Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy

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Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy ,CXKGT8CSWGTQ%JWJCP%JWPI#PFTGU6$NGK

Abstract Hepatic encephalopathy and brain edema are important complications in the course of a patient with acute liver failure. Presumed unrelated for many years, increasing evidence suggests that an increase in brain water is seen in all forms of hepatic encephalopathy. Ammonia, traditionally linked to the pathogenesis of hepatic encephalopathy, plays an important role in the increase in brain water. In acute liver failure, an osmotic disturbance in the astrocyte, in combination with an alteration of cerebral blood flow results in overt brain edema and intracranial hypertension. In cirrhosis, magnetic resonance techniques indicate the presence of a brain osmotic disturbance. Several clinical factors modulate the development of brain swelling. Key words: Hepatic encephalopathy, brain edema, ammonia, liver disease, cerebral blood flow. *GRCVKEGPEGRJCNQRCVJ[ *'KUCHTGSWGPVENKPKECNEQO RNKECVKQPQHRCVKGPVUYKVJCEWVGCPFEJTQPKENKXGTFKUGCUGCPF KUFGHKPGFCUVJGRTGUGPEGQHRQVGPVKCNN[TGXGTUKDNGEGTGDTCN F[UHWPEVKQPKPVJGCDUGPEGQHQVJGTMPQYPECWUGUQHDTCKP FKUGCUG$TCKPGFGOCKUFGHKPGFCUVJGGZEGUUKXGCEEWOWNC VKQPQHKPVTCEGNNWNCTCPFQTGZVTCEGNNWNCTHNWKFKPDTCKPVKUUWG CPFKUCFGCFN[EQORNKECVKQPQHRCVKGPVUYKVJCEWVGNKXGTHCKN 

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© 2019, Fundación Clínica Médica Sur, A.C. Published by Elsevier España S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Annals of Hepatology 2(1) 2003: 12-22

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A

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B Increase of volume

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RJQURJQETGCVKPG#62KPXCTKQWUGZRGTKOGPVCNOQFGNU QH#.(6JWUDTCKPGPGTI[HCKNWTGKUEQPUKFGTGFVQ

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DGCPKORTQDCDNGRCVJQIGPKEGXGPVCVNGCUVRTKQTVQVJG FGXGNQROGPVQHKPVTCETCPKCNJ[RGTVGPUKQP Cerebral blood flow and the pathogenesis of brain edema and intracranial hypertension in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oss of CBF autoregulation in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nfluence of CBF on brain edema in ALF +PRCVKGPVUYKVJ#.(EGTGDTCNJ[RGTGOKCJCUDGGPCU UQEKCVGFYKVJFGGRGTEQOCKPETGCUGFDTCKPGFGOCCPF JKIJGTOQTVCNKV[(WTVJGTOQTGKPVGTXGPVKQPUVJCVCD TQICVGCPKPETGCUGKP%$(UWEJCUJ[RQVJGTOKCQTKP FQOGVJCEKPCFOKPKUVTCVKQPJCXGDGGPUJQYPGHHGEVKXG HQTEQPVTQNNKPIQTFGNC[KPIVJGFGXGNQROGPVQHDTCKPGFG OCCPFKPVTCETCPKCNJ[RGTVGPUKQPKPJWOCPUCUYGNN CUKPCPKOCNOQFGNUQH#.(+PVJG2%#TCVYKVJ COOQPKCKPHWUKQPYGJCXGUJQYPCRTGFKEVCDNGCPFUG NGEVKXGTKUGQH%$(VJCVQEEWTRTKQTVQVJGFGXGNQROGPVQH DTCKPGFGOCKPVJGUGVVKPIQHPQTOCNU[UVGOKEJCGOQF[ PCOKEU6JTGGOQTGQDUGTXCVKQPUKPVJKUOQFGNUWIIGUV CPKORQTVCPVTQNGHQTCJKIJ%$(KPVJGRCVJQIGPGUKUQH

