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Viral Hepatitis: ABCDE

NEPMU-2
Norfolk, VA
(757) 444-7671
Objectives
• Describe the Clinical Syndromes of Viral
Hepatitis
• List the modes of Transmission
• Understand and be able to interpret
Diagnostic (laboratory) tests
• Know the Treatment and Occupational
Impact of Viral Hepatitis
• List Preventive Measures for each Hepatitis
type
• Describe Immunization protocols
Hepatitis
• Inflammation of the Liver that can be viral,
chemical or drug-induced
• Viral Hepatitis: Systemic infection which
causes inflammation of the liver
• Currently 5 recognized types of viral
hepatitis: A, B, C, D, E
• All 5 viruses cause similar illness, but
have distinct antigenic properties
Acute Hepatitis: Symptoms
Common Uncommon
• Malaise 76-94% • Respiratory
• Anorexia 71-96%
• Dark urine 65-94% symptoms
• Nausea 61-81% • Headache
• Abdominal pain 26-68%
• Scleral icterus 48% • Fever
• Vomiting 20-37% • Muscle pain
• Rash
• Joint pain
• Itching
Asymptomatic hepatitis is also common
Acute Hepatitis: Signs
Jaundice 70-90%
Hepatomegaly 14-69%
Tender liver 20-86%
Rash 40%
Splenomegaly 3-21%
Fever 1-8%
High LFTs 100%
Acute Viral Hepatitis by Type, United
States, 1982-1993

34%

47%
16% Hepatitis A
Hepatitis B
Hepatitis C
3% Hepatitis
Non-ABC

Source: CDC Sentinel Counties Study on Viral Hepatitis


Estimates of Acute and Chronic Disease
Burden for Viral Hepatitis, United States

HAV HBV HCV HDV


Acute infections
(x 1000)/year* 125-200 140-320 35-180 6-13

Fulminant
deaths/year 100 150 ? 35
Chronic 0 1-1.25 3.5
infections million million 70,000

Chronic liver disease


deaths/year 0 5,000 8-10,000 1,000
* Range based on estimated annual incidence, 1984-1994.
Other Viruses Associated
with Acute Hepatitis
Common in U.S.* Exotic**
• Cytomegalovirus • Yellow fever
• • Argentinean hemorrhagic
Epstein-Barr
fever
• Herpes simplex • Bolivian hemorrhagic fever
• Varicella zoster • Lassa fever
• Measles • Rift Valley fever
• Rubella • Marburg
• Ebola
• Coxsackie

* Each causes less than 1% of acute hepatitis. ** Not


seen in the U.S.
Hepatitis Laboratory Tests
• Liver function tests
 Enzymes produced by liver cells that increase when the liver is
stimulated or inflamed
• Antigen and Antibody tests
• Immunology Terms
 ANTIBODY (Immunoglobulin, Ig, Anti- ) A protein in the blood
generated in response to foreign proteins or polysaccharides.
Sometimes antibodies provide protection from infection.
 IgM : Acute Infection
 IgG : Appears slightly after IgM, may persist for life
 Total Ig = IgM + IgG
– Examples: Anti-HAV, Anti-HBsAg
 ANTIGEN (Ag)
 Substances that stimulate production of an antibody,
Usually protein components of an infectious agent
 Examples: HBsAg, HAV
Hepatitis A
“infectious hepatitis,
epidemic hepatitis”
• Caused by a small RNA enterovirus of the
picornavirus family
• Causes about 25-50% of acute hepatitis in
the U.S. and other developed countries
• High prevalence in west Pacific, Southeast
Asia, Africa and other developing
countries
Hepatitis A Virus
Geographic Distribution of HAV
Infection

Anti-HAV Prevalence
High
Intermediate
Low
Very Low
Hepatitis A: Clinical Aspects
• Onset: usually abrupt
• Duration
 Mild lasting 1-2 weeks
 Severe lasting months
 Rarely fatal
• Children usually asymptomatic
 5-10% jaundiced
 1-2 week duration
• Adults are usually symptomatic
 Jaundiced
 Nausea, vomiting, & fever are common.
Hepatitis A: Clinical Aspects
• Incubation
 15-45 days, average 30 days
• Greatest infectivity
 2 wks before jaundice appears
• Fecal viral shedding
 Greatest during late
incubation and prodrome
 Diminishes rapidly after
jaundice occurs
Hepatitis A: Transmission

