such as manifestation of neonatal cholestasis showed no prognostic significance. In contrast the laboratory parameters thrombocytes (p=0.008), bilirubin (p<0.001), prothrombin time (p<0.001), choline­sterase (p<0.001), gamma-GT (p=0.001) and GOT (p=0.002) showed a correlation with a liver transplantation and/or death.

Conclusion:

Prognosis is difficult to determine at an early stage of this disease, but various laboratory parameters can help to predict an outcome. Therefore a regular follow-up is necessary for the children.

Zusammenfassung

Hintergrund:

Nur einige Patienten mit Alpha1-Antitrypsin-Mangel (A1ATD) PiZZ entwickeln eine Leberzirrhose und eine portale Hypertension. Ziel dieser Studie war es, den Verlauf der Lebererkrankung bei A1ATD zu verfolgen und Prognosefaktoren dafür zu identifizieren.

Patienten:

Es wurden retrospektiv erhobene klinische Daten und Laborparameter aller Patienten mit PiZZ im Alter von<18 Jahren ­analysiert, die seit dem Jahr 1978 an der Medizi­nischen Hochschule Hannover untersucht wurden. 53 Kinder (im Alter zwischen 2 Tagen und 12 Jahren) entsprachen den Kriterien.

Methode:

Die Patienten wurden in 2 Gruppen eingeteilt: Gruppe 1 „schlechte Prognose“, beinhaltet die Kinder, die auf der Warteliste für eine Lebertransplantation stehen, lebertransplantiert wurden oder verstorben sind, und Gruppe 2 „gute Prognose“ die Kinder, die mit eigener Leber leben.

Ergebnisse:

Sämtliche untersuchten klinischen und anamnestischen Parameter wie z. B. Vorhandensein oder Abwesenheit einer neo­natalen Cholestase zeigten keine prognostische Signifikanz. Dafür korrelierten die Laborparameter Thrombozyten (p=0,008), Bilirubin (p<0,001), Quick (p<0,001), Cholinesterase (p<0,001), Gamma-GT (p=0,001) und GOT (p=0,002) mit einer Lebertransplantation.

Schlussfolgerung:

Prognosefaktoren für das Frühstadium dieser Erkrankung sind schwer zu ermitteln. In dieser großen Langzeitstudie konn­ten wir zeigen, dass verschiedene Labor­parameter den Verlauf der Lebererkrankung prognostizieren können, sodass regelmäßige Verlaufskontrollen der Patienten notwendig sind.

Key words

pediatric hepatology - alpha1-antitrypsin deficiency - prognostic marker - liver transplantation

Schlüsselwörter

pädiatrische Hepatologie - Alpha1-Antitrypsin-Mangel - Prognosefaktoren - Lebertransplantation
 

