Sei sulla pagina 1di 47

Ll\.X Ge D(sGAs6s

o Acur

o ?oxte

LI V6R.

O CHOpl

ut?At, ttE PAttr§

,tND DOUG - /N OUcfO

Dts Efrs E

rutTcs

Pn p

*s

tn e /axcr/ruNa*L

u-to

n*{us

Axo 6ÈAN

LtuEe DtsEAsrs

lN Herrre È

t

rNFtL?R AND

tt e?A Èouté, §cs.

4-

a

o

I

TI -T,:E

(fun(LphJoÉE

-4À's' BILE Dct cts'

t{

oh.

tr ItOo471

, *d*r"lA

(Hi

("r.1 ertì.{** -l

rr +)

o Gc.a

h^J

. à;"*?ffi. hyr,,'*$

^,0 - -

cc; c

!i,o ùyò

- e.rrì}tà àU a_

L'ucru

(h"b B,c r

ei n"Lh.q

c Oe.t

t. *,

2

EErr+sTAsrs

DlsEAsfs

TH

LI

L\Y6Li

L:-

o

V

F

5R-

-4) tf7

in

*yu"l^By,

"',l*.

' i,f.fir?t;,i:u;

.

§ah;:T"*-ft{:?oJ-

llc,Ior

zit o[

tr6, d,

7 htlneai c *"i

u

[efaotat^a oott,''Q "/

,fiF§lffi:

tor

t'

3

(ilì.};Hir--tr

:. il

,

.É,ai!

lrt

l. ttebch.

i* I L,uel

nct-brtl a u*

Dir.rx-

e) Cerì-b " h/ d,'r"tc, fLtlb& a\rr

t[

bì"feì^Fr^cr

g)-?fào

b\."{

Ly

Yu"'

aa (2At

-+

*,

*hc.o2rnrzi-r

)

1D fl+grn& o[ {\tt.- hot*.' tttt'tl

L. h/ p"

$e*

cr-wriq o F

Sy

AL

i.tèlen-tnc1

r.:

.

(€x carc

t-

: .5o)(

Ac. {ù?€g hrh.'hl"'a

iu

te,

Livca

"|

e )G,{elr

rn

J

rr4l (tcri 116 )

. qQeano-ee

h

*e,.oL.e;ÉJf

t

il;-*;,ffi;

bl|sggycrur.§

.Lro;.ffit

d.-rCqfa

ùwtoQe/r.

^.

?ralIT:, l!ts\, ,

§. t; pre

5

Tte.T*b.'ۓswl

àÀt boec ttzauw'

\ fnee ÉtY *d{

h.{O

rynthcCa

--)

tt v€R.

SGcl Cttou

/ ( ur.o)

E ST6RI f t CA Tt or

(

rar6LtcEstDfs)

oxtDfrTioN

Foo{ir,B: to*iAchov.

T'€€l: t

,ywtlr+coT.;$ 1t'"t^

(hS.

,ropl-

d^. |ertr)

ol Te

l. rhoU

-A 0beo

t'g

/

À ì- SL,

d. *ht o,

c. tl,

v.re i.r grrtf ot

Uh:&g5e9x /"" r.tra hv. rl"rq

c. ** c,uuà ?ndtd, lt.t b'q,bJ

r+,

AgUtdn, cfo tt,"1

TLr"+.,

[h"h.

t,

[-età^.,

t

r,^kt;hcr.

(ryrrtt - ?.,) b, tt. t,,r,

H*fitt;^r*#

.

r

yurti kl""l. /u,t r) t lno

\"F.uu .t.

lcr vreh crr

:';wrlu4

R

la.[

r c]: *[, nq [.c,T

I

Jll*arl;,1'

(r *J

irou,,

{c le.ot{:1,:'

ry

uo{-

rv'a.'§3 o|

p"of."

{4.,§

hlJ.

U ue^ -,er^'- o*

è. hotrro.rl-ubhou eu.f q

D:tori lLa LUor^.

. [lc.1or. nit.

)

rr

o

à; h

+ .1. ul,.ol-

td*'$,

o,'

hsrur

hJ

cyt ?. t+So oriCaac, yrf.

