VIRAL AND AUTOIMMUNE HEPATITIS - Columbia University · e of Hepatitis A f H titi A I f ti Hepatitis A Infection. HEPAT • Oral fecal route of traOral fecal route of tra • Excreted

VIRAL AND AHEPA

2020

Arthur M. MClinical ProfessClinical Profess

AUTOIMMUNEATITIS

1010

Magun, M.D.sor of Medicinesor of Medicine

WHAT IS HEWHAT IS HE• Inflammation of the liveInflammation of the live• Almost always, inflamm

liver enzymesliver enzymes• AST and ALT are the ke• Other Liver Function Te

abnormal in hepatitis inc• Bilirubin, albumin, a

gamma glutamyl trag g y

EPATITIS ?EPATITIS ?

rrmation implies elevation in

ey liver enzymesests (LFTs) which can be clude:alkaline phosphatase, anspeptidasep p

CAUSES OHEPA

• Viruses – hepatotrophicVi CMV EBV• Viruses – CMV, EBV

• Other infectious etiologi• Alcoholic hepatitis• Drug hepatitisDrug hepatitis• Ischemic hepatitis

Bili di h• Biliary disease – e.g. ch

OF ACUTE ATITIS

c – A through E

ies - TB, MAI, Fungus

h l d h lithi iholedocholithiasis

Human HepaHuman HepaHuman Hep

Virus Genome Gensize

Virus Genome Gensize

HAV RNA 7HAV RNA 7HAV RNA 7.positive sense, single stranded, linear

HBV DNA 3

HAV RNA 7.positive sense, single stranded, linear

HBV DNA 3HBV DNA 3.partially double stranded, circular

HCV RNA 9

HBV DNA 3.partially double stranded, circular

HCV RNA 9HCV RNA 9.positive sense, single stranded, linear

HDV RNA 1.

HCV RNA 9.positive sense, single stranded, linear

HDV RNA 1.HDV RNA 1.positive sense, single stranded, linear

HEV RNA 7.

HDV RNA 1.positive sense, single stranded, linear

HEV RNA 7.positive sense, single stranded, linearpositive sense, single stranded, linear

atitis Virusesatitis Virusespatitis Viruses

ome Envelope Family / genuse (kb) ome Envelope Family / genus

e (kb) 5 Picornaviridae5 Picornaviridae.5 - Picornaviridae

hepatovirus

2 + Hepadnaviridae

.5 - Picornaviridae hepatovirus

2 + Hepadnaviridae.2 + Hepadnaviridae

6 + Flaviviridae

.2 + Hepadnaviridae

6 + Flaviviridae.6 + Flaviviridaehepacivirus

.7 + Unclassified

.6 + Flaviviridaehepacivirus

.7 + Unclassified.7 Unclassified(viroid), delta virus

.5 - Unclassified,

.7 Unclassified(viroid), delta virus

.5 - Unclassified,togavirus andalpha virus-liketogavirus andalpha virus-like

OTHER INFECTIOOF ACUTE

• CMV - cytomegaloy gimmunocomprom

EPSTEIN BARR• EPSTEIN-BARR –lymphadenopath

• TB and M. avium in

OUS ETIOLOGIES HEPATITIS

ovirus; ;mised hostmononuclesosis;mononuclesosis;

hy; splenomegalyntracellurare (MAI)

SYMPTOMS OFHEPA

• Fatigue, naug ,• Yellow eyes, • Low-grade feve• Arthralgia myaArthralgia, mya

F ACUTE VIRAL ATITIS

usea, anorexia,dark urine, skiner, abdominal painalgia headachealgia, headache

SIGNS OF ACHEPA

• Jaundice• Jaundice• Hepatomegaly wp g y• Fever – low grade• Splenomegaly infre• Splenomegaly – infre

CUTE VIRAL ATITIS

with RUQ tenderness

equentequent

LIVER BLOABNORMALITIESABNORMALITIES

HEPA

• AST AND ALT - 100Bili bi ll• Bilirubin – generally e

conjugated and• Alkaline Phosphatase• Bilirubin and urobilinoBilirubin and urobilino

