Title: Diagnosing Viral Hepatitis An Alphabet Soup
1Diagnosing Viral Hepatitis -An Alphabet Soup
- Eugene G. Martin, Ph.D.Professor of Pathology
Laboratory Medicine - UMDNJ Robert Wood Johnson Medical School
Based upon slides available from the CDC
2Whats so Important about Viral Hepatitis?
- GLOBAL PROBLEM - Estimated 350,000,000 chronic
carriers (HBV HBC) worldwide - COMMON IN THE US 1990 - 4th most communicable
disease - DEADLY - 1 mortality rate
- SEQUELAE - Primary Hepatic Carcinoma
- PREVENTABLE Types A B
3Viral Hepatitis Lecture Goals
- Recognize
- Clinical lab presentation of viral hepatitis
- The importance of epidemiology, geography,
presentation and clinical history in assessing a
case of hepatitis - The major forms of viral hepatitis
- The significance of acute and chronic forms of
viral hepatitis - How to differentiate viral hepatitis from other
forms of hepatitis
4Case Study Mr. William Johnson
- 31 Year Old Electrician complaining of
- General Malaise
- Rash
- Itching
- Right Upper Quadrant Pain
- No Appetite
- Weight Loss
- He has no family members reporting exposure
- He was born in Zaire, but immigrated to the US at
age 10
Lets begin with a series of questions First,
what additional information should you be
interested in?
5Physical Examination
- Well-developed young man
- Not in acute distress
- Positive physical findings include
- Icterus - yellowing of the skin and the whites of
the eyes - Firm, enlarged and tender liver (tender
hepatomegaly)
- Now
- How typical is jaundice in a case of hepatitis?
- What significance can one attach to the tender
hepatomegaly?
6Viral Hepatitis Symptomatology
Viral hepatitis is USUALLY asymptomatic and when
symptomatic USUALLY the symptoms are non-specific.
7Differential Diagnosis Hepatitis
- Alcoholic Hepatitis
- Malignancy
- Biliary tract disease
- Viral hepatitis
- Toxic injury to the liver
- Ischemic injury to the liver
- Systemic viruses with secondary effects on the
liver e.g. CMV, Epstein Barr - Immunologic disorders - Autoimmune hepatitis
- Wilsons disease
How do you begin to sort your way through this ?
8Medications
- He reports that his doctor recently prescribed
Furadantin (nitrofurantoin) for treatment of an
e.coli related urinary tract infection.
Are medications a serious consideration when
one is considering the diagnosis of hepatitis?
9Other Questions to Think About?
- Can you rule out any type of hepatitis based upon
patient complaints? - How important is his occupation?
- How significant is his lack of exposure to
individuals with jaundice or a history of drug
abuse? - Primary Question Does Mr. Johnson Have
Hepatitis. If so, what is the likelihood he has
viral hepatitis?
10LAB TIP
- All patients with jaundice do not necessarily
have hepatitis and all cases of hepatitis are not
necessarily due to viruses.
11Bilirubin Metabolism
12Classification of Jaundice
- Percentage of Conjugated to Total Bilirubin
-
- Increased production eg. Hemolysis
- Impaired uptake by the liver eg. Portacaval
shunt - Defective conjugation eg. ABO incompatibility
- 20 ?
- Commonly seen in viral or alcoholic hepatitis
- 50 - Conjugated Hyperbilirubinemia
- Cholestasis
- Intrahepatic obstruction
- Extrahepatic obstruction
13Classic Pattern of Viral Hepatitis
- MARKEDLY INCREASED SGOT (AST) and SGPT (ALT)
- (10 to 100 X normal) - indicates severe
hepatocyte damage - AST Originates (liver, heart, Skeletal Muscle
and RBCs. Non-specificity issue. - ALT Found primarily in liver. Most elevations
reflect liver disease. - Patterns
- Both enzymes are increased to the same degree
VIRAL HEPATITIS - (ASTALT, 2X) ALCOHOLIC HEPATITIS
- A fluctuating temporal course frequently -
HEPATITIS C - Increased (GGTP) ?-glutamyl transpeptidase.
