Viral Hepatitis (Virus Hepatitis)

Hepatitis Viral : A, B, C,
D, E
Dr. Hugo Abel Pinto Ramrez

Especialidad en Medicina familiar y
Especialista en Urgencias, Maestra
en Farmacologa (2011)
1
Viral Hepatitis - Historical

Perspective
Infectious
Viral
hepatitis
Serum
Enterically
transmitted
Parenterally
transmitted
NANB
B D
F, G,
? other
Viral Hepatitis
A
Source of
virus
Route of
transmission
Chronic
infection
Prevention
feces
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
fecal-oral
percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
no
pre/postexposure
immunization
yes
yes
pre/postexposure
immunization
blood donor
screening;
risk behavior
modification
yes
pre/postexposure
immunization;
risk behavior
modification
no
ensure safe
drinking
water
Viral Hepatitis 1982-1993
34%
42%
3%
16%
Source: CDC Sentinel

Counties Study on Viral Hepatitis
Estimates of Acute and Chronic Disease

Burden for Viral Hepatitis, United States
Acute infections
(x 1000)/year*
Fulminant
deaths/year
Chronic
infections
HAV
HBV
HCV
HDV
125-200
140-320
35-180
6-13
100
150
35
1-1.25
million
3.5
million
70,000
5,000
8-10,000
1,000
Chronic liver disease
deaths/year
* Source: CDC -Range based on estimated annual incidence, 1984-1994.

Hepatitis A Virus (HAV)
HAV Transmission
Close personal contact
household contact, sex contact, child

day care centers
Contaminated food, water
infected food handlers, raw shellfish
Blood exposure (rare)
injecting drug use, transfusion
Hepatitis A - Clinical Features

Incubation period:
Mean 30 days
Range 15-50 days
Jaundice by
age group:
<6 yrs,
6-14 yrs
>14 yrs
Complications:
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
Chronic sequelae:
None
<10%
40%-50%
70%-80%
HAV - Typical Serologic Course

Symptoms
Total anti-HAV
Titer
ALT
Fecal
HAV
IgM anti-HAV
Dr. Hugo
Abel Pinto
Ramrez
Months
after
Exposure
1
2
2
4
Serological Testing
HAV total Ab appears 4-5 weeks after

infection and remains positive for the
patients lifetime
HAV IgM is present at the onset of symptoms
and usually disappears after 4-6 months.
The presence of total Ig without IgM indicates
past infection
10
HAV Immune Globulin
IM administration within 2 weeks after HAV

exposure is >85% effective in preventing
symptomatic infection.
HAV IG and vaccine does not alter
seroconversion rates but lower serum
antibody concentrations may be obtained.
HAV IG administration will alter normal
serological profiles for 6-12 months.
11
Hepatitis A Virus
Highest virus concentrations occur in stool

1-2 weeks before the onset of illness.
Transmission is most likely at this time.
Minimal virus present in stool 1 week after
the onset of jaundice.
In neonates and young children, virus may
be detected in stool for months.
12
Virus Detection
Culture is worthless except for research

purposes.
PCR detection is available but cannot
distinguish recent from past infection.
Nucleic acid sequencing is useful for
tracking HAV outbreaks.
13
Mitch, a 43 year old salesman, has

increasing fatigue x 5 days and
vague abdominal pain x 3 days. He
ate at the Stage Deli (site of a recent
HAV outbreak) 10 days previously.
His liver enzymes are within normal
limits.
HAV AB (total)
HAV IgM
Positive
Negative
Does he have HAV infection?
CDC Recommendations:
Testing and Vaccination
15
PRE-VACCINATION TESTING
Considerations:
Cost of vaccine
Cost of serologic testing (including visit)
Prevalence of infection
Impact on compliance with vaccination
Likely to be cost-effective for:
Persons born in high endemic areas

Older U.S. born adults
Older adolescents and young adults in certain groups
(e.g., Native Americans, Alaska Natives, Hispanics, IDUs)
16
POST-VACCINATION TESTING
Not recommended:
High response rate among vaccinees
Commercially available assay not sensitive

enough to detect lower (protective) levels of
vaccine-induced antibody
17
ACIP
RECOMMENDATIONS:
PERSONS AT INCREASED
RISK OF INFECTION
Men who have sex with men
Illegal drug users
International travelers
Persons who have clotting factor disorders
Persons with chronic liver disease

