Viral hepatitis-a-b-c-d.pp

Hepatitis Viral : A, B, C, D, E

Dr. Hugo Abel Pinto Ramírez
Especialidad en Medicina familiar y
Especialista en Urgencias, Maestría en
Farmacología (2011)

1

Viral Hepatitis - Historical Perspective

“Infectious” A Enterically
E
transmitted

Viral hepatitis NANB

Parenterally
“Serum” B D C transmitted
F, G,
? other
Dr. Hugo Abel Pinto Ramírez 2

Viral Hepatitis

A B C D E
Source of feces blood/ blood/ blood/ feces
virus blood-derived blood-derived blood-derived
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

Viral Hepatitis 1982-1993

34%
42%

16%
3%

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


Hepatitis A Virus (HAV)


HAV Transmission

xClose personal contact
household contact, sex contact, child
day care centers
xContaminated food, water
infected food handlers, raw shellfish
xBlood exposure (rare)
injecting drug use, transfusion


Hepatitis A - Clinical Features

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

HAV - Typical Serologic Course
Symptoms Total anti-HAV

ALT
Titer

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 12 24
MonthsHugo Abel Pinto Ramírez
Dr. after Exposure 9

Serological Testing
 HAV total Ab appears 4-5 weeks after
infection and remains positive for the
patient’s 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


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.


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.


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.


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) Positive
 HAV IgM Negative

Does he have HAV infection?

CDC Recommendations:
Testing and Vaccination


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)


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


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


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.”


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.


Indications for IG for Post-Exposure
Prophylaxis

 Person exposed to contaminated
food/water.

 Persons who ate food prepared by HAV+
food handler.


Hepatitis A Surveillance
and Response


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.


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


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.


Hepatitis E Virus


 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


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


Typical Serological Course - HEV
Symptoms
anti-HEV
ALT

IgM anti-HEV
Titer

Virus in stool

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Weeks Hugo Abel Pinto Ramírez
Dr. after Exposure 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 patient’s
lifetime


CDC Criteria for Testing Acute Phase Sera

 Discrete onset of illness with jaundice or
x Serum ALT >2.5 times the upper limit of normal
and
 HAV IgM negative
 HBV Core IgM negative
 HCV Ab negative


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


Steps to prevent HEV
transmission in home setting?

2. Safe sex practices
3. Do not share eating/grooming
utensils.
4. Respiratory precautions
5. Vigorous hand washing
6. No special requirements needed


Hepatitis C Virus


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 Claudia’s Risk of Infection?

1. High risk – HCV can be transmitted
sexually.
2. Low risk – The efficiency of sexual
transmission is low.


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

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


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


Hepatitis C Genotypes

Genotype: Countries Where Prevalent:
1a USA, England, Europe
1b USA, Japan, Europe
2a, 2b, 2c, 2d Japan, China
3a, 3b, 3c, 3d, 3e, 3f Scotland, England
4a, 4b, 4c, 4d, 4e, 4f,
4g, 4h, 4i, 4j Middle East, Africa
5a Canada, South Africa
6a Hong Kong, Macau


Hepatitis C: A Global Health Problem
170 Million Carriers Worldwide, 3-4 MM new cases/year

EAST
WEST FAR EAST ASIA
MEDITERRANEAN
EUROPE 60 M
20M
9M
U.S.A.
4M
SOUTH EAST ASIA
AFRICA 30 M
32 M

SOUTH
AMERICA
10 M AUSTRALIA
0.2 M

SOURCE, WHO 1999

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%

Natural History of Hepatitis C
10-20 years Acute Hepatitis C

Chronic Hepatitis
75%-85 %

Cirrhosis 20 %

Di Bisceglie, Hepatology, 2000

Natural History of Hepatitis C

Annual rate Cirrhosis 20 %

Decompensation HCC
6% 4%

Death
≈ 4%

Di Bisceglie, Hepatology, 2000

Acute HCV Infection with Recovery
HCV Ab
Symptoms +/-

HCV RNA
Titer

ALT

Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure 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

Acute HCV Infection with Progression to
Chronic Infection
HCV Ab
Symptoms +/-

HCV RNA
Titer

ALT

Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure 51

Hepatitis C Complications
 Hepatitis encephalopathy – if untreated can lead to:
 Confusion
 Disorientation
 Hallucination
 Stupor/Coma
 Jaundice
 Pruritus
 Renal damage/failure
 Hypo/Hyperthyroidism
 Varices of Esophagus, Stomach, Rectum
 Muscle Wasting

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.


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


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


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


Hepatitis C Antibody Test:
Signal to Cut Off (S/CO) Ratio

 S/CO ratio is a comparison of the pt’s positive
EIA result with the lab’s 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).


HCV RIBA Tests
 Used to resolve possible false
positive anti-HCV, particularly in low-
risk patients (blood donors)
 Use is analogous to HIV western blot

Core E1 E2/NS1 NS2 NS3 NS4 NS5
5’ UTR


HCV Screening Algorithm
Negative
(non-reactive)
EIA for Anti-HCV STOP

Positive (repeat reactive)
OR

Negative
RIBA for Anti-HCV RT-PCR for HCV RNA

Negative Indeterminate Positive Positive

Additional Laboratory Medical
STOP Tests (e.g. PCR, ALT) Evaluation
Negative PCR, Positive PCR,
Normal ALT 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


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.