OOD TEST IN ACUTE VIRAL IN ACUTE VIRAL

ATITIS

00-5000 IUl t d b thelevated – both

d unconjugatede – minimally elevatedogen increased in urineogen increased in urine

OUTCOMES OF VOUTCOMES OF V

ACUTE IL

CURCHRONIC HEPATITIS

VIRAL HEPATITISVIRAL HEPATITIS

LLNESS

RE FULMINANT HEPATITIS

HepatitisHepatitis

Hepatitis A Virus: Morp

• Nuc• Nuc

HepatitisHepatitis

27 nm27 nmuc

• ClasH

uc• Clas

H• One

geNon

• Onege

Non• Non• In v

hu

• Non• In v

hu• In v

hehi

• In vhehihihi

s A Viruss A Virus

phology and Characteristics

cleic Acid: 7.5 kb ssRNAcleic Acid: 7.5 kb ssRNA

s A Viruss A Virusc e c c d 5 b ssssification: Picornaviridae,

Hepatovirus

c e c c d 5 b ssssification: Picornaviridae,

Hepatoviruse serotype and multiple enotypesnenveloped acid and heat stable

e serotype and multiple enotypesnenveloped acid and heat stablenenveloped, acid and heat stablevitro model: monkey and uman cell cultures

nenveloped, acid and heat stablevitro model: monkey and uman cell cultures

vivo replication: in cytoplasm ofepatocyte; human and other igher primates

vivo replication: in cytoplasm ofepatocyte; human and other igher primatesigher primatesigher primates

HAV - EpidemiologyHAV - EpidemiologyGlobal Prevalenc

Gl b l P l fGl b l P l fGlobal Prevalence ofGlobal Prevalence of

HAV PrevalenceHAV PrevalenceHighHighHighHighIntermediateIntermediateLowLowVery LowVery Low

ce of Hepatitis A

f H titi A I f tif H titi A I f tif Hepatitis A Infectionf Hepatitis A Infection

HEPATHEPAT• Oral fecal route of tra• Oral fecal route of tra• Excreted in stool abo

clinical illness• 1 month incubation p1 month incubation p• Children often asymp• Never causes chronic

TITIS ATITIS Aansmissionansmissionout 2 weeks prior to

periodperiodptomaticc hepatitis

T pical SerologicT pical SerologicHAV HAV

Serological Course

Typical SerologicHepatitis A V

Typical SerologicHepatitis A V

ALTALT

Symptoms

F lF lFecalHAVFecalHAV

00 11 22 33 44Months aftMonths aft

00 11 22 33 44

c Co rse of Ac tec Co rse of Ac te

of Acute Hepatitis A

c Course of Acute Virus Infectionc Course of Acute

Virus Infection

Total anti-HAVTotal anti-HAVTotal anti HAVTotal anti HAV

IgM anti-HAVIgM anti-HAV

55 66 1212 2424fter exposurefter exposure

55 66 1212 2424

HEPATPREVENTION AN

• No treatment of infectio• Passive immunity with g

ameliorate disease in eainfection

• Gamma globulin can prexposureexposure

• Vaccine available to ind

TITIS A ND TREATMENTn availablegamma globulin can arly stages of the

event disease pre-

duce active immunity

HepatitisHepatitis

Hepatitis B Virus: Morph

•Nuc•Nuc

HepatitisHepatitis

42 nm42 nm

• Cla• Mu

A

• Cla• Mu

A42 nm42 nm

22 nm22 nm

A• Env

I

A• Env

I22 nm22 nm

HBsAgHBsAg

• In vht

• In vht

HBcAgHBcAg42 nm42 nm • In vca

• In vca

HBV DNAHBV DNA oo

s B Viruss B Virus

hology and Characteristics

cleic Acid: 3.2 kb DNAcleic Acid: 3.2 kb DNA

s B Viruss B Virus

assification: Hepadnaviridaeultiple serotypes and genotypes A F

assification: Hepadnaviridaeultiple serotypes and genotypes A FA-Fvelopedit d l i

A-Fvelopedit d l ivitro model: primary

hepatocyte culture and transfection of cloned HBV DNA

vitro model: primary hepatocyte culture and transfection of cloned HBV DNAvivo replication: in cytoplasm, cccDNA in nucleus; hepatocyte and other tissues, human and

vivo replication: in cytoplasm, cccDNA in nucleus; hepatocyte and other tissues, human and ,other primates

