Glucose abnormalities in non-alcoholic fatty liver disease and chronic hepatitis

[Guest guest]

Diabetes Metab Res Rev. 2009 May 14. [Epub ahead of print]

Glucose abnormalities in non-alcoholic fatty liver disease and chronic

hepatitis C virus infection: the role of iron overload.

Lecube A, Hernández C, Simó R.

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto

de Salud III (ISCIII), Diabetes and Metabolism Research Unit, Institut de

Recerca Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129,

08035 Barcelona, Spain.

Non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus

(HCV) infection are major causes of liver disease frequently described in

outpatient patients with glucose abnormalities. Hyperferritinemia, which

suggests that iron overload plays a decisive role in the pathophysiology of

insulin resistance and hyperglycemia, is a common finding in both disorders.

However, the role of the hepatic iron deposition differs from one to the other.

In NAFLD, a moderate liver iron accumulation has been observed and molecular

mechanisms, including the downregulation of the liver iron exporter

ferroportin-1, have been described. Iron overload will enhance intrahepatic

oxidative stress that promotes hepatic fibrosis, interfere with insulin

signalling at various levels and may hamper hepatic insulin extraction.

Therefore, liver fibrosis, hyperglycemia and hyperinsulinemia will lead to

increased levels of insulin resistance and the development of glucose

abnormalities. Furthermore, iron depletion by phlebotomy removes liver iron

content and reduces serum glucose and insulin resistance in NAFLD patients.

Therefore, it seems that iron overload participates in those glucose

abnormalities associated with NAFLD. Concerning chronic HCV infection, it has

been classically assumed that iron overload contributes to insulin resistance

associated with virus infection. However, recent evidence argues against the

presence of iron overload in these patients and points to inflammation

associated with diabetes as the main contributor to the elevated ferritin

levels. Therefore, glucose abnormalities, and specially type 2 diabetes, should

be taken into account when evaluating serum ferritin levels in patients with HCV

infection. Copyright © 2009 Wiley & Sons, Ltd.

PMID: 19444865

http://www.ncbi.nlm.nih.gov/pubmed