• PERSON TO PERSON (Fecal-Oral Routes)


• Poor personal hygiene
• Intimate contact
• Contaminated food or water
• Poor sanitation
• NOT transmitted by sharing utensils,
cigarettes, kissing
Concentration of Hepatitis A
Virus
in Various Body Fluids
Feces

Serum

Saliva

Urine

100 102 104 106 108 1010


Infectious Doses per ml
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
Hepatitis A: Diagnosis
• Acute symptoms
• Elevated LFTs
• Confirmation: IgM anti-HAV, appears early
and remains detectable for 4-6 months
• Total anti-HAV (combination of IgM & IgG)
is detectable early and persists lifelong. It
is not diagnostic of acute Hepatitis A.
• About 1/3 of the US population has anti-
HAV IgG
Sources of Hepatitis A Virus Infection by
Mutually Exclusive Groups, United States, 1983-93
40

30
Percentage of Cases

Personal
20 Drug use contact
Day care center

10
Foreign travel
Outbreak
0
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993
Year
Source: CDC, Viral Hepatitis Surveillance Program
Age-specific Mortality Due to
Hepatitis A
Age group Case-Fatality
(years) (per 1000)

< 3.0
5-14
5 1.6
15-29 1.6
30-49 3.8
>49 17.5
Total 4.1
Source: Viral Hepatitis Surveillance Program, 1983-1989
Hepatitis A: Prevention
• Immunization
• Sanitation & Education
 Safe food, water and ice
 Good personal hygiene
• Standard Immune globulin prophylaxis (IG)
 80 - 90% effective if given within two weeks of
exposure
 Immunization 2 weeks prior eliminates need
 Indications:
 Close personal contacts
 Day Care center outbreaks
 Fellow food handlers
 Restaurant patrons if deficiencies in hygiene or if handler
prepared unheated food
Hepatitis A Vaccine
• Two dose series: Initial plus booster in 6-12
months
 All Active duty and Select Reserves
 95% protection after first dose
 Four week period for antibody development
• HAVRIXR OR VAQTAR, interchangeable
• TWINRIXR (Hepatitis A&B combination vaccine)
 Three dose series
 Interchangeability: dose 1 with TwinrixR - give 2nd
dose of HAVRIXR OR VAQTAR A and 2 & 3rd dose of
HEP B vaccine
 Dose 1 and 2 with TwinrixR – Another dose of
HAVRIXR OR VAQTAR not necessary, give dose 3rd
dose of HEP B vaccine
Hepatitis A and Food Workers

• High potential for outbreaks


• Verify Diagnosis
• Evaluate food related duties, types of food
& preparation methods
 Some food related work low-risk
 Wearing gloves reduces risk
 Fellow food handlers are more at risk than
diners
Hepatitis E Virus
Hepatitis E
• Symptoms similar to hepatitis A: Malaise,
lethargy, anorexia, nausea and vomiting,
followed by dark urine, pale stools, and
jaundice
• Caused by Calicivirus
 Produces symptoms mostly in 15-40 year olds
 Children usually have sub-clinical infection
 Outbreak potential
 15-60 day incubation period, usually 5-6 weeks
• No chronic carriers: self-limited
• Severely affects pregnant women with a the
mortality rate of 10-20%
• Overall mortality rate is 0.5-3%
Hepatitis E
Epidemiologic Features
• Found mostly in less developed
countries
• Most outbreaks associated with
drinking water contaminated with
feces
• Minimal person-to-person
transmission
• U.S. cases usually have history of
travel to HEV-endemic areas
Geographic Distribution of
Hepatitis E

• Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC


Hepatitis
• Mostly located in India, Central & SE Asia, Middle East, Africa, Mexico
Hepatitis E: Diagnosis
• Serologic test available
• History: Evaluate risk factors, exposure
history
• Rule out hepatitis A
• IgG WILL NOT PROTECT
Hepatitis E Prevention and
Control Measures
• Travelers to HEV-Endemic Regions:
 Avoid drinking water (and beverages with
ice) of unknown purity, uncooked shellfish,
and uncooked fruit/vegetables not peeled
or prepared by traveler: “Boil it, cook it,
peel it or forget it”
 IG prepared from donors in Western
countries does not prevent infection
 Unknown efficacy of IG prepared from
donors in endemic areas
• No vaccine
Hepatitis B Virus
Hepatitis B Virus Structure
Hepatitis B
“serum hepatitis, post-
transfusion hepatitis”
• Double shelled DNA hepadnavirus
• Spread by sex, blood, and body fluids
• Severe disease
• Prolonged illness
• Chronic problems in ~ 10%
Geographic Distribution of Chronic
HBV Infection

