Team:Slovenia/ImplementationHepatitisC

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<h3>Hepatitis C virus infection</h3>
<h3>Hepatitis C virus infection</h3>
Hepatitis C is an infectious disease caused by the <b>hepatitis C virus (HCV)</b> which primarily infects the liver.  Hepatitis C is a serious worldwide health problem with a prevalence of <b>3% in the world’s population</b>. According to WHO, 170 million individuals are infected with an incidence of 3 to 4 million new cases per year. More than 350,000 people die yearly from hepatitis C-related diseases. In the US the HCV has surpassed HIV as a cause of death. Medical care costs associated with treatment of HCV infection are estimated to be more than $600 million per year just in the USA.</p>
Hepatitis C is an infectious disease caused by the <b>hepatitis C virus (HCV)</b> which primarily infects the liver.  Hepatitis C is a serious worldwide health problem with a prevalence of <b>3% in the world’s population</b>. According to WHO, 170 million individuals are infected with an incidence of 3 to 4 million new cases per year. More than 350,000 people die yearly from hepatitis C-related diseases. In the US the HCV has surpassed HIV as a cause of death. Medical care costs associated with treatment of HCV infection are estimated to be more than $600 million per year just in the USA.</p>
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<img src="https://static.igem.org/mediawiki/2012/6/64/Svn12_implementation_hepatitis_c_fig3.png"></img>
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<p><b>Figure 3. Hepatitis C prevalence</b> (<a href="http://en.wikipedia.org/wiki/File:HCV_prevalence_1999.png>http://en.wikipedia.org/wiki/File:HCV_prevalence_1999.png</a>).</p>
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<p>HCV accounts for 20% of all cases of acute hepatitis which is usually asymptomatic. In approximately 75% – 85% of patients, HCV persists as a chronic infection, placing infected persons at risk for developing <b>chronic liver disease</b>. The risk of liver <a href="http://en.wikipedia.org/wiki/Cirrhosis">cirrhosis</a> after 20 years of persistent hepatitis C infection is approximately 10-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing <a href="http://en.wikipedia.org/wiki/Hepatocellular_carcinoma">liver cancer</a> is 1 to 4% per year (Pawlotsky, 2004). It is the most common indication for orthotopic <a href="http://emedicine.medscape.com/article/431783-overview"liver transplantation</a> in the United States.</p>
<h2 style="color:grey;">References</h2>
<h2 style="color:grey;">References</h2>

Revision as of 11:42, 26 September 2012


Hepatitis C

We designed a device for the therapy of hepatitis C, composed of microencapsulated mammalian cells that include a genetic bistable toggle switch with a positive feedback loop, where in one state the cells produce interferon alpha (IFN-α) as the antiviral effector and in the second state they produce hepatocyte growth factor (HGF) to promote liver regeneration.

A pharmacokinetic model demonstrated that if the device is implanted into the liver it results in higher levels of IFN-α within the liver than systemically. More importantly, this type of application avoids the spikes of high IFN-α concentration that occur in treatment with IFN-α injections. This should decrease the severity of side effects of IFN-α experienced by a high percentage of patients.

We estimated, based on the detection of IFN-α produced by HEK293 cells, that sufficient quantities of the therapeutic protein could be produced by the amount of microencapsulated cells feasible in a real therapeutic application.

Figure 1. Therapy of hepatitis C by microencapsulated cells which can be regulated to produce and release therapeutic proteins into the liver tissue.

Figure 2. Scheme of the constructs for the regulated therapy of hepatitis C with interferon alpha (IFN-α) and hepatocyte growth factor (HGF). Each of the therapeutic effector is released in equimolar amount to the autoactivator.

Hepatitis C virus infection

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) which primarily infects the liver. Hepatitis C is a serious worldwide health problem with a prevalence of 3% in the world’s population. According to WHO, 170 million individuals are infected with an incidence of 3 to 4 million new cases per year. More than 350,000 people die yearly from hepatitis C-related diseases. In the US the HCV has surpassed HIV as a cause of death. Medical care costs associated with treatment of HCV infection are estimated to be more than $600 million per year just in the USA.

Figure 3. Hepatitis C prevalence (cirrhosis after 20 years of persistent hepatitis C infection is approximately 10-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing liver cancer is 1 to 4% per year (Pawlotsky, 2004). It is the most common indication for orthotopic in the United States.

References

Banfi, A., von Degenfeld, G., Gianni-Barrera, R., Reginato, S., Merchant, M.J., McDonald, D.M., and Blau, H.M. (2012) Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J. 26, 2486-2497.

Ortiz, L.A., Dutreil, M., Fattman, C., Pandey, A.C., Torres, G., Go, K., and Phinney, D.G. (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc. Natl. Acad. Sci. U S A 104, 11002-11007.

Szymczak, A.L., Workman, C.J., Wang, Y., Vignali, K.M., Dilioglou, S., Vanin, E.F., Vignali D.A. (2004) Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat. Biotechnol. 22, 589-94.


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