Hepatitis A, B, C, D, E, GB

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Hepatitis A, B, C, D, E, GB

• William Cassidy, MD
• Associate Professor of Medicine
• Louisiana State University Health Science Center
• Baton Rouge, Louisiana
• wcassi_at_lsuhsc.edu

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Overview

• Virus
• Mode of Transmission
• Epidemiology/ Risk Groups
• Presentation/ Diagnosis
• Natural History
• Treatment
• Prevention

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Hepatitis A

• Virus RNA picornovirus with an incubation period
  of 2-4 weeks.
• Mode of Transmission Fecal - oral

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Risk Factors Associated With HAV
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HAV - Related Morbidity and Mortality
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HAV - Related Morbidity and Mortality
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Hepatitis A

• Treatment Supportive
• Prevention Good sanitation, immuno-
• globulin, Hepatitis A vaccine

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Hep. A Vaccine, Who Should Receive

• Travelers to endemic countries
• Residents of high incidence communities
• Male homosexuals
• IVDU
• Chronic liver disease patients

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Overview

• Virus
• Mode of Transmission
• Epidemiology/ Risk Groups
• Presentation/ Diagnosis
• Natural History
• Treatment
• Prevention

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Hepatitis B

• Virus DNA hepadnavirus
• Subunits BsAg, BeAg
• HBeAg Reponsible for itis in
  hepatitis.

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Hepatitis B
Hepatocyte
HBV
sAg eAg DNA
Smooth endoplasmic reticulum
Nucleus
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Hepatitis BVirus enters cell and begins to
reproduce
Hepatocyte
HBV
DNA DNA DNA
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Hepatitis BVirus propagates, cell signals immune
system
Hepatocyte
eAg
DNA DNA DNA
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Hepatitis BT cells attack
T
T
T
T
eAg
DNA DNA DNA
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Hepatitis BInfection Controlled
T Cells win, yeah !!!!
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Hepatitis BVirus spreads to other cells
eAg
eAg
DNA
DNA
DNA
eAg
eAg
eAg
DNA
T Cells lose, Oh No !!!!
DNA
eAg
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Development of Chronic HBV

• Role of HBeAg as a tolergen in neonates.
• Alteration of natural history in those infected
  as neonates.

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Hepatitis B in the Immunotolerant
T
eAg
eAg
T
T
eAg
eAg
eAg
T
eAg
eAg
eAg
DNA
DNA
DNA
DNA
eAg
DNA
eAg
DNA
DNA
DNA
T
DNA
DNA
T
eAg
eAg
T
eAg
T
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Hepatitis B

• Mode of Transmission Blood Secretions

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Hepatitis B - Clinical Setting/ Epidemiology

• Countries areas with high endemicity
• Perinatal spread via HBsAg mothers
• Drug users
• Sexually promiscuous

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Incidence of acute HBV infection by age group
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Risk of developing chronic HBV by age group
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Epidemiology of Acute HBV

• 64 of adol. with acute B deny risk factors

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Hepatitis B

• Presentation Subclinical to fulminant
• Diagnosis
• Acute BcIgM, BsAg
• Chronic BsAg
• Natural History

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Hepatitis B Treatment

• Interferon
• Lamivudine
• Adefovir

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ACIP Eligibility Guidelines for HB Vaccination
March 1, 1998
Who to vaccinate?
All children and adolescents ages 0 through 18
years old. All high risk adults.
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Question

• How effective is immunologic memory?
• or
• Do we give booster shots?

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Immunologic Memory
Approximately 2.5 years later 50 participants
in the 5 mcg _at_ 0,6 month 50 participants in the
5 mcg _at_ 0,1,6 month All participants had
originally developed seroprotection. 5 mcg
booster dose given. Anti-HBs titers drawn 1 week
1 month later.
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Seroprotection 2.5 Yrs After Primary Vaccine
Series
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Geometric Mean Titers 2.5 Yrs After Primary
Vaccine Series
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Question

• Do we give booster shots?
• NO!
• Immunologic memory is prompt, vigourous and
  protective.

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Overview

• Virus
• Mode of Transmission
• Epidemiology/ Clinical Setting
• Presentation/ Diagnosis
• Natural History
• Treatment
• Prevention

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Hepatitis C

• Virus
• RNA Flavivirus
• Marked genetic heterogenity due to hypervariable
  region

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Hypervariable region 1

• Major neutralization epitope of HCV
• Mutates under immunologic pressure and becomes
  chronic
• Vaccines are difficult to develop
• Immunoglobulin not effective

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Hepatitis C Genotypes

• 6 major genotypes (1-6)
• 80 in U.S. are genotype 1a or 1b
• Genotype dictates length of therapy and predicts
  therapeutic response
• Genotype 1 requires longer therapy and has lower
  response

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Hepatitis C Mode of Transmission

• Blood, rarely sexual
• Increasing number of sexual partners is
  associated with higher rates of infection
• Monogamous couples at low risk

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Risk Factors Associated With HCV
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Hepatitis C - Prevalence Importance

• 4 million Americans infected
• 3.2 of African - Americans
• 2.1 of Mexican Americans
• 1.5 of non Hispanic whites
• 8,000- 10,000 deaths per year
• Leading cause of liver transplants