18
STD Treatment Guidelines

MMWR August 4, 2006 55
(RR11)
Vaccination
against hepatitis is the most

effective means of preventing sexual
transmission
of hepatitis A and B.
19
Indications for IG for Post-Exposure

Prophylaxis
Household and sexual contacts if exposure is within

2 weeks.
Childcare center employees and children when HAV

infection is identified in a child or employee.
Close school contacts if transmission within the

school has occurred.
20
Indications for IG for Post-Exposure

Prophylaxis
Person exposed to contaminated

food/water.
Persons who ate food prepared by HAV+ food

handler.
21
Hepatitis A Surveillance
and Response
22
Hepatitis A Surveillance & Response
Urgently reportable condition in S.C. Acute

HAV infection must be reported by phone to
health department within 24 hours.
Investigation of a case of hepatitis A must be

initiated by health department and district
epi staff within 24 hours of notification.
All cases must be reported to CDC.
23
Important Information
Date of onset of symptoms

Occupation
If child, whether child attends childcare
Names of household/sexual contacts
Restaurants attended 2-6 weeks prior to
symptoms
24
Management of Outbreaks
Initiate enteric precautions during the first 2

weeks of illness.
Refer symptomatic contacts to physician.
Exclude adults/children with HAV infection from

work/school until 1 week after onset of illness or
until IG PEP has been initiated.
Provide education re transmission, prevention, and

hygiene.
25
Hepatitis E Virus
26
Amita, a 23 year old student,

returned from India one month
ago where she spent 3 weeks
visiting her future in-laws. She
presented with fever, jaundice,
malaise, and significantly
elevated ALT levels. Antibody
tests were positive for HEV IgG
and IgM.
How does she prevent the spread of HEV to family and friends?
Hepatitis E Virus
Most outbreaks associated with

fecally contaminated drinking water
Minimal person-to-person transmission
U.S. cases usually have history of travel
to HEV-endemic areas
28
Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC

Hepatitis
Source: CDC
Hepatitis E Virus
Incubation period:
Average 40 days
Range 15-60 days
Case-fatality rate:
1%-3% overall
15%-25% in pregnancy
Illness severity:
Increased with age
Chronic sequelae:
None identified
30
Typical Serological Course - HEV

Symptoms
anti-HEV
ALT
Titer
IgM anti-HEV
Virus in stool
Dr. Hugoafter
Abel Pinto Ramrez
Weeks
1
0
1
1
1
2
1
3
31
Serological Profile
HEV IgM is usually present at the onset of

symptoms and persists for 3-4 months
HEV IgG is also present at the onset of
symptoms and persists for the patients
lifetime
32
CDC Criteria for Testing Acute Phase

Sera
Discrete onset of illness with jaundice or

Serum ALT >2.5 times the upper limit of normal
and
HAV IgM negative
HBV Core IgM negative
HCV Ab negative
33
HEV Detection
Culture is worthless
PCR can detect HEV RNA in serum and
stool specimens from 2 weeks before, to 2
weeks after, the onset of symptoms
Nucleic acid sequencing is useful for tracking
HEV outbreaks
34
Steps to prevent HEV

transmission in home setting?
1. Safe sex practices
2. Do not share eating/grooming
utensils.
3. Respiratory precautions
4. Vigorous hand washing
5. No special requirements needed
35
Hepatitis C Virus
36
Claudia is a 46 year old

divorced female.
She has a new man in her life.
She has had unprotected sex
for the past 3 weeks.
She just learned that her new
friend is HCV positive.
What is her HCV risk?
What is Claudias Risk of

Infection?
1.
2.
High risk HCV can be transmitted

sexually.
Low risk The efficiency of sexual
transmission is low.
38
HCV - Sources of Infection

