Professional Documents
Culture Documents
Dr.LeonardoBDairiSpPDKGEH
Manycausesofhepatitis
Infectious
Bacterial
Parasitic
Viral
Noninfectious
Leptospirosis
Syphillis
Tuberculosis
Toxoplasmosis
Amebiasis
EpsteinBarr
HerpesSimplex
VaricellaZoster
Coxsackievirus
Rubella
YellowFever
Alcohol
Drugs
Viralagentsthatprimarilyor
exclusivelyinfecttheliver
HepatitisAvirus
Infectioushepatitis
HepatitisBvirus
Serumhepatitis
HepatitisCvirus
Parenterallytransmitted
HepatitisEvirus
Entericallytransmitted
HepatitisDvirus
CoinfectionwithHBV
HepatitisGvirus
Parenterallytransmitted
ViralHepatitisHistoricalPerspective
Enterically
E
transmitted
Infectious A
Viral
hepatitis
NANB
Serum B D
Parenterally
C transmitted
F, G,
? other
ViralHepatitisOverview
Type of Hepatitis
A
Source of
virus
Route of
transmission
Chronic
infection
Prevention
feces
fecal-oral
no
blood/
blood/
blood/
blood-derivedblood-derived blood-derived
body fluids body fluids body fluids
E
feces
yes
yes
no
Initiallaboratoryevaluationof
jaundicedpatient
TEST PERFORMED
MEASUREMENT
Urine bilirubin
Conjugated bilirubin
Serum bilirubin
Conjugated and
unconjugated bilirubin
Hepatocellular damage
Alkaline phosphatase
Intrahepatic or extrahepatic
obstruction
Clotting mechanism
HEPATITIS
A
RNA Picornavirus
No chronic infection
An acute :
discrete onset of symptoms (e.g. fatigue, abdominal
pain, loss of appetite, nausea, vomiting),
jaundice or elevated serum aminotransferase levels
Never chronic
Adults often feel unwell for 6 weeks
Laboratory criteria
HAVCLINICALSYNDROMES
Incubation phase: long (6weeks-6month)
Prodromal phase: insidious
Flu-like: malaise, fatigue, anorexia, nausea,
abdominal discomfort, chills
Icteric phase: liver damage: jaundice, dark
urine, pale stools
Recovery: decline in fever; renewed appetite
HEPATITISACLINICALFEATURES
Jaundice by
<6 yrs
6-14 yrs
>14 yrs
Rare complications:
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
Incubation period:
Average 30 days
Range 15-50 days
Chronic sequelae:
None
age group:
<10%
40%-50%
70%-80%
EVENTSINHEPATITISAVIRUSINFECTION
Clinical illness
Infection
ALT
Response
IgM
IgG
Viremia
HAV in stool
Week
10
11
12
13
CONCENTRATIONOFHEPATITISAVIRUS
INVARIOUSBODYFLUIDS
Body Fluids
Feces
Serum
Saliva
Urine
100
102
104
106
108
1010
GLOBALPATTERNSOF
HEPATITISAVIRUSTRANSMISSION
Hi
Rate
Diseas
es
Low to high
Peak Age
of
Infection
Early childhood
Moderate
High
Late childhood/
young adults
Person to person;
food and waterborne
outbreaks
Low
Young adults
Very low
Adult
Person to person;
food and waterborne
outbreaks
Travelers; outbreaks
uncommon
Endemiciy
Low
Very low
Transmission
Patterns
Person to person;
outbreaks uncommon
GEOGRAPHIC DISTRIBUTION OF
HEPATITIS A VIRUS INFECTION
MANAGEMENT HEPATITIS A
Nospecifictreatment
Symptomatis
Prednisolone40mgPOdaily,taperingoff(2
4)weeks
Preventionisbetterthancure
PREVENTING HEPATITIS A
Hygiene(e.g.,handwashing)
Sanitation(e.g.,cleanwatersources)
HepatitisAvaccine(preexposure)
Immuneglobulin(preandpostexposure)
HEPATITIS A VACCINES
Highly immunogenic
97%-100% of children, adolescents, and adults have
Highly efficacious
In published studies, 94%-100% of children protected
HAVRIX
(GSK)
2 doses
360 EL.U.
Thailand
38,157
VAQTA
(Merck)
1 dose
25 units
New York
Vaccine
1-16 yrs
2-16 yrs
Vaccine Efficacy
(95 % Cl)
94%
(79%-99%)
1,037
100%
(85%-100%)
Efficacy
HEPATITIS A PREVENTION
IMMUNE GLOBULIN
Pre-exposure
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)
HEPATITISB
HBV
HBV
1/3worldspopulation
infected
350millionchronic
infected.
