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Volume 138, Issue 3, Pages 905-912 (March 2010)


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CME QuizEditorial Accompanies ArticleVideo AbstractLinking Article with CGHHFE Genotype, Parenchymal Iron Accumulation, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Luca Valenti, Anna Ludovica Fracanzani, Elisabetta Bugianesi, Paola Dongiovanni, Enrico Galmozzi, Ester Vanni, Elena Canavesi, Ezio Lattuada§, Giancarlo Roviaro§, Giulio Marchesini, Silvia FargionCorresponding Author Informationemail address

Received 10 September 2009; accepted 12 November 2009. published online 19 November 2009.

Background & Aims

Mutations in the hemochromatosis gene (HFE) (C282Y and H63D) lead to parenchymal iron accumulation, hemochromatosis, and liver damage. We investigated whether these factors also contribute to the progression of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods

We studied clinical, histologic (liver biopsy samples for hepatocellular iron accumulation), serologic (iron and enzyme levels), and genetic (HFE genotype) data from 587 patients from Italy with NAFLD and 184 control subjects.

Results

Iron accumulation predominantly in hepatocyes was associated with a 1.7-fold higher risk of a fibrosis stage greater than 1 (95% confidence interval [CI]: 1.2–2.3), compared with the absence of siderosis (after adjustment for age, body mass index, glucose tolerance status, and alanine aminotransferase level). Nonparenchymal/mixed siderosis was not associated with moderate/severe fibrosis (odds ratio, 0.72; 95% CI: 0.50–1.01). Hepatocellular siderosis was more prevalent in patients with HFE mutations than in those without; approximately one third of patients with HFE mutations had parenchymal iron accumulation (range, 29.8%–35.7%, depending on HFE genotype). Predominantly hepatocellular iron accumulation occurred in 52.7% of cases of patients with HFE mutations. There was no significant association between either the presence of HFE mutations or specific HFE genotypes and the severity of liver fibrosis.

Conclusions

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

 Department of Internal Medicine, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Italy

 Department of Gastroenterology, Università di Torino, Torino, Italy

§ Department of Surgery, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Italy

 Department of Internal Medicine, Università Alma Mater Bologna, Bologna, Italy

Corresponding Author InformationReprint requests Address requests for reprints to: S. Fargion, MD, Department of Internal Medicine, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Via F Sforza 35, 20122 Milano, Italia. fax: (39) 02-50320296

 This article has an accompanying continuing medical education activity on page e9. Learning Objective: Upon completion of reading this article, successful learners will be able to differentiate the effect of different patterns of iron overload on liver damage, understand the effect of mutations in the HFE gene of hereditary hemochromatosis in determining the predisposition to develop iron overload, and recognize the lack of utility of HFE mutations assessment in the absence of histological demonstration of hepatocellular iron accumulation in patients with nonalcoholic fatty liver disease.

 View this article's video abstract at www.gastrojournal.org.

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the following grants: FIRST Università di Milano 2007, 2008 (to L.V., S.F., A.L.F.); Ricerca corrente Ospedale Maggiore Policlinico 2006 and 2008 (L.V., S.F.); and Centro per lo Studio delle Malattie del Fegato e del Metabolismo.

PII: S0016-5085(09)02003-4

doi:10.1053/j.gastro.2009.11.013


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