Annals of Hepatology 2(1) 2003: 12-22

16

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Δ2Σσ KZΔπK? YJGTG .R KU VJG HKNVTCVKQP EQGHHKEKGPV QH VJG ECRKNNCT[ OGODTCPG#KUVJGECRKNNCT[OGODTCPGCTGCΔ2KUVJGJ[ FTQUVCVKERTGUUWTGITCFKGPVDGVYGGPVJGNWOGPQHVJGECRKN NCT[CPFVJGKPVGTUVKVKCNVKUUWGσ KKUVJGTGHNGEVKQPEQGHHK EKGPVQHUWDUVCPEGKQXGTVJGECRKNNCT[OGODTCPGCPFΔπKKU VJGQUOQVKERTGUUWTGITCFKGPVETGCVGFD[VJGEQPEGPVTCVKQP ITCFKGPVQHUWDUVCPEGKDGVYGGPDNQQFCPFVKUUWG %JCPIGUKP%$(CPFEGTGDTCNCWVQTGIWNCVKQPKP#.( EQWNFHCXQWTYCVGTHNWZKPVQVJGDTCKPD[CHHGEVKPIOCKPN[ UGXGTCNEQORQPGPVUQHVJG5VCTNKPIGSWCVKQP(KTUVCJKIJ GTJ[FTQUVCVKERTGUUWTGITCFKGPV Δ2KUCPQTOCNTGUWNVQH a)

CPKPETGCUGKP%$(KHPQPGYECRKNNCTKGUCTGQRGPGF#NUQ IKXGPVJCVCWVQTGIWNCVKQPKUNQUVKP#.(CUCEQPUGSWGPEG QHEGTGDTCNCTVGTKQNCTXCUQFKNCVCVKQPXCTKCVKQPUKPU[U VGOKECTVGTKCNRTGUUWTGYKNNITGCVN[KPHNWGPEGVJGJ[FTQ UVCVKERTGUUWTGKPVJGECRKNNCTKGU5GEQPFCPKPETGCUGKP %$(YQWNFTGUWNVKPKPETGCUGFCOOQPKCFGNKXGT[VQVJG DTCKP6JKUEQWNFYQTUGPΔπKD[KPFWEKPIHWTVJGTCEEWOW NCVKQPQHKPVTCEGNNWNCTINWVCOKPGCPFKPETGCUGQHDTCKPVKU UWGQUOQNCTKV[YJKEJYQWNFHCXQWTVJGHNWZQHYCVGTKPVQ VJGDTCKP(KPCNN[CPKPETGCUGKP%$(EQWNFNGCFVQCNCTI GTECRKNNCT[OGODTCPGCTGC #KHPGYECRKNNCTKGUYGTG QRGPGF ECRKNNCT[TGETWKVOGPVDWVVJGTGNGXCPEGQHUWEJ OGEJCPKUOKPVJGDTCKPKUEQPVTQXGTUKCN 5WDVNGCNVGTCVKQPUKPVJGRGTOGCDKNKV[QHDNQQFDTCKP DCTTKGTVJCVYQWNFCHHGEV.RCPFσ KJCXGDGGPRTGXK QWUN[FKUEWUUGF6JGPGVEQPUGSWGPEGQHCPKPETGCUGKP DNQQFHNQYKUVQTCKUGCOOQPKCFGNKXGT[VQVJGDTCKP+P FGGFUOCNNKPETGCUGUKPDNQQFHNQYYKNNITGCVN[KPETGCUG COOQPKC FGNKXGT[ VQ VJG DTCKP KP C J[RGTCOOQPGOKE UVCVG(Figure 3)

Clinical pathophysiology of the brain edema and intracranial hypertension #NNENKPKEKCPUTGEQIPK\GVJCVOWNVKRNGHCEVQTUECPRQ VGPVKCNN[KPHNWGPEGVJGFGXGNQROGPVQH*'6JWUKVKUPQV UWTRTKUKPIVJCVCYKFGCTTC[QHHCEVQTUECPCHHGEVVJGGZ RTGUUKQPQHDTCKPGFGOCCPFKPVTCETCPKCNJ[RGTVGPUKQPKP b)

30

1500

Plasma NH3 Levels NH3 - 200 mM

NH3 - 40 mM NH3 - 60 mM 1250

NH3 - 100 mM NH3 - 200 mM

20

15

10

% Increase in ammonia delivery

Ammonia delivery (mmol/100 g/min)