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

39
Sexual Transmission
Transmission efficiency is low

Rare between long-term steady
partners (1.5%)
Factors that facilitate transmission
between partners (e.g., viral load) are
unknown
Male to female transmission may be
more efficient
40
Other Transmission Issues
HCV is not spread by kissing, hugging,

sneezing, coughing, food or water, sharing
eating utensils or drinking glasses, or
casual contact
HCV infection status should not be used to

exclude patients from work, school, play,
child-care or other settings
41
Hepatitis C Genotypes
Genotype:
1a
1b
2a, 2b, 2c, 2d
3a, 3b, 3c, 3d, 3e, 3f
4a, 4b, 4c, 4d, 4e, 4f,
4g, 4h, 4i, 4j
5a
6a
Countries Where Prevalent:

USA, England, Europe
USA, Japan, Europe
Japan, China
Scotland, England
Middle East, Africa
Canada, South Africa
Hong Kong, Macau
42
Genotype Distribution
Hepatitis C: A Global Health

Problem
170 Million Carriers Worldwide, 3-4 MM new cases/year

WEST
EUROPE
9M
U.S.A.
4M
EAST
MEDITERRANEAN
20M
FAR EAST ASIA

60 M
SOUTH EAST ASIA

30 M
AFRICA
32 M
SOUTH
AMERICA
10 M
SOURCE, WHO 1999
AUSTRALIA
0.2 M
44
Acute Hepatitis C Clinical

Presentation and Natural History
HCV RNA can be detected in blood within 1-3 weeks after

exposure
Average time from exposure to seroconversion is 8-9 weeks
Average time from exposure to symptoms period 6-7 weeks
Liver injury (elevations in ALT) with 4-12 weeks
Symptoms develop in only of 20% of patients

Nonspecific 10%-20%
Jaundice in only 20%-30%
CDC. MMWR. 1998; 47(No. RR-19):1-39.

Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20S
NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002
45
Hepatitis C Infection
Incubation period
Average 6-7 weeks

Range 2-26 weeks
Case fatality rate
Low
Chronic infection
75%-85%
Chronic hepatitis
70% (most asx)
Cirrhosis
10%-20%
Mortality from CLD
1%-5%
46
Natural History of Hepatitis C

10-20 years
Acute Hepatitis C
Chronic Hepatitis
75%-85 %
Cirrhosis 20 %

Di Bisceglie, Hepatology, 2000
47
Natural History of Hepatitis C

Cirrhosis 20 %
Annual rate
Decompensation
6%
HCC
4%
Death
4%

Di Bisceglie, Hepatology, 2000
48
Acute HCV Infection with Recovery

HCV Ab
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
Months
Time after Exposure
Years
49
Chronic Hepatitis C
A leading cause of cirrhosis in the US
10,000-20,000 deaths/yr
This number expected to triple in the next 10 to 20
years (without therapy)
Associated with an increased risk of liver cancer
Most common reason for liver transplantation in the

United States
CDC. MMWR. 1998; 47(No. RR-19):1-39.

NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002
50
Acute HCV Infection with

Progression to Chronic Infection
HCV Ab
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
Months
Time after Exposure
Years
51
Hepatitis
C
Hepatitis encephalopathy if untreated can lead to:
Confusion
Complications
Disorientation
Hallucination
Stupor/Coma
Jaundice
Pruritus
Renal damage/failure
Hypo/Hyperthyroidism
Varices of Esophagus, Stomach, Rectum
Muscle Wasting
52
Extrahepatic Manifestations of
Hepatitis C
Hematologic: Mixed cryoglobulinemia

(10%25% of HCV patients)*
Renal: Glomerulonephritis
Dermatologic:
Porphyria cutanea tarda
Cutaneous necrotizing vasculitis
Lichen planus
Management of Hepatitis C. NIH Consensus Statement, 2002.

