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HCV_Zugell

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					• Only infects humans and chimpanzees
• This is a virus that mainly affects the Liver
  – Asymptomatic
• Only lives for about 16 hours outside the
  human body.
•   Ribonucleic acid (RNA)
•   10,000 units called nucleotides
•   family Flaviviridae and genus hepacivirus
•   40 to 60 nanometers in diameter
•   six major genetic types (genotypes) and many
    more subtypes
    – genotype 1 (1a and 1b), which accounts for 80% of
      hepatitis C virus cases in the U.S.
    – patients infected with genotypes 2 or 3 are much
      more likely to respond to interferon therapy. In
      contrast, patients infected with genotype 1
      (particularly 1b) or genotype 4 do not respond very
      well to interferon therapy
• More than 4 million Americans (1.3% of the
  U.S. population) and 170 million individuals in
  the world (3% worldwide)
•Drug use
  •Through injection
     •Sharing needles, spoons, cotton, water,
     etc.
  •Also nasal inhalation
     •Cocaine and Crystal Methamphetamine
•Blood products
   •Organ transplants
   •Blood transfusion
      •prior to implementation of HCV
      screening
         •In the U.S., this would refer to
         procedures prior to 1992
•Sexual activity
   •Rarely transmitted in this fashion
       •Spouses are encourage to use a condom
•Food
   •Rarely transmitted in this fashion
   •Even during kissing it is hard to obtain the
   virus. (unless and open sore is present)
•Hygiene
   •It is also not recommended that you share
   toothbrushes.
•Early signs:
   •fatigue, weight, retention of urine, muscular
   aches, poor appetite,
•Hepatitis C is most readily diagnosed when
serum aminotransferases are elevated and anti-
HCV is present in serum. The diagnosis is
confirmed by the finding of HCV RNA in serum
• apolipoprotein complexes
• low-density lipoprotein receptor
  (LDL-R)
• glycosaminoglycans (GAGs)
• On Cell Surface
• CD81
• scavenger receptor class B type 1 (SR-
  B1) development
• CLDN1
• The HCV accumulates in the liver.
  – Caused by human immune systems response to
    the HCV
     • includes cytotoxic (injurious to cells)
     • lymphocytes
     • specific inflammatory messengers (cytokines).
• HCV causes the following changes in liver
  tissue:
• Necrosis and inflammation at the edge of the
  portal areas, so-called “piecemeal necrosis” or
  “interface hepatitis”
• Necrosis of hepatocytes and focal
  inflammation in the liver parenchyma
• Inflammatory cells in the portal areas (“portal
  inflammation”)
• CYP2E1, an enzyme involved in the
  breakdown of alcohol in the live
• breaks down potentially toxic
  foreign substances (i.e.,
  xenobiotics), including alcohol.
• Enhanced activity results in the
  increased generation of
  acetaldehyde from alcohol, free
  radicals (e.g., superoxide [O2.] and
  hydroxyl [OH.]) that can cause liver
  injury by promoting excessive
  breakdown of fat molecules (i.e.,
  lipid peroxidation).
• free radicals most likely potentiate
  the HCV-associated oxidative
  stress and the resulting liver
  damage
•   By itself, ribavirin has little effect on HCV
•   Used in como with interferon
•   Rabavirin tab 200mg
•   2 times a day 2 pills each time
•   Side effects
    – anemia, fatigue, insommia depression, hair
      loss. nausesa & loss of appetite
• improvements in serum ALT levels &
  detectable HCV RNA in up to 70 percent of
  patients
• 48-week course
• Only 55% remain HCV Free
• protein NS5B is cleaved from the HCV polyprotein by the NS3
  serine protease, and functions as a RNA-dependent RNA
  polymerase
   – nucleoside polymerase inhibitors
       • inhibit the active site causing chain termination (for example,
         valopicitabine (NM-283), MK-0608, R1626, PSI-6130 and its
         prodrug R7128),
   – non-nucleoside polymerase inhibitors
       • allosteric inhibition resulting in a conformational change of the
         protein (for example, BILB 1941 and HCV-796)
•   Company                                      Drug                         Development Phase
•   Vertex                           Telaprevir (VX-950) Protease Inhibitor                Phase 3
•   Vertex                            VX-500 protease inhibitor                           Phase 1
•   Vertex                            VX-813 2nd gen protease inhibitor               Pre Clinical
•   Schering                          Boceprevir (SCH503034) Protease inhibitor           Phase 3
•   Intercell Novartis              IC41 Therapeutic Vacccine                             Phase 2
•   Chiron / CSL                      Therapeutic Vaccine CSL123                         Phase 2
•   Roche                               R1626 Polymerase inhibitor                       Phase 2
•   Intermune / Roche                 Protease inhibitor ITMN-191 R7227                   Phase 1
•   Roche / Pharmasset                 R7128 nucleoside polymerase inhibitor              Phase 1
•   Roche / Medivir                     HCV polymerase inhibitor                           R&D
•   Medivir / Tibotec                  TMC435 Protease inhibitor                         Phase 2
•   Medivir / Tibotec                  polymerase inhibitor                                R&D
•   Pfizer                               PF-868554 Non-Nuc Polymerase inhibitor          Phase 2
•   Benitec / Tacere Bio / Pfizer     RNA interference TT033                           Pre Clinical
•   ViroChem Pharma                     VCH-759 Non nuc Polymerase inhib                Phase 2
•   ViroChem Pharma                     Polymerase inhib                               Pre Clinical
•   ViroChem Pharma                     Polymerase inhib                                    R&D
•   Globeimmune                          GI 5005 Therapeutic Vaccine                      Phase 2
• Telaprevir, also known as VX-950 is an oral
  Protease Inhibitor (NS3-4A). It is being
  developed by Vertex Pharmaceuticals for the
  treatment of hepatitis C virus.
• Patients with Genotype 1 Hepatitis C support
  potential to shorten treatment duration in
  treatment-naïve, genotype 1 HCV patients.
• IC41 is a therapeutic peptide vaccine. It is
  being developed by Intercell AG for the
  treatment of hepatitis C.

  The vaccine consists of five synthetic peptides
  (IPEP83, 84, 87, 89,1426) harboring HCV CD4
  and CD8 T-cell epitopes and the synthetic
  adjuvant poly-L-arginine.
• Milk Thistle
  – Flowering plant from Europe
  – Said to repair and prevent liver damage.
• Alpha Lipoic
  – antioxidant
  – Used in body to create energy
• Millions of people are infected.
• Causes damage to the liver.
• Several different genotypes (1 most common
  in U.S.)
• Several treatment options
• Hard to transfer the virus
• A vaccine is in Phase 2 trails
1. http://www.vizier-
   europe.org/IMG/pdf/RDeFrancesco_VIZIER_2007.pdf
2. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichep
   c/
3. http://www.nature.com/nrd/journal/v6/n12/full/nrd2411
   .html
4. http://www.hcvdrugs.com/forum/list.php?17
5. http://journals.elsevierhealth.com/periodicals/ygast/articl
   e/S0016-5085(08)02048-9/abstract
6. http://en.wikipedia.org/wiki/Hepatitis_C
7. www.abbottmolecular.com/HepatitisCDemographic...
8. http://en.wikipedia.org/wiki/Milk_thistle

				
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posted:4/10/2011
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