Dr.

SUHAEMI, SpPD,FINASIM
Hepatitis dapat didefenisikan sebagai suatu
proses nekroinflamatorik yang mengenai sel
hati
ALT 2 X NORMAL
HEPATITIS
1. DRUGS
2. ALCOHOL
3. CHEMICAL
4. METABOLISM
5. AUTOIMMUN
6. etc

1. VIRAL
2. BACTERIA
- SPECIFIC
- NON SPECIFIC
3. PROTOZOA
NON INFECTION
INFECTION
VIRAL
1. HERPES SIMPLEX
2. EPSTEIN - BARR
3. VARICELLA
4. HUMAN IMUNODEFICIENCY
5. ENTEROVIRUS
6. ARBOVIRUS
7. etc
NON HEPATOTROPHIC
HEPATOTROPHIC HEPATITIS VIRAL
A HEPATITIS A VIRUS
B HEPATITIS B VIRUS
C HEPATITIS C VIRUS
D HEPATITIS D VIRUS
E HEPATITIS E VIRUS
G HEPATITIS G VIRUS
TT HEPATITIS TRANSFUSION TRANSMISSIBLE
VIRUS
1. NECROSIS CENTRILOBULAR
2. INFLAMMATORY INFILTRATE PORTAL AREA
3. LOBULAR ARCHITECTURE : INTACT
4. BILE STASIS & BILE DUCT PROLIFERATION ( NOT DAMAGE )
5. NEONATE GIANT CELL ( + )
6. DISORDER OF THE OTHER ORGANS
V.C
P.T
V.C
V.C
HEPATIC ACINUS
(RAPPAPORT)
HEPATIC LOBULE
(KIERNAN)
PT = PORTAL TRIADS
VC = VENA CENTRALIS
HEPATIC LOBULES AND ACINI


1. INJURY OF THE HEPATOCYTES
- JAUNDICE SERUM INDIRECT BILIRUBIN
- ALT, ASTC IRCULATION
- ABNORMALITY OF LIVER FUNCTION TEST
- PROTHROMBIN TIME ACUTE
- SERUM ALBUMIN CHRONIC

2. OBSTRUCTION CHOLESTASIS
- JAUNDICE SERUM DIRECT BILIRUBIN
- ACHOLIC STOOLS
- BILIRUBINURIA
- ALKALINE PHOSPHATASE, NUCLEOTIDASE & GT

3. SIGN OF INFECTION
SYMPTOMATIC ASYMPTOMATIC
ANICTERIC ICTERIC
ICTERIC
FLU LIKE
FLU LIKE BIOCHEMICAL SEROLOGY
IN APPARENT
SUB CLINICAL
RECOVERY
CARRIER
PROGRESSIVE
FULMINAN
T HEPATIC
FAILURE
CHRONIC
HEPATITIS
HEPATIC
CIRRHOSIS
CHRONIC ACUTE
VIRAL HEPATITIS
PRODROMAL
ICTERIC CONVALESCENT
-NON SPECIFIC
CONSTITUTIONAL

-GASTROINTESTINAL

-EXTRAHEPATIC
.SERUM SICKNESS



-CONSTITUTINAL SYMPTOM
IMPROVE
-PRURITUS
-SYMPTOMS AND SIGNS
GRADUALLY IMPROVE
ACUTE CHRONIC


NO SPECIFIC = ANTIVIRAL
TREATMENT = GENE THERAPY
= IMMUNOMODU-
LATION
ACUTE VIRAL HEPATITIS
1. SUPPORTIVE
A. BED REST
B. WATER AND ELECTROLYTES
C. DIET : FAT IS NOT LIMITED

2. DRUGS
A. HEPATOTOXIC DRUGS SHOULD BE AVOIDED
B. ANTIEMESIS IS NOT RECOMMENDED
C. CORTICOSTEROID IS NOT BENEFIT
D. URSODEOXYCHOLIC ACID
E. ANTIPRURITIC DRUGS
Acute infection:
Newly acquired
Lasts less than six months


Chronic infection:
Lasts six months or longer
Usually life-long


Resolved or Cleared:
Body fights off the virus
Person builds up antibodies


Jaundice Loss of Appetite

Fatigue Nausea

Abdominal Pain Joint Pain

Vomiting

Dark urine



Viral Hepatitis - Overview

A B C D E
Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of Hepatitis




Once within the cell
nucleus the
hepatitis B DNA
causes the liver cell
to produce, via
messenger RNA ;
HBs protein , HBc
protein , DNA
polymerase, the
HBe protein , and
other undetected
protein and
enzymes.
DNA polymerase
causes the liver cell
to make copies of
hepatitis B DNA
from messenger
RNA.



