L9 - Viral Hepatitis Flashcards
Hepatitis: Primary and Secondary Causes
Toxins?
Drugs • Anticonvulsants • Corticosteroids • Alcohol abuse Bacteria • Typhoid fever Parasites • Tapeworm Toxins • DDT • Mushrooms Viruses • Hepatitis A, B, C, D, E, G • CMV • EBV
Viral hepatitis:
A major global health concern?
• Viral hepatitis results from inflammation of the liver, caused by a viral infection
• Every year 1.4 million people die from viral hepatitis related cirrhosis and liver cancer
• The World Health Organization estimated that 1 in 3 people worldwide have
been infected by either HBV or HCV
• However, the majority of the infected population are unaware of their
condition.
Hepatitis Viruses?
Hepatitis A, B, C , D, and E are the main viral causes of hepatitis in humans
They have little in common besides the fact that the primary infection site is liver
They can be grouped by the route of transmission
• Fecal-oral route - hepatitis A (HAV) and hepatitis E (HEV)
• Blood-fluid route - hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV)
Acute Versus Chronic Hepatitis?
- All 5 types of viruses can cause acute viral hepatitis
- HAV and HEV typically cause acute hepatitis
- HBV, HCV, HDV can cause both acute and chronic infection
Acute Viral Hepatitis Symptoms?
Phase 1 - incubation
Asymptomatic phase (a couple of weeks to several months)
Phase 2 - pre-icteric
• Malaise, joint and muscle pain, fatigue, anorexia, nausea, vomiting
• Vague, dull right upper quadrant pain produced by swollen tender liver
• Flu like symptoms may also appear including fever for 3 10 days
Phase 3 - icteric
• Jaundice (elevated conjugated bilirubin), dark yellow urine, pale stools
Phase 4 - convalescence
• Symptoms gradually disappear and patient improves
Chronic Viral Hepatitis Symptoms?
Definition: persistent production of hepatitis virus for longer than 6 months
• A prolonged and indolent pre icteric phase usually indicated development of chronic hepatitis
• Depending on severity of disease may have the following symptoms:
• Fatigue, jaundice, right upper quadrant discomfort
The Viral Particle?
**Check slide 9/38
Antigens and Antibodies?
**Check slide 10/38
Primary and Secondary Immune Responses?
• Primary response: produced when antigen presented to the immune system for the first time. Memory lymphocytes are produced during the primary response and they will remember each epitope’s structure for possible future infections. • After the mature B cell stage, a cell may change from production of IgM to synthesis of IgG; this process is called class switching. This is a stable change in the cell’s genome and is transmitted to all progeny cells.
HBV Lifecycle
- NUCLEAR IMPORT: Virions bind to hepatocyte surface receptors and are internalized. The envelope is subsequently removed and the viral DNA moves into the nucleus.
- REPAIR: Viral genomes are repaired to form a covalently closed circular DNA (cccDNA) that is the stable template for viral messenger RNA (mRNA)
transcription. - TRANSCRIPTION AND TRANSLATION: The viral
mRNA is translated in the cytoplasm to produce the
viral surface, core, polymerase, and X proteins. - ENCAPSIDATION: Newly synthesized viral
polymerase remains associated with viral DNA,
forming a complex around which the core protein
assembles. Progeny viral capsids assemble,
incorporating genomic viral RNA (RNA packaging). - RNA is reverse-transcribed into viral DNA.
- BUDDING: The resulting cores can either bud into
the endoplasmic reticulum to be enveloped and exported from the cell or recycle their genomes into the nucleus for conversion to cccDNA.
Hepatitis A?
Picornavirus
25 33% of acute hepatitis in US and worldwide
Laboratory assessment:
• IgM anti HAV ~ acute infection
• IgG anti HAV~ after infection or immunization
Hepatitis A: Routes of Transmission?
Transmission usually occurs enterically (fecal-oral )* via:
• Close person to person contact
• Ingestion of contaminated food or water
• Routes facilitated by poor hygiene and sanitation
Hepatitis A: Individuals at Risk?
- Those in close contact with an infected individual
- Children in daycare centers (where hepatitis A outbreaks occur)
- Travelers to areas with widespread disease and where clean water and proper sewage disposal are unavailable
Hepatitis A: Clinical Course?
- Onset of symptoms is usually abrupt and lasts ~ 1 8 weeks
- Jaundice develops in 70-80 % of adults
- HAV replicates in the liver and is shed in the stool
- The concentration of virus in stool declines after jaundice appears
- Most HAV infected adults will recover and develop immunity
Hepatitis A Virus Infection?
**Check slide 16/38