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Editorial
. 2019 Dec 12:4:82.
doi: 10.21037/tgh.2019.11.13. eCollection 2019.

Non-invasive assessment for alpha-1 antitrypsin deficiency-associated liver disease: new insights on steatosis and fibrosis in Pi*ZZ carriers

Siyer Roohani  1 , Frank Tacke  1
Affiliations
Editorial

Non-invasive assessment for alpha-1 antitrypsin deficiency-associated liver disease: new insights on steatosis and fibrosis in Pi*ZZ carriers

Siyer Roohani et al. Transl Gastroenterol Hepatol. .
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Pathogenesis of alpha-1 antitrypsin (AAT) deficiency and non-invasive assessment of steatosis and fibrosis. AAT is a serine protease inhibitor synthesized in the liver. In case of the Pi*ZZ mutation (Pi for protease inhibitor), the AAT molecules polymerize in the endoplasmic reticulum of hepatocytes, which triggers two main pathophysiological mechanisms. Firstly, the polymerization of AAT in hepatocytes inflicts chronic damage by inducing inflammation, apoptosis and mitochondrial damage, which increases the chance for fibrosis, liver cirrhosis and eventually hepatocellular carcinoma (i.e., toxic-gain-of-function phenotype). Secondly, the resulting deficiency of AAT in the serum and pulmonary tissue leaves the neutrophil elastase activity in the pulmonary tissue unchecked. This leads to accelerated degeneration of elastic tissue, usually more pronounced in the lower lobes than in the upper lobes, and ultimately to pulmonary emphysema (i.e., loss-of-function phenotype). By forming a prospective European AAT deficiency registry of 554 Pi*ZZ carriers and 234 controls, Strnad and colleagues assessed liver fibrosis and steatosis by using transient elastography (FibroScan) and serum markers. Additionally, histological and mechanistic analyses was performed on a transgenic mouse model overexpressing the Pi*Z allele.
See this image and copyright information in PMC

Comment on

  • Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.
    Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simões C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P; European Alpha1-Liver Study Group. Hamesch K, et al. Gastroenterology. 2019 Sep;157(3):705-719.e18. doi: 10.1053/j.gastro.2019.05.013. Epub 2019 May 20. Gastroenterology. 2019. PMID: 31121167

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