25

1000

750 NH3 - 100 mM 500 NH3 - 60 mM

5

0

250

NH3 - 40 mM

0 CBF-40 CBF-60 CBF-100 CBF-120 mL/100g/min mL/100g/min mL/100g/min mL/100g/min

0

75 150 % Increase in CBF

225

Figure 3.+PHNWGPEGQHEGTGDTCNDNQQFHNQYQPCOOQPKCFGNKXGT[VQVJGDTCKP6JGTKIJVRCPGNUJQYUECNEWNCVGFCDUQNWVGXCNWGUQHCOOQPKCFGNKXGT[HQT FKHHGTGPVXCNWGUQHEGTGDTCNDNQQFHNQYCPFNGXGNUQHRNCUOCCOOQPKC+PVJGNGHVRCPGNKVKUUJQYPVJGRGTEGPVCIGKPETGCUGQHCOOQPKCFGNKXGT[TGNCVK XGVQVJGPQTOCNCOOQPKCFGNKXGT[VQVJGDTCKP ECNEWNCVGFHQTPQTOCNCOOQPKCRNCUOCNGXGNUQHOKETQ/CPFEGTGDTCNDNQQFHNQYQHO.I OKP9KVJKPETGCUGFCOOQPKCNGXGNUCPKPETGCUGKPEGTGDTCNDNQQFHNQYNGCFUVQFKURTQRQTVKQPCVGKPETGCUGUQHCOOQPKCFGNKXGT[VQVJGDTCKP

-9DTXHURHWDO%UDLQHGHPDLQDFXWHOLYHUIDLOXUH

VJGENKPKECNUGVVKPI 9GYKNNGZCOKPGUGXGTCNRJ[UKQNQI KECNXCTKCDNGUCRRN[KPIEQPEGRVURTGXKQWUN[TGXKGYGF 

Infection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ecrotic liver +ORTQXGOGPVQHDTCKPGFGOCCPFEQPVTQNQHKPVTCETCPK CNRTGUUWTGCHVGTVQVCNJGRCVGEVQO[JCUDGGPTGRQTVGFKP RCVKGPVUYKVJ#.(#PKPETGCUGFTGNGCUGQHE[VQMKPGU HTQOVJGPGETQVKENKXGTUWIIGUVUCPKPHNCOOCVQT[GNGOGPV KPVJGKPVTCETCPKCNJ[RGTVGPUKQPQH#.(*QYGXGTEQP HQWPFKPIHCEVQTUYGTGRTGUGPVKPVJGUGUVWFKGUUWEJCUVJG WUGQHGZVTCEQTRQTGCNFGVQZKHKECVKQPOGVJQFUQTOKNFJ[ RQVJGTOKCENQWFKPIVJGCUUGUUOGPVQHVJGGHHGEVQHJGR CEVGEVQO[per se Temperature 6GORGTCVWTGKUCEQORQPGPVQHVJGU[UVGOKEKPHNCO OCVQT[ TGURQPUG U[PFTQOG 9JGTGCU J[RQVJGTOKC JCU DGGPUJQYPVQGZGTVDGPGHKEKCNGHHGEVUKPFGETGCUKPIDTCKP GFGOCCPFKPVTCETCPKCNRTGUUWTGKPRCVKGPVUCPFCPKOCN OQFGNUQH#.(J[RGTVJGTOKCKUCFGNGVGTKQWUGXGPV *[RGTVJGTOKCYCUUJQYPVQRTGEGFGUWTIGUQHKPVTCETCPK CNRTGUUWTGKPRCVKGPVUYKVJ#.(VQKPETGCUGEGTGDTCN DNQQFHNQYKPFQIUCPFVQKPETGCUGDNQQFDTCKPDCTTKGT RGTOGCDKNKV[KPUQOGCPKOCNOQFGNU(GXGTUJQWNFDG XKIQTQWUN[VTGCVGFKPRCVKGPVUYKVJ#.( Agitation 'RKUQFGUQHCIKVCVKQPQHVGPRTGEGFGUWTIGUQHKPVTCETC PKCNRTGUUWTGKPRCVKGPVUYKVJ#.(OCMKPIVJGRTGXGP VKQPCPFVTGCVOGPVQHCIKVCVKQPCPKORQTVCPVCURGEVKPVJG OCPCIGOGPVQHVJGUGRCVKGPVU#IKVCVKQPOC[TGHNGEVKP ETGCUGGZVTCEGNNWNCTDTCKPINWVCOCVGNGXGNU2TQRQHQN KUVJGRTGHGTTGFCRRTQCEJVQJCPFNGVJKUUKVWCVKQP

17

Arterial pressure and cerebral blood flow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