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


Histologic Staging
Stage 0 Stage 1 Stage 2
No Fibrosis Portal Fibrosis Few septa

Stage 3 Stage 4
Numerous septa Cirrhosis


Diagnostic Evaluation of HCV Infection


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


Treatment


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


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

Rationale for the development of
a once-weekly pegylated
interferon α-2b


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.


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 (protein)
H m
Bailon et al., Bioconjugate Chemistry, 2001
Wyss et al., Current Pharmaceutical Design, 2002


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
100
Relative clearance (%)

80

60 PEG 12,000
(used in PEG-IFN α-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

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


Predicting Response to Treatment


Response Rate to Treatment
Based on Genotype

Genotype: Response Rate:
1a/1b 41% of patients
2-6 75% of patients
Overall Response 52% of patients


HCV Kinetics


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


Treatment Definitions
 The First aim is to clear  The Second aim is to
HCV RNA from prevent relapse in
peripheral blood, a patients who cleared
necessary, but not HCV RNA during
sufficient condition to induction, in order to
achieve a sustained achieve a sustained
virological response. virological response

Adapted from Pawlotsky JM, Hepatology vol. 32, #5, 2000


Patterns of Response to Initial
Antiviral Therapy

7
Nonresponder
(χ < 0.2)
6 1st Phase
Serum HCV RNA

Flat-partial responder
5 (0.0 < δ < 0.2)

Slow-partial responder
4 (0.1 ≤ δ < 0.4)
2nd Phase

3
detection limit
2
Rapid responder
1 (δ ≤ 0.4)
0 1 2 3 7 14 21 28
Days


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


Resources
 S.C. Hepatitis C Coalition
 SC DHEC Hepatitis Nurse Consultant
 Elona Rhame, RN
 Pharmaceutical Companies
 Physician Referral List


*

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


Surveillance/Reporting
 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.


Hepatitis B


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: 0.5%-1%
 Chronic infection: <5 yrs, 30%-90%
≥ 5 yrs, 2%-10%
 Premature mortality from
chronic liver disease: 15%-25%


Geographic Distribution of Chronic HBV Infection

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


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


Antibody to HBsAg
 Anti-HBsAg
 Identification of individuals who have resolved
HBV infections.
 Determination of immunity after immunization.


Hepatitis B Envelope Antigen
 HBeAg
 Identification of infected individuals at
increased risk for transmitting HBV


Antibody to HBe

 HBeAb or anti-HBe
 Identification of infected individuals with lower
risk for transmitting HBV


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.


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)


Acute HBV Infection with Recovery

Symptoms
HBeAg anti-HBe

Total anti-HBc
Titer

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure 96

Progression to Chronic HBV Infection
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titer

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure 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


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 Positive
Anti-HBc Positive

Anti-HBc-IgM Positive
Anti-HBs Negative
Anti-HBs Ratio <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.

HBsAg Positive
What is his
HBV Status? Anti-HBc Positive
Anti-HBc-IgM Negative
Anti-HBs Negative
HBe Ag Positive
Anti-Hbe Negative

Chronic Active Hepatitis

 High levels of HBV in blood
 Increased risk of cirrhosis
 Increased risk of liver cancer


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.

• High viral load
Can he work as a • Increased risk of virus
food handler in
transmission
your hospital?

HBV Transmission

 Parenteral
 Sexual
 Perinatal

 Risk of transmission increases
with the level of HBV DNA in
serum and HBeAg positive


HBV Concentrations in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk


Outcome of HBV Infection

Infection

Symptomatic
Asymptomatic
acute hepatitis B

Resolved Resolved Chronic
Chronic infection
Immune Immune infection

Cirrhosis Cirrhosis
Asymptomatic Asymptomatic
Liver cancer Liver cancer


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 Dr. Hugo Abel Pinto Ramírez 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


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


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

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


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

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)


Indications for
Post-Vaccination Serologic Testing

 Persons at occupational risk

 Infants born to HBsAg+ mothers

 Immunocompromised persons


Sexual Contacts to Acute HBV

 Sexual contacts of persons with acute 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.


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.


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.


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.


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.


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.


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.


Approved Therapies for HBV Infection
 Interferons
 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)
 Nucleoside analogues
 Lamivudine (100 mg qd)
 Entecavir (0.5 mg qd; 1 mg if lamivudine resistance)
 Nucleotide analogues
 Adefovir (10 mg qd)


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.

Hepatitis D Virus


HDV Transmission
 Percutanous exposures
injecting drug use
 Permucosal exposures
sex contact


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


HBV - HDV Coinfection
Symptoms

ALT Elevated

anti-HBs
Titer

IgM anti-HDV

HDV RNA

HBsAg
Total anti-HDV

Time after Exposure

HBV - HDV Superinfection
Jaundice

Symptoms

Total anti-HDV
ALT
Titer

HDV RNA
HBsAg

IgM anti-HDV

Time after Exposure

 GRACIAS POR SU ATENCIÓN
 Para ver otros temas relacionados:
 Visite: Blog SIN BANDERA
http://hugopintoramirez.blogspot.mx/
 Visite: http://www.slideshare.net/HugoPinto4


Viral hepatitis-a-b-c-d.pp

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (7)

Similar to Viral hepatitis-a-b-c-d.pp

Similar to Viral hepatitis-a-b-c-d.pp (20)

More from Hugo Pinto

More from Hugo Pinto (20)

Recently uploaded

Recently uploaded (20)

Viral hepatitis-a-b-c-d.pp

Editor's Notes