Hepatitis

Dr.LukmanHakimZain
DivisiGastroenterologiBagIPD
FKUSU/RSHAMMedan.
 Manycausesofhepatitis
Leptospirosis
Infectious Bacterial Syphillis
Tuberculosis
Toxoplasmosis
Parasitic Amebiasis

EpsteinBarr
HerpesSimplex
Viral VaricellaZoster
Coxsackievirus
Rubella
YellowFever
Alcohol
Noninfectious Drugs
 Vialagentsthatprimarilyor
exclusivelyinfecttheliver
HepatitisAvirus Infectioushepatitis
HepatitisBvirus Serumhepatitis
HepatitisCvirus Parenterallytransmitted
HepatitisEvirus Entericallytransmitted
HepatitisDvirus CoinfectionwithHBV
HepatitisGvirus Parenterallytransmitted
Viral Hepatitis - Historical
Perspective
Infectious A Enterically
E
transmitted

Viral NANB
hepatitis

Parenterally
Serum B D C transmitted
F, G,
? other
 Viral Hepatitis -
Overview
Type of Hepatitis
A B C D E
Source of feces blood/ blood/ blood/ feces
virus blood-derivedblood-derived blood-derived
body fluids body fluids body fluids
Route of fecal-oral percutaneouspercutaneous 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
 Initiallaboratoryevaluationof
jaundicedpatient
TESTPERFORMED
Urinebilirubin
Serumbilirubin
Alanineaminotransferase(ALT)
Aspartateaminotransferase(AST)
Alkalinephosphatase
Prothrombintime,partial
thromboplastintime,plateletcount,
bleeding
Bloodcountwithbloodsmearexam
MEASUREMENT
Conjugatedbilirubin
Conjugatedandunconjugatedbilirubin
Hepatocellulardamage
Heptocellulardamage
Intrahepaticorextrahepaticobstruction
Clottingmechanism
Redbloodcellmorphology,parasites,
atypicallymphocytes
 HEPATITIS A VIRUS

RNAPicornavirus
Singleserotypeworldwide
Acutediseaseandasymptomaticinfection
Nochronicinfection
Protectiveantibodiesdevelopinresponseto
infectionconferslifelongimmunity
 ACUTE HEPATITIS A CASE
DEFINITION FOR SURVEILLANCE

Clinicalcriteria
Anacuteillnesswith:
discreteonsetofsymptoms(e.g.fatigue,abdominalpain,lossof
appetite,intermittentnausea,vomiting),and
jaundiceorelevatedserumaminotransferaselevels

Laboratorycriteria
IgMantibodytohepatitisAvirus(antiHAV)positive
CaseClassification
Confirmed.Acasethatmeetstheclinicalcasedefinitionandislaboratory
confirmedoracasethatmeetstheclinicalcasedefinitionandoccursina
personwhohasanepidemiologiclinkwithapersonwhohaslaboratory
confirmedhepatitisA(i.e.,householdorsexualcontactwithaninfected
personduringthe1550daysbeforetheonsetofsymptoms).
HEPATITIS A - CLINICAL FEATURES
Jaundice by <6 yrs <10%
age group: 6-14 yrs 40%-50%
>14 yrs 70%-80%
Rare complications: Fulminant hepatitis
Cholestatic hepatitis

Relapsing hepatitis

Incubation period: Average 30 days

Range 15-50 days

Chronic sequelae: None

EVENTS IN HEPATITIS A VIRUS INFECTION
Clinical illness

Infection ALT

IgM IgG
Response

Viremia

HAV in stool

0 1 2 3 4 5 6 7 8 9 10 11 12 13
Week
 CONCENTRATION OF HEPATITIS A VIRUS
IN VARIOUS BODY FLUIDS
Feces
Body Fluids