OGCPCTVGTKCNRTGUUWTGOKPWUKPVTCETCPKCNRTGUUWTGOWUV DGOCKPVCKPGFCDQXGOO*IVQCXQKFVKUUWGJ[RQZKC ,WIWNCTDWNDQZ[IGPUCVWTCVKQPUNQYGTVJCPCTGKP FKECVKXGQHEGTGDTCNKUEJGOKCYJKNGUCVWTCVKQPUITGCVGT VJCPKPFKECVGFGETGCUGFOGVCDQNKEFGOCPFUQHVJG DTCKPQTOQTGEQOOQPN[EGTGDTCNJ[RGTGOKC Glucose and lactate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őJ[RQZKEŒ OGEJCPKUVKE GZRNCPCVKQP (KTUV 6QHVGPI CPF EQNU JCXG UJQYPCPKPETGCUGKPGZVTCEGNNWNCTNCEVCVGKPRCVKGPVUYKVJ #.(CPFFGGR*'D[OGCPUQHDTCKPOKETQFKCN[UKU 0QVCDN[ KPETGCUGU KP GZVTCEGNNWNCT INWEQUG CPF NCEVCVG RTGEGFGFUWTIGUQHKPVTCETCPKCNRTGUUWTGYKVJQWVCTKUGKP GZVTCEGNNWNCTINWVCOCVG0QEJCPIGKPNCEVCVGR[TWXCVG TCVKQCPFPQGXKFGPEGQHVKUUWGJ[RQZKCYGTGFGVGEVGFKP OQUVUWDLGEVU$CUGFQPVJGUGHKPFKPIUVJGCWVJQTURTQ RQUGFVJCVNCEVCVGOC[DGKORNKECVGFKPVJGEGTGDTCNXC UQFKNCVCVKQPCPFUWTIGUQHKPVTCETCPKCNRTGUUWTGKP#.( 5GEQPF
Annals of Hepatology 2(1) 2003: 12-22

