Viral Hepatitis
Hepatitis Virus Outline
Hepatitis
- an ancient disease, the etiology has only recently (50 yrs.) been revealed.
Hepatitis
- An inflammatory disease
- necrosis of hepatocytes
- mononuclear response destroys liver architecture
- Liver excretion of bile pigments such as bilirubin into the intestine is interrupted
Bilirubin
- Bilirubin: greenish-yellow pigment accumulates in the blood and tissues
- Jaundice -
- yellow tinge in the skin and eyes
- caused by bilirubin
Types of Jaundice
- Pre hepatic: Hemolytic Jaundice
- normal feces, anemia, reticulocytes
- Hepatic: Hepatocellular Jaundice
- fecal fat, bilirubinuria, Alkaline phosphatase high, gamma globulins high
- Post Hepatic: Obstructive Jaundice
- fecal fat, bilirubinuria, alkaline phosphatase high
Jaundice of the Newborn
- bilirubin increases from birth
- caused by
- 1:excessive hemolysis
- 2:immature liver function
Hepatitis symptoms
- Swelling and tenderness of liver
- Jaundice -yellow tinge in the skin and eyes
- transaminase, alkaline phosphatase levels increased
Viral Hepatitis
- Liver infection caused by several UNRELATED VIRUSES
- Inflammation and necrosis of the liver
- 50% of HAV & HBV are subclincal
Hepatitis types
- Hepatitis A - HAV "infectious hepatitis"
- Hepatitis B - HBV "serum hepatitis"
- Hepatitis C - HCV non A, non B
- Hepatitis D - HDV Delta virus
- Hepatitis E - HEV similar to type “A”
Hepatitis A
Hepatitis A Clinical manifestations
- asymptotic or anicteric in children
- 3-5 week incubation period
- malaise - flu like symptoms
Hepatitis A Structure
Hepatitis A Host Defenses
- antibodies develop late in incubation period
- IgM
- within a week of dark urine
- peaks a week later
- lasts 40-60 days
- IgG
- after IgM
- peaks 60-80 days
- lasts many years
Hepatitis A Epidemiology
- Global distribution- underreported
- Overcrowding & poor sanitation
- Infected food handlers common vector
Annual Incidence Viral food borne diseases
- Total Viral food borne 30,883,391
- Total Microbial food borne incidence
Hepatitis A Diagnosis
- Viral antigens
- Immunoelectron microscopy
- RIA
- ELISA
- Immune Adherence hemagglutination (old method)
Hepatitis A Control
- Improve hygiene and sanitation
- Human immunoglobulin
- 2 IU anti Hepatitis A /kg body weight
- HAV vaccines in clinical field trials
Hepatitis B
Hepatitis B Clinical Manifestations
- typical viral hepatitis symptoms
- 4-26 week incubation period
- CHRONIC PERSISTENT HEPATITIS
Hepatitis B Structure
- dsDNA, circular, 3200 nucleotides
- enveloped icosahedral virus
Australia antigen “Dane particle”
- small pelomorphic particles 20-22nm
- excess viral capsids released into blood stream
3 forms of HBV
Dane Particles
Hepatitis B Host Defenses
- Cell mediated Immunity
- important for recover in acute phase
- autoimmune liver damage in chronic infections
- Humoral Immunity
- not always protective
- HBsAg for Vaccines
- Interferon
- not detected during infection
- exogenous application effective
Hepatitis B Epidemiology
- Parenterally ie via blood, saliva, menstrual and vaginal discharges, semen and breast milk
- infected blood and blood products
- perinatally from mother to child
Hepatitis B Prevalence
Western Europe 0.2-0.5% 4-6% USA
Eastern Europe 2-7 % 20-55% USSR
Hepatitis B Diagnosis
Hepatitis B Serology
- Hepatitis B surface antigen- HBsAg
- Hepatitis B core antigen- HBsCAg
- Soluble core associated antigen HBeAg
Corresponding antibodies to each antigen occur
Hepatitis B Control
- Passive Immunization
- HBV immunoglobulin
- 250-500 IU within 48 hours
- neonates of infected mothers -immediately after birth
- Active Immunization
- HBsAg
- recombinant DNA in yeast
HBV & Cancer
1. Transformation of the cell by virus
2. Helper virus if the transforming virus is defective
3. Co-carcinogen, chemical, cigarette smoke
Transformed cells
Primary Hepatocellular Carcinoma
- Highest incidence:
- Central Africa
- Southeast China
- Pacific Islands, Borneo, Sarawak, Taiwan
- Icteric symptoms:
- jaundice, dark urine, pale stools
- Global 250,000- 1,000,000 deaths /year
- U.S.A. 5000 deaths / year
Acute HBV & Cancer
90% 1% Resolution Fulminant Hepatitis
Hepatitis C
Hepatitis C Clinical Manifestations
- 50% of patients have chronic liver damage
- associated with hepatocellular carcinoma
Hepatitis C is probably caused by several different viruses
Hepatitis C Epidemiology
- in USA causes 90% of post transfusion hepatitis
- Mother to infant transmission
Hepatitis C Diagnosis
- C100-3 recombinant viral antigen
- anti c100-3 marker of chronic infection
PPT Slide
oral/fecal, water & food 2-7 weeks
fever, G-I tract disorder
blood/serum, close contact
blood/serum, intimate contact
Hepatitis D
Hepatitis D
- Dependovirus, it is defective and cannot produce infection unless the cell is also infected with HBV.
- Viroid - a naked strand of RNA that enters the cell in piggy-back fashion.
Hepatitis D Clinical Manifestations
- Dual infection is more severe than HBV
- severe rapidly progressive hepatitis
Hepatitis D Structure
- shares coat protein of HBV
Hepatitis D Epidemiology
- hemophiliacs and IV drug users
- Contaminated blood and blood products
Geographic distribution of HDV
Hepatitis D Diagnosis
- Delta antigen
- Immunofluorescence
- RIA
- ELISA
Hepatitis E Virus
Hepatitis E
- predominantly found in developing countries but is world wide.
- symptoms similar to HAV but mortality 1-2% (ten times that of Hepatitis A).
- epidemics - India, Pakistan, Nepal, Burma, North Africa and Mexico.