Moderate elevations. - Slightly increased Alkaline Phosphatase (1-3 X
normal) indicates mild cholestasis - Slightly increased Lactate Dehydrogenase (LDH)
(1-3 X normal) - Normal sedimentation rate and complete blood
count (CBC) - Severe liver-cell necrosis MAY RESULT in
- Decreased serum albumin,
- Decreased serum cholesterol,
- Prolonged prothrombin time, and
- Serum bilirubin 25 mg/dl
14Bilirubinuria
- Bilirubin levels in urine
- Hemoglobin breakdown results in bilirubin
production (unconjugated). - In the liver, bilirubin is conjugated to an acid
to make conjugated bilirubin. - Conjugated bilirubin is water soluble and can be
excreted in urine. - Abnormal bilirubin values
- Pre-hepatic (unconjugated DOES NOT appear in
urine) - anemia's
- excessive breakdown of RBC
- Hepatic
- hepatitis
- cirrhosis
- obstruction of biliary duct
- toxic liver damage
- Post-hepatic
- biliary tree obstruction
15Use of Urine Chemistry
?Gut delivery of bilirubin ? less enterohepatic
return of bilinogen
OR ? hepatocyte capacity to
take up and re-excrete bilinogen
16Staging Acute Hepatitis
- Anicteric phase (I)
- ? urine bilirubin
- ? urine urobilinogen
- ??? SGOT (AST), ??? SGPT (ALT) - level reflects
the severity of liver damage usually precedes
jaundice - ? (WBC) count with relative lymphocytosis some
atypical lymphocytes common - Normal sedimentation rate
17Staging Acute Hepatitis
- Icteric Phase (II)
- Majority of patients are NOT Icteric!!
- Increased serum bilirubin (8 mg/dl - 15 mg/d) -
rises in 10-14 days, then declines in 2-4 weeks. - Slightly increased serum alkaline phosphatase
reflects mild cholestasis. - Decreased urine urobilinogen absent urobilinogen
at the peak of disease. - Fall in SGOT (AST) and SGPT (ALT) indicates
diminishing liver-cell necrosis. - Increased sedimentation rate
- Increased serum iron reflects release from
damaged liver cells.
18Staging Acute Hepatitis
- Recovery phase (III)
- Bilirubinuria precedes disappearance of
bilirubinemia - Urine urobilinogen reappears.
- Normal sedimentation rate
- Slight decrease in serum albumin
- Mild elevation in ? globulin
19Mr. Johnsons CHEMISTRY
Urine
Blood
20Mr. Johnson - Summary
- Albumin Low end Nrml.
- LDH - ? 2x
- Alk. Phos. - ? 2x
- GGTP (862) - ? 18x
- ALT (4200) - ??? 70x
- AST (3488) - ??? 63x
- AST/ALT .83
- Mixed Hyperbilirubinemia 5.0 Conjugated/12.4
Total ? 40 Conjugated -
- Urobilinogen - Absent
- Urine Bilirubin -
Conclusion Consistent with Icteric HEPATITIS,
possibly one close to resolving since
bilirubinuria OFTEN precedes the disappearance of
bilirubinemia
So now we need to know what is causing Mr.
Johnsons hepatitis.
21Screening to a serologic diagnosis
- Biochemical alterations tell you that an
individual has hepatitis - The presence or absence of a viral antigen or
antibody indicates the type and stage of a viral
disease - Ultimately, some diagnoses are based upon
exclusion!!
22Causes of Hepatitis
- Non-Viral
- Toxic Injury
- Drug abuse ETOH
- Anesthetics Halothane
- Antibiotics e.g. Nitrofurantoin
- Acetaminophen Overdose
- Ischemic injury
- Metabolic Disorders
- Wilsons disease
- Viral
- Primary
- Hepatitis A ? G, Sen-V
- Secondary
- CMV
- Herpes Simplex
- Epstein Barr Inf. Mono.