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Hepatitis C

• Presentation Typically subclinical,
  rarely fulminant
• Diagnosis History, HCV AB, HCV
  RNA

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Factors Affecting the Rate of Fibrosis
3
2.5
gt40 Years lt40 Years
2
1.5
1
lt5
6-10
11-15
16-20
gt20
4
3
gt50 g Alcohol/Day lt50 g Alcohol/Day
Fibrosis Stage
2
1
lt10
11-20
21-30
31-40
gt40
4
3
Men Women
2
1
lt10
11-20
21-30
31-40
41-50
Duration of Infection (Years)
Poynard T et al. Lancet. 1997349825.
II-11
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Staging of Fibrosis on Liver Biopsy
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Grading of Inflamation on Liver Biopsy
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Histologic Progression of HCV
Normal
Mild Chronic Hepatitis
Moderate Chronic Hepatitis
Cirrhosis
II-8
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Hepatitis C Natural History

• Variable
• Several studies showing that many if not most
  have very indolent or non progressive courses

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Hepatitis C Treatment

• Pegylated interferon alfa plus ribavirin

III-32
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Overview

• Virus
• Mode of Transmission
• Epidemiology/ Clinical Setting
• Presentation/ Diagnosis
• Natural History
• Treatment
• Prevention

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Hepatitis D

• Virus incomplete RNA virus, needs a BsAg to
  replicate

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Hepatitis D (Delta) Virus
d antigen
HBsAg
RNA
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Hepatitis D

• Incubation Period - 2- 4 weeks
• Mode of Transmission - Blood and Secretions

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Hepatitis D - Clinical Features

• Coinfection - Acute HDV and HBV
• severe acute disease
• low risk of chronic infection
• Superinfection Acute HDV superimposed upon
  chronic HBV
• usually develop chronic HDV infection
• high risk of severe chronic liver dz

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HBV - HDV Coinfection
Typical Serologic Course
Symptoms
ALT Elevated
anti-HBs
Titer
IgM anti-HDV
HDV RNA
HBsAg
Total anti-HDV
Time after Exposure
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HBV - HDV Superinfection
Typical Serologic Course
Jaundice
Symptoms
Total anti-HDV
ALT
Titer
HDV RNA
HBsAg
IgM anti-HDV
Time after Exposure
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Hepatitis D - Prevention

• HBV-HDV Coinfection
• Pre or postexposure prophylaxis to prevent HBV
  infection
• HBV-HDV Superinfection
• Education to reduce risk behaviors among persons
  with chronic HBV infection

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Overview

• Virus
• Incubation Period
• Mode of Transmission
• Epidemiology/ Risk Groups
• Presentation
• Natural History
• Diagnosis
• Treatment / Prevention

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Hepatitis E

• Incubation Period - Average 40 days
• Range 15-60 days
• Mode of Transmission Fecal oral

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Hepatitis E - Epidemiologic Features

• Most outbreaks associated withfecally
  contaminated drinking water
• Minimal person-to-person transmission
• U.S. cases usually have history of travel to
  HEV-endemic areas

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Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in gt25 of
Sporadic Non-ABC Hepatitis
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Hepatitis E - Clinical Features

• Case-fatality rate Overall, 1-3 Pregnant
  women, 15-25
• Illness severity Increased with age
• Chronic sequelae None identified

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HEV Diagnosis

• Diagnosis History, HEV antibody

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Hepatitis E Virus Infection
Typical Serologic Course
Symptoms
ALT
IgG anti-HEV
IgM anti-HEV
Titer
Virus in stool
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Weeks after Exposure
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Prevention of HEV- in Endemic Regions

• Avoid drinking water of unknown purity, uncooked
  shellfish, and uncooked fruit/vegetables not
  peeled or prepared by traveler
• IG prepared from donors in Western countries does
  not prevent infection

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Prevention of HEV- in Endemic Regions

• Unknown efficacy of IG prepared from donors in
  endemic areas
• Vaccine?

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Overview

• Virus
• Incubation Period
• Mode of Transmission
• Epidemiology/ Risk Groups
• Presentation
• Natural History
• Diagnosis
• Treatment / Prevention

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Hepatitis G (GB)

• Blood borne flavivirus, related to HCV
• Benign clinical course
• No treatment required
• No vaccines available
• Diagnose with HGV RNA
• Appears to benefit HIV patients

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Question Which virus(es) are sexually spread

• HAV
• HBV
• HCV
• All the above

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A Chinese family is moving back to China. What
vaccines should the 2 yr old receive?

• HAV
• HBV
• BOTH OF THE ABOVE
• NONE OF THE ABOVE

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Which newborn is at greatest risk for
contracting HBV

• Mother is HBsAg , HBeAg -
• Mother is HBsAg -, HBeAg -
• Mother is HBsAg , HBeAg

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A 10 year old child has acute hepatitis, which
diagnostic panel is the best?

• HAV Ab, HBcIgM, HCV Ab
• HAV IgM, HBsAg, HCV Ab
• HAV IgM, HBsAg, HCV IgM
• HAV IgM, HBcIgM, HCV Ab

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Which Panel Below is Best to Detect Chronic Viral
Hepatitis

• HAV Ab, HBsAg, HCV Ab
• HBsAg, HCV Ab
• HAV IgM, HBsAg
• HAV IgM, HCV Ab

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