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Transcript
Hepatitis LINK Viral Hepatitis is a group of disease that infect the liver. Three viruses Hepatitis A, Hepatitis B and Hepatitis C are the most frequent viruses. Hepatitis A • Hepatitis A is a frequent virus of childhood and is not considered a deadly and serious infection. • It is most commonly transmitted via the fecal-oral route through contaminated food or drinking water. Hepatitis A • Hepatitis A (HAV) has a single positive stranded (+) RNA in the genome. • No medications are prescribed for HAV, the body clears the infection on its own. Hepatitis B • Hepatitis B is an infectious viral disease transmitted by body fluids or needles (including unprotected sex) • Hepatitis B can cause severe acute infections and severe chronic infections. Hepatitis B • Health care workers are immunized against Hepatitis B • HBV has a double stranded DNA genome. • HBV infection can progress to cirrhosis (scarring of the liver) and hepatocellular cancer (HCC). Hepatocellular carcinoma = HCC The precise mechanism whereby hepatitis progresses to HCC is not known. Treatment of HBV Interferon alpha • Interferons are proteins produced by the immune system in response to viruses • Interferons serve to activate the immune system, specifically MHC 1 (major histocompatibility complex 1), thus giving a signal to T cells. • Link Pegylated Interferon alfa-2a • This protein derivative is formed by the addition of polyethylene glycol (structure above) to the interferon, leading to an enhanced lifetime of the interferon Link Nucleoside Analogs Approved for Treatment of HBV Lamivudine Adefovir dipivoxil Entecavir Telbivudine • These nucleoside analogs interfere with the action of the HBV reverse transcriptase (see link), becoming incorporated into the growing DNA strand and terminating reverse transcription. • Unfortunately, HBV can become resistant to these drugs. Hepatitis C (HCV) • Hepatitis C is transmitted through blood routes, needles, tattoos and sexual activity. • Hepatitis C is a quiet virus that may not be noticed • This virus may slowly eat away at your liver causing scarring and damage and finally almost total liver destruction. • Link Prevelance of HCV • Hepatitis C (HCV) has a single positive stranded (+) RNA in the genome. Treatment of HCV • Current treatment is a combination off pegylated interferon alpha (Pegasys and PEG-Intron) combined with the antiviral drug ribavirin for a period of 24 to 48 weeks. • Link • Link • Link Ribavirin Ribavirin Adenosine Guanosine • Ribavirin resembles both adenosine and guanosine and may become incorporated into growing strands of RNA • However the carboxamide group pairs equally well with both uracil or cytosine, thus leading to mutations in RNA-dependent RNA polymerases. • Ribavirin also acts as an inhibitor of inosine 5’monophosphate dehydrogenase, a crucial enzyme in the biosynthesis of RNA. • Link Assigned Reading • Harris, J. Milton; Chess, Robert B. Effect of PEGylation on pharmaceuticals. Nature Reviews Drug Discovery (2003), 2(3), 214-221.