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
Hepatitis B virus?
• Partially double-stranded circular DNA virus
• Virus consists of a central core (HBcAg) nucleocapsid containing viral DNA and a
surrounding envelope containing the surface protein/surface antigen (HBsAg)
Hepatitis B virus: Routes of Transmission?
Transmission occurs via contact/exchange of bodily fluids*:
• Needle stick (drug use or occupational exposure)
• Transplant/transfusion with unscreened blood/blood products
• Acupuncture/tattooing/body piercing with unsterilized needles
• Sexual transmission
Hepatitis B virus: Individuals at Risk?
• Injection drug users
• Unsafe sexual practices
• Occupational contact with blood: (medical/dental workers, lab techs,
paramedics, etc.)
• Institutionalized populations (prisoners)
Hepatitis B virus: Clinical Course?
- Incubation period about 60 90 days
- Onset is often subtle
- HBV causes clinical illness
(jaundice) in 30 - 50 % - Most HBV infected adults will recover within six months and develop immunity
• Of those infected, 2-10 % will progress to chronic infection
• Of those who become chronically infected, 15-25 % die prematurely as a result of chronic liver disease
Hepatitis B virus: Diagnostic Markers?
**Check slide (20/38)
Hepatitis B Diagnostic Profile: Acute Infection?
- Incubation: 60-90 days
- Acute infection: 2wk - 3 mo
- Early recovery: 3-6 mo
- Serial testing is employed to follow the patient’s progress
- Acute Hepatitis:
• Surface antigen (HBsAg) +
• Envelope antigen (HBeAg) +
• Anti HBc (IgM) +
Hepatitis B Diagnostic Profile: Resolving Infection?
• Seroconversion from HBeAg to anti-Hbe • Seroconversion from HBsAg to anti-HBs • Also indicates the establishment of immunity
Hepatitis B Diagnostic Profile: Chronic Infection?
Definition: • HBsAg is present for more than six months * • Chronic Infection = HBsAg and HBeAg are elevated
Hepatitis B: Summary
of Diagnostic Markers
HBsAg • Indicator of infection (acute or chronic) HBeAg • Indicator of infection (acute or chronic) Anti-HBc(IgM) • Indicator of acute infection Anti-Hbe • Indicator of disease resolution Anti-HBs • Indicator of recovery & immunity
HBV DNA Viral Load Testing?
If confirmed HBV infection based on serologic testing
• Measure HBV DNA level at baseline (i.e., prior to starting therapy)
• Measure 3-6 month intervals while on anti-viral therapy
• More frequent testing may be indicated for suspected resistance to antiviral therapy
Hepatitis C?
• Flavivirus
• Single stranded RNA virus
• Small (<50 nm); lipid enveloped
• 20% of viral hepatitis cases; most common cause of chronic viral hepatitis
• Lab Tests
Screen for HCV exposure: anti - HCV Abs, IgG becomes positive ~9 weeks post
exposure
• Active infection: HCV RNA analysis
• CDC-recommends one time HCV test for those born 1945-1965 using HCV antibody test
Protein C=Core; Protein E= envelope
Hepatitis C: Routes of Transmission?
Transmission occurs through contact with blood*:
• Needle stick (drug use and occupational exposure)
• Transplant/transfusion with unscreened blood/blood products
• Acupuncture/tattooing/body piercing with unsterilized needles
• Perinatal infant born to an HCV infected mother
Hepatitis C: Individuals at Risk?
• Injection drug users
• Unsafe sexual practices
• Occupational exposure to blood: (medical/dental workers, lab techs,
paramedics, etc.)
• Institutionalized populations (prisoners)
• Transfusion/transplant recipients prior to 1992
Hepatitis C: Clinical Course?
• 60-70 % of infected persons may be asymptomatic
• 20-30 % with acute HCV might have jaundice
• About 60-85 % of become chronically infected
(10-20 % of those with chronic infection develop cirrhosis, liver cancer, or liver failure
• Hepatocellular carcinoma develops in 1-5 % of individuals (over 20-30
years)
• HCV is a leading cause of liver transplantation
• Various factors, including alcohol use and co infection with HIV, can affect the clinical course of HCV (abstinence from alcohol in infected individuals is recommended)
Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection?
• Variable incubation period: 2-26 weeks.
• The average time from exposure to the development of symptoms is 6-7 weeks
• Acute HCV infection may take ~8-9 weeks for seroconversion to anti HCV to occur
• Individuals positive for HCV antibody are considered potentially infectious
• HCV is diagnosed by detecting antibodies
specific to hepatitis C virus (anti-HCV)
• Retesting for anti-HCV may be necessary if the initial result is negative (can take > 2 months to become positive)
• Anti-HCV does NOT distinguish between
acute, chronic or resolved infection
HCV RNA Testing (Nucleic Acid Testing)?
- HCV RNA measures the level of circulating virus in an infected individual - referred to as the “viral load.”
- HCV RNA can be used to:
• As a follow-up test for a positive anti-HCV test result
• Evaluate suspect HCV infection before seroconversion to anti HCV
occurs
• Assess viral load before antiviral therapy is administered
• Monitor the effectiveness of antiviral therapy
• Detect HCV infection in cases with ambiguous serology
Viral Hepatitis Overview
**Check slide 31/38
Viral hepatitis Summary?
• Viral hepatitis is a major cause of morbidity and mortality worldwide.
• Hepatitis viruses are heterogeneous in their molecular makeup, routes of
transmission, duration of incubation phases, and likelihood of progression
towards chronic hepatitis and associated complications including mortality.
• Understanding of hepatitis virus infectious cycle and immune response mechanisms has allowed development of lab tests that allow for assessment of hepatitis infection or immunity status in symptomatic patients.