53
Chronic 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
54
Claudia needs to see her

family physician.
She wants to be tested for
HCV.
What test do you recommend?
Diagnostic Tests for HCV
Anti-HCV
RIBA (supplemental assay)
Qualitative PCR
Quantitative PCR
Genotyping assays
56
HCV Antibody Tests
Screening tests - total antibody detected

Sensitivity is about 95%
Predictive value
High Risk Population: 90-95%

Low Risk Population: 50-60% (false
positives)
False Negatives due to window period

and immunosuppression
57
Hepatitis C Antibody Test:

Signal to Cut Off (S/CO)
Ratio
S/CO ratio is a comparison of the pts positive

EIA result with the labs positive EIA control.
A positive EIA test with a s/co ratio of 3.8 or

higher is indicative that the pt truly has HCV
and that the RIBA test will be positive (95%97% predictive value).
58
HCV RIBA Tests
Used to resolve possible false

positive anti-HCV, particularly in lowrisk patients (blood donors)
Use is analogous to HIV western blot
Core
E1
E2/NS1
NS2
NS3
NS4
NS5
5 UTR
59
HCV Screening
Algorithm
EIA for Anti-HCV
Negative
(non-reactive)
STOP
Positive (repeat reactive)
OR
RIBA for Anti-HCV
Negative
STOP
Negative
Indeterminate
Additional Laboratory
Tests (e.g. PCR, ALT)
Negative PCR,
Normal ALT
RT-PCR for HCV RNA

Positive
Positive
Medical
Evaluation
Positive PCR,
Abnormal ALT
Source: MMWR 1998;47 (No. RR 19)
Diagnosis of Viral Hepatitis in the Primary Care

Setting: Patients Who Have Risk Factors
A single normal ALT level does not rule out

chronic viral hepatitis
ALT levels may be intermittently normal in a

significant number of patients who have
chronic hepatitis C
61
Diagnosis of Chronic Viral Hepatitis

Serologic Testing
Patients should be tested if they:
Have known risk factors for viral hepatitis

Indicate possible risk factors for hepatitis
Have elevated liver enzymes
Management of Hepatitis C. NIH Consensus Statement, 1997.
62
Liver Biopsy
May be guided by CT or ultrasound
Provides information regarding

Degree of inflammation
Disease severity
Tissue damage
Presence/absence of cirrhosis
Helps determine
Degree of disease progression
Cause of liver disease
Need for treatment
63
Histologic Staging
Stage 0
Stage 1
No Fibrosis
Stage 2
Few septa
Portal Fibrosis
Stage 3
Numerous septa
Stage 4
Cirrhosis
64
Diagnostic Evaluation of HCV Infection
65
Hepatitis C Screening and Diagnosis

Summary
Suspect disease on the basis of risk factors, not

symptoms
Positive anti-HCV result indicates current infection

until refuted
Measurement of HCV RNA may be required to

establish diagnosis in selected cases
66
Treatment
67
Treatment for Hepatitis C
Interferon + Ribavirin x 6-12 months about 40% 50% sustain viral clearance > 3 years.
Predictive Factors for Treatment Response:
Genotype 2 and 3
Low initial viral load levels
Young age
Low Fibrosis Score (Liver Biopsy)
Female
68
Treatment Side Effects
Depression
Sleep Disturbances (Insomnia)
Irritability
Anger
Psychosis
Excessive Fatigue
Nausea/Diarrhea/Decreased Appetite/Weight Loss
Anemia/Neutropenia
Autoimmune Disorders, especially Thyroiditis
Decreased Libido
Menstrual Irregularities
69
Rationale for the development

of a once-weekly pegylated
interferon -2b
70
Rationale for Pegylation of Protein

Pharmaceuticals
Pegylation = binding of ethylene oxide polymers to

drug molecule
Decreases clearance
Prolonged half-life
Sustained blood levels
Decreases proteolysis
Decreases immunogenicity
Youngster S, et al. Curr Pharm Des. 2002;8:99.