.',> lt7 \urc.ttu.tc. (b, cx cr,.h.*)

ca q c-ti u.te ( uudou tB

h, ti

lì.lcr d.i reglcrr tney CouiJo.

i u,arorr.l àsh a; knì

(r

t

()ea.hrrràr o1rùc,ter)

*n

hzr

({.*idr§ou) o. 'toxdaa

A,ueà

t*L

(uu,l

r

Aurl- drut itrtcal.,.n.ouJ

J.ÈC urbi*

e,ud

ltc-t*te"Q;eu 6

r,-urir.

H/t *U€iq.*h

C*-O-:'O''O

csrlaov'

baCA'r'

a ft** fn"+' /g

t

iqO-&bh

o uletea

Ptt

=:-(-un:Jflmg[ffi]-g

--

--

-

-D

,

-

-

't

'

1'-

PhYr.'

Lìrra/, .stl , .oll"?:§o' o[

;("\

,pilL *AG.Toui

:t"'

c'

ac.à" (coruS.BIL.J

rgr',q ^

Li Prd 'o€*bQ

,i;t!-- 9*s

-tl

riC. B[ L.

Éù

J

e11;r-*

,Da

,oùJ.Bru (*rfi.,sffir,

pr. dF.l

+

E L r Hl NtTrorJ Ls

léLr c

5

?FoR.n*Itoltt -- ruNSporaf

Ì.GA cdt^

Brt

Spt*r

Li\rr

(+or

)

\h.rr,"

?- [so

3o.y.

,l

rcFrctr uc

uc

rrl

\

)

Èl ur R,OBrru

t

Bt ur tuB »tN/Attt/r

(il?.f"

*'*)

A

LBufllru

"of.r oF orss§

rrLìuor

aeu!*

F

AU

*i,,u.4t to,

&P*rrc,

tsr re,

t

6fruBLAD0ea,

snALt lNtESt -

?

t brdl. e\t.

UNeoN§.BlL.

_D

BtUtAgy oRSTcucTroo

b r.ra u Ro

B rLl p.

rN urt N es /Fec as

qrycsur3Ét'i

lN

?LftSn

A

-7Y

L qsz

u

\z

-

lc

3!_ecU sATra{,

,

f^0soRi?rr

/ntdrrirL

URcBttl

Noetr*.

u

( co U en_r)

ù

?àp?rArr

R§f èsaR s?o

y

g5f+.r,Nrs

/ae

cl ru codJ

6^tI.

*PrN-oAcH TD Ttl,

rplTl,l ht?P6G

tlttt

P^f tcNT

3ù È tNgnu

?pDu

cr lorJ

c llg

no av_s_l$

( ct^r. r. eJ

il

o ,NE FFE( TluE Eel?flCo P

CBre I hl rGr 1 taÒn è.t. /Thd.)

@lT eLsRnNc6

. tull6 etTAD DteoRDFÉS

O

-4,

(*

tr.tralrrt ct

ashJ)

F"t")

g@

(lr.rI

(i*h* .A

covrJ "e.)-

-

#tiffl

-tu'.t

,

bìA pnt,

dretà

au'.a,/ot

stl$ilH,};il,t'i',.

Lf, bOR*TOBY

,N

T6STS

Lrrl 6g Drs€As6S

l2

.t,

eNtt n6 4ssnts

D

RELE*SE

rù?o r'rf

oF

G^ltyrrj

H€p*tte

BtooD

(,^ru/ttecl/ohst)

c TRArrtS*nrU4sES

As ?rr Tt T6

i., i.;,-' "

1+o t§/w

jì*E'no re ro Strrrl.lì

a|flr,ro crute

+ As?t«tmc Ter^rf.

(*Sf;

eOtJ

ì+ AtArrNr rRANs C arT; scPu

RtruEcr *cr@

Tfle

Dl sg rtsg ?eD 6gss

S1c,

.

IALT

. *31

$ Serrrrivfh

t)

ILorr t-"t.

,ìo

Ddo.?^irh,r,

zl.a'fe

h

L f€e

qLaa ,nyo.,/mqel.

(a r rs{. tra otcalt.r$J

t5

pttos?[*trsc

D *t"xALtrut

(Is- ts tv /t t)

. 0l( {rueh.oq

'

F.td.

