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.

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.

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.

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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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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.

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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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Assigned Reading• Harris, J. Milton; Chess, Robert B.

Effect of PEGylation on pharmaceuticals. Nature Reviews Drug Discovery (2003), 2(3), 214-221.