Acute/fulminant
Inactivecarrierstate
ChronicHepatits
Livercirrhosis
HepatocellularCarcinoma.
HBV,GlobalHealthProblem
HBsAg
Positif, %
Taiwan
10.0-13.8
Vietnam
5.7-10.0
China
5.3-12.0
Africa
5.0-19.0
Philippines
5.0-16.0
Thailand
4.6-8.0
Japan
4.4-13.0
Indonesia
4.0
South Korea
2.6-5.1
India
2.4-4.7
High ( 8%)
Russia
1.4-8.0
US
0.2-0.5
Prevalensi HBsAg
8genotypes(AH):
and
Moreadvancedliverdisease
Lowerresponseratetointerferon
GreaterriskofHCCdevelopment.
HBVnomenclature
HBV:hepatitisBvirus
HBsAg:hepatitisBvirussurfaceantigen
HBcAg:hepatitisBviruscoreantigen
HepatitisBVirus(HBV)
3213
S1
pre polymerase
157
Domain Reverse
transcriptase/ DNA
polymerase mengalami
overlap dengan gen
permukaan
56
8
2
preS2
4 overlapping open
reading frames
2458
D
YM
EcoRI
3221, 1
DR1
(-)
re
co
19
03
pre
co
183
7
re
834
230
(+)
A er
RN im
DR2 pr
1622
1816
7
13
MMWR.2003;52:133.OttMJandArudaM.JPediatrHealthCare.1999;13:211216.
RibeiroRM,etal.MicrobesandInfection.2002;4:829835.
NATURALCOURSEOFCHRONICHBV
INFECTIONS
The HBV three detectable antigens :
1. HBsAg Surface antigen
2. HbcAg Core antigen
3. HBeAg e antigen
Chronic infection HBsag persistence for more than 6
months
HBsAg non infectious
HBcAg represents the nucleocapsid of the virus
presence indicates infectivity, found in the liver not in
the serum.
HBeAg found in the serum
a. Viral replication
b. Infectivity
Modes of Transmission
Transfusion
(blood, blood
products)
Fluids
(blood, semen)
Hepatitis B
Organs &
tissue
transplantation
Shared needles
& syringes
Child to child
HBVCLINICALSYNDROMES
ACUTE INFECTION
Incubation phase: long (6weeks-6month)
Prodromal phase: insidious
Flu-like: malaise, fatigue, anorexia, nausea, abdominal
discomfort, chills
FaseInfeksiKronikHepatitisB
Increasing age
HBeAg+/antiHBe
HBeAg - / anti-HBe +
HBV DNA
ALT
FASE IMMUNE
TOLERANCE
FASE IMMUNE
CLEARANCE
FASE INACTIVE
CARRIER HBsAg
FASE REACTIVATION
FaseInfeksiKronikHepatitisB
Increasing age
HBeAg+/antiHBe
HBeAg - / anti-HBe +
HBV DNA
ALT
FASE IMMUNE
TOLERANCE
FASE IMMUNE
CLEARANCE
FASE INACTIVE
CARRIER HBsAg
FASE REACTIVATION
Rekomendation to
treat
FaseInfeksiKronikHepatitisB
Increasing age
HBeAg+/antiHBe
HBeAg - / anti-HBe +
HBV DNA
ALT
FASE IMMUNE
TOLERANCE
FASE IMMUNE
CLEARANCE
FASE INACTIVE
CARRIER HBsAg
FASE REACTIVATION
FaseInfeksiKronikHepatitisB
Increasing age
HBeAg+/antiHBe
HBeAg - / anti-HBe +
HBV DNA
ALT
FASE IMMUNE
TOLERANCE
FASE IMMUNE
CLEARANCE
FASE INACTIVE
CARRIER HBsAg
Rekomendation to
treat
FASE REACTIVATION
41
HBVDIAGNOSIS
CLINICALL
LABORATORY
Liverenzymes
Serology
HBeAg,HBcAg,virus:activeinfection
AntiHBcIgM:acuteactiveinfection
AntiHBeIgG:acuteinfection
Healthy Liver
Hepatic Fibrosis
Cirrhosis
Liver Cancer
Healthy Liver
Hepatic Fibrosis
Cirrhosis