,.y

a

stsal,

hsÉ.

§g,

[à.1

Ulr d,.cFr,

4,rs sr$.J

*-? Iùonlr^-te ìu carrrc

h:[,. {r. y';r,L.r:"

I

@

-D Lsrrgc r'ucarqra(a+or)

.

o oT tt€ps

,

?;:Àth'Fal'§'"ra'(

rS§Jx*1!{!

[:

'*o

§

Ò t(.H§*,?{il$nÈH.,

o LDH 6,"ù

J. CLGII*NCg oF

t+

nE Tt Èo LlTes-/DcuoJ

e

o

a

eAerrncr,

ì,rfd

Ia

?rd[ fu{

li,*"ì!"'rlmP

ìràrcd

ttJr{Qer.r

B\ rt R.Ù BIN

GF

Èrrg

^arps ( lusatyr,r*'U

a.

ft nHorur0

k

Nltl

+ltlt»e^'bn 4-

Gat+

Q{

ntbr t

otuhr §**

f"r uiurr*Gs

+fl;

(*t'È

'

)3r*gls

.hrr:tfJffj,

3. SY NT}IETIe,

lF u N Crrolrj

Pro ?nea

fT

=-f

d+*

ttJ rrn6

Thro rnLrr

t r

t do "" i

+ ottnt .

.?"

:'i'ù"&:,-t"H,,

drcr.l

aynth

, f^r.

t;:",

in q

a.r

cch., ll.a.t

t5

o Lt eo plorErrrs

t*-V t- Qr

lr rr^ ir rr -

r

^

4 . lwunu,u.oeo àc

+t

t, e4f 4

l6

o 6uo èurrtS

+ (ox)

o

t

w "*b ( F.r*o l biC. errrt-,

cus. INE

€.x*ruino}iou "I unj n::é/cà.la

,.

&Lt Nt cAL *P?fàoAcl{

lt

àUon?

24

t

( l.,t*

E r.r ,

?u,r,uilwa ì

towt

lau 4 ,.Jtua,nt .C

, ^§.cirr,

cholcatvr;:

(tn[r.f {

!D ier aec,urtLl)

iuv,.drtq r

ycltro,l dia. , q)y,fla,.t

{+

rt".t t jt"t

Lo drrr-

tc

/

A^^K aa.'nJ

41l,

obrtr.r eÀ'os

o Ab Aorr.rrr,.t djeco ,.L,n{,

(dJ r'Fe.rh'.u a[ l/ttno*i

Q.igrrq

PflVs tcAL Ex *n

. *4

.

. P

scLgRRC lc;r,

L.

S_p tg6e fg

ALnAÉ

Bav Tltenn

. X *llaon AS

o Èto A RoNAc cHttt éeJ

, "

T6AùL CtPeuL.

-

FtA

^qlLA

H€P*noi

pptaa-'TaéFDop

ACUTE VIRRL ttE?frTtns

A,B

( nun

te, D, E

yilrae,r, b"t .t"

B)

Ct-rNtCS :

I

['-u

cv.À

lderr*,'ea.[

q,y*t +. to +* lur.n-rif

rqt ,}.;u;*l- t" .hy wa6

C€Jrr Cl*

lLt-.[ho L :

novì-e.hVetote, -- (i.n"r,t^rvclea À/ boiL'q li

-»'

UV, lr*l"ald \ ohAnr".J

ohe ? g?o h/p.

lnc ùr*['au

ì

4.y

Ro pU ro\'o ta 1 U ve L

t ?.,r, acuc4- r bita, 3Tcola

Avtf b.od"; ea l

.p

P ?ef

L,D

tr,Te., u

, blood (tnub)

tc

iQLrrrvr

s^h

.(.

e ,o)

