H EPATITIS V IR A L

IN FEC TIO N

DAP SRI MASYENI

FKIK UNIVERSITAS WARMADEWA

Type of
Hepatitis
A

Source of
virus
Route of
transmission
Chronic
infection
Prevention

feces

blood/
blood/
blood/
blood-derived blood-derived blood-derived
body fluids
body fluids
body fluids

feces

fecal-oral

percutaneous percutaneous percutaneous

permucosal
permucosal
permucosal

fecal-oral

no

yes

pre/postexposure
immunization

pre/postexposure
immunization

yes

yes

blood donor
pre/postscreening;
exposure
risk behavior immunization;
modification risk behavior
modification

no

ensure safe
drinking
water

Viral Hepatitis - Historical

Perspectives
Infectious
Viral
hepatitis
Serum

Enterically
E
transmitted

NANB
Parenteral
B D
C ly
transmitte
F, G, TTV
d
? other

H EPATITIS A V IR U S
RNA PICORNA
VIRUS
- Single serotype
worldwide
-Acute &
asymptomatic
disease
NO CHRONIC
INFECTION
protective
antibodies develop
in response to
infection confers

Transmission
Close personal contact

(e.g., household contact, sex contact, child

day care centers)
Contaminated food, water

(e.g., infected food handlers, raw shellfish)

Blood exposure (rare)

(e.g., injecting drug use, transfusion)

Hepatitis A - Clinical
Features

Incubation period:
Average 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

C linical m anifestations
Asymptomatic to fulminant
Prodromal /pra icteric phase : insidious onset

of malaise, mialgia, atralgia, anorexia,

feverish, nausea or vomiting, abd.
discomfort, flu like syndrome
Icteric phase : after 5-10 days or earlier, dark
urine, pruritus
Convalescen : icteric disappear, symptomless
Physic : hepatomegaly, mild splenomegaly,
lympadenopathy
Cholestasis : icteric and pruritic for a few
months

Global Patterns of
Hepatitis A Virus
Transmission
DiseasePeak Age
Endemicity Rate of Infection
Transmission Patterns
High
Moderate

Low
Very low

Low to
Early
Person to person;
High childhood outbreaks uncommon
High

Late
Person to person;
childhood/ food and waterborne
young adultsoutbreaks

Low Young adultsPerson to person;

food and waterborne
outbreaks
Very low Adults Travelers; outbreaks
uncommon

Hepatitis A Infection
Typical Serological Course
Total anti-HAV

Symptom
s

Titre

ALT

Fecal
HAV

IgM anti-HAV

Months after exposure

1
2

2
4

Laboratory D iagnosis
Acute infection is diagnosed by the detection

of HAV-IgM in serum by EIA.

Past Infection i.e. immunity is determined by

the detection of HAV-IgG by EIA.

Others : AST, ALT, bilirubin

M anagem ent
Out patient/inpatient (dehidration/

fulminant hepatitis)
Nutrisi
Rest
Supportif treatment
Cholestasis : ursodioksikolic acid,
kolestiramin.

Hepatitis A Prevention Immune Globulin

Pre-exposure
travelers

to
intermediate
HAV-endemic regions

and

high

Post-exposure (within 14 days)

Routine
household and other intimate contacts
Selected situations
institutions (e.g., day care centers)
common source exposure (e.g., food prepared by
infected food handler)

Vaccine
Pre exposure
High effective , protect 94-100%
High immunogenic 100 %
Antibody within 15 days in 85-90%

subject
Well tolerated, safe, effective protect 20
y
HAVRIX, adult : 2 dose interval 6-12 mo,
children >2 years, 3 dose at 0,1 and 612 mo

Post exposure
- unclear

H epatitis B Virus Infection

More than 350 million chronically

infected worldwide
Established cause of chronic
hepatitis and cirrhosis
Human carcinogencause of up to
80% of hepatocellular carcinomas
More than 600,000 deaths worldwide
in 2002, WHO (2015) CFR:0.5-1%

G lobalPatterns of
Chronic H BV 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 (<2%): 12% of global population

lifetime risk of infection <20%
most infections occur in adult risk groups

W ays to contract the virus.

Having unsafe non-condom sex.
Sharing personal items such as

razors, especially with Hepatitis B

virus on them.
Using infected needles during
excessive illegal drug use.
Contamination on tattoo needles.

TR A N SM ISIO N
Blood/blood product
Sexual transmission
Percutan/mucosal penetration
Vertical transmision : mother to child
Fecal-oral : no evidence support

Risk G roups
Persons with multiple sex partners

and dont use condoms.

Men that have sex with men.
Any sexual contact with an infected
person will give you this disease.
Using sterile needles and condoms
will help prevent you from getting
this disease.

