22. Viral Hepatitis - 3/5/2009 Alphabet Soup Viral...

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3/5/2009 1 Viral Hepatitis What every pharmacist needs to know… Alphabet Soup •A •B C • C •D •E • What do we have against the letter F? •G What I’m not going to talk about… - Acute liver disease - No chronic form - Most importantly - no treatment, no drugs! • D - need to have B first • F - doesn’t exist (yet) • G - doesn’t cause liver disease That leaves… • Hepatitis B - HBV Hepatitis C HCV • Hepatitis C - HCV • Both chronically infect the liver and called hepatitis but that’s about where the similarity ends Hep B vs Hep C HBV HCV - partially DS DNA virus -3.2kb - 4 genes - 5 proteins - + sense enveloped ss RNA virus - 1 polyprotein - Cleaved to 3 structural and 7 NS proteins Outline •HBV – The virus – The problem - public health The problem public health – The disease - natural history – The treatment • HCV – Ditto….
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3/5/2009 2 Hepatitis B - Some Sobering Facts - 400 Million people chronically infected - 2 billion with evidence of “past” infection - Over 1 million deaths annually Why are so many people infected? In high prevalence areas, main routes of transmission are: 1. Maternal-fetal 2. Percutaneous – Medical/IVDU/Kids playing! 3. +/- Sexual Does the route matter? Yes…and to show why, some data… Outcome Depends on Age of Acquisition + Source Perinatal 1-5 yo >10 yo 90-95% 20-50% <5% chroni cc hroni hronic Mom e Ag +ve 85-90% chance of transmitting to baby Mom e Ag -ve 31% chance of transmitting to baby Why is this true? The answer, unfortunately, lies in the virology! uncoating At achment and Penetration HBV Replication Golgi complex transport to cel nucleus CCC DNA DNA repair HBV RNA Transcripts Pregenomic RNA O- 5’Cap (A)n 3’ Translocation dAdAdG new (-) strand DNA synthesis pgRNA DNA Synthesis Encapsidation of pg RNA Release envelope proteins S, M, L Polymerase Protein Core Proteins e Ag Transcripts HBV - a very clever virus! 1. cccDNA By “disguising” itself as a host chromosome, manages to persist and evade immune response Stays in the host, probably FOREVER!! 2. e Antigen P d d b th i BUT t f th i Produced by the virus BUT separate from the virus Not needed to replicate – may be there as a “toleragen” If present, high replication…but converse not necessarily true 3. Reverse transcription Strange for a DNA virus to use this pathway – it’s the only one Very relevant for HIV co-infected patients…drugs are the same Another important point • HBV is non-cytopathic (generally) • Liver damage caused by immune response to virus • Battle takes place in the liver and hepatocytes are the innocent bystanders that take all the hits innocent bystanders that take all the hits!
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3/5/2009 3 HBV DNA ALT What happens in classical acute infection? HBeAg+ HBeAb+ ? Consider trt Infection HBcAb IGM+ HBcAb IgG+ HBV DNA HBsAg+ HBsAb+ If fulminant or Not clearing??
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This note was uploaded on 05/09/2010 for the course LMP 232 taught by Professor Crandall during the Spring '10 term at University of Toronto- Toronto.

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22. Viral Hepatitis - 3/5/2009 Alphabet Soup Viral...

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