àÀr-u' n3 c.e

nr>|o"ie : l

: lgG (rh4ol.f

i

285 VIRAI HEPATITIS

Acute viÉl hepatitis is a systemic irilection a.ffecting the liver predoo-

inantly. Alnost all cases of acute viIal hepatitis are caused by otre of frve vilal ageDts: hepatitis A virus (HAy), hepatitis B virus (HB\,),

hepatitis C vins (IICV), the lIBv-associated

D virus QID\), and hepatitis

delra agent or hepatitis

E vi s (HED. Other transtusion-trans-

mitted agents, e.g.,

identified but do not cause hepatitis. All these humalt hepatitis yiruses

arc RNA vi.uses, except for hepatitis B, which is a DNA virus. Al- ihough these agents caa be distinglished by the molecular and an-

tigenic properties, all types of yiral hepatitis Foduce cliùicaÌly similar illnesses. These range Irom asymptomatic and inapparent to fulminant

and fatal acute idections comrnon to all types, on the one hand,

"hepatitis G" vi s imd'TI" virus, have been

and from subclinical persistent hfections to rapidty

Fogrcssive

chrcnic liver disease with cirhosis and even hepatocellular calcinoma, common to the bloodbome t ?es (IIBV, HCV, atrd HDV), on the

other.

Vltl)L()GY AilD m0[0GY I H.patili5 A Hepatitis A virus is a ronenvel- oped 27-nm, heat-, acid-, and ether-resistait RNA virus in the hepa-

family (Fig. 285-1). Its yirioD con-

tovirus genus of tle picomavins tains foul capsid polr?eptides,

designated \?l

to VP4, which are

cleaved postfanslationally from the polyprotein product of a 7500- nucleotide genome. Inaclivation of viral activjry can be achjeved by boiling for 1 min, by contact with formaldehyde and chlorine, or by ultaviolet idadiation. Despite trucleotide sequsnce variatio[ of up to 2070 among isolates ol HAV, all stains of this virus are itrlmùnolog- icaly indistinguishable and belong to one serotype. Hepatitis A has an incubation period of approximately 4 weeks. Its replication is lim- ited to the liver, but the virus is present iII the liver, bile, Etools, alld blood dudng the late inorbation period and acute Feicteric phase ol

illress. Despiie p€rsislence of virus in Lhe liver, viml shedding in feces,

vi-remia, and infectivity diminish rapidly once jaundice becomes ap-

pareol. HAV can be cultivared reproducibly in viEo.

Antibodies to }lAV (anti-HAV) can be detect€d dudog acùte illness

when serum aminotransfetase activity is elevated and fecal HAV shed-

ding is still occuIrilÌg. This early antibody rcsponse is predominantly

of the IgM class and pe$ists for seveml months, Érely for 6 to 12

months. DùinE convalescence, howevet, anti-HAV of the IgG class

trecomes the predominant antibody (Fig. 285-2). Therefore, the diag-

nosis of hepatitis A is made duriag acute illness by demomfatiBg anti- HAV of the IgM class. Afle! acute illdess, a i-HAV of the Igc class ,emains detectable indefrnitely, and patienls with serum anti-HAV are

iiùnuoe to rcinfection. Neutratizing antibody activity parallels lhe ap- pea.rance of anti-HAV, and the IgG anti-HAV Fesent in imoune glob- ulin accounls for the protection ir affords against IIAV infectioo.

-0

JaundicÉ E

lnr-r [------l

4

I

Anti-HAV

12

Weeks atter exposurc

18

IIGURI 285-2 Scheme of tgp,crl clinical and labontory featurcs of

fl€patitis B Hepatitis B vims is a DNA virus with a

pact gedomic sEucturo; despite its small, circulaa,

HBV DNA codes for four sets of viral Foducts wilh a

tiparticle structuie. HBV achieves its genomic economy by

an efficieat strategy of encoding Foteins ftom four S, C, P, alld X (Fig. 285-3), as detailed below. ODce

ùniqùe among viruses, HBV is now recogDized as one of

anirnal viruses, hepadnaviruses (hepatoùopic DNA classifed as hepadnavirus type 1 . Similar yiruses iofect

of woodchuck, ground and uee squhrels, and Pekiù ducks,

the most carefirlly characierized.

Like HBV, all have ùe

tinctive thrce morphologic forms, have coùnterparts to

and nùcleocapsid virus àntigens of IiBV, replicate iDthe i{ extGhepatic sites, contain their orÀn endogenoùs DNA have Éartially double-shanded aDd pattially are associated with acute and chrcoic hepatitis and

cinomq and rcly on a replicative

strategy unique among

bur q?ical of retroviruse§. I stead of DNA replication d DNA template, hepadnaviflses rcly on leverse traDscriptio

by the DNA polymerase) of mirus-srand DNA from a

RNA intermediate.

