Hepatitis: Diah Puspita Rini, DR., SPPK

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HEPATITIS

Diah Puspita Rini, dr., SpPK


• Hepatitis is inflammation of the liver which
can be caused by viruses, medications, or
toxic agents.
• Non viral : miliary TB, staphylococcal
bacteriemia, salmonelloses, amebiasis,
drugs, etc.
• Viral hepatitis :, Hepatitis A,B,C,D,E
CMV, Herpes, Epstein Barr virus, Rubella
Viral Hepatitis

1 Hepatitis
Click A Title
to add
5 Hepatitis E

2 Hepatitis B Title
Click to add
6 Hepatitis G

3 7 Hepatitis TT
Hepatitis C

4 Hepatitis D 8 Hepatitis Sen

3
VIRAL HEPATITIS
A Major Public Health Problems

• Cause Morbidity & Mortality


• Chronic Hepatitis B & C

Liver
Cirrhosis HCC

4
SYMPTOMS
a short, mild, flu-like illness
nausea, vomiting and diarrhoea
loss of appetite
weight loss
jaundice (yellow skin and white of eyes,
darker yellow urine and pale faeces)
itchy skin
abdominal pain
Type of 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
Hepatitis A (HAV)
• Due to non enveloped, single stranded
RNA picornavirus
• Serum AST and ALT increased to
hundreds for 1 to 3 weeks
• Relative lymphocytosis is frequent
Serologic test for HAV
• Ig M anti HAV :
– appears at the same time as syptoms in > 99% of
cases
– peaks within first month, becomes nondetectable in 12
(usually 6)
– Presence confirms diagnosis of recent acute infection
• Anti HAV total:
– Predominantly IgG
– Almost always positive at onset of acute hepatitis and
is usually detectable for life
– Found in ± 50% of population, indicaes previous
exposure to HAV
Hepatitis A Infection
Typical Serological Course
Symptoms Total anti-
HAV

Titre ALT

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 12 24

Months after exposure


Hepatitis B (HBV)
• Due to enveloped, double stranded DNA
hepadna virus
• Divided into 3 stages:
1. Acute hepatitis: lasts 1-6 months, mild/ no
symptoms
 AST & ALT increased > tenfolds
 Serum bilirubin is usually normal or slightly
increased
 HBsAg gradually arises to high titer and persist,
HBeAg also appears
2. Chronic hepatitis: transaminase increased >
50% for > 6 months, most cases resolve but
some develop cirrhosis and liver failure
 AST & ALT fall to 2-10x normal range
 HBsAg usually remains high and HBeAg
remains present
3. Chronic carrier: are usually but not always
healthy and asymptomatic
 AST and ALT fall to normal or < 2x normal
 HBsAg positive > 6 months, HBc IgM negative,
but anti HBc positive
Hepatitis B Virus
Modes of Transmission
 Sexual - sex workers and homosexuals are
particular at risk.
 Parenteral - IVDA, Health Workers are at
increased risk.
 Perinatal - Mothers who are HBeAg positive
are much more likely to transmit to their
offspring than those who are not. Perinatal
transmission is the main means of
transmission in high prevalence populations.
Concentration of Hepatitis B
Virus in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine


serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
HBV : Structure
Hepatitis B Lab Markers
Marker Abbreviation Use

Hepatitis B surface antigen HBsAg Detection of acutely or chronically


infected persons; antigen used in
hepatitis B vaccine
M class immunoglobulin IgM Anti-HBc Identification of acute or recent
antibody to hepatitis B core HBV infections (including those in
antigen HBsAg-negative persons during the
“window” phase of infection)
Antibody to hepatitis B core Anti-HBc Identification of persons with acute,
antigen HBcAb resolved, or chronic HBV infection
(not present after vaccination)
Antibody to Hepatitis B surface Anti-HBs Identification of persons who have
antibody HBsAb resolved infection with HBV;
determination of immunity after
immunization
Hepatitis B e antigen HBeAg Identification of infected persons at
increased risk for transmitting HBV

Antibody to Hepatitis B e Anti-HBe Identification of infected person with


antigen HBeAb lower risk for transmitting HBV
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Titer

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

HBeAg

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

HBeAg anti-HBe

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe

Titer
IgM anti-HBc
HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg anti-HBs

Window
Period

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Progression to Chronic Hepatitis B Virus
Infection Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
Acute vs. Chronic HBV Infection