H epatitis B Virus
Hepadnaviridae family (DNA)
Numerous antigenic

components

Humans are only known host

May retain infectivity for at least

1 month at room temperature

H BV
DNA virus,
hepadnaviridae
hepatotropik
Sferis particle, 42 nm
Envelope : lipoprotein,
surface antigen, HbsAg
Core, nucleocapsid
Nucleus, HBV DNA, 3,2
kb, antigen hep B core
(Hbc Ag), hep B e
antigen, (HbeAg)

Hepatitis B Virus
HBsAg

HBcAg
HBeAg

H epatitis B ClinicalFeatures
Incubation period 6 weeks to 6 months

(average 120 days)

Viremia weeks-months
Nonspecific prodrome of fever, malaise,
headache, myalgia
Illness not specific for hepatitis B
At least 50% of infections asymptomatic
Developed chronic VHB in 1-5% adults,

90% neonatus, 50% infants

H epatitis B Com plications

Fulminant hepatitis
Hospitalization
Cirrhosis
Hepatocellular carcinoma
Death

D iagnosis of H BV infection
HbsAg + before IgM anti HBc
HBV DNA : gold standard, expensive
HbeAg , after HbsAg, infectious

status except in HB escape mutant

Seroconversi within 3 months or
develops chronic HB infection

M anagem ent of acute H BV

infection
Out patient/ in patient
Adequate nutrition
Rest
Supportive treatment

NATURAL HISTORY OF HBV

Slide 7

The phases of chronic hepatitis B

Immune
tolerance

Immune
clearance

HBeAg+ve

<

Immune
control

Immune
escape

HBeAgve

><

HBV-DNA

ALT
HBeAg +ve
chronic hepatitis

Inactive (carrier)
state*

*Previously considered to be healthy carriers

HBeAg ve active
chronic hepatitis

>

OVERVIEW OF ALGORITHM USED TO

DETERMINE NEED FOR TREATMENT OF
HBV
HBeAg Positive
HBV DNA >20,000 IU/mL

HBeAg Negative
HBV DNA >2,000 IU/mL
ALT Level

Elevated ALT

Normal ALT
Monitor ALT
Q3mos for 1y

Treat

Consider Liver
Biopsy If >40yrs

Significant fibrosis or
inflammation
Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008
Lok AS et al Hepatology,Slide
200912

Who should be considered for treatment?

Immune
tolerance

Immune
clearance

HBeAg+ve

<

Immune
control

><

Immune
escape

HBeAgve

>

HBV-DNA

ALT

treat

treat
HBeAg +ve
chronic hepatitis

Inactive (carrier)
state

HBeAg ve/+ve active

chronic hepatitis

APPROVED HBV TREATMENTS 2009

Interferon alfa-2b 1991
Lamivudine 1998
Adefovir 2002
Entecavir 2005
Peginterferon alfa-2a 2005
Telbivudine 2006
Tenofovir - 2008
For HIV:
o Emtricitabine
o Tenofovir + emtricitabine (single pill co-formulation)

Strategy to Elim inate H epatitis B

Virus Transm ission -U nited States
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk

groups
Vaccination of adolescents
Vaccination of adults in high-risk
groups

H epatitis B Vaccine
Composition
Efficacy
Duration of

Immunity

Schedule

Recombinant HBsAg

95% (Range, 80%-100%)

>15 years
3 Doses

Booster doses not routinely

recommended

H epatitis B Vaccine Form ulations

Recombivax HB (Merck)

- 5.0 mcg/0.5 ml (pediatric)

- 10 mcg/1 ml (adult)
- 40 mcg/1 ml (dialysis)
Engerix-B (GSK)

- 10 mcg/0.5 ml (pediatric)
- 20 mcg/1 ml (adult)

Recommended Dose of Hepatitis B

Vaccine
Recombivax HB Engerix-B
Dose
Dose (mcg)
(mcg)
Infants and children 0.5 ml (5)
0.5 ml (10)
<11 years of age
Adolescents 11-19
years
Adults >20 years

0.5 ml (5)
1.0 ml (10)

0.5 ml (10)
1.0 ml (20)

Indications for H epatitis B Vaccine

Infants
Adolescents 11-12 years of age
Selected adults

Hepatitis B Vaccine
Routine Infant Schedule

Minimum
Dose
Interval
Usual Age
Primary 1 0-2 months*
--Primary 2 1- 4 months 1 month
Primary 3 6-18 months 2 months
*ACIP prefers the first dose of hepatitis B vaccine be
given soon after birth and before hospital discharge.