Harris JM, et al. Clin Pharmacokinet. 2001;40:539.
71
Why PEG as a Protein-Modifying Agent?
Inert
Water soluble
Can be made any size and shape
O
CH 3- (OCH 2CH 2) n- O - C- N
H
(protein)
m
Bailon et al., Bioconjugate Chemistry, 2001

Wyss et al., Current Pharmaceutical Design, 2002
72
Pegylation: Effects on Half-life

Longer
Shorter
PEG Molecular Weight (PEG size)
The clinical relevance of this in vitro data has not been established.
Adapted from Youngster et al., Current Pharmaceutical Design, 2002, 8:2139-215
73
Pegylation: Antiviral Activity

More
Less
PEG Molecular Weight (PEG size)
The clinical relevance of this in vitro data has not been established.
Adapted from Grace M et al., AASLD 2003, Abstract #1928
74
Relationship between PEG size and

Renal Clearance
PEG 5,000
Relative clearance (%)
100
80
PEG 12,000
60
(used in PEG-IFN -2b )
40
20
PEG 20,000
0
10
30
80
100
Stokes radius (Angstroms)

Wyss et al., Current Pharmaceutical Design, 2002
Xian-Hui He et al., Life Sciences, 1999
75
HCV-Positive Persons
for Whom Treatment is
Recommended
Persistently elevated liver enzyme (ALT) levels
Presence of HCV RNA (viral load)
A liver biopsy indicating fibrosis or at least moderate

inflammation and necrosis
Cessation of continuing alcohol/substance use
HCV + HIV coinfection: especially difficult
Goal: Clear HCV, restore LFT, reverse pathology

76
Predicting Response to
Treatment
77
Response Rate to Treatment

Based on Genotype
Genotype:
1a/1b
2-6
Overall Response
Response Rate:
41% of patients
75% of patients
52% of patients
78
HCV Kinetics
79
Goals of HCV Therapy
Primary: HCV RNA below limits of detection

at end of treatment
Secondary:
Inhibition of disease progression

Reduction of incidence of hepatocellular
carcinoma
Reduction in need for liver transplant
80
Treatment Definitions
The First aim is to clear

HCV RNA from
peripheral blood, a
necessary, but not
sufficient condition to
achieve a sustained
virological response.
The Second aim is to

prevent relapse in
patients who cleared
HCV RNA during
induction, in order to
achieve a sustained
virological response
Adapted from Pawlotsky JM, Hepatology vol. 32, #5, 2000
81
Patterns of Response to Initial

Antiviral Therapy
Serum HCV RNA
7
6
Nonresponder
( < 0.2)
1st Phase
Flat-partial responder
(0.0 < < 0.2)
Slow-partial responder
(0.1 < 0.4)
2nd Phase
3
2
detection limit
Rapid responder
( 0.4)
1
0 1 2 3
14
21
28
Days
82
Changing Paradigms
Speed of response is an important predictor of sustained

virologic response.
66% of patients with HCV genotypes 2 and 3 had
undetectable HCV levels within 4 weeks of treatment
Sustained virologic response.
90% for 24 week treatment arm

75% for 16 week treatment
Relapse rates

Shiffman, et al., N. Eng. J. Med 2007;357:124-134

83
Resources
S.C. Hepatitis C Coalition
SC DHEC Hepatitis Nurse Consultant
Elona Rhame, RN
Pharmaceutical Companies
Physician Referral List
84
SC Hepatitis C
Coalition
803-898-9562
Mick Carnett, CDP, CRPS, D.Div., Executive

Director
Informational & support services to providers & patients

Brochures/literature
Presentations
Annual Statewide Hepatitis C Summit
Statewide Physicians Referral List
ETV program, HCC videos, PSAs
85
Surveillance/Reportin
g
Hepatitis C is reportable to the health

department within 7 days.
Acute and chronic HCV cases are reported

by health department to CDC via CHESS.
86
Hepatitis B
87
Clinical Features
Incubation period:
Mean: 60-90 days

Range: 45-180 days
Clinical illness (jaundice):
<5 yrs, <10%

5 yrs, 30%-50%
Acute case-fatality rate:

Chronic infection:
0.5%-1%
<5 yrs, 30%-90%
5 yrs, 2%-10%
Premature mortality from

chronic liver disease:
15%-25%
88
Geographic Distribution of Chronic HBV

Infection
HBsAg Prevalence
8% - High
2-7% - Intermediate
<2% - Low

89
Hepatitis B Surface Antigen
HBsAg
Detection of acutely or chronically infected

individuals. Antigen components used in HBV
vaccine
Should undergo testing to assess the status of

their liver disease
Assess hepatic synthetic function: serum albumin, prothrombin time