Liver Cancer
HBV Complications
Chronic HBsAg antigenemia
Chronic persistent hepatitis (CPH)
Chronic active hepatitis (CAH)
Chronic lobular hepatitis (CLH)
Liver cirrhosis
Hepatocellular carcinoma
MANAGEMENT HBV
PREVENTION OF LIVER
CIRRHOSIS,HEPATOMA
AND MORTALITY
Supretion
replikation of
HBV
MANAGEMENT
1. Evaluation of the disease
2. Non-specific/specific therapy
3. Monitoring and surveillance
The diagnosis of CHB infection HBsAg at least 6
month
HBeAg and Anti-HBe Viral replication and thus
infectivity.
ALT/AST measured inflammation
Liver Biopsy is more accurate
USG/Fibro Scan parenchymal impairment, fibrosis
Early cirrhosis ussually not detected by ultrasound
MANAGEMENT
Non-spesific advice
General advice
CHB infection potentially infectious should not share
toothbrushes or shaving equipment
Household contacts and sexual partners should have their hepatitis
serology determined and should be immunized if found negative
for HBsAg, anti-HBs and anti HBc
When a woman becomes pregnant inform her gynecologist
about her HBV status appropriate steps can be taken to
immunize her baby at birth
A Baby born to HBeAg-positive mother should be given hepatitis B
immune-globulin at the same time
MANAGEMENT
Diet
Nutritious diet to maintain normal body weight
May be needed protein, salt and water restriction
Exercise
Subjects with asymptomatic infection should
continue their regular form of exercise
With cirrhosis should avoid strenuous jogging and
heavy weight lifting
MANAGEMENT
Alcohol and Drugs
Should be avoided Potentially hepatotoxic
agents or regular alcohol intake, steroids and
immunosuppressive agents
In Endemic countries patients need steroids or
immunosuppressive drugs,HBV status checked to
prevent HBV flares.
55
TreatmentofChronicHepatitisB
Drugs for Chronic HBV inf
1.
2.
3.
4.
5.
6.
7.
8.
9.
PhasesofChronicHBVInfection:
CandidatesforTherapy
Phases of Chronic HBV Infection
Immune
Tolerance
Immune Clearance/
HBeAg-Positive
CHB
Nonreplicative
(Inactive Carrier)
Reactivation/
HBeAg-Negative
CHB
HBV DNA,
IU/mL
105 - 1010
104 - 1010
< 104
103 - 108
HBeAg
HBeAg+
HBeAg+
HBeAg-
HBeAg-
ALT
Normal
High or fluctuating
Normal
High or fluctuating
--
Active inflammation
on liver biopsy
HBsAg may
become
undetectable
Active inflammation
on liver biopsy
No
Yes
No
Yes
Other
Candidates
for therapy?
YimHJ,etal.Hepatology.2006;43:S173S181.
RekomendationtreatmentpatientHBeAg(+)/(APASL2008)
RekomendationTreatmentPatientHBeAg()/(APASL2008)
RekomendationTreatmentPasientCirrhosis(APASL2008)
61
RekomendasiterapidariEASL(European
AssociationfortheStudyoftheLiver)2009
IndikasiterapisamauntukpasienHBeAg(+)danHBeAg
().Memenuhi3kriteria:kadarserumHBVDNA,kadar
serumaminotransferase&grade/tingkathistologi.