HBsAg Prevalence
≥ 8% - High
2-7% - Intermediate
<2% - Low
Hepatitis B: Clinical Aspects
• Incubation period: 45-180 days, average
60-90 days
• Onset insidious (subtle and treacherous)
• Symptoms more severe
 Malaise, arthralgias, rash, nausea & vomiting
• Often hospitalized
• One in 200 die from acute disease
• Chronic liver disease kills ten times as
many
Hepatitis B: Transmission
• Virus present in blood, semen, saliva
• Percutaneous
 Contaminated needles (tattoos, piercing, drugs,
etc)
 Blood transfusion
 Perinatal
• Permucosal
 Sexual contact
 Continuous close contact
Concentration of Hepatitis B
Virus
in Various Body Fluids
Low/Not
High Moderate Detectable

blood semen urine


serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk
Hepatitis B: Diagnosis
1. Symptoms
2. Elevated LFTs
3. Confirmed by serology
 IgM anti-HBc (IgM core antibody)
 HBsAg (surface antigen)
 HBsAb/anti-HBs (antibody to surface antigen )
 HBcAb/anti-HBc (antibody to core antigen)
 HBeAg (E antigen)
 HBeAb/anti-HBe (antibody to E antigen)
Hepatitis B Serology

IgM anti-HBc (core antibody)


 Appears early
 Persists for 6 months
HBsAg (surface antigen)
 Detectable 30-60 days after exposure
 May indicate chronic carrier status
HBsAb (antibody to surface antigen)
 Develops after resolved infection
 Indicates long term immunity
Hepatitis B Serology
Anti-HBc/HBcAb (antibody to core antigen)
 Develops in all HBV infections
HBeAg (E antigen)
 Indicates HBV replication
 Correlates with high infectivity
 Present in acute or chronic infection
Anti-HBe (antibody to E antigen)
 Develops in most HBV infections
 Correlates with lower infectivity
Chronic Carrier State

}
90% of infants Risk of chronic
30% of 5 year olds infection is lower
6% of adults after acute illness

Prolonged infection can occur


without signs or symptoms of
acute or chronic illness
Chronic Carrier State
• 10% / yr lose HBeAg - become noninfectious
• 1-2% / yr lose HBsAg - become non-carriers
• 25 % will develop chronic active disease
• 20% will develop cirrhosis
• 5% will develop hepatocellular cancer

• HBV causes 85% of primary liver


cancer worldwide
Chronic Carrier State
2 positive HBsAg tests 6 months apart
or
Positive HBsAg with
Negative anti-HBc IgM
Chronic Carriers
• Active duty Navy or Marine Corps HBV
carriers, who do not have evidence of chronic
persistent or recurrent active hepatitis not
restricted from full duty
• Asymptomatic HBV carriers need annual
evaluation
• HBV carriers with persistent symptoms or
elevated LFTs, need periodic evaluation

• Medical Department personnel who are


chronic carriers are not restricted

Hepatitis B is an STD

• Many prostitutes in the Philippines,


Thailand, and developing countries are
hepatitis B carriers

• Sexual activity is #1 risk factor in U.S.


Rate of Reported Hepatitis B by Age Group
25 United States, 1990

20
,000))

15
Rate (per 100,000

10

0
0-14 15-19 20-29 30-39 40+
Age Group (Years)
Source: CDC Viral Hepatitis Surveillance Program
Hepatitis B Prevention
• Education
 Needles, sex, universal precautions
• Vaccine
 Pre-exposure, active immunity
• HBIG
 Post-exposure
 Passive immunity
Hepatitis B Vaccine
• Recombivax-HER or Engerix-BR
Interchangeable - 3 dose series
Day zero, day 30, 6 months
1/2 dose (0.5 ml) OK for under age 30