,other primates

4

Hepatitis B Virus - ReplicationHepatitis B Virus - ReplicationHepatitis B Virus: V

Viral entryViral entry

NucleusNucleus

Viral Replication. Pt. 1



UncoatingUncoating

Nuclear importNuclear import

cccDNAcccDNA

RepairRepair TranscriptioTranscriptio

cccDNAcccDNA

5’5’

5’5’ 3’3’ 2.4/22.4/2

3.5 kb RNA3.5 kb RNA


onon

3’3’2.1 kb RNA2.1 kb RNA



UncoatingUncoating


cccDNAcccDNA


cccDNAcccDNA

TraTra

5’5’

5’5’ 3’3’ 2.4/22.4/2TraTra



Positive strand Positive strand synthesissynthesis

Removal ofRemoval of

onon

Removal of pregenomeRemoval of pregenome

anslationanslation

Negative strand synthesis


3’3’2.1 kb RNA2.1 kb RNAanslationanslation

EncapsidationEncapsidation



UncoatingUncoating Assembly & buddingAssembly & budding


HBHBcccDNAcccDNA


cccDNAcccDNA

TraTra

5’5’

5’5’ 3’3’ 2.4/22.4/2TraTra


ExportExport


ExportExport

Positive strand Positive strand

ERER

BsAgBsAgsynthesissynthesis

Removal ofRemoval of

onon

Removal of pregenomeRemoval of pregenome

anslationanslation



3’3’2.1 kb RNA2.1 kb RNAanslationanslation

EncapsidationEncapsidation

Hepatitis B Virus - ImmunopathogenesHepatitis B Virus - ImmunopathogenesHepatitis B Virus: Immune Res

