1. Hugh B. Fackrell Filename: Hepatite.ppt
Viral Hepatitis
Hugh B. Fackrell
Filename: Hepatite.ppt

2. Hepatitis Virus Outline
Definitions
Classification
Structure
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
Baron’s Web Site

3. Hepatitis
an ancient disease, the etiology has only recently (50 yrs.) been revealed.

4. 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

5. Bilirubin
Bilirubin: greenish-yellow pigment accumulates in the blood and tissues
Jaundice -
yellow tinge in the skin and eyes
caused by bilirubin

6. 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

7. Jaundice of the Newborn
Premature infants
bilirubin increases from birth
peaks at one week
caused by
1:excessive hemolysis
2:immature liver function

8. Hepatitis symptoms Swelling and tenderness of liver
Jaundice -yellow tinge in the skin and eyes
dark urine
transaminase, alkaline phosphatase levels increased

9. Viral Hepatitis Liver infection caused by several UNRELATED VIRUSES
Inflammation and necrosis of the liver
50% of HAV & HBV are subclincal

10. 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”

11. “Infectious hepatitis” “Epidemic hepatitis” HAV
Hepatitis A
“Infectious hepatitis”
“Epidemic hepatitis”
HAV

12. Hepatitis A Clinical manifestations
asymptotic or anicteric in children
3-5 week incubation period
liver inflammation
malaise - flu like symptoms
self limiting
low mortality

13. Hepatitis A Structure Picornavirus Only one serotype
Enterovirus type 72
27-29 nm icosahedral
ssRNA

14. Hepatitis A Host Defenses
antibodies develop late in incubation period
IgM
within a week of dark urine
peaks a week later
lasts days
IgG
after IgM
peaks days
lasts many years

15. Hepatitis A Epidemiology
Global distribution- underreported
Fecal-oral route,
person to person
water
Overcrowding & poor sanitation
Infected food handlers common vector

16. Annual Incidence Viral food borne diseases
Total Viral food borne 30,883,391
Total Microbial food borne incidence
38,629,64
Norwalk-like viruses
23,000,000
Rotavirus
3,900,000
Astrovirus
Hepatitis A
83,391
Food-Related Illness and Death in the United Stateshttp://
CDC

17. Hepatitis A Diagnosis Clinical manifestions Viral antigens
Immunoelectron microscopy
RIA
ELISA
Immune Adherence hemagglutination (old method)
Viral antibodies

18. Hepatitis A Control No specific control Improve hygiene and sanitation
Human immunoglobulin
2 IU anti Hepatitis A /kg body weight
HAV vaccines in clinical field trials

19. Hepatitis B
“Serum hepatitis”
HBV

20. Hepatitis B Clinical Manifestations
typical viral hepatitis symptoms
4-26 week incubation period
more severe than HAV
CHRONIC PERSISTENT HEPATITIS
CHRONIC ACTIVE HEPATITIS

21. Hepatitis B Structure Hepadnavirus dsDNA, circular, 3200 nucleotides
enveloped icosahedral virus
42 nm

22. Australia antigen “Dane particle”
small pelomorphic particles 20-22nm
tubular forms
excess viral capsids released into blood stream

23. 3 forms of HBV

24. Dane Particles

25. 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

26. Hepatitis B Epidemiology
Parenterally ie via blood, saliva, menstrual and vaginal discharges, semen and breast milk
infected blood and blood products
sexual contact
perinatally from mother to child

27. Hepatitis B Prevalence
AREA HBsAg anti HBsAg
Western Europe % % USA
Eastern Europe % % USSR
China % % Asia

28. Hepatitis B Diagnosis Electron microscopy Viral DNA polymerase
Viral DNA probes
Serology

29. Corresponding antibodies to each antigen occur
Hepatitis B Serology
Hepatitis B surface antigen- HBsAg
10 subtypes
Hepatitis B core antigen- HBsCAg
Soluble core associated antigen HBeAg
Corresponding antibodies to each antigen occur

30. Hepatitis B Control No specific control Passive Immunization
HBV immunoglobulin
IU within 48 hours
neonates of infected mothers -immediately after birth
Active Immunization
HBsAg
recombinant DNA in yeast

31. HBV & Cancer 1. Transformation of the cell by virus
2. Helper virus if the transforming virus is defective
3. Co-carcinogen, chemical, cigarette smoke

32. Transformed cells lose contact inhibition continue to divide
form random aggregations
can become invasive
Not warts: Papovavirus

33. Primary Hepatocellular Carcinoma
Highest incidence:
Central Africa
Southeast China
Pacific Islands, Borneo, Sarawak, Taiwan
Icteric symptoms:
jaundice, dark urine, pale stools
Global ,000- 1,000,000 deaths /year
U.S.A deaths / year

34. Acute HBV & Cancer Acute Hepatitis B
90% 1% Resolution Fulminant Hepatitis
50%
Resolution
Chronic Active
Asymptomatic Carrier
Hepatitis
Chronic
Cirrhosis
Hepatic Cell Carcinoma
Extrahepatic Disease

35. Hepatitis C
HCV
Non -A Non-B

36. Hepatitis C Clinical Manifestations
resembles HBV
persistent carrier state
50% of patients have chronic liver damage
associated with hepatocellular carcinoma

37. Hepatitis C is probably caused by several different viruses

38. Hepatitis C Epidemiology
in USA causes 90% of post transfusion hepatitis
Mother to infant transmission

39. Hepatitis C Diagnosis C100-3 recombinant viral antigen
anti c100-3 marker of chronic infection

40. Hepatitis A HAV Hepatitis B HBV Hepatitis C HCV Structure
Cultured in cells
Epidemiology
Transmission
Incubation period
Symptoms
Jaundice
Onset
Vaccine
Diagnostic tests
RNA
yes
endemic & epidemic
oral/fecal, water & food weeks
fever, G-I tract disorder
1 case in 10
acute/short
not available
DNA no
endemic
blood/serum, close contact
1-6 months
fever, rash, arthritis
common
gradual/chronic
yes
HBV no
endemic
blood/serum, intimate contact
2-8 weeks
similar to HBV
common
acute/chronic
not available
yes

41. Hepatitis D
HDV

42. 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.

43. Hepatitis D Clinical Manifestations
Dual infection is more severe than HBV
fulminating hepatitis
severe rapidly progressive hepatitis
severe exacerbations

44. Hepatitis D Structure 35-37 nm virus particle
shares coat protein of HBV
small RNA genome
one serotype

45. Hepatitis D Epidemiology
hemophiliacs and IV drug users
Contaminated blood and blood products

46. Geographic distribution of HDV

47. Hepatitis D Diagnosis Clinical manifestations Delta antigen
Immunofluorescence
RIA
ELISA
Anti delta antigen
same as above

48. Hepatitis E Virus

49. Hepatitis E fecal/oral route
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.