  • References

  • 1 Alam S, Li Z, Janciauskiene S et al. Oxidation of Z {alpha}1-antitrypsin by Cigarette Smoke Induces Polymerization: A Novel Mechanism of Early-onset Emphysema. Am J Respir Cell Mol Biol 2010; 45: 261-269
    PubMedSuche in Google Scholar
  • 2 American Thoracic Society, European Respiratory Society . 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: 818-900
    CrossrefPubMedSuche in Google Scholar
  • 3 Bakula A, Socha P, Pawlowska J et al. Good and bad prognosis of alpha-1-antitrypsin deficiency in children: when to list for liver transplantation. Transplant Proc 2007; 39: 3186-3188
    CrossrefPubMedSuche in Google Scholar
  • 4 Bartlett JR, Friedman KJ, Ling SC et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 2009; 302: 1076-1083
    CrossrefPubMedSuche in Google Scholar
  • 5 Brunt EM, Blomenkamp K, Ahmed M et al. Hepatic progenitor cell proliferation and liver injury in alpha-1-antitrypsin deficiency. J Pediatr Gastroenterol Nutr 2010; 51: 626-630
    CrossrefPubMedSuche in Google Scholar
  • 6 Danks DM, Campbell PE, Smith AL et al. Prognosis of babies with neonatal hepatitis. Arch Dis Child 1977; 52: 368-372
    CrossrefPubMedSuche in Google Scholar
  • 7 Davis ID, Burke B, Freese D et al. The pathologic spectrum of the nephropathy associated with alpha 1-antitrypsin deficiency. Hum Pathol 1992; 23: 57-62
    CrossrefPubMedSuche in Google Scholar
  • 8 de Haan W. A marker associated with increased risk for severe liver disease in cystic fibrosis. Clin Genet 2010; 77: 434-435
    CrossrefPubMedSuche in Google Scholar
  • 9 Elema JD, Boersma R, Reerink-Brongers E. Proceedings: Clinical observations and histopathology of the liver in infants and children with alpha1-antitrypsin deficiency. Arch Dis Child 1975; 50: 663
    PubMedSuche in Google Scholar
  • 10 Elzouki AN, Segelmark M, Wieslander J et al. Strong link between the alpha 1-antitrypsin PiZ allele and Wegener’s granulomatosis. J Intern Med 1994; 236: 543-548
    CrossrefPubMedSuche in Google Scholar
  • 11 Eriksson SG. Liver disease in alpha 1-antitrypsin deficiency. Aspects of incidence and prognosis. Scand J Gastroenterol 1985; 20: 907-911
    CrossrefPubMedSuche in Google Scholar
  • 12 Esquivel CO, Vicente E, Van Thiel D et al. Orthotopic liver transplantation for alpha-1-antitrypsin deficiency: an experience in 29 children and ten adults. Transplant Proc 1987; 19: 3798-3802
    PubMedSuche in Google Scholar
  • 13 Flotte TR, Mueller C. Gene therapy for alpha-1 antitrypsin deficiency. Hum Mol Genet 2011; 20: R87-R92
    CrossrefPubMedSuche in Google Scholar
  • 14 Francavilla R, Castellaneta SP, Hadzic N et al. Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. J Hepatol 2000; 32: 986-992
    CrossrefPubMedSuche in Google Scholar
  • 15 Fuchs S, Schwerk N, Pfister E-D et al. Lungenfunktionsmessung mittels Multiple Breath Washout zur Erfassung früher Lungenveränderungen bei Patienten mit 1-Antitrypsinmangel. GPGE Aachen 2011; Germany
    PubMedSuche in Google Scholar
  • 16 Göbel U, Heinrich B, Krauth KA et al. Evaluation der Prozess- und Ergebnisqualität der Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED). Klin Padiatr 2010; 222: 92-97
    Thieme ConnectPubMedSuche in Google Scholar
  • 17 Göbel U, Gortner L. Disease management programs for adults with often diseases and competence networks for children and adolescents with rare diseases. Klin Padiatr 2011; 223: 1-3
    Thieme ConnectPubMedSuche in Google Scholar
  • 18 Gordon P, O’Donnell ME, Collins A et al. Successful endovascular treatment of multiple mesenteric arterial aneurysms associated with alpha-1-antitrypsin deficiency. J Vasc Surg 2010; 52: 467-470
    CrossrefPubMedSuche in Google Scholar
  • 19 Herrmann U, Dockter G, Lammert F. Cystic fibrosis-associated liver disease. Best Pract Res Clin Gastroenterol 2010; 24: 585-592
    CrossrefPubMedSuche in Google Scholar
  • 20 Ibarguen E, Gross CR, Savik SK et al. Liver disease in alpha-1-antitrypsin deficiency: prognostic indicators. J Pediatr 1990; 117: 864-870
    PubMedSuche in Google Scholar
  • 21 Janciauskiene SM, Bals R, Koczulla R et al. The discovery of alpha1-antitrypsin and its role in health and disease. Respir Med 2011; 105: 1129-1139
    CrossrefPubMedSuche in Google Scholar
  • 22 Kaushal S, Annamali M, Blomenkamp K 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: 700-709
    CrossrefPubMedSuche in Google Scholar
  • 23 Kaye AJ, Rand EB, Munoz PS et al. Effect of Kasai procedure on hepatic outcome in Alagille syndrome. J Pediatr Gastroenterol Nutr 2010; 51: 319-321
    Suche in Google Scholar
  • 24 Kemmer N, Kaiser T, Zacharias V et al. Alpha-1-antitrypsin deficiency: outcomes after liver transplantation. Transplant Proc 2008; 40: 1492-1494
    CrossrefPubMedSuche in Google Scholar
  • 25 Köhnlein T, Rifai K. Alpha1-antitrypsin deficiency. Internist (Berl) 2010; 51 (Suppl. 01) 269-276
    CrossrefPubMedSuche in Google Scholar
  • 26 Lewindon PJ, Shepherd RW, Walsh MJ et al. Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy. Hepatology 2011; 53: 193-201
    CrossrefPubMedSuche in Google Scholar
  • 27 Marciniak SJ, Lomas DA. Alpha1-antitrypsin deficiency and autophagy. N Engl J Med 2010; 363: 1863-1864
    CrossrefPubMedSuche in Google Scholar
  • 28 Miranda E, Perez J, Ekeowa UI et al. A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with alpha1-antitrypsin deficiency. Hepatology 2010; 52: 1078-1088
    CrossrefPubMedSuche in Google Scholar
  • 29 Perlmutter DH. Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates. Annu Rev Med 2011; 62: 333-345
    CrossrefPubMedSuche in Google Scholar
  • 30 Petrache I, Hajjar J, Campos M. Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency. Biologics 2009; 3: 193-204
    PubMedSuche in Google Scholar
  • 31 Prachalias AA, Kalife M, Francavilla R et al. Liver transplantation for alpha-1-antitrypsin deficiency in children. Transpl Int 2000; 13: 207-210
    CrossrefPubMedSuche in Google Scholar
  • 32 Sandstrom CS, Ohlsson B, Melander O et al. An association between Type 2 diabetes and alpha-antitrypsin deficiency. Diabet Med 2008; 25: 1370-1373
    PubMedSuche in Google Scholar
  • 33 Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet 2005; 365: 2225-2236
    CrossrefPubMedSuche in Google Scholar
  • 34 Talmud PJ, Martin S, Steiner G et al. Progression of atherosclerosis is associated with variation in the alpha1-antitrypsin gene. Arterioscler Thromb Vasc Biol 2003; 23: 644-649
    CrossrefPubMedSuche in Google Scholar
  • 35 Teh LG, Steven MM, Capell HA. Alpha-1-antitrypsin associated liver disease in rheumatoid arthritis. Postgrad Med J 1985; 61: 171-172
    CrossrefPubMedSuche in Google Scholar
  • 36 Udall Jr JN, Dixon M, Newman AP et al. Liver disease in alpha 1-antitrypsin deficiency. A retrospective analysis of the influence of early breast- vs bottle-feeding. JAMA 1985; 253: 2679-2682
    CrossrefPubMedSuche in Google Scholar