HBVHBV

HBVHBV

HepatocytHepatocyt

sis sis sponses and Pathogenesis, pt. 1

VV

testes


IgIg

HBVHBVgg

B cellB cellB cellB cell

HBVHBV

HepatocytHepatocyt


CD4Class II

CD4Class II

THTH

Antigen presenting cells


CTLCTL

CD8Class I

CD8Class I

VV

testes


IgIg

HBVHBVgg


HBVHBV

HepatocyteHepatocyte


CD4Class II

CD4Class II

THTH


Antigen presenting cellsCytokinesCytokines

CTLCTL

CD8Class I

CD8Class I

C t kiC t ki

VV

CytokinesCytokines

Nonspecific i fl tNonspecific i fl t

esesinflammatory cellsinflammatory cellsDirect

cytotoxicity ?Direct

cytotoxicity ? NK,NKT cells

NK,NKT cells


IgIg

HBVHBVgg


ApoptosisApoptosis HBVHBV

HepatocyteHepatocyte

ClearanceClearance


CD4Class II

CD4Class II

THTH


Antigen presenting cellsCytokinesCytokines

CTLCTL

CD8Class I

CD8Class I

C t kiC t ki

VV

CytokinesCytokines

Nonspecific i fl tNonspecific i fl t

esesinflammatory cellsinflammatory cellsDirect

cytotoxicity ?Direct

cytotoxicity ? NK,NKT cells

NK,NKT cells

HEPATITISNATURAL

• Transmission –Horizontal parentHorizontal - parentVertical - mother to

• 6 8 week incubation• 6-8 week incubation• 20% pf patients have

4% f d lt ti t d• 4% of adult patients d• Treatment and vaccin

S B VIRUS HISTORY

teral secretions sexualteral, secretions, sexual, o child

serum sickness prodromel h i h titievelop chronic hepatitis

e available

S l i lS l i lHBV - Diagnosis HBV - Diagnosis

Clinical Significance of Serolo

Serological Markers

Serological Markers

HBsAg

Anti-HBc IgM

HBsAg

Anti-HBc IgMAnti HBc IgM

HBeAg

A ti HB

Anti HBc IgM

HBeAg

A ti HBAnti-HBe

Anti-HBs

Anti-HBe

Anti-HBs

Anti-HBc IgG and HBsAg

Anti-HBc IgG and anti-HBs

Anti-HBc IgG and HBsAg

Anti-HBc IgG and anti-HBsgg

Cli i lCli i l

gical Markers for HBV Infection

ClinicalSignificance ClinicalSignificancegg

Acute/Chronic infection

Acute infection

Acute/Chronic infection

Acute infectionAcute infection

High infectivity

L i f ti it

Acute infection

High infectivity

L i f ti itLow infectivity

Immunity

Low infectivity

Immunity

Chronic infection

Resolved infection

Chronic infection

Resolved infection

HBV - Diagnosis HBV - Diagnosis Acute HBVAcute HBV

Serological Markers o

Acute HBVAcute HBVHBV DNA

HBeAg

HBsAg

0 2 4 0 2 4 Months Months

V InfectionV Infectionof Acute HBV Infection

V InfectionV Infection

Anti-HBsAnti-HBsA ti HBA ti HB

Anti-HBeAnti-HBe

Anti-HBcAnti-HBc

Anti-HBc IgMAnti-HBc IgM

6 6 Years Years

HepatitisHepatitis

Hepatitis C Virus: Morph

•Nu•Nu

HepatitisHepatitis

• CH

• CH

• G

• En

• G

• En40-60 nm40-60 nm

• Inhr

• Inhrr

• Inh

r

• Inhhhhh

s C Viruss C Virus

hology and Characteristics

ucleic Acid: 9.6 kb ssRNAucleic Acid: 9.6 kb ssRNA

s C Viruss C Virus

lassification: Flaviviridae, Hepaciviruslassification: Flaviviridae, Hepacivirus

enotypes: 1 to 6

nveloped

enotypes: 1 to 6

nveloped

n vitro model: primary hepatocyte and T cell cultures; replicon system

n vitro model: primary hepatocyte and T cell cultures; replicon systemreplicon system

n vivo replication: in cytoplasm, hepatocyte and lymphocyte;

replicon system

n vivo replication: in cytoplasm, hepatocyte and lymphocyte;hepatocyte and lymphocyte; human and other primateshepatocyte and lymphocyte; human and other primates

Hepatitis C VirusHepatitis C Virus

Genome and GGenome and G

Hepatitis C Virus: Genom

5’ UTR5’ UTRCC E1E1 E2E2 NS2NS2 NS3NS3

NNP7P7

Genome and GGenome and G

5 UTR5 UTR NNP7P7

Structural protein coding region

Structural protein coding region

NoNocoding regioncoding region

CC E1E1 E2E2 NS2NS2 NS3NS3

CoreCore ProteaseProteasePrCoPrCo

EnvelopeEnvelope Serine protease

Serine protease HeHe

Gene ProductsGene Products

me and Gene Products, pt.2

3’3’NS4ANS4ANS4BNS4B NS5ANS5A NS5BNS5B


3’ UTR3’ UTRNS4ANS4A

onstructural protein coding region

onstructural protein coding regioncoding regioncoding region

AA NS4NS4 NS5ANS5A NS5BNS5BBBAA BBrotease ofactorrotease ofactor

RNA polymeraseRNA polymeraselicaselicase

Hepatitis C VirusHepatitis C Virus


Hepatitis C Virus: The Fu

Core (C) NucleocaCore (C) Nucleoca


E1 and E2 Envelopehyperv

7 N t

E1 and E2 Envelopehyperv

7 N tp7 NonstrucNS 2 NS 2-3 prNS 3 Protease

p7 NonstrucNS 2 NS 2-3 prNS 3 ProteaseNS 3 Protease

and RNNS 4 Cofactor

NS 3 Proteaseand RN

NS 4 CofactorNS 4B FormatioNS 5A InterferoNS 4B FormatioNS 5A InterferoNS 5B RNA-depNS 5B RNA-dep

s and Functionss and Functions

unctions of Gene Products

apsidapsid

s and Functionss and Functions

e proteinsvariable region in E2t l i h l (?)

e proteinsvariable region in E2t l i h l (?)ctural, ion channel (?)