- Varicella Zoster
- Parvo B19
23Rule Out Toxic Hepatitis
- In toxic hepatitis, AST 3500 U/L
- If Yes ? Consider toxic or ischemic hepatitis
- If No ? precede to r/o viral hepatitis,
particularly if there is no history of drug
exposure - Mr. Johnson AST is 3488 which is close. In
addition, he was treated with a drug that could
conceivably cause a toxic hepatitis. - Proceed to screen for a viral hepatitis we may
yet conclude that he has a pharmacologic hepatitis
24Drugs and Hepatitis
- Chronic Active Hepatitis
- Allopurinol (Lopurin) - Anti-gout medication
- Dantrolene sodium (Dantrium) Muscle relaxant
- Halothane Anesthetic
- Isonazide (INH) - TB therapy
- Methyldopa (Aldomet) Antihypertensive
- Methotrexate Chemotherapeutic
- Nitrofurantoin (Furadantin) Urinary Tract
Infections - Cholestatic Hepatitis
- Chlordiazepoxide (Librium) Anti-anxiety
- Imipramine (Tofranil) Anti-depressant
- Nitrofurantoin (Furadantin) Urinary Tract
Infections
25The single biggest error
- When a patient presents with signs and symptoms
of an acute hepatitis - More than half the time, the cause is an
undiagnosed, non-viral cause of hepatitis - a
reaction to a chemical or pharmacologic substance
the most common
26Screening Results Hepatitis B
Acute or ChronicHep. B
27 Viral Hepatitis - Overview
Type of Hepatitis
A
B
C
D
E
Source of
blood/
blood/
blood/
feces
feces
virus
blood-derived
blood-derived
blood-derived
body fluids
body fluids
body fluids
Route of
percutaneous
percutaneous
percutaneous
fecal-oral
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
28Estimates of Acute and Chronic DiseaseBurden 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.
29Acute 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
30HEPATITIS A VIRUS
31HEPATITIS A VIRUS
- RNA Picornavirus
- Single serotype worldwide
- Acute disease and asymptomatic infection ONLY!
- No chronic infection
- Protective antibodies develop in response to
infection - confers lifelong immunity
32- HEPATITIS A - CLINICAL FEATURES
Jaundice by age group 6-14 yrs
40-50
14 yrs 70-80 Rare complications
Fulminant hepatitis
Cholestatic hepatitis
Relapsing
hepatitis Incubation period Average 30
days
Range 15-50 days Chronic sequelae None
33Acute Type A Hepatitis
University Diagnostic Laboratories 1998
34REPORTED CASES OF HEPATITIS A, UNITED STATES,
1952-2002
Frequency declining since 1996
Source NNDSS, CDC
35Hepatitis A Incidence, United States, 1980-2002
1995 vaccine licensure
1996 ACIP recommendations
1999 ACIP recommendations
2002 rate 2.9
2002 rate provisional
36PERSONS AT INCREASED RISK OF HEP A INFECTION
- Men who have sex with men (MSM) 10
- Illegal drug users 6
- International travelers 5
- Daycare Child or Employee 6
- Unknown 46
37Mr. Johnson A serology
Interpretation
Mr. Johnson has been exposed to the Hepatitis A
virus at some point in the past, but has already
recovered from this disease. Hepatitis A is not
the cause of his current illness.
38Hepatitis B Virus
39Hepatitis B Overview
- Serious Causes death from liver disease in up to
25 of those infected at birth. - Cancer related Liver cancer especially prevalent
in areas of world where hepatitis B is common. - Disease of refugees New arrival Southeast Asian
refugees (1 out of 2 is immune, 1 out of 7 is a
carrier, 1 out of 3 is susceptible). - Preventable Safe, effective, and affordable
vaccination is available.