Prevaccination Serologic Testing

Not indicated before routine vaccination of

infants or children

May be considered when vaccinating

adolescents in groups with high rates of HBV

infection
Alaskan Natives
Pacific Islanders
Children of immigrants from endemic countries
Family members of HBV carriers

HBsAg, Anti HBc, Anti HBs post vaccine

evaluation

H epatitis C Virus Infection

Hepatitis C both acute and chronic hepatitis infection
Clinical manifestation : mild illness --- serious, lifelong illness.
The hepatitis C virus is a bloodborne
130150 million people globally have chronic hepatitis C

infection.
A significant number of those who are chronically infected will
develop liver cirrhosis or liver cancer.
Approximately 500 000 people die each year from hepatitis Crelated liver diseases.
Antiviral medicines can cure approximately 90% of persons
with hepatitis C infection, thereby reducing the risk of death
from liver cancer and cirrhosis, but access to diagnosis and
treatment is low.
There is currently no vaccine for hepatitis C; however research
in this area is ongoing.

Transm ission
The hepatitis C virus is a bloodborne virus
injecting drug use through the sharing of
injection equipment;
in health care settings due to the reuse or
inadequate sterilization of medical equipment,
especially syringes and needles;
the transfusion of unscreened blood and blood
products;
HCV can also be transmitted sexually and can
be passed from an infected mother to her
baby; (much less common).

H epatitis C :RN A virus,hepacivirus (fl

aviviridae)

Sym ptom s
The incubation period: 2 weeks to 6

months.
Approximately 80% asymptomatic.
Symptoms : fever, fatigue,
decreased appetite, nausea,
vomiting, abdominal pain, dark urine,
grey-coloured faeces, joint pain and
jaundice (yellowing of skin and the
whites of the eyes).

D iagnosis
Screening for anti-HCV antibodies .
Viral nucleic acid test for HCV RNA is

needed to confirm chronic HCV

infection because about 1545% of
people infected with HCV
spontaneously clear the infection by
a strong immune response.
Genotyping ( 7 genotypes, >>
genotype-1 ) treatment

Treatm ent
Hepatitis C does not always require treatment. When

treatment is necessary, the goal of hepatitis C treatment is

cure. The cure rate depends on several factors including the
strain of the virus and the type of treatment given.
The standard of care for hepatitis C is changing rapidly. Until
recently, hepatitis C treatment was based on therapy with
interferon and ribavirin (48 weeks) threatening adverse
reactions.
Recently, direct antiviral agents (DAA) for 12 weeks , >>
effective, safer and better-tolerated. Although the
production cost of DAAs is low, the initial prices are very high
and likely to make access to these drugs difficult even in
high-income countries.
DAA : proteinase inhibitor: boceprevir (BOC) , telaprevir
(TVR)

THANK YOU

 Highest rate of people that get it are

in the 20 to 49 year old age group.

There has been a great decline in
infected children due to routine
vaccinations.
An estimated 1.25 chronically
infected americans (20-30% get it in
childhood).
About 400 million people are
carrying this disease around.

THERAPEUTIC ENDPOINTS OVER TIME

Improved
Improved
Anti-HBs+ survival
histology
Loss of
Anti-HBe+
HBsAg
Loss of
HBeAg
Loss of
HBV DNA

TIME

HBV CONTROL
Inflammatory: normalize serum ALT, biopsy
Virologic: decrease HBV DNA
Immune: seroconversion
o HBeAg to HBeAb
o HBsAg to HBsAb
HBV never cured but controlled

Slide 9

Postvaccination Serologic Testing

Health care workers who
have contact with patients or
blood should be tested for
antibody after vaccination.

M anagem ent ofN onresponse to

H epatitis B Vaccine
Complete a second series of three doses
Should be given on the usual schedule of

0, 1 and 6 months

Retest 1 to 2 months after completing

the second series

Booster a dose when antiHBs < 10
Good protection anti HBs 10-100
Excellent if antiHBs > 100

 Hepatitis C virus (HCV) causes both acute and chronic

infection. Acute HCV infection is usually asymptomatic, and is

only very rarely associated with life-threatening disease. About
1545% of infected persons spontaneously clear the virus
within 6 months of infection without any treatment.
The remaining 5585% of persons will develop chronic HCV
infection. Of those with chronic HCV infection, the risk of
cirrhosis of the liver is 1530% within 20 years.
Geographical distribution
Hepatitis C is found worldwide. The most affected regions are
Africa and Central and East Asia. Depending on the country,
hepatitis C infection can be concentrated in certain populations
(for example, among people who inject drugs); and/or in
general populations. There are multiple strains (or genotypes)
of the HCV virus and their distribution varies by region.