roteasee nucleotide triphosphatase

ctural, ion channel (?)rotease

e nucleotide triphosphatasee, nucleotide triphosphatase, NA helicaser for NS 3 protease activity

e, nucleotide triphosphatase, NA helicaser for NS 3 protease activityon of membranous webn sensitivity sequence

on of membranous webn sensitivity sequence

pendent RNA polymerasependent RNA polymerase

Hepatitis C Virus - ReplicationHepatitis C Virus - Replication

LipoproteinsLipoproteins

Hepatitis C Virus: V


EntryEntry

Viral Replication, pt. 1

Hepatitis C Virus - ReplicationHepatitis C Virus - ReplicationHepatitis C Virus: V


EntryEntry

NS4BNS4BNN

UncoatingUncoating

SS

NS3/4ANS3/4ANS2NS2

ERER

TranslationTranslation

CCERER


S5BS5B

E1E1CC

NS5ANS5A

E2E2RR

E1-E2E1-E2ChaperonesChaperones

Nucleus




ProgenyProgeny


EntryEntry

ReplicationReplication

genomegenome

NS4BNS4B

++NN

UncoatingUncoating

SS

NS3/4ANS3/4ANS2NS2

ERER


CCERER


y y ee

S5BS5B

E1E1CC

NS5ANS5A

E2E2RR


Nucleus




ProgenyProgeny


EntryEntry

ReplicationReplication

genomegenome

NS4BNS4B

++NN

UncoatingUncoating

SS

NS3/4ANS3/4ANS2NS2

ERER


CCERER


ExportExporty y ee

AssemblyAssembly

E1-E2E1-E2

GolgiGolgiS5BS5B

E1E1CC

ggNS5ANS5A

E2E2RR


Nucleus

Hepatitis C VHepatitis C VImmunopathImmunopath

Hepatitis C Virus: Immune Respo

Hepatitis C Virus -

HHHC

Virus -Virus -hogenesishogenesis

onses and Pathogenesis, pt. 1

- Immunopathogenesis

HCVHCVCV

HCVHCV

HepatocytesHepatocytes

Hepatitis C Virus - ImmunopathogenesHepatitis C Virus - ImmunopathogenesHepatitis C Virus: Immune Res

IgIg

HCVHCVHCVHCVB B

sis sis Antigen Antigen

sponses and Pathogenesis, pt. 2

gpresenting cells

gpresenting cells

CD4Class II

CD4Class II

THTH

CytokinesCytokines

CD8Cl I

CD8Cl I

cellcell

CTLCTLClass IClass I

HCVHCVHCVHCV



IgIg

HCVHCVHCVHCVB B



gpresenting cells

gpresenting cells

CD4Class II

CD4Class II

THTH

CytokinesCytokines

CD8Cl I

CD8Cl I

cellcell


HCVHCV

CytokinesCytokines Nonspecific inflammatoryNonspecific inflammatory

HCVHCV

inflammatory cellsinflammatory cells



IgIg

HCVHCVHCVHCVB B

Apoptosisor cytopathic

replication


replicationSteSte

ViralClearance

ViralClearance



gpresenting cells

gpresenting cells

CD4Class II

CD4Class II

THTH

CytokinesCytokines

CD8Cl I

CD8Cl I

cellcell


HCVHCV


atosisatosisHCVHCV



Hepatitis C Virus - ImmunopathogenesHepatitis C Virus - ImmunopathogenesAutoimmunityAutoimmunityCryoglobulinsCryoglobulins

Hepatitis C Virus: Immune Res

IgIg

AutoimmunityAutoimmunity

Lympho-proliferative

Lympho-proliferative

CryoglobulinsCryoglobulins

Immune modulation

Immune modulation

HCVHCV

Lymphoid cells

Lymphoid cells

pdisorders

pdisorders

HCVHCVB B


replication


replicationSteSte

ViralClearance

ViralClearance



gpresenting cells

gpresenting cells

CD4Class II

CD4Class II

THTH

CytokinesCytokines

CD8Cl I

CD8Cl I

cellcell


HCVHCV


atosisatosisHCVHCV


HepatocytesHepatocytes NK,NKT cells

NK,NKT cells

HEPATITISHEPATITIS • Most common cause ofMost common cause of • 1.5% of population in U• Parenteral transmission• Parenteral transmission• 6-8 week incubation pe

A t i f ti ll• Acute infection generall• 80% develop chronic di• No vaccine available• Treatment – 40-80% cu