18

NGXGNUQHINWVCOKPGYJKEJKPETGCUGFKPVJGRTGEQOCUVCIG DWVFKFPQVUWDUGSWGPVN[TKUGVJGKPETGCUGKPNCEVCVGEQT TGNCVGF YKVJ VJG UGXGTKV[ QH GPEGRJCNQRCVJ[ $CUGF QP VJGUGHKPFKPIUVJGCWVJQTUUWIIGUVGFVJCVCNVGTCVKQPUQH EGNNWNCTINWEQUGCPFGPGTI[OGVCDQNKUOTCVJGTVJCPVJG KPVTCEGNNWNCT CUVTQE[VKECEEWOWNCVKQPQHINWVCOKPGYGTG VJGOCLQTECWUGQH*'CPFDTCKPGFGOCKPVJCVOQFGN (WTVJGTUVWFKGUVQKPXGUVKICVGVJGTQNGQHINWEQUGCPFNCE VCVGKP*'CPFDTCKPGFGOCCTGPGGFGFCPFEQWNFJCXG KORQTVCPVTGRGTEWUUKQPUKPVJGENKPKECNOCPCIGOGPVQH VJGUGRCVKGPVU Water and electrolyte abnormalities 5QFKWOEQPEGPVTCVKQPKUVJGOCKPHCEVQTFGVGTOKPKPI RNCUOCQUOQNCTKV[WPFGTPQTOCNEQPFKVKQPU*[RQPCVTG OKCKUEQOOQPKPEKTTJQUKUCPFYCVGTGNGEVTQN[VGCDPQT OCNKVKGUCTGCEQOOQPRTGEKRKVCPVQH*'6JGTGNCVKXGN[ JKIJ HTGSWGPE[ QH EGPVTCN RQPV[PG O[GNKPQN[UKU KP J[ RQPCVTGOKEEKTTJQVKEUWDLGEVUCHVGTNKXGTVTCPURNCPVCVKQP KURTQDCDN[CTGHNGEVKQPQHVJGRTQHQWPFCNVGTCVKQPQHQU OQTGIWNCVKQP CPF QUOQEQORGPUCVKQP KP VJG DTCKP QH VJGUGRCVKGPVU'ZVTGOGECTGUJQWNFDGVCMGPKPVJGEQT TGEVKQP QH J[RQPCVTGOKC DGHQTG FWTKPI CPF CHVGT NKXGT VTCPURNCPVCVKQP 6JGEQPUGSWGPEGUQHJ[RQPCVTGOKCYGTGUVWFKGFKPGZ RGTKOGPVCNOQFGNU+PVJGTCVYKVJRQTVCECXCNCPCUVQOQUKU KPFWEVKQP QH EJTQPKE J[RQPCVTGOKC D[ FGUCOKPQ& CTIKPKPGXCUQRTGUKPVTGCVOGPVFGETGCUGFVJGNGXGNUQHDTCKP QTICPKEQUOQN[VGU+PHWUKQPQHCOOQPKCTGUWNVGFKPVJG GZRGEVGFTKUGQHINWVCOKPGCPFCTGFWEVKQPQHVCWTKPGCPF O[QKPQUKVQN VJG OCKP QTICPKE QUOQN[VGU KP DQVJ PQT OQPCVTGOKECPFJ[RQPCVTGOKETCVU+ORQTVCPVN[KPHWUKQP QHCOOQPKCTGUWNVGFKPCJKIJGTFGITGGQHDTCKPGFGOCKP J[RQPCVTGOKEEQORCTGFVQPQTOQPCVTGOKETCVUFGURKVGCP CVVGPWCVGFTKUGQHINWVCOKPGKPVJGHQTOGT6JGUGQDUGTXC VKQPUUWIIGUVVJCVEJTQPKEJ[RQPCVTGOKCOCMGUVJGDTCKP OQTGXWNPGTCDNGVQCPCOOQPKCKPFWEGFQUOQVKEFKUVWT DCPEGYKVJUWDUGSWGPVDTCKPUYGNNKPI+PEQPVTCUVKPETGCU KPIRNCUOCQUOQNCTKV[D[KPHWUKQPQHJ[RGTVQPKEUCNKPGJCU DGGP QDUGTXGF VQ TGFWEG KPVTCETCPKCN J[RGTVGPUKQP KP #.(KVUWUGKUDGKPIGXCNWCVGFKPQPIQKPIENKPKECNVTKCNU #NVGTCVKQPUQHRQVCUUKWOEQWNFCNUQKPHNWGPEG*'D[CN VGTKPIPQTOCNCOOQPKCOGVCDQNKUO*[RQMCNGOKCKPETGCU GUTGPCNCOOQPKCIGPGUKUCPFUGGOUVQTGUWNVKPDQVJKP ETGCUGFWTKPCT[GZETGVKQPCPFXGPQWUUGETGVKQPQHCOOQ PKCCUUGGPKPJWOCPUYKVJEJTQPKERQVCUUKWOFGRNGVKQP 5GTWORQVCUUKWOCPFWTKPGHNQYUKIPKHKECPVN[EQTTGNCVGF YKVJMKFPG[COOQPKCRTQFWEVKQPYKVJUGTWORQVCUUKWO CEEQWPVKPIHQTQHXCTKCVKQPUKPCOOQPKCRTQFWEVKQP Ammonia metabolism #JKIJN[QTEJGUVTCVGFKPVGTQTICPOGVCDQNKUOCPFVTCH HKEMKPIQHCOOQPKCCPFINWVCOKPGKURTGUGPVKPRJ[UKQNQI KECNEQPFKVKQPU%JTQPKECPFCEWVGNKXGTHCKNWTGTGUWNVKPJ[ RGTCOOQPGOKCCPFNGCFUVQCPKORQTVCPVFKUVWTDCPEGQH