40Geographic Distribution of Chronic HBV Infection
HBsAg Prevalence
³8 - High
2-7 - Intermediate
41Global Patterns of Chronic HBV Infection
- High (8) 45 of global population
- lifetime risk of infection 60
- early childhood infections common
- Intermediate (2-7) 43 of global population
- lifetime risk of infection 20-60
- infections occur in all age groups
- Low (
- lifetime risk of infection
- most infections occur in adult risk groups
42Risk Factors Associated with Reported Hepatitis
B, 1990-2000, United States
Source NNDSS/VHSP
Other Surgery, dental surgery, acupuncture,
tattoo, other percutaneous injury
43Hepatitis B by Year, United States, 1966 - 2000
Infant immunization recommended
HBsAg screening of pregnant women recommended
Vaccine licensed
OSHA rule enacted
Adolescent Immunization recommended
Decline among MSM HCWs
Decline among injecting drug users
Source NNDSS
44Transmission - HBV
- Percutaneous transmission
- Sharing of injection drug use equipment, needle
stick injury, ear-piercing, body piercing,
tattooing, inadequate sterilization of medical
equipment, scarification - Household transmission
- Less risk but significant can occur in settings
such as shared toothbrushes, razors, combs,
washcloths
- Concentration of HBV in body fluids
- High Blood, serum, wound exudates
- Medium saliva, semen, and vaginal secretions
- Low/not detectable urine, feces, sweat, tears,
breastmilk - Perinatal Transplacental transmission, rare
(2-5) - Sexual transmission Unprotected sex
45Hepatitis B Clinical Features
- Incubation period ranges from 45-180 days
- Average is 60-90 days
- Onset is insidious
- Clinical illness (jaundice) olds 30-50 for 5 yrs
- Acute case-fatality rate 0.5-1
- Chronic infection 5
yrs old, 2-6 - Premature mortality fromchronic liver
disease 15-25
46Acute HBV Infection with Recovery
Typical Serologic Course
anti-HBe
HBeAg
Symptoms
Total anti-HBc
Titer
anti-HBs
IgM anti-HBc
HBsAg
0
4
8
12
16
20
24
28
32
36
52
100
Weeks after Exposure
47Acute vs. Chronic Infection
- A chronic infection may result from an inadequate
immunologic response to the initial infection by
the virus
48Outcome of Hepatitis B Virus Infection by Age at
Infection
100
100
Pool of carriers in U.S. is 1-1.25 million
persons.
80
80
Chronic Infection
60
60
Symptomatic Infection ()
Chronic Infection ()
40
40
20
20
Symptomatic Infection
0
0
Birth
1-6 months
7-12 months
1-4 years
Older Children and Adults
Age at Infection
49The presence of HBsAg indicates an ACUTE or
CHRONIC hepatitis B infection HBsAg DOES NOT
correlate with infectivity HBeAg DOES CORRELATE
with infectivity The presence of HBeAg means the
patient is infectious!!
Progression to Chronic HBV Infection
Acute (6 months)
Chronic (Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
- HBsAg indicates an ACUTE or CHRONIC hepatitis B
infection - HBsAg DOES NOT correlate with infectivity
- HBeAg DOES CORRELATE with infectivity
- HBeAg means the patient is infectious!!
CHRONIC VS ACUTE ACUTE hepatitis B IgM
antibodies to Hepatitis B core antigen (HBc
IgM) CHRONIC hepatitis B infection will NOT have
HBc IgM Both will be HBsAg
IgM anti-HBc
Years
0
4
8
16
20
24
28
36
12
32
52
Weeks after Exposure
50Mr. Johnson Serology
Interpretation
Chronic type B Hepatitis - only moderately
infection (HBeAg Negative). He has begun
seroconversion, but it is incomplete. Worries
Doe he have any risk factors which would make
Delta hepatitis a concern? If so, screen for Hep
D.
51- The clinician may be EASILY misled into
thinking that the acute illness represents
infection with hepatitis B virus rather than
other agents whenever the HBsAg carrier state has
not been previously recognized. - Robert Perillo, M.D.
- Gastroenterology Vol. 85, No. 1
52The Consequence
- This Khmer woman died of hepatoma, four months
after arriving in a refugee camp in Thailand.