Then plus-strand DNA is hanscdbd

nus-sfand DNA template by the DNA-depeodeDr DNA

and converted in the hepatoc).te nucleus to a covalently

DNA, which sefles as . template for messenger RNA and

RNA. Vilal proteins are taNlated by the messenger

proteins and ge[ome are packaged into virions and

hepaloc,,te. AldEugh IIBV is difficult to cultivate in vitro

ventional sense from clinical material, several cell lines transfected witi HBV DNA. such transfected cells rcplication of the intact virus and its compoDent prcteiDs.

ylML FRlTElllS AND PARITCIES Ofthe three particulate forms ble 285-l), the most numerous are the 22-nm particles,

tl6l]ll 285-1 letr. Ele.lrcn dicroqraph of 2r-nm hepatils A virus panicle! purjfied from stoot of a patient lYith

acule hepatitjs A virus infection and aqqrcgated bq hepatitis A anùbodu. Rig,tt. Bectron microqraph

serufi from a patient tyith hepatìls B infeclioa, demonsirating

lhe 4z-nm $rions, tubular foms, and spherjral 22-nm

parlicles oi hepatith B surface antigen. 132,000x. (Hepatitir D rcsembìes 42-nm vìfions of hepatitis B but is smaller,

35 t0 3i nm, hepatilis E resembìes hepatilis A virus but is slightlu laEer, 32 to:t4 nm; hepatitis C ùas not been rsualted defìnitivelU.)

of concentrated

as §pherical or long these are antigenically

from the outer surface or

ofHBV and arc thought to viral e[velope prctein. rum by a factor of 100 or 1000

parcd with the spheres aad

large, 42-nm. double-shelled ticles, which Epresent the

B virion (Fig. 285-l) . The

teilr eipressed on the outer vtion afld on the smaller

bular shuctuaes is refeEed to

surface antigen (HBsAg). The

tion of IlBsAg aod virus

btood may rcach 500 pgtnl- ad

particles per milliliter,

envelope Fotein, HBsAg, is drc the S gene of IIBV,

&

Hete.h[ro È , (DNA)

'

Hts. ,B ( -*) - .,.il i,ili

Htso

l*

A3 Ut e!- !.n.)

rna,r, Kca .+ +tÈ y ?r.Pacch

|lBo Ag+ flB.Às r

( 107. y,*Wt;U7 o$

t't,ot o rer.' ari otr by n^"tt-)

Hg a ASt tlts"*3-

L

cs.na,lca

( lo z [.-h.h L.\)

[f*,

2l

rT------

l

Anti-HBe

lgc Anli-HBc

-----za

t=tr

F.--.-Jt l---.lr--

during which all three forms of HBV circulate, including intact vftiotrs. Over time, the replicative phase of chrcnic IIBV infection gives way to a relatively nonreplicatiye praJe. This occurs at a Éte of apprcxi- mxely l\Vo per year and is accompanied by setoconve$ion ftom

I{BeAg:positive to antiHBe-positive. In most cases, this seioconver-

sion coincides wiù a aansient, aéute hepatitis-like elevation in ami- no[ansferase activiry, believed to rcflect cell-mediated immune cleat- ance of virus-infected hepatorytes. In the nomeplicative phase of

Anti-HBs

812 16 20 24 28 32 36

in hepatocyle nu-

clei, it teDds to be integated into the host genome. In this phase, only

spherìcal and tubular lolms of PBy, not intact yiriorr, circulate, atrd

liver injùry tends to subside. Most such patie s would be character-

ized as inactil)e HBV calar'?ru. In teality, the design tions replicatfue

100 xrd nonreplicative ue only relativei even in the so-called nomepli-

cative phase, HBV replication can be detected with highly sensitive

cfuonic'inlection. \yhen HBV DNA is demonstrable

H

Weeks atter exposure

'285-4 Srheme of Ìgpical clìnical and laboratoru

amplncation probes such as the polltnemse chain rcactio!

eCR).

features of aclle viral hep-

Still, the distinctions are pathophysiplogically and clinicaly meaning- ful. Occasionally, noEeplicative HBV infection convefis back to rcp- licative infection, Such sponta{eous rcactivarions arc accompanied by

reexpression of lIBeAg and HBV DNA, and sometimes of IgM aoti- HBc. as well as by exacerbarions of liver injury.