Assess for hypersplenism: CBC (plts, wbc decreased)
Assess for viral replication status: HBeAg and HBV DNA
90
Antibody to HBsAg
Anti-HBsAg
Identification of individuals who have resolved

HBV infections.
Determination of immunity after immunization.
91
Hepatitis B Envelope Antigen
HBeAg
Identification of infected individuals at

increased risk for transmitting HBV
92
Antibody to HBe
HBeAb or anti-HBe
Identification of infected individuals with lower

risk for transmitting HBV
93
Antibody to HBV Core Antigens
Anti-HBc or HBcAb
Identification of persons with acute, resolved,

or chronic HBV infection.
Anti-HBc is not present after immunization.
94
IgM Antibody to HBcAg
IgM anti-HBc or HBc IgM
Identification of acute or recent HBV infections

(including those in HBsAg-negative persons
during the window phase of infection)
95
Acute HBV Infection with Recovery

Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titer
anti-HBs
IgM anti-HBc
HBsAg
12
16
20
24
28
32
Weeks after Exposure
36
52
100
96
Progression to Chronic HBV Infection

Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
8 12 16 20 24 28 32 36
Weeks after Exposure
52
Years
97
Chronic Hepatitis B Infection
Defined as testing positive for the HBsAg for

more than 6 months
Patients are at increased risk for progressive
liver disease and hepatocellular carcinoma
98
35 year old Medical Technologist who cut her hand.

She was removing the top from a Vacutainer tube
when the tube broke.
Test
Result
HBsAg
Negative
Anti-HBc
Negative
Anti-HBc-IgM
Negative
Anti-HBs
Positive
Anti-HBs Ratio
23.1
29 year old automotive engineer who presented

with fatigue x 2 weeks and mild jaundice. Liver
enzyme levels were significantly elevated.
Test
Result
HBsAg
Anti-HBc
Positive
Positive
Anti-HBc-IgM
Anti-HBs
Anti-HBs Ratio
Positive
Negative
<2.1
James is a 23 year old food

service employee. He was tested
as part of his pre-employment
physical examination. He was
diagnosed with HBV infection one
year ago.
What is his
HBV Status?
HBsAg
Anti-HBc
Anti-HBc-IgM
Anti-HBs
HBe Ag
Anti-Hbe
Positive
Positive
Negative
Negative
Positive
Negative
Chronic Active Hepatitis
High levels of HBV in blood

Increased risk of cirrhosis
Increased risk of liver cancer
102
James, a 23 year old food service

employee. He was tested as part
of his pre-employment physical
examination. He was diagnosed
with HBV infection one year ago.
Can he work as a
food handler in
your hospital?
High viral load

Increased risk of virus
transmission
HBV Transmission
Parenteral
Sexual
Perinatal
Risk of transmission increases
with the level of HBV DNA in
serum and HBeAg positive
104
HBV Concentrations in Various Body

Fluids
High
Moderate
blood
serum
wound exudates
semen
vaginal fluid
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breast milk
105
Outcome of HBV Infection

Infection
Symptomatic
acute hepatitis B
Asymptomatic
Resolved
Immune
Chronic infection
Asymptomatic
Cirrhosis
Liver cancer
Resolved
Immune
Chronic
infection
Asymptomatic
Cirrhosis
Liver cancer
106
Chronic HBV Infection
Immune tolerant patient
HBeAg positive and HBeAb negative

Viral load 100,000 to 1 billion copies/mL
Normal ALT
No necroinflammation in the liver
Chronic Active Hepatitis B (Viral Load > 100,000

cy/mL)
HBeAg positive (wild type virus)

HBeAg negative (pre core or core promoter mutants)
Elevated ALT and/or active liver biopsy
Increased risk for progression to cirrhosis and ESL
disease and candidates for therapy
Chronic HBV Infection
Inactive HBsAg Carrier
HBeAg negative and HBeAb positive

Viral load 100 to 10,000 copies/mL
Normal ALT
Resolution of necroinflammation in the liver
Reduced risk of progressive liver disease
Resolution
HBsAg negative, HBsAb positive

Viral load <<< 20,000 copies/mL
HBeAg negative and HBeAb positive
Normal ALT
108
HBV DNA Testing
Assess of viral replication in chronic HBsAg carriers.

