α1-antitrypsin mutations in NAFLD

High prevalence and association with altered iron metabolism but not with liver damage

Luca Valenti, Paola Dongiovanni, Alberto Piperno, Anna Ludovica Fracanzani, Marco Maggioni, Raffaela Rametta, Paola Loria, Maria Antonietta Casiraghi, Elda Suigo, Roberto Ceriani, Erica Remondini, Paola Trombini, Silvia Fargion

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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 AATPiS/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 damage in the 212 patients submitted to biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty-eight patients (10.8%) carried non-MM genotypes versus 4/114 (3.5%) controls (P = .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348 [201-648]; P = .001) with similar transferrin saturation. The difference was more evident in males (P <.0001) and significant in patients not carrying HFE genotypes associated with iron overload (P = .015). The prevalence of non-MM genotypes was higher in patients with hyperferritinemia than in those without (28/195, 14% vs. 10/158, 6%, P = .016), and AAT mutations were associated with higher prevalence of sinusoidal siderosis (17/27, 63% vs. 70/180, 39%; P = .02), and sinusoidal/total iron score (46.3 ± 38% vs. 25.1 ± 35%, P = .01). Although ferritin was independendy associated with fibrosis (P = .047), AAT mutations favoring sinusoidal iron deposition did not affect liver damage. In conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal iron accumulation, but not with more severe liver damage in NAFLD.

Original languageEnglish
Pages (from-to)857-864
Number of pages8
JournalHepatology
Volume44
Issue number4
DOIs
Publication statusPublished - Oct 2006

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Iron
Mutation
Liver
Genotype
Ferritins
Fibrosis
Siderosis
Iron Overload
Fatty Liver
Transferrin
Non-alcoholic Fatty Liver Disease
Cross-Sectional Studies
Alleles
Inflammation
Biopsy

ASJC Scopus subject areas

  • Hepatology

Cite this

α1-antitrypsin mutations in NAFLD : High prevalence and association with altered iron metabolism but not with liver damage. / Valenti, Luca; Dongiovanni, Paola; Piperno, Alberto; Fracanzani, Anna Ludovica; Maggioni, Marco; Rametta, Raffaela; Loria, Paola; Casiraghi, Maria Antonietta; Suigo, Elda; Ceriani, Roberto; Remondini, Erica; Trombini, Paola; Fargion, Silvia.

In: Hepatology, Vol. 44, No. 4, 10.2006, p. 857-864.

Research output: Contribution to journalArticle

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abstract = "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 AATPiS/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 damage in the 212 patients submitted to biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty-eight patients (10.8{\%}) carried non-MM genotypes versus 4/114 (3.5{\%}) controls (P = .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348 [201-648]; P = .001) with similar transferrin saturation. The difference was more evident in males (P <.0001) and significant in patients not carrying HFE genotypes associated with iron overload (P = .015). The prevalence of non-MM genotypes was higher in patients with hyperferritinemia than in those without (28/195, 14{\%} vs. 10/158, 6{\%}, P = .016), and AAT mutations were associated with higher prevalence of sinusoidal siderosis (17/27, 63{\%} vs. 70/180, 39{\%}; P = .02), and sinusoidal/total iron score (46.3 ± 38{\%} vs. 25.1 ± 35{\%}, P = .01). Although ferritin was independendy associated with fibrosis (P = .047), AAT mutations favoring sinusoidal iron deposition did not affect liver damage. In conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal iron accumulation, but not with more severe liver damage in NAFLD.",
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AU - Valenti, Luca

AU - Dongiovanni, Paola

AU - Piperno, Alberto

AU - Fracanzani, Anna Ludovica

AU - Maggioni, Marco

AU - Rametta, Raffaela

AU - Loria, Paola

AU - Casiraghi, Maria Antonietta

AU - Suigo, Elda

AU - Ceriani, Roberto

AU - Remondini, Erica

AU - Trombini, Paola

AU - Fargion, Silvia

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AB - 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 AATPiS/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 damage in the 212 patients submitted to biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty-eight patients (10.8%) carried non-MM genotypes versus 4/114 (3.5%) controls (P = .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348 [201-648]; P = .001) with similar transferrin saturation. The difference was more evident in males (P <.0001) and significant in patients not carrying HFE genotypes associated with iron overload (P = .015). The prevalence of non-MM genotypes was higher in patients with hyperferritinemia than in those without (28/195, 14% vs. 10/158, 6%, P = .016), and AAT mutations were associated with higher prevalence of sinusoidal siderosis (17/27, 63% vs. 70/180, 39%; P = .02), and sinusoidal/total iron score (46.3 ± 38% vs. 25.1 ± 35%, P = .01). Although ferritin was independendy associated with fibrosis (P = .047), AAT mutations favoring sinusoidal iron deposition did not affect liver damage. In conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal iron accumulation, but not with more severe liver damage in NAFLD.

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