MAECUUR y;RA 15 Variation occurs throughout the HBV genome, aIlal clhical isolates of HBV diat do not exp.ess srpical vial poteins have

been attributed to mutations in individual or even multiple gene 1o- cations. For example, variants have Leet described that lack nucleo-

capsid proteins, envelope prcteins, or boih. Two categdries of HBV have attractèd the most attention. One of these was identified initially in Mediterranean coùntries among patients with an unusual serclogic-

clinical profile. They have severc chrcnic HBV infection and detect-

able llBV DNA but with arti-HBe iNtead of IIBeAg. These patients

were found to be infected widr an HBV mutaflt that contained an alteration in the precore rcgion rcndering the virus incapable of en- coding HBeAg. Although several potertial mutation sites exist_ifl the pre-C region, the regioriof the C gine necessary for the express'ion of

IlBeAg (see '.vfuology and Etiology," above), ihe most commonly

encountered in such patients is a single base substitutioq ftom G to

A, which occurs in the second to last codon of the pre-C gene at nìrcleotide 1896. This substitution results in the rcplacement of the

TGG tryptoph;n codon by a stop coalon (TÀG), which plevent5 the

tmnslation ol HBeAg. Another mutation, in the core prcmoter region, prcvents transcriptiofl of the coding region for IIBeAg and yields ar

with current or recenl acuE hepadtis B. including ùose in ùe

window, have IgM anti-HBc in their serum. In patients who

from hepatitis B in the temote past as well as those

HBV iDfection, a !ÌIBc is predominantly of the IgG

IDfrequently, in no more thaa 1 to 57o of patients wirh acute

levels of HBsAg are too low to be detected; in such

ùe presence of IgM a[ti-HBc estabìishes the diaglosis of acute

B. When isolated anti-Imc occuts h the rare patient with

hepatitis B whose HBsAg level is below the sensitivity thrcsh- eontemporary immunoassays (a low-level carrier), the anti-ÌIBc

IgG class. Geoerally, in pe$ons who have recovercd ftom B, anti-HBs and anti-ÌIBc persist indefinitely.

temporal association bètween the appearance of anti-HBs and

of HBV infection as well as ihe observation that persons

in serum are protected against rcinfection with IIBV ùat anti-HBs is the protectù)e antibod), Therclorc, strategies

of HBV inJection are based on

Foviding

susceptible

with circulating anti-HBs (see belov). Occasionally, in 10 to patients with chonic hepatitis B, ìow-level, low-affinity anti-

be detected. This antibody is directed against a subtype de- different from Ìàat represented by the pÀrient's IIBsAg; irs

is thought to reflect the stimulation of a rcìated clone of cells, but it has no clinical rclevance and does not

clearance of hepatitis B.

other readily detectable serologic marker of HBV infection, appea$ concùrrendy with or shtrfily after HBsAg. 1ts ap-

e coincides temporally with high levels of virus replication and ihe presenge- of circulatirg intact vidons and detectabte HBV Pre-Sl and prc-S2 proteins aÌe also expressed dudng periods but assays for the§e gene products are not routinely In selflimited HBV iafections, HBeAg-becomes undetect-

after peak elevations iII afiinotansfeÉse activity, beforc

of HBsAg, and gnti-HBe then becomes detectable,

with a period of relatively lower infectivity (Fig. 285-4). harkers of IIBV replica'tion appear Ealsiently during acute testing for such markers is of little clinical utility in typical

acùte IIBV iDJection. In contast, marke$ of HBV replication

valuable information in patients \eith prohacted infections.

ftom the pattem

§?ical

of acute HBV infections, in

HBV infection, HBsAg rcmains detectable beyond 6 months,

is primadly of the IgG class, and anti-HBs is either unde-

le or detectable at low levels (see'Laboratory

Fearures,' below)