27 nm
Transmission route: fecal-oral
Clinical presentation
- Jaundice: Adults- 30%, Children- <5%
- Fulminant: <1%
Diagnostic tests
- Acute infection: IgM anti-HAV
- Chronic infection: Not applicable
Immunity: IgG anti-HAV
Case-fatality rate: 0.1 2.7%
Chronic infection: None

Hepatitis A Virus
Nucleic Acid: 7.5 kb ssRNA
A virus that attacks the liver

Can cause:
temporary liver inflammation
rare cases, could cause liver failure

30% of people in the United States
have evidence of past infection

From 1995-2006, Hepatitis A has
declined by 90% to the lowest rate
ever recorded (CDC)

Hepatitis A is transmitted by oral-
fecal
route


Fecal
HAV
Symptoms
ALT
ALT
IgM anti-HAV
IgM anti-HAV
Total anti-HAV
Total anti-HAV
Months after Exposure
Months after Exposure
T
i
t
e
r
T
i
t
e
r
Typical Serologic Course
Typical Serologic Course
0 1 2 3 4 5 6 12 24
Hepatitis A Virus Infection
Hepatitis A Virus Infection
Hepatitis B Virus
Hepadnaviridae member that primarily infects liver cells
50 to 100 times more infective than HIV
Multiple genotypes exist (A-H)
DNA virus found in blood and body fluids
Able to survive in dried blood for longer than 1 week
HBsAg
HBV
DNA
HBcA
g
42 nm
People from endemic regions
Babies of mothers with chronic HBV
Intravenous drug abusers
People with multiple sex partners
Hemophiliacs and other patients requiting
blood and blood product treatments
Health care personnel who have contact with
blood
Residents and staff members of institutions for
the mentally retarded

Concentration of Hepatitis B Virus
in Various Body Fluids
High Blood ,Serum, Wound exudates
Moderate Semen, vaginal and menstrual
secretions, Saliva, amniotic fluid
Low/Not
Detectable
Urine , Feces, Sweat , Tears , Breast milk
A battery of serological tests are used for the diagnosis of acute
and chronic hepatitis B infection.
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or immunity to HBV
infection.
anti-HBc IgM - marker of acute infection.
anti-HBcIgG - past or chronic infection.
HBeAg - indicates active replication of virus and therefore
infectiveness.
Anti-Hbe - virus no longer replicating. However, the patient can
still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate
than HBeAg especially in cases of escape mutants. Used mainly
for monitoring response to therapy.
HBsAg:Present in acute or chronic infection.
HBsAb:Present in recovery or immunization.
Anti -HB Core: May be Total (IgG&IgM) or
IgM. Lifelong marker of past and active
infection in either acute or chronic.
HBeAg:Acute infection, and extremely
infectious.
Anti-Hbe: Usually prognostic for resolution.
HAV-Total and HAV-IgM:Anti -HAV.
Anti-HCV:Usually IgG

HBcAg HBsAg HBeAg
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Weeks after Exposure
Titer
IgM anti-HBc
Total anti-
HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52
Years
HBV
DNA
Hepatitis B: Disease Progression
Acute
Infection
Chronic
Infection
Cirrhosis Death
1. Torresi J et al. Gastroenterology. 2000.
2. Fattovich G et al. Hepatology. 1995.
3. Moyer LA et al. Am J Prev Med. 1994.
4. Perrillo R et al. Hepatology. 2001.
5%-10%
1
10-30%
1
23% within 5 years

Liver Cancer
(HCC)
Chronic HBV is the 6th
leading cause of liver
transplantation in the
US
4

Liver
Transplantation
Liver Failure
(Decompensation)
2-6%
90% in perinatal
30-90% in children<5yrs old
5% in healthy adults
Higher in HIV, immune suppressed

Acute
hepatitis
B
Recovery
from
acute
hepatitis
B
Chronic
HBeAg +
disease
Chronic
HBeAG
disease
Successfu
l
Vaccinatio
n
Resistanc
e to
antiviral
agents
HBsAg

Anti-HBs

Anti-HBc
IgM

Anti-HBc

HBeAg

Anti-HBe

(in some
cases)