C CLINICALC CLINICAL f chronic hepatitis in USAf chronic hepatitis in USASA carries the virus

n blood sexualn – blood, sexualriod

ildy mildsease

ure rate

HCV - DiagnosisHCV - Diagnosis

A t HCVA t HCV

Acute hepati

Acute HCVAcute HCV10001000

600600

800800

400400

600600ALT(IU/L)ALT(IU/L) SymptomsSymptomsSymptomsSymptoms

200200

Ti ATi ATi ATi A

000000 2222 4444 6666 8888 10101010 1111

WeeksWeeksWeeksWeeks

Hoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15S

Time ATime ATime ATime A

V I f tiV I f ti

itis C infection

V InfectionV InfectionHCV RNA positiveHCV RNA positive

AntiAnti--HCVHCV

pp

ssss

N lN lN lN l

Aft EAft EAft EAft E

2222 24242424 1111 2222 3333 4444 5555 6666MonthsMonthsMonthsMonths

7777

Normal Normal ALTALTNormal Normal ALTALT

After ExposureAfter ExposureAfter ExposureAfter Exposure

HCV - Natural HistoryHCV - Natural History

O t F ll i HO t F ll i H

Outcome Following

Outcome Following HOutcome Following HAcute hepatitis CAcute hepatitis C

Chronic infectionChronic infection80%80%80%80%

Chronic hepaChronic hepa70707070

Chronic hepaChronic hepa

CirrhCirrhCirrhCirrh

TimeTimeTimeTimeTimeTime(yr)(yr)

TimeTime(yr)(yr)

1010

H titi C I f tiH titi C I f ti

Hepatitis C Infection

Hepatitis C InfectionHepatitis C Infection

atitisatitis0%0%0%0%atitisatitis

hosishosis20%20%20%20% HCCHCC

1 1 -- 4%/yr4%/yr1 1 -- 4%/yr4%/yr

hosishosisDecompensationDecompensation

4 4 -- 5%/yr5%/yr4 4 -- 5%/yr5%/yr

2020 3030

HEPATITISHEPATITIS• HEPATITIS D

– Also known as delta agent– Uses the HBsAg protein coa– Hepatitis B must be present

HEPATITIS E• HEPATITIS E– Water borne virus resemblin– Endemic in Asia, Northern AEndemic in Asia, Northern A– Rarely seen in USA

S D AND ES D AND E

at – coinfection or preexist

g hepatitis AAfrica and MexicoAfrica and Mexico

CHRONIC HCHRONIC H

• Elevated liver enzymesElevated liver enzymes greater than 6 months wpathologic findingspathologic findings

• Many different diseaseshepatitishepatitis

• Liver biopsy is frequentdi idiagnosis

HEPATITISHEPATITIS

(AST and/or ALT) for(AST and/or ALT) for with characteristic

s can cause chronic

ly performed for definitive

PATHOLOGY HEPA

• Portal tracts peri-portalPortal tracts, peri portalinvolved

• Liver biopsy:• Liver biopsy:chronic inflammation

increased inflammincreased inflammmainly plasma c

I fl ti fib• Inflammation fib

OF CHRONIC ATITIS

regions and lobules are regions and lobules are

n atory cellsatory cellscells and lymphocytes

b i i h ibrosis cirrhosis

ETIOLOGY OF CENZYME EL

• Viral infection – B and C• Autoimmune

D• Drugs• Metabolic – Wilson’s

• Fatty liver - Steatohepatitis• Alcoholco o• Others – CHF, hemochrom

celiac disease, and others.

