α1‐Antitrypsin mutations in NAFLD: High prevalence and association with altered iron metabolism but not with liver damage

@article{Valenti20061AntitrypsinMI,
  title={$\alpha$1‐Antitrypsin mutations in NAFLD: High prevalence and association with altered iron metabolism but not with liver damage},
  author={Luca Valenti and Paola Dongiovanni and Alberto Piperno and Anna Ludovica Fracanzani and Marco Maggioni and Raffaela Rametta and Paola Loria and Maria Antonietta Casiraghi and Elda Suigo and Roberto L. Ceriani and Erica Remondini and Paola Trombini and Silvia Fargion},
  journal={Hepatology},
  year={2006},
  volume={44}
}
Hyperferritinemia, a common feature of nonalcoholic fatty liver disease (NAFLD), has been associated with steatohepatitis and fibrosis. Heterozygosity for α1‐antitrypsin (AAT) mutations is a cofactor of liver damage, and AAT influences inflammation and iron metabolism. This study evaluated the prevalence of the common AAT PiS/PiZ mutants in 353 patients with NAFLD, 195 of whom had hyperferritinemia, versus 114 matched controls and their influence on iron metabolism and the severity of liver… 

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  • G. CheeneyLincoln Pac M. Westerhoff
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  • 2019
Results indicate PASD+ A1AT globules are commonly observed in NASH, suggesting a synergistic relationship toward liver fibrosis, and the high frequency of SERPINA1 Z alleles in liver transplantation patients supports the utility of pretransplant genotyping.

HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease.

Iron deposition predominantly in hepatocyes is associated with more severe liver damage in patients with NAFLD, and HFE mutations cannot be used to identify patients with hepatocellular iron accumulation.

Liver disease in adults with α1-antitrypsin deficiency

Heterozygosity for the Z-allele predisposes for the development of CSPH, confirming its role as a genetic (co)factor in liver disease.

Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

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...

References

SHOWING 1-10 OF 46 REFERENCES

Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis

Increased ferritin with normal transferrin saturation is frequently found in patients with hepatic steatosis, but it reflects iron overload only in those patients in whom it persists despite an appropriate diet.

Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis.

  • Luca ValentiP. Dongiovanni S. Fargion
  • Medicine, Biology
    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
  • 2003

Increased risk of chronic liver failure in adults with heterozygous α‐antitrypsin deficiency

The data suggest that individuals carrying a single PI*Z allele for α1 AT may be at increased risk of developing cirrhosis and liver failure, even in the absence of an identifiable coexisting liver disease.

Steatosis is a cofactor in liver injury in hemochromatosis.

Findings indicate that obesity-related steatosis may have a role as a cofactor in liver injury in hemochromatosis and suggests that obesity should be actively addressed in the management of patients with hemochROMatosis, as well as other liver diseases.

Lack of association between porphyria cutanea tarda and α1,-antitrypsin deficiency

Objective: To determine whether α1-antitrypsin deficiency is involved in the patho-genesis of chronic liver disease in patients with porphyria cutanea tarda and in their recently described high

Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency

The Italian Registry for Severe A ATD was established in 1996 as a result of a nationwide screening programme sponsored by the two major Italian scientific respiratory societies and succeeded in identifying a relatively large cohort of AATD individuals.

Heterozygous α1-Antitrypsin phenotypes in patients with end stage liver disease

Evidence is provided of an association of heterozygous Z alpha1-antitrypsin phenotype with end stage liver disease of several etiologies, not hepatitis C virus alone.

Increased risk of chronic liver failure in adults with heterozygous alpha1-antitrypsin deficiency.

The prevalence of heterozygous 1AT phenotypes in a well-characterized cohort of patients presenting with chronic liver failure before orthotopic liver transplantation (OLT) suggests that individuals carrying a single PI*Z allele for 1AT may be at increased risk of developing cirrhosis and liver failure, even in the absence of an identifiable coexisting liver disease.