Hepatitis
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.
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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.
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.
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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
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• 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.
Lamivudine Adefovir dipivoxil
Nucleoside Analogs Approved for Treatment of HBV
TelbivudineEntecavir
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.
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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.
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Ribavirin
• Ribavirin resembles both adenosine and guanosine and may become incorporated into growing strands of RNA
Adenosine
Ribavirin
Guanosine
• 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.
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