PQTOCNDQF[PKVTQIGPJQOGQUVCUKU HQTTGXKGYUGG&KH HGTGPVENKPKECNHCEVQTUKPHNWGPEGper seVJGRNCUOCNGXGNUQT VJGGHHGEVUQHCOOQPKCKPVJGDTCKPKPNKXGTHCKNWTG Muscle wasting 'XGPVJQWIJINWVCOKPGU[PVJGVCUGCEVKXKV[KPUMGNGVCN OWUENGKUNQYKVUTGNCVKXGKPETGCUGFOCUUEQORCTGFVQ QVJGTQTICPUVJCVEQPVCKPVJKUGP\[OGOCMGUVJGOWUENG QPGQHVJGOCKPINWVCOKPGU[PVJGUK\KPIQTICPU&WGVQ VJGKPETGCUGFRNCUOCCOOQPKCNGXGNUKPNKXGTHCKNWTGVJG OWUENGDGEQOGUCPKORQTVCPVCOOQPKCFGVQZKH[KPIQT ICP #XQKFCPEG QH OWUENG YCUVKPI KP EKTTJQUKU CPF UVKOWNCVKQPQHCOOQPKCOGVCDQNKUOKPVJGOWUENGCTGKO RQTVCPVRQVGPVKCNVJGTCRGWVKEVCTIGVUKPEJTQPKECPFCEWVG NKXGTHCKNWTG Gastrointestinal bleeding )CUVTQKPVGUVKPCNDNGGFKPIKUCMPQYPRTGEKRKVCPVQH*' $NQQFKPVJGFKIGUVKXGVTCEVJCUDGGPUJQYPVQDGCRQVGPV UVKOWNWUHQTVJGKPVGUVKPCNRTQFWEVKQPQHCOOQPKC+P VJG TCV YKVJ RQTVCECXCN CPCUVQOQUKU UKOWNCVGF ICU VTQKPVGUVKPCNDNGGFKPINGFVQKPETGCUGFNGXGNUQHCOOQPKC CPFINWVCOKPGKPVJGDTCKPCPFVQYQTUGPKPIQHJGRCVKE GPEGRJCNQRCVJ[KPFKECVKPICOGEJCPKUVKECUUQEKCVKQP Acid-base abnormalities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edatives 6JGTQNGQHUGFCVKXGUCURTGEKRKVCPVUQH*'KUYGNNTGEQI PK\GF 4GEGPV TGRQTVU KORNKECVG GPFQIGPQWU DGP\QFKC\ GRKPGNKMGEQORQWPFUKPVJGRCVJQIGPGUKUQH*'CPFDTCKP GFGOC+PKUQNCVGFCUVTQE[VGUFKHHGTGPVDGP\QFKC\GRKPGUKP FWEGFRTQVGKPV[TQUKPGPKVTCVKQPCPFHTGGTCFKECNRTQFWE VKQPKPCOCPPGTUKOKNCTVQVJCVRTQFWEGFD[COOQPKC CPFGZCEGTDCVGFCOOQPKCKPFWEGFCUVTQE[VGUYGNNKPI

-9DTXHURHWDO%UDLQHGHPDLQDFXWHOLYHUIDLOXUH

5GFCVKQPKUFKHHKEWNVVQCXQKFKPVJGCIKVCVGFRCVKGPVYKVJ #.(DWVDGP\QFKC\GRKPGUUJQWNFDGCXQKFGF

Conclusion *GRCVKEGPEGRJCNQRCVJ[QHEJTQPKENKXGTFKUGCUGCPF DTCKPGFGOCQHCEWVGNKXGTHCKNWTGJCXGDGGPEQPUKFGTGF VYQFKUVKPEVCPFWPTGNCVGFENKPKECNGPVKVKGUHQTOCP[[GCTU 'XGPVJQWIJVJGKTRCVJQIGPGUKUKUUVKNNPQVHWNN[TGUQNXGF CPGYRCTCFKIOJCURTQITGUUKXGN[FGXGNQRGFYJGTGDQVJ GPVKVKGUCTGFKHHGTGPVGNGOGPVUQHCEQPVKPWQWUURGEVTWO *GRCVKEGPEGRJCNQRCVJ[CPFDTCKPGFGOCUGGOVQUJCTG EQOOQPRCVJQIGPKETQQVUYKVJCMG[TQNGQHCOOQPKC CPFCETKVKECNKPXQNXGOGPVQHVJGCUVTQE[VGKPDQVJEQORNK ECVKQPU6JGUVWF[QHQPGJGNRUVQWPFGTUVCPFVJGQVJGT YJGTGCU#.(HCEKNKVCVGUVJGUVWF[QHECWUCNTGNCVKQPUJKRU KPCHKTOGTOCPPGTEJTQPKENKXGTHCKNWTGIKXGUVJGQRRQT VWPKV[VQUVWF[DTCKPEQORGPUCVKPIOGEJCPKUOU6JKUKP VGITCVGFXKGYRTQXKFGUCNUQCDGVVGTRGTURGEVKXGVQLWFIG VJGRCVJQRJ[UKQNQIKECNTGNGXCPEGVJCVQVJGTHCEVQTUOC[ JCXGKPVJGOCPKHGUVCVKQPQHVJGFKUGCUG