285-51. During early chronic i{BV infecùon, HBV DNA can be

Ì episomal form. This replicatire Jrage of HBV infection is the

maximal infectivity and liver injury; HBeAg is a qualitative

both in seùm and in hepatocyte nuclei, wherc it is preslnt in

and HBV DNA a quantitative ma*eÌ of this replicative phase,

HBsAg

\

HBV DNA

Anti-HBc

lgM anli-HBc

0123456 12 24 36 4A 60

Months after exposure

AntiHBe

120

flGURf 285-5 Scheme of tupical labordtoru features of chroni. viral hepatitis B. iBeÀg ard HBv DNA can be oeteded rn seun during lhe replEonve phase ol ehrcnit infedìon, whkh is assorìated with i fectir/itu and liver injuru. SeroconveEìon from the replicative phase la the nonrcplicdlve phose occu6 at a Éte ot approrjmatelu l0 1o 15% per Uear aid is henìded bg an acute hepallis-likÉ elevaton of ALT actjvit!; du nq the nonreplicaiive phase, intectivitq and Iìver iijury are Iìrnìled.

i

?hT+{o6i

horae o[ thc t'np . viun,

cy to p e ll,.: c.

lrnunuho[og re rrap oUrr

o a- ino<.t ive ttep. B

It"4.L :

r, L've,t

Virrerr nat

.y

I

tla3!d+e,

ovl

hye r

ca,z,r"'era 6t,6

o1lr"p.k.

T: a0t4

hort+ B AS

ceu ?u^{**

T: cotÀc

cY

4Z

PftTHoLo qY :

f,tu)

PflNLoBULAA lNFl LreATtoar/

\xr rrH rtoNot.tu cLE,{È c aLLS (Ll

fr)

;

he poli c- ee?-Q- he c ro+i a (drS)ru)

hy p* p\er."'o o[ k"[, 1", * Un

-)

el

ol%fot'a

. c-Q!- y'èS c.acrtc.{n'o,^

ho

f.-h'

(,",'{.ah. IZ*;

Ifqc.'n J

p," uri q to

rnr,orwiuzc, tp.ut?

Ivnrn ( L.-rto oLov, bQ-

qrìrtd. EIì

of vi rct

ìd,eu k

l'*ho,*

Pe{k ,l', / s* [r

t- c^1l"fe,

Vi

-4, Poì" ol >e?§loe

T

i"

1i"h qS

I1j

P*Q'

Pc/l^o t/)

ozoQ 4rute.

-+o - peeaou

. contè.m, nof,.d

rni C K, ehctl,fi

.

Peor

tood, sretre,
*

lmaJ)

)ernitc.tio,. (+

r No ttAV cerrie r

?ebetndFior. drrc te

,*È c,U v.i ce€ i

e* i olra

"te

tqlO : .t 07, )?zob Bi .

cv ideuG3

h. pti\ir

"l ot

H.P B.:

+ p*,t:

-) 2/3

'ihoc. penchtoheourl

latiovr

ho hi elozT

po/r-

a^telqod inoa.[.

",1

z,

. HBe Ag it in c.ttvnoal-

.

'

.

.

v e? /

bodT lO

'C

. 2? rnc,h e,nd,

qre i"

)e,x qsL

lq[i yq

|.cti o qa (_I)

co nto.e* +

ferinltrQ

3s o

tno lr)Lr.?.

"l cor.crr

r*]taoT

Wor

ìu *hc

Ld,'

o.r _ o.s ./, f r. *h.

UJ hoÈ.

É[;

5 - Lo?. In thc F.tr:

26

+ Reà,i {e"tro nes.h co u *t- ea

L-D Eraàc,we,rrB èuÌr o nS B

+

+

US - ru"r{ €,uatpc

>po1ad*'c.

( ;t *f

tttx^a ) h.u^-Ft tg

I

I

Tno-nr{rrr"'otN7

h l-o

D*S

lQ+o '. to/,

Nouru: l: loo/oo§

qae^^

a

§.ytrP

i3vrr:

lr, c

bo-[, o ,^ I

'g-a

A ->

4 w e'c Ka

B,D+ h-tz

e.+ +

É-l5-6

Pf e* r-Q. , ,yft hl"*r, :

(Uot *J

- aho rrx do,

F\'t*

s

![oil/t{Lc, , Vowt

t

h'"1

mol,oi i.

