Title: Viral Hepatitis
1Viral Hepatitis
- Hugh B. Fackrell
- Filename Hepatite.ppt
2Hepatitis Virus Outline
- Definitions
- Classification
- Structure
- Multiplication
- Clinical manifestations
- Epidemiology
- Diagnosis
- Control
Barons Web Site
3Hepatitis
- an ancient disease, the etiology has only
recently (50 yrs.) been revealed.
4Hepatitis
- An inflammatory disease
- necrosis of hepatocytes
- mononuclear response destroys liver architecture
- Liver excretion of bile pigments such as
bilirubin into the intestine is interrupted
5Bilirubin
- Bilirubin greenish-yellow pigment accumulates
in the blood and tissues - Jaundice -
- yellow tinge in the skin and eyes
- caused by bilirubin
6Types 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
7Jaundice of the Newborn
- Premature infants
- bilirubin increases from birth
- peaks at one week
- caused by
- 1excessive hemolysis
- 2immature liver function
8Hepatitis symptoms
- Swelling and tenderness of liver
- Jaundice -yellow tinge in the skin and eyes
- dark urine
- transaminase, alkaline phosphatase levels
increased
9Viral Hepatitis
- Liver infection caused by several UNRELATED
VIRUSES - Inflammation and necrosis of the liver
- 50 of HAV HBV are subclincal
10Hepatitis 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
11Hepatitis A
- Infectious hepatitis
- Epidemic hepatitis
- HAV
12Hepatitis AClinical manifestations
- asymptotic or anicteric in children
- 3-5 week incubation period
- liver inflammation
- malaise - flu like symptoms
- self limiting
- low mortality
13Hepatitis AStructure
- Picornavirus
- Only one serotype
- Enterovirus type 72
- 27-29 nm icosahedral
- ssRNA
14Hepatitis AHost 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
15Hepatitis AEpidemiology
- Global distribution- underreported
- Fecal-oral route,
- person to person
- water
- Overcrowding poor sanitation
- Infected food handlers common vector
16Annual 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
- 3,900,000
- Hepatitis A
- 83,391
CDC
17Hepatitis ADiagnosis
- Clinical manifestions
- Viral antigens
- Immunoelectron microscopy
- RIA
- ELISA
- Immune Adherence hemagglutination (old method)
- Viral antibodies
18Hepatitis AControl
- No specific control
- Improve hygiene and sanitation
- Human immunoglobulin
- 2 IU anti Hepatitis A /kg body weight
- HAV vaccines in clinical field trials
19Hepatitis B
20Hepatitis BClinical Manifestations
- typical viral hepatitis symptoms
- 4-26 week incubation period
- more severe than HAV
- CHRONIC PERSISTENT HEPATITIS
- CHRONIC ACTIVE HEPATITIS
21Hepatitis BStructure
- Hepadnavirus
- dsDNA, circular, 3200 nucleotides
- enveloped icosahedral virus
- 42 nm
22Australia antigenDane particle
- small pelomorphic particles 20-22nm
- tubular forms
- excess viral capsids released into blood stream
233 forms of HBV
24Dane Particles
25Hepatitis BHost 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
26Hepatitis BEpidemiology
- 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
27Hepatitis BPrevalence
- AREA HBsAg anti HBsAg
- Western Europe 0.2-0.5 4-6
USA - Eastern Europe 2-7 20-55 USSR
- China 8-20 70-95
Asia
28Hepatitis BDiagnosis
- Electron microscopy
- Viral DNA polymerase
- Viral DNA probes
- Serology
29Hepatitis BSerology
- Hepatitis B surface antigen- HBsAg
- 10 subtypes
- Hepatitis B core antigen- HBsCAg
- Soluble core associated antigen HBeAg
Corresponding antibodies to each antigen occur
30Hepatitis BControl
- No specific 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
31HBV Cancer
- 1. Transformation of the cell by virus
- 2. Helper virus if the transforming virus is
defective - 3. Co-carcinogen, chemical, cigarette smoke
32Transformed cells
- lose contact inhibition
- continue to divide
- form random aggregations
- can become invasive
- Not warts Papovavirus
33Primary 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
34Acute HBV Cancer
- Acute Hepatitis B
- 90 1
Resolution Fulminant Hepatitis - 50
Resolution
Chronic Active
AsymptomaticCarrier
Hepatitis
Chronic
Cirrhosis
HepaticCell Carcinoma
ExtrahepaticDisease
35Hepatitis C
36Hepatitis CClinical Manifestations
- resembles HBV
- persistent carrier state
- 50 of patients have chronic liver damage
- associated with hepatocellular carcinoma
37Hepatitis C is probably caused by several
different viruses
38Hepatitis CEpidemiology
- in USA causes 90 of post transfusion hepatitis
- Mother to infant transmission
39Hepatitis CDiagnosis
- C100-3 recombinant viral antigen
- anti c100-3 marker of chronic infection
40Hepatitis A HAV
Hepatitis B HBV
Hepatitis C HCV
RNA yes endemic epidemic oral/fecal,water
food2-7 weeks fever, G-I tract disorder 1 case
in 10 acute/short not available yes
DNA no endemic blood/serum,close contact 1-6
months fever, rash, arthritis common gradual/chron
ic yes yes
HBV no endemic blood/serum,intimate contact 2-8
weeks similar to HBV common acute/chronic not
available yes
Structure Cultured in cells Epidemiology Transmiss
ion Incubation period Symptoms Jaundice Onset Vac
cine Diagnostic tests
41Hepatitis D
42Hepatitis 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.
43Hepatitis DClinical Manifestations
- Dual infection is more severe than HBV
- fulminating hepatitis
- severe rapidly progressive hepatitis
- severe exacerbations
44Hepatitis D Structure
- 35-37 nm virus particle
- shares coat protein of HBV
- small RNA genome
- one serotype
45Hepatitis DEpidemiology
- hemophiliacs and IV drug users
- Contaminated blood and blood products
46Geographic distribution of HDV
47Hepatitis DDiagnosis
- Clinical manifestations
- Delta antigen
- Immunofluorescence
- RIA
- ELISA
- Anti delta antigen
- same as above
48Hepatitis E Virus
49Hepatitis 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.