HBV DNA


(sequence
pol
region)
Interpretation of Serologic
Markers
1. Vaccinate Sexual and household contacts
2. Newborns of HBV-infected mothers
HBIG and
hepatitis B vaccine at delivery
3. Test for response to vaccination
infants of HBsAg-positive mothers (9 to 15 months )
health care workers,
dialysis patients, and
sexual partners
4. Follow-up testing of vaccine responders
Annually for chronic hemodialysis patients
1-2 months
(3) Hepatitis B Vaccination:
The vaccin is given in three
stages.
(1) The initial injection.
(2) A second injection one
month later.
(3) A third injection 6
months after the first
injection.
Fecal-oral transmission (human to human)
Contaminated water supplies in tropical or
subtropical developing countries
Mainly young adults
Can infect primates, swine, sheep, rats
Swine may be reservoir of infection in North
America
Maternal-infant transmission occurs and is
often fatal

32 nm
Hepatitis E Virus
Nucleic Acid: 7.5 kb ssRNA
Acute Hepatitis C
Chronic Hepatitis
85 %
Cirrhosis 20 %
Di Bisceglie, Hepatology, 2000
Natural History

Faster
progression
older age at
infection
alcohol
HIV infection
post-
transplant
2
0
-
3
0

y
e
a
r
s

2
0
-
5
0

y
e
a
r
s

40 million
170 million
10 million
HIV
HCV
United States
30% of patients who
are HIV-infected are
co-infected with
HCV
HIV
2003 approximately
1 million persons in
the US with
HIV/AIDS


Staples CT. Clin Infect Dis 1999
HCV +
HIV
Drug use
Transfusion/blood products
Organ transplantation
Sexual
< 5% heterosexual monogamous couples
No recommendations for condom use
increased with multiple partners
??? increased if HIV co-infection ???
Vertical (mother to child)
HCV alone: 2-5%
HIV/HCV: 25%
No treatment given teratogenic meds

Mast EE. J Infect Dis 2005
Veronese L. Antimicrob Agents Chemother 2000
Acute Hepatitis C
Chronic Hepatitis
85 %
Cirrhosis 20 %
Di Bisceglie, Hepatology, 2000
Natural History

Faster
progression
older age at
infection
alcohol
HIV infection
post-
transplant
2
0
-
3
0

y
e
a
r
s

2
0
-
5
0

y
e
a
r
s

Antibody tests
3 generations
ELISA
positive 8-10 weeks

HCV RNA
PCR or branched DNA
documents viremia
response to treatment

Genotype 1
Most common in USA
> 90% for African
Americans
Requires 48 weeks of
treatment
Lowest response rates
Genotype 2 and 3
Less common in USA
24 weeks of treatment
Higher response rates

1
6
3
4
5
2
Simmonds P, Journal of Hepatology, 1999
Baseline viral load
Week 12 HCV RNA
Week 24 HCV RNA
< 2 log reduction
HCV RNA
> 2 log reduction
HCV RNA
HCV RNA
negative
HCV RNA
positive
Peginterferon alfa
Self-administered subcutaneous injection
Weekly

Ribavirin
Capsule
Twice daily
Complementary and alternative therapies
Milk thistle (Silybum marianum) from
the aster family
Active extract is silymarin, found in the
fruit
Anti-oxidant properties
Used in Europe for jaundice since the
16th century
Not anti-viral
Studies in progress

Nucleic Acid: 1.7 kb ssRNA
Classification: unclassified,
related to viroids; deltavirus
Transmission: sex, IVDA
Clinical features
- Fulminant: 2 7.5%
- Chronic infection
Superinfection: 80%
Coinfection: < 5%

Diagnostic tests
-Acute infection: IgM anti-HDV
-Chronic infection: IgG anti-HDV, HBsAg
+

35-37nm
Virus particle 36
nm in diameter
encapsulated
with HBsAg,
derived from
HBV
Delta antigen is
associated with
virus particles
ssRNA genome
Coinfection
Superinfection
B
B
D
D
1. NIH Consensus Development Conference Statement; March 24-26, 1997.
2. Davis GL et al. Gastroenterol Clin North Am. 1994;23:603-613.
3. Koretz RL et al. Ann Intern Med. 1993;119:110-115.
4. Takahashi M et al. Am J Gastroenterol. 1993;88:240-243.
HCV infection
Chronic HCV Cirrhosis Hepatic Failure
Liver Cancer
Liver Transplant
Candidates
60-85%
1
~20%
4
~ 20%
3
20%-50%
2
Time: 20-30 years
Inflammation Grade
Measure of severity and ongoing disease
activity
0-4 (METAVIR)
Inflammation leads to scarring/fibrosis

Fibrosis Stage
Amount of fibrous scar tissue
0-4 (METAVIR)
Stage 4 = cirrhosis
Indicates long-term disease progression
No fibrosis
Cirrhosis
Brunt EM. Hepatology. 2000;31:241-246.