hrÀet )

pt^otclto§ie. ,.,,

= {ev eu

.(- i

t hchòto'"§4

LVuJ c§0, [="dJ

-

l.e*YeÀ

Jc.uat' èt I Ohorre- :

l-l

Fg'-#,fTÈ,

t-3

-

2- tt wcc lra

rrrcntha (§toahctL'-t)

-

'

?4

-)

-)

LA BoRATo Èf

ASr G

4oo- h,

BIUI R.U

eor) ;

oo§

BIV

f fob*e'h

/

L

?fr

FsATùPfS

Aur

(tn Pr)

(coÀJ T +

C" r

n

aa'

I

ruru carog)

Serulagic Tests of Patìent's Serun

lsM

inti-HAV

lgM

Ànfi-Hlt Anti-HN Diùgnostic lnteryÉtstion

4lté

?BoGÀlos I s

A-

lecoYezl 3loo'/'

l;+y rrte :] ry

p.ti tt 1

È)

ca.1i

{-t

Bx'. firerrdn nt h.

C So r. tto"t

-+)

he b-{i h'a (e)

I

+

+

cl{g§Nrc- HEPATTTTS

6 rnourfia

ETIOI.o6Y

È.tr.

c

9,

ts

d*! n ft"riua

P* ttto ro

6v

cHg. ?Ecsrs?

H*tffi*t

e$R.

Aetrvf (A t ir.;

,

1"o,tì[u,

t b"[u h

t

l*"0n. to dzrLel

I R,E Hos tS

3,

x. + uoArQon oaYti,ln,'o6

= {itn

.-9

etiLogc"l A"e,trrrJr uot poti b4

f

Prc /r"xdua

ola

Cfr€uta)

1

( h.h a/r)

P ],n[".h

I

atowt)

g ?' t P:h

ttqt

a^sr.h!hÈ,

Jo.[lc, C lt.ùro. Lu,/'wte

(

(

euré r^.t

-'

P

lr*

I

C^o^àùou.a&t

1.*"-É"-)

e LS

L" oTn

f,l*lrt

Fe

lv

h

sTArtoNS

hcfutg,arll,

nl.og;t

C Jdrr olic, nàrlr{, uou

clT $tt?

6on pLr

h t

intr.-hc-br.

4 rrJ-#r'--o'ila*

'

J

Ht eeclH@utrat

32

E}Tro0D 6

f*tty huct -+ a.0c[" &.c .

J

o eDì,

h.G.l,

[.*f.r

I

hehok h,

4vt L.arf

,*::rytr*mr

4,lt3qHf,oH

Gtor

Grcl

:ffi+

i:{,ti

rlr

qxitlo

ae.*-ÀJ

)

c.Lytt

31.

PO RTAI-

,t-NtTo # HY

@

tFr

+t'??E «TGNsto,rr

ttc,prtrc.

/

Atta,E

LIVsE

LO UU

f REssrr(€

$

\elrn ceuA G qr"o

-;

§^!ffiill{"(

7.C

IiGAs tì*EO.

?tgssut€ ,^, TH€

llrt»

PoÉTlu

svrr

tlEP ùErrùr

ELI NICAL I?AUIfESf,

Foat (-

u^

O Dc,,"bFrrue,,"t^

a/rTr.ur.rie

-D

o[

co[d1Là

lhc ruùB

§9uo o[

:[L:*:r*.,,ocr^d caofhc,

(veRrcàs)

trrnbcL. ?-0.

ebdour, urC.

(

C.U-U

-+)

:t

eivt

-a henouord-ii.i*

o

BLEEDTNG V4R(crS

(to:6oy.

c

l

"rt

cc

epi ec

ili;'L*

I t t"[

)q

,-a

->

hc unoteirnèrr'.

he Yn.toòrcì it /w&,,nt

. *sc lT€s

36

= ?*qn

lQr^ra

ce.stb)'

iu the f e.*".ì-ou{

. SP-}" <hwic LTnpt f.t uitr.our

' l{cptic L7upr. fo.r"

" R.t r^tto,,

ta'a v.ry

.|

'

tjotr

,oCì*tr Ly

(u*)

o

=[*[frm*(:ì;L

F"f"

;yrocta.

me

t

?c, nel.

PArHocEuesr-s r

^^

crclrfi^fJ

ut<