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(GTGPEK2.QEMYQQF#/WNNGP-6CTVGT49GKUUGPDQTP-$NGK #6 *GRCVKE GPEGRJCNQRCVJ[ōFGHKPKVKQP PQOGPENCVWTG FKCIPQUKU CPFSWCPVKHKECVKQPHKPCNTGRQTVQHVJGYQTMKPIRCTV[CVVJGVJ9QTNF %QPITGUUGU QH )CUVTQGPVGTQNQI[ 8KGPPC  Hepatology    9CTG#,&ŏ#IQUVKPQ#0%QODGU$%GTGDTCNGFGOCCOCLQTEQO RNKECVKQP QH OCUUKXG JGRCVKE PGETQUKU Gastroenterology    $WUVCOCPVG,4KOQNC#8GPVWTC2,0CXCUC/%KTGTC+4GIIKCTFQ 8 4QFGU , 2TQIPQUVKE UKIPKHKECPEG QH JGRCVKE GPEGRJCNQRCVJ[ KP RCVKGPVUYKVJEKTTJQUKUJ Hepatol 1ŏ)TCF[,)#NGZCPFGT),*C[NNCT-/9KNNKCOU4'CTN[KPFKEC VQTUQHRTQIPQUKUKPHWNOKPCPVJGRCVKEHCKNWTGGastroenterology   $GTPWCW,)QWFGCW#2Q[PCTF6&WDQKU(.GUCIG);XQPPGV$ &GIQVV%GVCN/WNVKXCTKCVGCPCN[UKUQHRTQIPQUVKEHCEVQTUKPHWNOK PCPVJGRCVKVKU$Hepatology %CUVGNNU#5CNOGTQP,/0CXCUC/4KOQNC#5CNQ,#PFTGW* /CU#GVCN.KXGTVTCPURNCPVCVKQPHQTCEWVGNKXGTHCKNWTGCPCN[UKUQH CRRNKECDKNKV[ Gastroenterology    *QQHPCING,*%CTKVJGTU4.,T5JCRKTQ%#UEJGT0(WNOKPCPVJG RCVKEHCKNWTGUWOOCT[QHCYQTMUJQRHepatology 1ŏ)TCF[,)5EJCNO599KNNKCOU4#EWVGNKXGTHCKNWTGTGFGHKPKPI VJGU[PFTQOGULancet %QTFQDC,$NGK#6$TCKPGFGOCCPFJGRCVKEGPEGRJCNQRCVJ[Semin Liver Dis -CVQ/*WIJGU4&-GC[U469KNNKCOU4'NGEVTQPOKETQUEQRKE UVWF[QHDTCKPECRKNNCTKGUKPEGTGDTCNGFGOCHTQOHWNOKPCPVJGRCVKE HCKNWTGHepatology 6TCDGT2)&CN%CPVQ/)CPIGT&4$NGK#6'NGEVTQPOKETQUEQRKE GXCNWCVKQP QH DTCKP GFGOC KP TCDDKVU YKVJ ICNCEVQUCOKPGKPFWEGF HWNOKPCPV JGRCVKE HCKNWTG WNVTCUVTWEVWTG CPF KPVGITKV[ QH VJG DNQQF DTCKPDCTTKGTHepatology 6TCDGT2&CN%CPVQ/)CPIGT&$NGK#6'HHGEVQHDQF[VGORGTC VWTGQPDTCKPGFGOCCPFGPEGRJCNQRCVJ[KPVJGTCVCHVGTJGRCVKEFGXCU EWNCTK\CVKQP Gastroenterology    /CVMQYUM[L-#/CTTGTQ,#%CTTQNN4'&CPKNMQXKEJ#8)TGGP 4/$GP[C48#\QZ[OGVJCPGKPFWEGFHWNOKPCPVJGRCVKEHCKNWTGKP %$.,OKEGEJCTCEVGTK\CVKQPQHCPGYCPKOCNOQFGNAm J Physiol )

19

 )QXG%&*WIJGU4&'FG4,9KNNKCOU44GIKQPCNEGTGDTCNGFGOC CPF EJNQTKFG URCEG KP ICNCEVQUCOKPGKPFWEGF NKXGT HCKNWTG KP TCVU Hepatology  &KZKV8%JCPI6/$TCKPGFGOCCPFVJGDNQQFDTCKPDCTTKGTKPICNCE VQUCOKPGKPFWEGFHWNOKPCPVJGRCVKEHCKNWTGTCVU#PCPKOCNOQFGNHQT GXCNWCVKQPQHNKXGTUWRRQTVU[UVGOUASAIO Trans 
20