53HBV leads to liver cancer
- Hepatocellular Carcinoma HCC
- Epidemiologic correlation in many populations
- Risk for HCC is 12-300 times greater in HBsAg
persons - HBV DNA is incorporated into DNA of hepatoma
cells - Incidence
- Peak incidence is in 40-60 yr olds
- In Taiwan, 1 cause of death for men 40 yrs
- 0.25-1 million deaths/year in the world
- Over 1500 persons die/yr in the U.S. from HCC
- HCC is 3-4x more common in HBsAg men than women
- 5-year survival rate for HCC is 2.3.
- Hepatitis B vaccine is the first vaccine to
prevent cancer.
54Hepatitis B Prevention
- Hepatitis B Immune Globulin (HBIG)
- Provides temporary passive protection
- Indicated in certain postexposure settings
- Hepatitis B Vaccine
- Vaccinate all children 0-18 years of age
- Birth dose preferred
- Vaccinate all high-risk individuals
- Test before vaccination
- Hepatitis B Prenatal Testing
- Test EVERY pregnant woman during every pregnancy
55Hepatitis C Virus Infection
Incubation period Average 6-7 weeks Range 2-26
weeks Acute illness (jaundice) Mild (
fatality rate Low Chronic infection 60-85 Chroni
c hepatitis (usually asymptomatic) 10-70
Cirrhosis
56Serologic Pattern Acute HCV Infection with
Recovery
anti-HCV
Symptoms /-
HCV RNA
Titer
ALT
Normal
6
1
2
3
4
0
1
2
3
4
5
Years
Months
Time after Exposure
57Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
anti-HCV
Symptoms /-
HCV RNA
- If youre only looking at anti-HCV you will be
UNABLE to differentiate Acute HCV with recovery
FROM Chronic HCV without recovery!!!
Titer
ALT
Normal
6
1
2
3
4
0
1
2
3
4
5
Years
Months
Time after Exposure
58Hepatitis C Virus Infection, United States
- New infections per year 1985-89 242,000
- 2001 25,000
- Deaths from acute liver failure Rare
- Persons ever infected (1.8) 3.9 million
(3.1-4.8) - Persons with chronic infection 2.7 million
(2.4-3.0) - HCV-related chronic liver disease 40 - 60
- Deaths from chronic disease/year 8,000-10,000
- 95 Confidence Interval
59Sources of Infection for Persons With Hepatitis C
Injecting drug use 60
Sexual 15
Transfusion 10 (before screening)
Occupational 4
Other 1
Unknown 10
Iatrogenic perinatal
Source Centers for Disease Control and Prevention
60Reported Cases of Acute Hepatitis C by Selected
Risk Factors, United States, 1982-2001
Injecting Drug Used
Sexual
Health related work
Transfusion
1982-1990 based on non- A, non-B hepatitis
61Chronic Hepatitis C Factors Promoting
Progression or Severity
- Increased alcohol intake
- Age 40 years at time of infection
- HIV co-infection
- Other
- Male gender
- Chronic HBV co-infection
62Injecting Drug Use and HCV Transmission
- Highly efficient
- Contamination of drug paraphernalia, not just
needles and syringes - Rapidly acquired after initiation
- 30 prevalence after 3 years
- 50 after 5 years
- Four times more common than HIV
63Occupational Transmission of HCV
- Inefficient by occupational exposures
- Average incidence 1.8 following needle stick
from HCV-positive source - Associated with hollow-bore needles
- Case reports of transmission from blood splash to
eye one from exposure to non-intact skin - Prevalence 1-2 among health care workers
- Lower than adults in the general population
- 10 times lower than for HBV infection
64Perinatal Transmission of HCV
- Transmission only from women HCV-RNA positive at
delivery - Average rate of infection 6
- Higher (17) if woman co-infected with HIV
- Role of viral titer unclear
- No association with
- Delivery method
- Breastfeeding
- Infected infants do well
- Severe hepatitis is rare
65Sexual Transmission of HCV
- Occurs, but efficiency is low
- Rare between long-term steady partners
- Factors that facilitate transmission between
partners unknown (e.g., viral titer) - Accounts for 15-20 of acute and chronic
infections in the United States - Sex is a common behavior
- Large chronic reservoir provides multiple
opportunities for exposure to potentially
infectious partners
66Post-exposure Management for HCV
- Immunoglobulin, antivirals are not recommended
for prophylaxis - Follow-up after needlesticks, sharps, or mucosal
exposures to HCV-positive blood - Test source for anti-HCV
- Test worker if source anti-HCV positive
- Anti-HCV and ALT at baseline and 4-6 months later
- For earlier diagnosis, HCV RNA at 4-6 weeks
- Confirm all anti-HCV results with RIBA
- Refer infected worker to specialist for medical
evaluation and management
67Mr. Johnson HCV serology
Interpretation
Mr. Johnson has no evidence of exposure to
hepatitis C Hepatitis C is not likely to be the
cause of his current illness.