• If a dose missed, continue where with next


scheduled dose: DO NOT RESTART
SERIES

• Recombivax-HER, Engerix-BR or TwinrixR: all


are three-dose series
Hepatitis B Vaccine
• Required
 All recruits
 Health care workers
 Hospital Corps & dental techs
 New Medical Department officers
 Patients with STDs
 Public safety workers
 Correctional facility workers
 Compliance with OSHA regulations
Hepatitis B Vaccine
• Pre-vaccination screening
Not recommended

• Post-vaccination testing
Identify non-responders in high risk jobs
Non-responders receive one additional 3-
dose series of hepatitis B vaccine, but not
a third
HBIG (Hepatitis B immune
globulin)
• Post-exposure prophylaxis
 Passive immunity
 High concentration of anti-HBs
• Indications
 Perinatal exposure to HBsAg+ mother
 Percutaneous or permucosal exposure to
HBsAg+ blood
• Sexual exposure to HBsAg+ person
 Also need 3 dose vaccine series
Hepatitis D (Delta) Virus
δ antigen HBsAg

RNA
Hepatitis D
• Virus-like particle
• Defective RNA virus
• Requires HBV co-infection to replicate

• ANYONE WHO IS HBsAg(+) IS AT


RISK
Hepatitis D: Transmission

• Similar to Hepatitis B
• No fecal-oral transmission
• Highest rates in Italy, Venezuela, Africa,
Romania, central Asia and the Middle East
Hepatitis D: Diagnosis
• Serologic test for hepatitis D antibody
Hepatitis D: Complications
• 10-15% develop cirrhosis within two years
• 70% eventually develop cirrhosis
• 2-20% fatality rate
• 25-50% of fulminant liver failure in hepatitis
B actually due to hepatitis D co-infection

• Hepatitis D Prevention:
 Hepatitis B vaccine
Hepatitis C
“transfusion related non-A, non-
B hepatitis”
• Caused by RNA flavivirus
• Accounts for 16% acute hepatitis in U.S.
• Transmission similar to hepatitis B
 Blood, sex, body fluids
• Usually asymptomatic or mild disease
• Chronic infection very common
• 20% of community acquired hepatitis
• 90% post-transfusion hepatitis
• Blood banks started screening in 1990: <1% risk
now
Hepatitis C Diagnosis
1. Symptoms
2. Elevated LFTs
3. Rule out other causes of hepatitis
4. Confirmed by serology
 Serologic test detects HCV antibody
 Positive in chronic cases
 May not be positive in acute phase
 Rule out other causes of acute hepatitis

Submit MER on acute cases only


Hepatitis C: Typical
Serologic Course
HCV
antibody
Symptom
s Person is
sick, but test
for Hep C is
Titer

negative

ALT
(liver
functio
n test)
Norma
l
0 1 2 3 4 5 6 1 2 3 4
Month Years
s Time after
Exposure
Features of Hepatitis C

Incubation period Average 6-7 weeks


Range 2-26 weeks
Acute illness (jaundice) Mild (<20%)
Case fatality rate Low
Chronic infection 75%-85%
Chronic hepatitis 70% (most asx)
Cirrhosis 10%-20%
Chronic Liver Disease Mortality 1%-5%
 Chronic disease often improves after 2-3 years
 Increases risk of liver cancer
Hepatitis C Virus Epidemiology, U.S.
• New infections (cases)/yr
 1985-89: 242,000 (42,000)
 1998: 40,000 (6,500)

• Deaths from acute liver failure: Rare


• Persons ever infected (1.8%): 3.9 million
• Persons with chronic infection: 2.7 million
 Percent of chronic liver disease - HCV-related
40% - 60%
• Deaths from chronic disease/year 8,000-10,000
Transmission of HCV
• Percutaneous
 Injecting drug use
 Clotting factors before viral inactivation
 Transfusion, transplant from infected donor
 Therapeutic (contaminated equipment, unsafe
injection practices)
 Occupational (needle stick)
• Permucosal
 Perinatal
 Sexual
Sources of Infection for
Persons with Hepatitis C
Injecting drug use 60%
Sexual 15%

Transfusion 10%
(before screening)

