Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi*ZZ)

被引：8

作者：

Fromme, Malin ^{[1
]}

Hamesch, Karim ^{[1
]}

Schneider, Carolin, V ^{[1
]}

Mandorfer, Mattias ^{[2
]}

Pons, Monica ^{[3
,4
]}

Thorhauge, Katrine H. ^{[5
,6
]}

Pereira, Vitor ^{[7
]}

Sperl, Jan ^{[8
]}

Frankova, Sona ^{[8
]}

Reichert, Matthias C. ^{[9
]}

Benini, Federica ^{[10
]}

Burbaum, Barbara ^{[1
]}

Kleinjans, Moritz ^{[1
]}

Amzou, Samira ^{[1
]}

Rademacher, Laura ^{[1
]}

Bewersdorf, Lisa ^{[1
]}

Verbeek, Jef ^{[11
]}

Nevens, Frederik ^{[11
]}

Genesca, Joan ^{[3
,4
]}

Miravitlles, Marc ^{[12
]}

Nunez, Alexa ^{[12
]}

Schaefer, Benedikt ^{[13
]}

Zoller, Heinz ^{[13
]}

Janciauskiene, Sabina ^{[14
]}

Waern, Johan ^{[15
]}

Oliveira, Antonio ^{[7
]}

Maia, Luis ^{[16
]}

Simoes, Carolina ^{[17
]}

Mahadeva, Ravi ^{[18
]}

Fraughen, Daniel D. ^{[19
]}

Trauner, Michael ^{[2
]}

Krag, Aleksander ^{[5
,6
]}

Lammert, Frank ^{[9
,20
]}

Bals, Robert ^{[21
]}

Gaisa, Nadine T. ^{[22
]}

Aigner, Elmar ^{[23
]}

Griffiths, William J. ^{[24
]}

Denk, Helmut ^{[25
]}

Teumer, Alexander ^{[26
,27
]}

Mcelvaney, Noel G. ^{[19
]}

Turner, Alice M. ^{[28
]}

Trautwein, Christian ^{[1
]}

Strnad, Pavel ^{[1
,29
]}

机构：

[1] Univ Hosp RWTH Aachen, Med Clin Gastroenterol Metab Dis & Intens Care 3, Hlth Care Provider European Reference Network Rare, Aachen, Germany

[2] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Hlth Care Provider European Reference Network Rare, Vienna, Austria

[3] Univ Autonoma Barcelona, Hosp Univ Vall Hebron, Vall Hebron Barcelona Hosp Campus, Vall Hebron Inst Res,Liver Unit,Hlth Care Provider, Barcelona, Spain

[4] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

[5] Odense Univ Hosp, Dept Gastroenterol & Hepatol, Odense, Denmark

[6] Univ Southern Denmark, Fac Hlth Sci, Dept Clin Res, Odense, Denmark

[7] Ctr Hosp Funchal, Dept Gastroenterol, Madeira, Portugal

[8] Inst Clin & Expt Med, Hlth Care Provider European Reference Network Rare, Dept Hepatogastroenterol, Prague, Czech Republic

[9] Saarland Univ, Med Ctr, Dept Med 2, Hlth Care Provider European Reference Network Rare, Homburg, Germany

[10] Spedali Civili & Univ, Dept Med, Gastroenterol Unit, Hlth Care Provider European Reference Network Rare, Brescia, Italy

[11] Katholieke Univ Leuven, Univ Hosp, Dept Gastroenterol & Hepatol, Hlth Care Provider European Reference Network Rare, Leuven, Belgium

[12] Hosp Univ Vall Hebron, Vall Hebron Barcelona Hosp Campus, Vall Hebron Inst Recerca, Pneumol Dept,CIBER Enfermedades Respiratorias, Barcelona, Spain

[13] Med Univ Innsbruck, Dept Internal Med 1, Innsbruck, Austria

[14] Hannover Med Sch, Clin Pneumol, Hannover, Germany

[15] Sahlgrens Univ Hosp, Dept Med, Gastroenterol & Hepatol Unit, Hlth Care Provider European Reference Network Rare, Gothenburg, Sweden

[16] Ctr Hosp Univ Porto, Porto, Portugal

[17] Hosp Santa Maria, Lisbon, Portugal

[18] Cambridge Univ Hosp, Dept Resp Med, Cambridge, England

[19] Beaumont Hosp, Royal Coll Surg Ireland, Irish Ctr Genet Lung Dis, Dublin, Ireland

[20] Hannover Med Sch, Hannover, Germany

[21] Saarland Univ, Med Ctr, Dept Med 5, Homburg, Germany

[22] Univ Hosp RWTH Aachen, Inst Pathol, Aachen, Germany

[23] Paracelsus Med Univ, Dept Med 1, Salzburg, Austria

[24] Cambridge Univ Hosp NHS Fdn Trust, Dept Hepatol, Cambridge, England

[25] Med Univ Graz, Inst Pathol, Graz, Austria

[26] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany

[27] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany

[28] Univ Birmingham, Inst Appl Hlth Res, Birmingham, England

[29] Univ Hosp RWTH Aachen, Med Clin Gastroenterol Metab Dis & Intens Care 3, Pauwelsstr 30, D-52074 Aachen, Germany

来源：

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY | 2024年 / 22卷 / 02期

关键词：

Fibroscan; Pi*Z; Liver Fibrosis; SERPINA1; alpha(1)-Antitrypsin Deficiency; Augmentation Therapy; DISEASE; INHIBITION; MECHANISM; THERAPY; VARIANT;

D O I：

10.1016/j.cgh.2023.08.038

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: alpha 1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi(& lowast;)Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. Methods: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi(& lowast;)ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi(& lowast;)ZZ adults with and 35 without augmentation. Results: Compared with nonaugmented subjects, augmented Pi(& lowast;)ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. Conclusions: The first evaluation of AAT augmentation on the Pi(& lowast;)ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi(& lowast;)ZZ-associated liver disease.

引用

页码：283 / 294

页数：12

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