Annals of Hepatology 2(1) 2003: 12-22

 $QUOCP&-&GWV\0'&G)TCCH##XF*WNUV498CP'KLM*/ $QXGG9//CCU/#GVCN%JCPIGUKPDTCKPOGVCDQNKUOFWTKPI J[RGTCOOQPGOKC CPF CEWVG NKXGT HCKNWTG TGUWNVU QH C EQORCTCVKXG *0/4 URGEVTQUEQR[ CPF DKQEJGOKECN KPXGUVKICVKQP Hepatology   5VTCWUU)+-PWFUGP)/-QPFTWR,/QNNGT-.CTUGP(5%GTGDTCN OGVCDQNKUOQHCOOQPKCCPFCOKPQCEKFUKPRCVKGPVUYKVJHWNOKPCPV JGRCVKEHCKNWTGGastroenterology  %JWPI%)QVVUVGKP,$NGK#6+PFQOGVJCEKPRTGXGPVUVJGFGXGNQR OGPV QH GZRGTKOGPVCN COOQPKCKPFWEGF DTCKP GFGOC KP TCVU CHVGT RQTVCECXCNCPCUVQOQUKUHepatology 
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21

8CSWGTQ,5EJKQFV(%JWPI%4CFGOCMGT#9.GG9/$NGK#6 2TGFKEVQTU QH RTQITGUUKQP VQ FGGR JGRCVKE GPEGRJCNQRCVJ[ KP CEWVG NKXGT HCKNWTG TGUWNVU QH VJG 75 #EWVG .KXGT (CKNWTG 5VWF[ )TQWR Hepatology# 9QPI /. $QPIKQTPQ 2$ CN5JGMJNGG # 'URQUKVQ # -JCVTK 2 .KEKPKQ,+.DGVC+.TGEGRVQTV[RG+CPFK015IGPGGZRTGUUKQP KPTCVDTCKPXCUEWNCVWTGCPFRGTKXCUEWNCTCTGCUNeuroreport  ,CNCP42QNNQM#5JCJ5/CFJCXCP-5KORUQP-.KXGTFGTKXGF RTQKPHNCOOCVQT[ E[VQMKPGU OC[ DG KORQTVCPV KP RTQFWEKPI KPVTCE TCPKCNJ[RGTVGPUKQPKPCEWVGNKXGTHCKNWTGJ Hepatol 4Q\IC,2QFGUVC..G2CIG'*QHHOCP#/QTUKCPK'5JGT.9QQNH )/ GV CN %QPVTQN QH EGTGDTCN QGFGOC D[ VQVCN JGRCVGEVQO[ CPF GZVTCEQTRQTGCNNKXGTUWRRQTVKPHWNOKPCPVJGRCVKEHCKNWTGLancet   ,CNCP49KNNKCOU46JGKPHNCOOCVQT[DCUKUQHKPVTCETCPKCNJ[RGT VGPUKQPKPCEWVGNKXGTHCKNWTGJ Hepatol /WPQ\5,/QTKV\/,$GNN40QTVJTWR$/CTVKP24CFQOUMK, (CEVQTU CUUQEKCVGF YKVJ UGXGTG KPVTCETCPKCN J[RGTVGPUKQP KP ECPFK FCVGUHQTGOGTIGPE[NKXGTVTCPURNCPVCVKQPTransplantation  -QFCMCV5-)QRCN2$9GPFQP,+PVTCETCPKCNRTGUUWTGKUTGNCVGFVQ DQF[VGORGTCVWTGKPCEWVGNKXGTHCKNWTGLiver Transpl%  -CVUWOWTC*-CDWVQ/*QUQVCPK-*CPFC;-QDC[CUJK*-WDQVC6 6JGKPHNWGPEGQHVQVCNDQF[J[RGTVJGTOKCQPDTCKPJCGOQF[PCOKEUCPF DNQQFDTCKPDCTTKGTKPFQIUActa Neurochir (Wien)  /WGNNGT 5/ +PETGCUGF DNQQFDTCKP DCTTKGT RGTOGCDKNKV[ FWTKPI J[ RGTVJGTOKCKPVJGCYCMGTCVTrans Am Neurol Assoc -QFCMCV5-)QRCN2$9GPFQP,#*[RGTIN[ECGOKCKUCUUQEKCVGF YKVJKPVTCETCPKCNJ[RGTVGPUKQPKPRCVKGPVUYKVJCEWVGNKXGTHCKNWTG=CD UVTCEV?Liver Transpl% 0CMCMKOWTC-(NGKUEJGT,'&TWOOQPF,%5EJGNNGT/5
22

Annals of Hepatology 2(1) 2003: 12-22

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