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Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis |
Katarzyna Sikorska, Agnieszka Bernat and Anna Wróblewska |
Gdynia, Poland
Author Affiliations: Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Powstania Styczniowego 9b, 81-519 Gdynia, Poland (Sikorska K); Pomeranian Center of Infectious Diseases and Tuberculosis, Smoluchowskiego 18, 80-214 Gdansk, Poland (Sikorska K); Intercollegiate Faculty of Biotechnology UG-MUG, Laboratory of Molecular Diagnostics, Kladki 24, 80-822 Gdansk, Poland (Bernat A and Wróblewska A)
Corresponding Author: Katarzyna Sikorska, MD, PhD, Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Powstania Styczniowego 9b, 81-519, Gdynia, Poland (Tel/Fax: +48-58-3491760; Email: ksikorska@gumed.edu.pl) |
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Abstract BACKGROUND: The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases.
DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis.
RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology.
CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.
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