Assess the risk of progression toward cirrhosis and
hepatocellular carcinoma.
Decision to treat.
Assess treatment efficacy and failure
109
Hepatitis B Vaccine
Licensed in 1982; currently recombinant (in US)
3 dose series, typical schedule 0, 1-2, 4-6 months - no
maximum time between doses (no need to repeat
missed doses or restart)
2 dose series (adult dose) licensed by FDA for 11-15
year olds (Merck)
Protection ~30-50% dose 1; 75% - 2; 96% - 3; lower in
older, immunosuppressive illnesses (e.g., HIV, chronic
liver diseases, diabetes), obese, smokers
110
Indications for Pre-Exposure Vaccination
Children < 19 yrs of age
Persons at risk for sexual transmission.
MSM
Current/past IDU
Family member of HBsAg + adoptees
Persons at occupational risk
Hemodialysis patients
111
Indications for Pre-Exposure Vaccination
Clients/staff of institutions for developmentally

disabled
Persons receiving clotting factors
International travelers in high/intermediate areas
Inmates
Adults 19 years of age & older desiring protection

112
Indications for Post-Exposure

Prophylaxis
Infants born to HBsAg + mothers

Persons who have percutaneous or permucosal
exposure to blood
Sex partners of persons with acute HBV
Household contacts of persons with acute HBV if
blood exposure or if unimmunized infant
Sex partners of persons with chronic HBV
Household contacts of persons with chronic HBV
Victims of sexual assault
113
Indications for Pre-Vaccination

Serologic Testing:
Unimmunized sexual contacts of persons with acute

and chronic Hepatitis.
Unimmunized household contacts of persons with

acute HBV if there has been a blood exposure.
Unimmunized household contacts of person with

chronic HBV.
Unimmunized persons in populations with high rates

of HBV (IDU, inmates)
114
Indications for
Post-Vaccination Serologic
Testing
Persons at occupational risk
Infants born to HBsAg+ mothers
Immunocompromised persons
115
Sexual
Contacts
towith
Acute
Sexual
contacts
of persons
acuteHBV
HBV
regardless of age:
Test if unimmunized
Administer HBIG and first hep B dose at time test is
obtained.
If negative, continue hepatitis vaccination series.
116
Household Contacts to Acute

Cases
Children (>12 months of age), Adolescents, and
Adult Household Contacts to Acute Cases:
Not at increased risk unless blood exposure.

Only if blood exposure has occurred in past 14 days, test
and give HBIG and first dose of hepatitis B vaccine.
If negative, continue vaccination series.
117
Sexual and Household

Contacts
to Chronic Cases
Sexual Contacts (regardless of age):
If unimmunized, test and give first dose of vaccine.

If test is negative, continue series.
Household Contacts (regardless of age):
If unimmunized, test and give first dose of vaccine.

If test is negative, continue series.
118
Victims of Sexual Assault
If offender is HBsAg positive or status is unknown

and victim is unimmunized:
If offender has acute HBV infection - give HBIG and

hepatitis B vaccine.
If offender has chronic HBV infection give vaccine.
119
Healthcare Worker Pre-Exposure

Vaccination
Administer vaccination series.

Obtain postvaccination serology at 1-2 months after
completion of series.
If anti-HBs levels are > 10 mIU/mL, employee is a
responder.
If anti-HBs levels are < 10 mIU/mL, employee is a
non-responder. Revaccinate and repeat serology.
120
Postvaccination Serology
Testing
Infants born to HBsAg positive mothers.

