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Lack of effect of pentoxifylline on portal pressure and hepatic haemodynamics in cirrhosis
LACK OF EFFECT OF PENTOXIFYLLINE ON PORTAL PRESSURE AND HEPATIC HAEKODYNAMICS IN CIRRHOSIS. F Feu. JC Garcia-Pa&. L Ruiz de1 Arbol. I Cirera. p Pizcueta. J Bosch. J Rod&. Liver Unit. Hospital Clinic i Provincial. University of Barcelona. Exoerimental studies have shown that oentoxifvlline’ ~decreases intrahepatic resistance in tie isolated perfused cirrhotic liver, suggesting that this agent may have beneficial effects on portal and liver function in patients with pressure cirrhosis. The present study was aimed at investigating this possibility by measuring the haemodynamic effects of the drug in a series of 16 patients with cirrhosis receiving an iv infusion of 3 mglmin for 60 min) or pentoxifylline (n-g. placebo (~7) in a double blind investigation. There were no changes in patients receiving Pentoxifylline caused mild arterial vasoplacebo. dilation, reducing systemic vascular resistance (6.2i5.32. p
P4501IIA-MEDIATED
CYTOCHROME DAPSONE C.
IN
NORMAL
Flemine
G.
Gueneerich.
Hav.
R.
A.
RYDROmTION
P&s.
G.
R.
Wilkinson.
end Biochemistry. TN 37232, USA
N-hydroxylation of dapSO"e (DDS) to its ("DA) is mediated by the Gytochrome A correlation between catalytic. P450 system. activity and PGSOIIIA4 level in human liver selective inhibition by monoclonal lniCtOSOUKS: antibody to P45OIIIA4 but not to other antiisozymes:and a reductionin oxidationby mechanisnbased inhibitors of P45OIIIA4 all suggested HDA formationis predominantlydependenton this fow of P450. In healthy subjects the urinary recovery of "DA accountedfor only 30% Of a" oral dose; however. there was a good &rrzlation between davsone‘s clearance (CLJ and the fractional metabolic clearance to HDA (CL,& (r-0.97, PCO.01). Ihis relationshipwas also present in cirrhoticpatients despite CL and & being reduced by 24% and 48X, respectively. A single point urinary excretion trait measurement of hydroxylation confirmed e similar reduction in HDA formation. These findings indicate that DDS oxidation to HDA is mediated by P45OIIIA4 and that this pathway is a major determinant of mtersublect variabilftv in DDS clearance. Furthermore.&rhosis reduce;P4501IIA4 activity. DDS may be a clinicsllysafe and useful probe of P45OIIIA4 activity2" viva.
hydroxylamine
AlTIBOOIES
(HBV) HARHERS IP ALCOHOL INDUCED LIVER DISfASE
3rd Departrent
EaiIia Hospital.
beta-blockers
during
EISfor
bleeding
(OV).
of antibodies to HCV and of HBV -ariers alas inve-
variceal reblecfroa OV were en
contra-indications
to betr-
excluded. Yhc remaining 29 patients were randomized
anti-HCV antibodies YIL 36.42 (aaler 16.2 fcsalts 12.%);
sarker of HBY infection ~1s detected
in 03.6% of :+e patients
(males 51.3%. fesaler 25.021. HCV seropositivity
square test p- 0.0139). Patients were divided in 3 grouos acco~ding '.o the hisielogic.al features: norw? qe (I'). chronic alcoholic hepatitis
within 5 days from cessation of bleeding.
W "13 stopped in 4 pa-
tizs related
with the positivity of at least one marker af llEY infection (chi
rateby
conditions
HBsAg
in 3 patients (5.5% all males) while EL least one
to receive CIS (14) or EIS plus oral Y in doses reducing heart 25%. N ~a$ started in stable haemodinamically
2 DS 52.7~12.!I
dith alcohol induced liver disease. The overall prevalence of
~2s positive
single blind pilot study
ding. Forty-t-o patients vith recent haemorrhagc wre
varices
L.Lindner.