Serum

Saliva

Urine

100 102 104 106 108 1010

Infectious Doses per mL
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
 GLOBAL PATTERNS OF
HEPATITIS A VIRUS TRANSMISSION
Diseas Peak Age Transmission
Endemicity
e of Patterns
Rate Infection
High Low to high Early childhood Person to person;
outbreaks uncommon
Moderate High Late childhood/ Person to person;
young adults food and waterborne
outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adult Travelers; outbreaks
s uncommon
GEOGRAPHIC DISTRIBUTION OF
HEPATITIS A VIRUS INFECTION
HEPATITIS A VIRUS TRANSMISSION
Closepersonalcontact
(e.g.,householdcontact,sexcontact,child
daycarecenters)

Contaminatedfood,water
(e.g.,infectedfoodhandlers)

Bloodexposure(rare)
(e.g.,injectiondruguse,rarelyby
transfusion)
 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 protective levels of antibody within 1
month of receiving first dose; essentially
100% have protective levels after second dose

Highly efficacious
In published studies, 94%-100% of children
protected against clinical hepatitis A after
equivalent of one dose
HEPATITIS A VACCINE EFFICACY
STUDIES Site/ Vaccine Efficacy
Age Group (95 % Cl)
Vaccine N

HAVRIX Thailand 38,157 94%

(GSK) 1-16 yrs (79%-99%)
2 doses
360 EL.U.

VAQTA New York 1,037 100%

(Merck) 2-16 yrs (85%-100%)
1 dose
25 units

JAMA 1994;271:1363-4; N Engl J Med 1992;327:453-7

 DURATION OF PROTECTION AFTER
HEPATITIS A VACCINATION

Persistenceofantibody
Atleast58yearsamongadultsandchildren
Efficacy
Nocasesinvaccinatedchildrenat56yearsoffollow
up
Mathematicalmodelsofantibodydeclinesuggest
protectiveantibodylevelspersistforatleast20
years
Othermechanisms,suchascellularmemory,
maycontribute
 COMBINED HEPATITIS A
HEPATITIS B VACCINE
ApprovedbytheFDAinUnitedStatesforpersons>18
yearsold
Contains720EL.U.hepatitisAantigenand
20g.HBsAg
Vaccinationschedule:0,1,6months
Immunogenicitysimilartosingleantigenvaccinesgiven
separately
Canbeusedinpersons>18yearsoldwhoneed
vaccinationagainstbothhepatitisAandB
Formulationforchildrenavailableinmanyothercountries
 HEPATITIS A PREVENTION
IMMUNE GLOBULIN
Preexposure
travelerstointermediateandhigh
HAVendemicregions

Postexposure(within14days)
Routine
householdandotherintimatecontacts

Selectedsituations
institutions(e.g.,daycarecenters)

commonsourceexposure(e.g.,

foodpreparedbyinfectedfoodhandler)
 SAFETY OF HEPATITIS A VACCINE
Mostcommonsideeffects
Soreness/tendernessatinjectionsite50%
Headache15%
Malaise7%
Nosevereadversereactionsattributedtovaccine
Safetyinpregnancynotdeterminedrisklikelylow
Contraindicationssevereadversereactiontopreviousdoseorallergytoavaccinecomponent
Nospecialprecautionsfor
immunocompromisedpersons
 TREATMENT
SUPPORTIVE
OPNAMEBILAGEJALABERAT
TIDAKADAPENGOBATANANTI
VIRUS
HepatitisBVirus
HBV
 HBVnomenclature
HBV:hepatitisBvirus
HBsAg:hepatitisBvirussurfaceantigen
HBcAg:hepatitisBviruscoreantigen
HepatitisBVirusInfection

GlobalFacts
2billionpeopleinfected.
>400millionchroniccarrierofthevirus.
75%ofthechroniccarriersareChinese.
Annualincidenceoflivercancerintheworld:
530,000casesofwhich
316,000cases(59.4%)duetohepatitisB
Lai CL, et al, Lancet, 2003
 HowDoYouAcquirethe
Infection
Transfusion and Newborns of long-term
inAsiaPacific? carriers
transplant recipients

Individuals with
Intravenous
multiple
drug users
sexual partners

Healthcare Prisoners and other

workers institutionalised people
 HowDoYouAcquirethe
Infection
Transfusion and Newborns of long-term
transplant recipients intheWest? carriers

