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α 1‐Antitrypsin mutations in NAFLD: High prevalence and association with altered iron metabolism but not with liver damage
Author(s) -
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
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21329
Subject(s) - medicine , siderosis , fibrosis , gastroenterology , transferrin saturation , ferritin , nonalcoholic fatty liver disease , hereditary hemochromatosis , liver biopsy , genotype , steatosis , cirrhosis , hemochromatosis , fatty liver , liver disease , allele , biology , pathology , biopsy , disease , gene , genetics , serum ferritin
Hyperferritinemia, a common feature of nonalcoholic fatty liver disease (NAFLD), has been associated with steatohepatitis and fibrosis. Heterozygosity for α 1 ‐ 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 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 independently 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. (H EPATOLOGY 2006;44:857–864.)