CHRONIC LIVER LEVATIONS

s

matosis, ulcerative colitis,

CHRONIC HEPA• Cirrhosis develops in 20% • Liver failure and hepatomap

cirrhotics• Diagnosis of chronic hepat

– chronic AST and ALT epatients have normal live

– positive serology – HB– positive DNA or RNA in– diagnostic liver biopsy

• Treatment available with va

ATITIS B AND Cof patientsa develop in about ½ of p

titis made on basis of:levations (though some er enzymes) BsAg or anti HCV blood

arying success ratesy g

Chronic HBChronic HBHBV - Diagnosis HBV - Diagnosis

Serological Markers of

Chronic HBChronic HBHBV DNA

HBeAg

MonthsMonths

BV InfectionBV Infection

f Chronic HBV Infection

BV InfectionBV Infection

Anti-HBeAnti-HBe

Anti-HBc IgGAnti-HBc IgG

HBsAgHBsAg

gg


YearsYears

HBV - Diagnosis HBV - Diagnosis Acute HBVAcute HBV

Serological Markers o

Acute HBVAcute HBVHBV DNA

HBeAg

HBsAg

0 2 4 0 2 4 Months Months

V InfectionV Infectionof Acute HBV Infection

V InfectionV Infection

Anti-HBsAnti-HBsA ti HBA ti HB

Anti-HBeAnti-HBe

Anti-HBcAnti-HBc


6 6 Years Years

Dynamics of the different phvirus (HBV(

Wong S N et al Arch Intern Med 2006;166:9 12

Copyright restrictions may apply.

Wong, S. N. et al. Arch Intern Med 2006;166:9-12.

hases of chronic hepatitis B V) infection)

Serologic eventsSerologic events

antiHBsAg

anti-HBs HBeAg

A HBVAcute HBV Infection + - +

Vaccine Responder - + -pExposure with

Immunity - + -

Chronic HBV (Wild (Type) + - +

Chronic HBV (Precore Mutant) + - -

Inactive Carrier + - -

in HBV infection in HBV infection

Anti Anti HBc anti HBc HBVAnti-HBe

Anti-HBcIgG

anti-HBcIgM

HBVDNA ALT

- + + + ↑↑

- - - - Normal

+/- + - - Normal

- + - + ↑ / N

+ + - + ↑ /N

+ + - -/+ Normal

HCV - DiagnosisHCV - Diagnosis

Ch i HCCh i HC

Acute hepati

Chronic HCChronic HC10001000

600600

800800

400400

600600ALT(IU/L)ALT(IU/L) SymptomsSymptomsSymptomsSymptoms

200200

Ti ATi ATi ATi A

000000 2222 4444 6666 8888 10101010 1111

WeeksWeeksWeeksWeeks

Hoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15SHoofnagle JH, Hepatology 1997; 26:15S

Time ATime ATime ATime A

CV I f tiCV I f ti

itis C infection

CV InfectionCV InfectionHCV RNA positiveHCV RNA positive

AntiAnti--HCVHCV

pp

ssss

N lN lN lN l

Aft EAft EAft EAft E

2222 24242424 1111 2222 3333 4444 5555 6666YearsYearsYearsYears

7777

Normal Normal ALTALTNormal Normal ALTALT

After ExposureAfter ExposureAfter ExposureAfter Exposure

AUTOIMMUNAUTOIMMUN

• Genetically predisp• Genetically predisp• Environmental age• Autoimmune T-cel

• liver antigens lead• necroinflammatory

E HEPATITISE HEPATITIS

posed hostposed host ent exposure triggering l mediated response

directed atdirected at ding toy response

AUTOIMMUNAUTOIMMUN

• Associated with• Associated with diseases –

Hashimoto’s tulcerative colitisulcerative colitishemolytic anemITP diabetes cITP, diabetes, cpolymyositis, pe


other autoimmuneother autoimmune

thyroiditis ss

miaceliac diseaseceliac disease,ericarditis, SLE, MCTD

AUTOIMMUNAUTOIMMUN• Clinical presentation• Clinical presentation

generally femalefatigue, jaundice,hypergammaglobuhypergammaglobuelevated AST and

E HEPATITISE HEPATITIS––

ulinemiaulinemia, ALT

AUTOIMMUNAUTOIMMUN

• Labs- presence of asautoantibodies ANAautoantibodies – ANALKM, smooth muscleDi ti li bi• Diagnostic liver biopsand plasma cell infiltr

• Treatment - steroidsimmunosuppressants


ssociated A thyroid antibodiesA, thyroid antibodies, e

i t f h titisy – interface hepatitis rations and s

ENENNDND

Documents

VIRAL AND AUTOIMMUNE HEPATITIS - Columbia University · e of Hepatitis A f H titi A I f ti Hepatitis A Infection. HEPAT • Oral fecal route of traOral fecal route of tra • Excreted