Hepatitis C virus interference via hepcidin synthesis

Iron overload, a common feature of chronic liver disorders, has been linked with oxidative DNA damage, insulin resistance and liver steatosis, and with triggering of hepatic stellate cells thus inducing liver fibrosis. Recently, a key iron regulatory hormone, hepcidin, was discovered. This hormone has been found to suppress intestinal absorption of iron through its binding to ferroportin. Hepcidin is synthesized in the liver from its precursor protein, prohepcidin.

A research article to be published on April 14, 2010 in the World Journal of Gastroenterology addresses the question as to whether serum prohepcidin levels are associated with HCV infection activity as well as with the efficacy of PEG-interferon/ribavirin therapy. The studied group consisted of 53 chronic hepatitis C patients, who were followed during anti-HCV therapy with pegylated-IFN+ribavirin. Prohepcidin serum concentrations as well as other iron metabolism parameters were measured at many time-points, including baseline, 4th, 12th, 24th and 48th (genotype 1) week of antiviral therapy and 24th week after termination of the treatment (week 72).

The authors found comparable levels of serum prohepcidin in chronic hepatitis C and healthy individuals. Interestingly, baseline prohepcidin was significantly higher in HCV genotype 3a than in HCV-1. This new finding was explained by differences in iron metabolism in patients with genotype 3. Baseline serum prohepcidin in a study by Jaroszewicz et al showed a strong positive correlation with serum ferritin. Moreover, an association between baseline serum prohepcidin and ALT activity was found. The new finding of the study was the association between serum prohepcidin and PEG-IFN/ribavirin efficacy in chronic hepatitis C. The authors demonstrated a statistically significant, gradual decrease of serum prohepcidin which occurred only during successful antiviral treatment in HCV-1 and 3a individuals. In contrast, in non-sustained viral responders the prohepcidin serum concentrations did not change significantly compared to baseline values.

Data obtained by the research group led by Professor R. Flisiak from the Department of Infectious Diseases and Hepatology of Medical University in Bialystok indicate that in situations of liver function impairment, the prohepcidin synthesis as well as activity or expression of converting enzymes might be altered and affect circulating prohepcidin concentrations. Their finding could also suggest HCV interference with hepcidin synthesis at the level of prohormone synthesis or maturation in the liver.

Reference: Jaroszewicz J, Rogalska M, Flisiak I, Flisiak R. Successful antiviral therapy is associated with a decrease of serum prohepcidicin in chronic hepatitis C. World J Gastroenterol 2010; 16(14): 1747-1752
http://www.wjgnet.com/1007-9327/full/v16/i14/1747.htm

Correspondence to: Robert Flisiak, Professor, Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Zurawia Str 14, Bialystok 15-540, Poland. flisiakr@poczta.onet.pl

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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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