68HCV Infection Testing Algorithmfor Diagnosis of
Asymptomatic Persons
STOP
Negative
Screening Test for Anti-HCV
Positive
OR
Negative
NAT for HCV RNA
RIBA for Anti-HCV
Negative
Positive
Positive
Indeterminate
STOP
Additional Laboratory Evaluation (e.g. PCR, ALT)
Medical Evaluation
Negative PCR, Normal ALT
Positive PCR, Abnormal ALT
Source MMWR 199847 (No. RR 19)
69Medical Evaluation and Managementfor Chronic HCV
Infection
- Assess for biochemical evidence of Chronic Liver
Disease - Assess for severity of disease and possible
treatment, according to current practice
guidelines - 40-50 sustained response to antiviral
combination therapy (peg interferon, ribavirin) - Vaccinate against hepatitis A
- Counsel to reduce further harm to liver
- Limit or abstain from alcohol
70Hepatitis D (Delta) Virus
d antigen
HBsAg
RNA
71(No Transcript)
72Geographic Distribution Hepatitis Delta
Taiwan
Pacific Islands
HDV Prevalence
High
Intermediate
Low
Very Low
No Data
73Hepatitis Delta
- CLINICAL FEATURES
- Coinfection
- severe acute disease
- low risk of chronic infection
- Superinfection
- usually develops chronic HDV infection
- high risk of severe chronic liver disease
- MODES OF TRANSMISSION
- Percutanous exposures
- injecting drug use
- Permucosal exposures
- sex contact
74HBV HDV Co-infection Tupical Serologic Course
Symptoms
ALT Elevated
anti-HBs
Titer
IgM anti-HDV
HDV RNA
HBsAg
Total anti-HDV
Time After Exposure
75HBV - HDV Superinfection
Typical Serologic Course
Jaundice
Symptoms
Total anti-HDV
ALT
Titer
HDV RNA
HBsAg
IgM anti-HDV
Time After Exposure
76Mr. Johnson Delta serology
Interpretation
Mr. Johnson has evidence of chronic Hepatitis B
AND evidence of a super-infection with the Delta
Hepatitis virus. Upon further discussion, Mr.
Johnson admits that he is an intravenous drug
user. He has a high risk of serious, long term
liver disease. If you didnt look you wouldnt
know!
77Hepatitis E Virus
78Clinical Features Hepatitis E
- Most outbreaks are associated with fecally
contaminated drinking water - Minimal person-to-person transmission
- U.S. cases usually have history of travel to
HEV-endemic areas
- Incubation Period 40 Days (range 15-60 Days)
- Case Fatality Rate 1- 3
- EXCEPT PREGNANT WOMEN 15-25 !!
- Illness severity Increases with age!
- No Chronicity
79Hepatitis E Infection
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
Time After Exposure - weeks
80Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in 25 of
Sporadic Non-ABC Hepatitis
81Hepatitis
82Prevention and Control Measures
- Avoid drinking water (and beverages with ice) 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 - Unknown efficacy of IG prepared from donors in
endemic areas - Vaccine?
83RISK FACTORS - HEPATITIS A, 1990-2000, UNITED
STATES
Source NNDSS/VHSP
84 Hepatitis D - Prevention
- HBV-HDV Coinfection
- Pre or post-exposure prophylaxis to prevent HBV
infection - HBV-HDV Superinfection
- Education to reduce risk behaviors among persons
with chronic HBV infection