PasiendapatditerapibilakadarHBVDNA>2000IU/ml
(10.000 kopi/ml) dan atau kadar ALT diatas BANN, dan
biopsi hati menunjukkan moderate sampai severe necro
inflammation dan atau fibrosis memakai sistim skor
standar (contoh paling sedikit grade A2 atau tingkat F2
skorMETAVIR.
62
HBV Prevention
Screenbloodproducts
Sterilizationofneedles,etc.
Avoidingintimatecontact,e.g.,
householdorsexualcontacts
Vaccination
HEPATITIS
FULMINANT
HEPATITIS FULMINANT
Hepaticfailurewithin23weeks.
Reactivationofchronicoracutehepatitis
Massivenecrosis,shrinkage,wrinkled
Collapsedreticulinnetwork
Onlyportaltractsvisible
Littleormassiveinflammation
Morethanaweekregenerativeactivity
Completerecoveryorcirrhosis.
OGRADY dkk :
Basedliverfailure,onsetofjaundice,encepalopathy
HYPERACUTE LIVER FAILURE,intervalless
than7days
ACUTE LIVER FAILURE,interval8and28days
SUBACUTE LIVER FAILURE,intervalbetween
5and12weeks
Clinical features
ICKTERUS PROGRESIF
BILIRUBIN > 20mg %
NAUSEA,MALAISE,VOMITING,FEVER.LIVER
SIZE SMALL.COMA MAY RAPIDLY (FEWDAYS).
TACHYCARDIA,HYPOTENSION,HYPERVENTILAT
ION ,CEREBERAL OEDEME ARE LATER
FEATURES
PROLONG PROTROMBIN TIME,ALT/AST
INCREASE
ETIOLOGI
VIRAL HEMORAGIC FEVER VIRUS
HEPATITIS VIRUS
SITOMEGALOVIRUS
HEPATITIS A
HERPES SIMPLEX VIRUS
HEPATITIS B
EPSTEIN BARR VIRUS
HEPATITIS C
PARAMIXOVIRUS
HEPATITS E
ADENOVIRUS
HEPATITIS G
DRUG/ TOXIN,
HALOTHANE
ISCHEMIC
ACETAMINOFEN
ISCHEMIC HEPATITIS
ISONIAZID-RIFAMPICIN
SURGICAL SHOCK
ANTIDEPRESANT
ACUTE BUCCHIARY SYNDROME
NSAID
VALPROIC ACID
MISCELLANEUS (RARE)
MUSHROOM POISONING
HEAT STROKR
HERBAL REMEDIES
SEVERE BACTERIAL INFECTION
AMANITA POISONING
MASSIVE MALIGNANT INFILT.
YELLOW PHOSPORUS
BACILLUS CEREUS EMETIC TOXIN
PREGNANCY RELATED
ACUTE FATTY LIVER OF PREGNANCY
HELLP SINDROME
MANAGEMENT
FARMAKOLOGI
N-ASETIL SISTEIN
PROSTAGLANDIN
HAEMOPERFUSI ARANG
KOLOUMN HEPATOSIT
MOLEKULER
REGULASI SITOKIN
REGULASI KASKADE KOAGULASI
INHIBISI APOPTOSIS
HEPATOSIT GROWTH FACTOR
HEPATOSIT TRANSPLANT
TRANSPLANTASI
LIVER TRANSPLANT
HEPATITISC
Introduction
Hepatitis C virus (HCV) infection is one of the main
causes of chronic liver disease worldwide
The long-term hepatic impact of HCV infection is
highly variable, from minimal changes to chronic
hepatitis, extensive fibrosis, and cirrhosis with or
without hepatocellular carcinoma (HCC)
Introduction
Prior to the 1990s, the principal routes of HCV infection
were via blood transfusion, unsafe injection procedures,
and intravenous drug use.
