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Performance of enhanced liver fibrosis plasma markers in asymptomatic individuals with ZZ α1-antitrypsin deficiency.

Janciauskiene, Sabina LU ; Wallmark, Anders LU ; Piitulainen, Eeva LU ; Köhnlein, Thomas; Welte, Tobias and Sveger, Tomas LU (2011) In European Journal of Gastroenterology and Hepathology 23(8). p.716-720
Abstract
OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is a common genetic cause of chronic liver disease. According to retrospective studies, up to 25% of those with homozygous ZZ (Glu 342 to Lys) AATD suffer from liver cirrhosis and/or liver cancer in late adulthood. We hypothesized that the plasma markers for liver fibrosis, necrosis, and apoptosis may identify AATD individuals at higher risk for liver diseases. METHODS: The study cohort included 52 clinically healthy ZZ AATD individuals of 34 years of age, identified in the Swedish neonatal screening of 1972-1974, and 81 age-matched controls with normal MM AAT variant. We analyzed plasma levels of the enhanced liver fibrosis (ELF) panel, including plasma tissue inhibitor of... (More)
OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is a common genetic cause of chronic liver disease. According to retrospective studies, up to 25% of those with homozygous ZZ (Glu 342 to Lys) AATD suffer from liver cirrhosis and/or liver cancer in late adulthood. We hypothesized that the plasma markers for liver fibrosis, necrosis, and apoptosis may identify AATD individuals at higher risk for liver diseases. METHODS: The study cohort included 52 clinically healthy ZZ AATD individuals of 34 years of age, identified in the Swedish neonatal screening of 1972-1974, and 81 age-matched controls with normal MM AAT variant. We analyzed plasma levels of the enhanced liver fibrosis (ELF) panel, including plasma tissue inhibitor of metalloprotease-1, amino-terminal propeptide of type III collagen and hyaluronic acid (HA), and the M30 and M65 antigens, markers for apoptosis/necrosis. RESULTS: Higher levels of tissue inhibitor of metalloprotease-1 (52%, P<0.001), amino-terminal propeptide of type III collagen (12%, P<0.05), HA (17% not significant), and M65 (13.4%, P=0.043) were found in ZZ than in MM patients. In the ZZ group, plasma levels of AAT correlated with M65 (P<0.01) and with HA (P<0.05). On the basis of the ELF panel, M30 and M65, a logistic regression model enabled us to correctly classify 81.2% of the originally grouped ZZ and MM cases with a sensitivity of 73.1% and a specificity of 86.4%. CONCLUSION: The ELF markers are associated with ZZ AATD at early adulthood, and can be considered as a useful tool to identify ZZ cases at an increased risk of developing liver diseases later in life. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
enhanced liver fibrosis, alpha 1-antitrypsin deficiency, liver disease, plasma markers
in
European Journal of Gastroenterology and Hepathology
volume
23
issue
8
pages
716 - 720
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000292503100012
  • pmid:21617532
  • scopus:79960698421
ISSN
1473-5687
DOI
10.1097/MEG.0b013e328347daaf
language
English
LU publication?
yes
id
b84305b4-287f-41c2-88a3-250dd8b3359c (old id 1972045)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21617532?dopt=Abstract
date added to LUP
2011-06-07 23:00:39
date last changed
2017-11-12 03:01:09
@article{b84305b4-287f-41c2-88a3-250dd8b3359c,
  abstract     = {OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is a common genetic cause of chronic liver disease. According to retrospective studies, up to 25% of those with homozygous ZZ (Glu 342 to Lys) AATD suffer from liver cirrhosis and/or liver cancer in late adulthood. We hypothesized that the plasma markers for liver fibrosis, necrosis, and apoptosis may identify AATD individuals at higher risk for liver diseases. METHODS: The study cohort included 52 clinically healthy ZZ AATD individuals of 34 years of age, identified in the Swedish neonatal screening of 1972-1974, and 81 age-matched controls with normal MM AAT variant. We analyzed plasma levels of the enhanced liver fibrosis (ELF) panel, including plasma tissue inhibitor of metalloprotease-1, amino-terminal propeptide of type III collagen and hyaluronic acid (HA), and the M30 and M65 antigens, markers for apoptosis/necrosis. RESULTS: Higher levels of tissue inhibitor of metalloprotease-1 (52%, P&lt;0.001), amino-terminal propeptide of type III collagen (12%, P&lt;0.05), HA (17% not significant), and M65 (13.4%, P=0.043) were found in ZZ than in MM patients. In the ZZ group, plasma levels of AAT correlated with M65 (P&lt;0.01) and with HA (P&lt;0.05). On the basis of the ELF panel, M30 and M65, a logistic regression model enabled us to correctly classify 81.2% of the originally grouped ZZ and MM cases with a sensitivity of 73.1% and a specificity of 86.4%. CONCLUSION: The ELF markers are associated with ZZ AATD at early adulthood, and can be considered as a useful tool to identify ZZ cases at an increased risk of developing liver diseases later in life.},
  author       = {Janciauskiene, Sabina and Wallmark, Anders and Piitulainen, Eeva and Köhnlein, Thomas and Welte, Tobias and Sveger, Tomas},
  issn         = {1473-5687},
  keyword      = {enhanced liver fibrosis,alpha 1-antitrypsin deficiency,liver disease,plasma markers},
  language     = {eng},
  number       = {8},
  pages        = {716--720},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {European Journal of Gastroenterology and Hepathology},
  title        = {Performance of enhanced liver fibrosis plasma markers in asymptomatic individuals with ZZ α1-antitrypsin deficiency.},
  url          = {http://dx.doi.org/10.1097/MEG.0b013e328347daaf},
  volume       = {23},
  year         = {2011},
}