Acute Chronic
• HBsAg+ < 6 mos. • HBsAg + for at least 6
• IgM anti-HBc + months
positive
• Also known as a
• Infection will resolve
and person will have “carrier”
lifelong immunity • Infection does not
• HBsAb+ and HBcAb+ resolve and the
person remains
infectious
• HBsAb- and HBcAB+
Serologic diagnosis of viral hepatitis
Significance HBsAg HBeAg Anti-HBc Anti-HBc Anti-HBs
IgG IgM IgG

Acute HBV + + - + -

Chronic HBV, + + + - -
Active replication

Chronic HBV, + - + - -
quiescent

Resolved HBV - - + + -

Postvaccine - - - - +
Immune HBV

Quiescent = inactive = quiet


26
Possible Outcomes
Possible Outcomes ofof
Hepatitis B
Hepatitis B Infection
Infection
Acute HBV Chronic HBV Chronic hepatitis B
infection infection HBeAg-positive

Fulminant HBsAg Reactivation


Recovery hepatitis carrier

Chronic hepatitis B
HBeAg-positive
Cirrhosis
HDV
Chronic hepatitis B superinfection
HCC HBeAg-positive
Prevention
• Vaccination - highly effective recombinant vaccines are now
available. Vaccine can be given to those who are at increased risk
of HBV infection such as health care workers. It is also given
routinely to neonates as universal vaccination in many countries.
• Hepatitis B Immunoglobulin - HBIG may be used to protect
persons who are exposed to hepatitis B. It is particular efficacious
within 48 hours of the incident. It may also be given to neonates
who are at increased risk of contracting hepatitis B i.e. whose
mothers are HBsAg and HBeAg positive.
• Other measures - screening of blood donors, blood and body fluid
precautions.
HEPATITIS C (HCV)
30
Risk Factors Associated
with Transmission of HCV

 Transfusion or transplant from infected donor


 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-
positive contact
 Multiple sex partners
 Birth to HCV-infected mother
HCV INFECTION

INCUBATION
1 ACUTE
2
PERIOD INFECTION

6 -7 WEEKS 60 -80% ASYMPTOMATIC


20- 30% WITH JAUNDICE

(Range 2 – 26 weeks)
80 -85%
CHRONIC HEPATITIS

32
Hepatitis C Virus Infection
Typical Serologic Course
anti-HCV

Symptoms

Titre

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after
Exposure
PROGRESSION
• ACUTE HEPATITIS C
– 15-40% will spontaneously resolve, generally
within the first 6-18 months after acute onset.
– 60-85% will progress to chronic infection
• CHRONIC
– 85-90% stable
– 10-15% progress to cirrhosis
PROGRESSION
• CIRRHOSIS
Factors of poor prognosis:
– 75% slowly progressive -Age >40 years
-Alcohol > 50g/Hour
– 25% progress to HCC -Male gender
-Duration of infection
– 2-4% liver failure -Co-infection HBV/HIV

• HCC -Tobacco consumption

– Risk increases for every year for a patient


with chronic hepatitis C.
– Patients without signs of cirrhosis can develop
HCC
Diagnosis
of HCV Infection

Indirect tests: Direct tests :


detect components of the
antibody HCV particle
against HCV
1.HCV RNA(PCR)
1. Anti HCV
• Qualitative
2. RIBA • Quantitative
(recombinant
immunoblot assay)
2. HCV Core antigen
Usefull in detecting
window peroid
36
Prevention of Hepatitis C

 Screening of blood, organ, tissue


donors

 High-risk behavior modification

 Blood and body fluid precautions


CASE STUDIES
Jada went to her doctor for a routine
physical. A hepatitis panel was done
and her results were as follows:

HBsAg Negative
anti-HBs Positive
anti-HBc Negative
Question 1
• How would you interpret her results?
Answer
• She received the hepatitis B vaccine and
is protected (immune)
Jeff went in for a routine annual
physical. His doctor decided to run a
hepatitis panel. His results are as
follows:
HBsAg Positive
anti-HBs Negative
anti-HBc Positive
IgM anti-HBc Positive
HBeAg Positive
Question 1
• How would you interpret his results?
Answer
• He has acute hepatitis B infection.
Soal Kasus
• Laki2 datang dengan keluhan demam 14
hari, sklera tampak ikterus, nyeri tekan
abdomen kanan atas
• Pemeriksaan Lab apa yg anda usulkan?
– HBsAg (-)
– HBsAb (+)
– IgM anti HAV (+)
– anti HBc (-)
• Apa diagnosis pasien ini?
??QUESTIONS??

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