Alpha-1-Antitrypsin Deficiency Liver Disease.

  title={Alpha-1-Antitrypsin Deficiency Liver Disease.},
  author={Dhiren Patel and Jeffrey H. Teckman},
  journal={Clinics in liver disease},
  volume={22 4},
Development of an RNAi therapeutic for alpha-1-antitrypsin liver disease.
In mice, sustained RNAi treatment reduced hepatic Z-AAT polymer, restored ER and mitochondrial health, normalized expression of disease-associated genes, reduced inflammation and prevented tumor formation, and RNAi therapy holds promise for the treatment of patients with AATD-associated liver disease.
Liver Cirrhosis Secondary to Autoimmune Hepatitis in a Patient with Alpha-1 Antitrypsin ZZ Phenotype: A "Double Hit" Phenomenon
The case of a young 28-year-old female who was initially followed for thrombocytopenia and was found to have cirrhosis of the liver with autoimmune histological features is presented suggesting the possibility that another “second hit” can contribute to a more rapid progression of liver disease.
Alpha-1 Antitrypsin Deficiency: a Rare Disease?
This review focuses on the current state of knowledge of AATD, including the wide range of presentations, diagnosis, and clinical management, and discusses the relevance of heterozygous state with mild or moderate A ATD in the development of both lung and liver disease.
Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency
This study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.
Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum
The SERPINA1 mutation spectrum is revisited, with a greater emphasis on variants fitting the aforementioned processes of AATD pathogenesis, and those selected were selected based on their clinical significance and wider geographic distribution.
DEFI‐ALFA: The French key to the alpha1 mystery?
  • M. Fromme, M. Oliverius, P. Strnad
  • Medicine, Biology
    Liver international : official journal of the International Association for the Study of the Liver
  • 2019
The article from Ruiz et al, describing a large, multi‐centre French cohort of pediatric AATD cases, represents an important and badly needed step in the right direction.
Mild Iron Overload as Seen in Individuals Homozygous for the Alpha-1 Antitrypsin Pi*Z Variant Does Not Promote Liver Fibrogenesis in HFE Knockout Mice
Neither mild iron overload seen in these individuals nor the presence of HFE mutations constitute a major contributor to liver fibrosis development, but Pi*ZZ individuals display minor alterations in serum iron parameters.
Alpha-1 Antitrypsin Replacement in Patients With COPD.
Patients with COPD or adult-onset asthma are encouraged to undergo aggressive screening for Alpha-1 antitrypsin deficiency, which is a significant risk factor for COPD development and progression.


Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Understanding and Future Therapy
There is a high degree of variability in the clinical manifestations among PI*ZZ homozygous patients, suggesting a strong influence of as yet poorly characterized, genetic and environmental disease modifiers.
Alpha-1 antitrypsin and liver disease: mechanisms of injury and novel interventions
Management of α1AT liver disease is based on standard supportive care and liver transplant, however, increased understanding of the cellular mechanisms of liver injury has led to new clinical trials.
Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates.
Exciting recent results have shown that a drug that enhances autophagy can reduce the hepatic load of aggregated protein and reverse fibrosis in a mouse model of this disease.
Alpha-1 Antitrypsin Deficiency
  • W. Künzer
  • Biology, Medicine
    Methods in Molecular Biology
  • 2017
Pi type MM guarantees a normal concentration of alpha-1-AT in the serum, whereas Pi type ZZ causes of serious alpha- 1-AT deficiency which bears a particularly high risk of disease.
Alpha-1-antitrypsin deficiency: diagnosis and treatment.
A 30-Year Perspective on α1-Antitrypsin Deficiency
The disease spectrum is discussed (including emphysema, liver, and vasculitic diseases) and the variable clinical expression of the deficiency state is focused on.
Intracellular processing of alpha1-antitrypsin.
  • R. Sifers
  • Biology
    Proceedings of the American Thoracic Society
  • 2010
This article focuses on the discovery and characterization of a biosynthetic quality control system that contributes to the secretion of AAT by first facilitating its properStructural maturation, and then by orchestrating the selective elimination of those molecules that fail to attain structural maturation.
Rapamycin reduces intrahepatic alpha-1-antitrypsin mutant Z protein polymers and liver injury in a mouse model
This is the first report of a successful in vivo method for reduction of intrahepatic a1AT mutant Z polymerized protein in the polymerized conformation on PiZ mice, a well-characterized model which recapitulates human a 1AT liver disease.
The mechanism of Z α1-antitrypsin accumulation in the liver
Z antitrypsin polymerized in vitro has identical properties and ultra-structure to the inclusions isolated from hepatocytes of a Z homozygote, and the concentration and temperature dependence of this loop–sheet polymerization has implications for the management of the liver disease of the newborn Z hom allele.
A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency.
Biochemical characteristics of alpha 1-AT Z degradation in the protected hosts were found to be similar to those of a common ER degradation pathway previously described in model experimental cell systems for T-cell receptor alpha subunits and asialoglycoprotein receptor subunits, raising the possibility that the lag in degradation in a susceptible host is a defect in this commonER degradation pathway.