Individuals with
Intravenous
multiple
drug users
sexual partners

Healthcare Prisoners and other

workers institutionalised people
 HBVEpidemiology
Horizontaltransmission
Persontopersonspread
Parenteral
Sexual
Verticaltransmission
Chronicallyinfectedmothertochild
Atbirthorviabreastmilk
 HBVPathology
Portalofentry
Percutaneousismostefficient
Sexualorperinatalisless
efficientbutmajorsource
Intobloodstreamandtoliver
Hepatocytes
Littlecytopathology
Immunepathology
HBVEpidemiology
 HBVClinicalSyndromes
ACUTEINFECTION
Incubationphase:long
Prodromalphase:insidious
Flulike:malaise,fatigue,anorexia,nausea,abdominaldiscomfort,
chills
Ictericphase:liverdamage:jaundice,darkurine,pale
stools
Recovery:declineinfever;renewedappetite
HBVDiagnosis
Clinical
Symptoms
LookslikeHAV
 HBVDiagnosis
Laboratory
Liverenzymes
Serology
HBeAg,HBcAg,virus:activeinfection
AntiHBcIgM:acuteactiveinfection
AntiHBeIgG:acuteinfection
 HBVComplications
Fulminatehepatitis
Chronichepatitis
5%10%ofHBVinfections
10%oftheseprogresstocirrhosis/liverfailure
Athigherriskforfulminanthepatitis
Healthy Liver Hepatic Fibrosis

Cirrhosis Liver Cancer

Healthy Liver Hepatic Fibrosis

Cirrhosis Liver Cancer

 HBVComplications
ChronicHBsAgantigenemia
Chronicpersistenthepatitis(CPH)
Chronicactivehepatitis(CAH)
Chroniclobularhepatitis(CLH)
Livercirrhosis
Hepatocellularcarcinoma
Postviral;asymptomaticcarrier
state;HBsAgonly
Postviral;elevatedtransaminase;no
progressiontoliverdisease
Postviral;progressestoliver
disease
Postviral;noprogressiontoliver
disease;elevatedtransaminase
levels
2030yearsofpersistentHBV
infectionleadingtoliverinjury
 TreatmentofChronicHepatitisB
C. When
Chronic HBV inf & Cirrhotic & HBV DNA 10 4

copies/ ml
D. How
5 Drugs for Chronic HBV inf
1. Interferon Alfa 2b ( 1992)
2. Peginterferon Alfa 2a ( 5/2005 )
3. Lamivudin ( 1998 )
4. Adifovir dipivoxil ( 2002 )
5. Entecavir ( 3/ 2005 )
6. Telbivudine ( 2/2007)
7. Tenofovir
the clinician needs to differentiate between the patient who is
an inactive carrier typical presentation:
a. Older age d. Low HBV DNA levels < 10000
copies/ml
b. Normal serum ALT e. Histology showing no inflammation
but
c. HBeAg-negative varying amounts of fibrosis

and the patient who has HBeAg-negative chronic hepatitis

typical presentation:
a. Older age d. Elevated HBV DNA > 10000
copies/ml
b. Elevated serum ALT
c. HBeAg-negative

the first group of patients does not need immediate treatment,

but the second group does.
Treatment Strategy of CHB
Decompensated Cirrhosis or End-Stage Liver Disease (HBeAg+ or HBeAg -)

Decompensated Cirrhosis or End Stage Liver Disease (HBeAg+ or HBeAg -)

Treatment indicated
Consider/refer to transplant center for
evaluation for OLT
Entecavir, adefovir, lamivudine or
combination are first-line options
Entecavir and adefovir preferred over lamivudine
ACT HBV Asia-Pasific
due to its high rate of drug resistance, especially
Steering Committee
In decompensated cirrhosis
Members, Chronic
hepatitis B; treatment
alert. Liver Int. 2006 Response No Response

Closely monitor hepatic function and DNA;

May delay OLT OLT
 HBVPrevention
Screenbloodproducts
Sterilizationofneedles,etc.
Avoidingintimatecontact,e.g.,
householdorsexualcontacts
Vaccination
Subunitvaccines
HBsAg