Chronic HCV
60% to 85%
Resolved
15% to
40%
Cirrhosis
10% to 15%
After 20
yrs
Stable
25%
Slowly
progressiv
e
75%
HCC
10
20
Time after infection
HepatitisCVirusInfection
PopulationatRisk
Transfusionofbloodproductsbefore1992
Intravenousdruguse
Nasalinhalationofcocaine
Chronicrenalfailureondialysis
Incarceration
Occupationalexposuretobloodproducts
Transplantationofanorgan/tissuegraftfromanHCV
positivedonor
Bodypiercingandpotentiallytattoo
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1,
2006.
HCVRiskFactors
receivedblood,bloodproducts,or
anorgantransplantpriorto1992
ever,evenonce,shareddrug
paraphernalia
everbeenstuckbyausedblood
needle
beenonkidneydialysis
hadatattooorbodypiercing
hadmultiplesexpartners,or
sexualactivitythatinvolved
contactwithblood
sharedpersonalcareitems(razors,
toothbrushes,etc.)withother
people
combatveteran
Malegender
ChronicHBVcoinfection
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
3
4
Months
2
3
Years
HCV Counseling
Donotdonateblood,bodyorgans,other
tissueorsemen
Donotshareitemsthatmighthaveblood
onthem
personalcare(e.g.,razor,toothbrush)
hometherapy(e.g.,needles)
Covercutsandsoresontheskin
HCV Counseling
HCV Diagnosis
Mostpatientsasymptomatic
Abnormalliverfunctiontests;AST/ALT
HepatitisCantibody(EIA)
RIBA
HCVRNAlevels
Liverbiopsy:gradeandstagedamage
Diagnosis Hepatitis C
Kelompok resiko tinggi / terpapar darah yang diduga
terkontaminasi HCV: skrining Anti-HCV
Quantitative assays
Anti-HCV positif
Qualitative assays
High sensitivity
( 50 IU/mL)
Hepatitis C Kronik
(asimtomatik)
Singkirkan penyebab lain (virus, obat,
autoimunitas)
DiagnosisofChronicViralHepatitis:
SerologicTesting
PatientsshouldbetestedforHCVandHBV
ifthey:
haveknownriskfactorsforviralhepatitis
indicatepossibleriskfactorsforhepatitis
haveelevatedliverenzymes
expressadesiretoknowtheirHCVand/orHBV
status
ChronicHCVInfection:Recommendedpretreatment
evaluation
Test
Purpose
HCV-RNA by PCR
Confirm viremia.
Antinuclear antibody
1- Antitrypsin phenotype
Hepatitis C genotype
Liver biopsy
HCV Therapy
Pegylated Interferon injections weekly
AND
Ribavirin pills (or liquid) twice daily
HEPATITISD
HEPATITIS AKUT - D
Terdeteksi bersamaan dengan virus Hepatitis B.
Prevalensi HDV (+) berhubungan dengan
prevalensi infeksi HBV (+).
HDV lebih dominan didaerah tropikal dan
subtropik,di
negara berkembang drpd negara
maju (Barat).
Klinis bervariasi dr asimptomatis sampai berat
80% kasus kronik hepatitis D menjadi sirosis
dalam
5-10 tahun.
Gold standard d/: HDV RNA (+) atau HDAg (+)
liver.
HEPATITISE
HEPATITIS E
Nonenveloped spherical RNA virus
Transmission fecal oral,main target
hepatocyte
Endemic in India,Southeast and Central Asia
The largest affected in young adult (15-40 years)
Incubation period 2 10 weeks
Clinical same with HepatitisA,but generrally
more severe
Diagnosed presence anti HEV (+) / IgG or IgM,
HEV RNA (+)
TREAEMENT,supportive and no effective vaccine
available
Prvention,improved sanitation,sanitary
handling,food,water, boil of water
HEPATITISG
HEPATITIS G
DILD
Wilsons disease
It is important to exclude wilsons disease
as a cause of chronic hepatitis when it
apprears in patients younger than 35 years.
Liver disease often precedes symptoms
attributed to central nervous system
involvement and the appearance of KayserFleischer rings and may be the initial
presentation in 50 % of cases.
Elevated urinary and hepatic copper levels
are diagnostic.
Improvement may be achieved by early
treatment with D-penicillamine.
Autoimmune chronic
hepatitis