Persons at high risk of occupational exposure.
Persons who are immunocompromised and at
continued risk of infection.
Persons receiving clotting factors.
121
Postvaccination Testing
Persons who were tested 1-2 months after

completion of series and had anti-HBs levels > 10
mIU/mL should not receive any further testing.
122
Approved Therapies for HBV

Infection
Interferons
Nucleoside analogues
Interferon alpha 2b (5 million units qd or 10 million units

TIW for 12-24 weeks)
Pegylated interferon alpha 2a (180 ug once/week for 48
weeks)
Lamivudine (100 mg qd)
Entecavir (0.5 mg qd; 1 mg if lamivudine resistance)
Nucleotide analogues
Adefovir (10 mg qd)

123
Hepatitis B Surveillance
Acute Hepatitis B is an urgently reportable condition.

It must be reported by phone to the health department
within 24 hours.
Chronic Hepatitis B is a reportable condition and must

be reported to health department within 7 days.
Perinatal Hepatitis B is a reportable condition and

must be reported to health department within 7 days.
124
Hepatitis D Virus
125
HDV Transmission
Percutanous exposures
injecting drug use
Permucosal exposures
sex contact
126
Geographic Distribution of HDV Infection
Taiwan
Pacific Islands
HDV Prevalence
High
Intermediate
Low
Very Low
No Data
Hepatitis D - Clinical Features
Coinfection
severe acute disease
low risk of chronic infection
Superinfection
usually develop chronic HDV infection
high risk of severe chronic liver disease
128
HBV - HDV Coinfection

Symptoms
Titer
ALT
Elevated
IgM anti-HDV
antiHBs
HDV RNA
HBsAg
Total antiHDV
Time after Exposure
HBV - HDV Superinfection

Jaundice
Symptoms
Total anti-HDV
Titer
ALT
HDV RNA
HBsAg
IgM anti-HDV
Time after Exposure
GRACIAS POR SU ATENCIN

Para ver otros temas relacionados:
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Viral Hepatitis (Virus Hepatitis)

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Viral Hepatitis (Virus Hepatitis)

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Hepatitis Viral : A, B, C,

Dr. Hugo Abel Pinto Ramrez

Viral Hepatitis - Historical

Dr. Hugo Abel Pinto Ramrez

Viral Hepatitis 1982-1993

Source: CDC Sentinel

Estimates of Acute and Chronic Disease

Chronic liver disease

* Source: CDC -Range based on estimated annual incidence, 1984-1994.

Hepatitis A Virus (HAV)

Dr. Hugo Abel Pinto Ramrez

household contact, sex contact, child

Contaminated food, water

infected food handlers, raw shellfish

Blood exposure (rare)

injecting drug use, transfusion

Dr. Hugo Abel Pinto Ramrez

Hepatitis A - Clinical Features

Dr. Hugo Abel Pinto Ramrez

HAV - Typical Serologic Course

HAV total Ab appears 4-5 weeks after

Dr. Hugo Abel Pinto Ramrez

HAV Immune Globulin

IM administration within 2 weeks after HAV

Dr. Hugo Abel Pinto Ramrez

Highest virus concentrations occur in stool

Dr. Hugo Abel Pinto Ramrez

Culture is worthless except for research

Dr. Hugo Abel Pinto Ramrez

Mitch, a 43 year old salesman, has

Does he have HAV infection?

Dr. Hugo Abel Pinto Ramrez

Likely to be cost-effective for:

Persons born in high endemic areas

High response rate among vaccinees

Commercially available assay not sensitive

Dr. Hugo Abel Pinto Ramrez

Men who have sex with men

Illegal drug users

Persons who have clotting factor disorders

Persons with chronic liver disease

STD Treatment Guidelines

against hepatitis is the most

Dr. Hugo Abel Pinto Ramrez

Indications for IG for Post-Exposure

Household and sexual contacts if exposure is within

Childcare center employees and children when HAV

Close school contacts if transmission within the

Indications for IG for Post-Exposure

Person exposed to contaminated

Persons who ate food prepared by HAV+ food

Dr. Hugo Abel Pinto Ramrez

Dr. Hugo Abel Pinto Ramrez

Hepatitis A Surveillance & Response

Urgently reportable condition in S.C. Acute

Investigation of a case of hepatitis A must be

Dr. Hugo Abel Pinto Ramrez

Date of onset of symptoms

Dr. Hugo Abel Pinto Ramrez

Initiate enteric precautions during the first 2

Refer symptomatic contacts to physician.

Exclude adults/children with HAV infection from

Provide education re transmission, prevention, and

Dr. Hugo Abel Pinto Ramrez