Other* 5%
Unknown 10%

*Nosocomial; Health-care work; Perinatal


Source: Centers for Disease Control and Prevention
Post-transfusion Hepatitis C
• Responsible for 90% of post-transfusion
hepatitis in U.S. prior to 1990
• 1960s: 25%
• 1970s: 7-12% post-transfusion risk
• 1980s: 1-4% risk (ALT screening 1986)
• 1990s: < 1% risk in (screening started
1990)
• Most cases now community acquired
• Problem among Viet Nam veterans
Routine HCV Testing Not
Recommended
(Unless Risk Factor Identified)
• Ever injected illegal drugs
• Received clotting factors made before 1987
• Received blood/organs before July 1992
• Ever on chronic hemodialysis
• Evidence of liver disease
• Children born to HCV-positive women

• Healthcare, emergency, public safety workers after


needle stick/mucosal exposures to HCV-positive
blood
Medical Evaluation and
Management for Chronic HCV
• Assess for biochemical evidence of chronic
liver disease
• Assess for severity of disease and possible
treatment
• Vaccinate against hepatitis A and B
• Counsel to reduce further harm to liver and
prevent transmission to others
• Refer to support group
Hepatitis C Prevention
• Screening of blood, organ, tissue donors
• Blood and body fluid precautions
• Education
 High-risk behavior modification
 Same risk factors as hepatitis B
 Blood > sex > Perinatal

• No vaccine
• IG does not protect
Viral Hepatitis - Review
Type of Hepatitis
A
A B
B C
C D
D E
E
Source of feces blood/ blood/ blood/ feces
blood-derived blood-derived blood-derived
virus body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral


transmission permucosal permucosal permucosal

Chronic no yes yes yes no


infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe


exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
Review
DIAGNOSIS TREATMENT
A IgM ANTI-HAV IG WITHIN 2 WEEKS OF EXPOSURE

B HBsAg – INFECTIOUS
HBeAg – DEGREE OF INFECTIVITY
VACCINATION AND ADMINISTRATION OF
HBIG WITHIN 24 HOURS OF NEEDLE STICK, 14
DAYS AFTER SEXUAL CONTACT
IgM anti-HBc – ACUTE INFECTION
CHRONIC HEPATITIS TREATED WITH ALPHA
Anti-HBs – VACCINATED OR CLEARED
INTERFERON AND LAMIVUDINE
INFECTION

C ANTI-HCV Peginterferon alfa-2b, Peginterferon alfa-2a,


Ribavirin

D ANTI-HDV SAME AS HEPATITIS B

E ANTI-HEV SEROLOGY DEVELOPED NONE


BUT NOT COMMERCIALLY
AVAILABLE IN U.S.
Review: Disposition of
Carries/Chronic Infections
• Hepatitis A/E
 Enteric precautions for first 2 weeks but no more
than one week after jaundice
• Hepatitis B
 No restrictions on chronic carriers including
medical personnel
 HBeAg positive Medical personnel need expert
review before performing invasive procedures
• Hepatitis C
 No restrictions on chronic carriers
Case #1
• 22 y/o Food handler
 Positive for HBsAg
 Negative for Anti-HBs
 Negative for HAV antibody
 Normal LFTs
 No Symptoms
• Is galley work permitted?
Case #2
• 22 y/o HM3
 Positive for HBsAg
 Negative for anti-HBs
 Negative for anti-HAV
 Normal LFTs
 No Symptoms
• Can the HM3 work in the blood bank?
Case #3
• CHT worker
 Exposed to human sewage while repairing
pipes

• Is hepatitis B vaccine needed?


• Is immune globulin needed?
• Does spouse need shots?
Case #4
• 24 y/o Mess specialist
 Chronic fatigue for past 4 wks
 Abdominal pain 3-4 weeks ago -- resolved
 LFTs not elevated
 Positive for anti-HAV
• DOES EVERYONE IN THE CREW NEED
IgG?
Case #5
• 30 y/o Sailor
 Abdominal pain for 2 wks
 Now has yellow eyes
 LFTs significantly elevated
 Positive anti-HBs
 Negative HBsAg
 Negative anti-HAV
• What is the diagnosis?
Case #5
• Additional info:
 Negative for HEP C antibody
 No history of unsafe sex in past 6 months
 No history of tattoos or other needle use
 No history of alcohol abuse
 PPD converter
• Taking INH for past 2 months
Questions?

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