Internal Medicine and Blood Center. Reggia EeilIa naspital. Italy Tte prevalence
about the efficacy of
ter:ing N in :he p-evention of prt-eradication rolled in the study: IL (33.3rl)r.%
CasaIi. E. Carta?trti.
stigated in 55 patients (39 males 16 females. a?
oesophagcal
Ye report the results of a randomized
plockrrr
of Digestive
Italy
fcr a-d conflicting reports are available
H. Bcltraai. 8.
AID HE?AI:TiS B VIRUS
I. Ranghi. P. Rivasi.P. Zanoni- A.C. PIancher 3rd DeFadaent of
E. Ricci. 6. Eedogni
of Internal lledicinr and Department
Endoscopy. Fqgio
TO HEPATITIS C VIRUS (KY)
G. fornaciari.
G. Fornaciari. C. Gumina. 6. Berfoni. C. Barri. R. Conigliaro. Y. GigIioli. G. Giovannini. l.G. Tortilla.
P,
Departmentsof Pharmacology Vanderbilt University. Nashville.
PIC INJtCllOC SCLtRDlHERAPY IESlING NAGOLOL (N)
F.
Branch
PREVEYIION OF VARICEAL PEBLEEOINC DURING THE COUPSf Of ElDOSC~ (LIS): A RA1100lllZEDPILOT IAIAL
OF
SUBJECTSAND CIRRHOTICS.
HC\I positi"itY
liver or oinital chnn-
(IO) wd
cirrhosis
(28).
ras related rith increasing severity of liver di-
tients (28.6Y) for ride effects.
sease (p= 0.0251) while in HBV positive patients .C obsewed
RISULIS: in patients receiving only EIS we observed 4 rebleeding
ly a greater rate of chronic alcohoiic hepatitis
(29.5%) and 3 deaths (21.42) while in the I group there were 1
Only two patients had a positive HC:' result and a noraal liver.
rrbleeding
'de found a very high Prevalence oi anti-XV
(7.1%) and 1 death (7.12); the differences
CONCLUSIONS:
our results indicate a mild beneficial
in the prevention of variceal reblcrding:
uere WS.
effect of N
lack of statistical
II
ents with
alcoholic
gnificancc raY be ascribed to the small number of patients studi
ship between anti-KY se.
In conclusion nadolol
seems of liaittd utility during the course of sclzrltherapy ly for its lor clinical applicabilit)l
mai:
disease
anfib:Cies
as previously
reortrd.
in patiLiver
lesions nay be related to HCV according to the St*ong relation-
cd. N utility ir limited bY high number of non eligible patients and by relevant rate of side effects.
liver
on-
Ic- 0.062).
prevalence and the severity sf liver disea
P4501IIA-MEDIATED
CYTOCHROME DAPSONE C.
IN
NORMAL
Flemine
G.
Gueneerich.
Hav.
R.
A.
RYDROmTION
P&s.
G.
R.
Wilkinson.
end Biochemistry. TN 37232, USA
N-hydroxylation of dapSO"e (DDS) to its ("DA) is mediated by the Gytochrome A correlation between catalytic. P450 system. activity and PGSOIIIA4 level in human liver selective inhibition by monoclonal lniCtOSOUKS: antibody to P45OIIIA4 but not to other antiisozymes:and a reductionin oxidationby mechanisnbased inhibitors of P45OIIIA4 all suggested HDA formationis predominantlydependenton this fow of P450. In healthy subjects the urinary recovery of "DA accountedfor only 30% Of a" oral dose; however. there was a good &rrzlation between davsone‘s clearance (CLJ and the fractional metabolic clearance to HDA (CL,& (r-0.97, PCO.01). Ihis relationshipwas also present in cirrhoticpatients despite CL and & being reduced by 24% and 48X, respectively. A single point urinary excretion trait measurement of hydroxylation confirmed e similar reduction in HDA formation. These findings indicate that DDS oxidation to HDA is mediated by P45OIIIA4 and that this pathway is a major determinant of mtersublect variabilftv in DDS clearance. Furthermore.&rhosis reduce;P4501IIA4 activity. DDS may be a clinicsllysafe and useful probe of P45OIIIA4 activity2" viva.
hydroxylamine
AlTIBOOIES
(HBV) HARHERS IP ALCOHOL INDUCED LIVER DISfASE
3rd Departrent
EaiIia Hospital.
beta-blockers
during
EISfor
bleeding
(OV).
of antibodies to HCV and of HBV -ariers alas inve-
variceal reblecfroa OV were en
contra-indications
to betr-
excluded. Yhc remaining 29 patients were randomized
anti-HCV antibodies YIL 36.42 (aaler 16.2 fcsalts 12.%);
sarker of HBY infection ~1s detected
in 03.6% of :+e patients
(males 51.3%. fesaler 25.021. HCV seropositivity
square test p- 0.0139). Patients were divided in 3 grouos acco~ding '.o the hisielogic.al features: norw? qe (I'). chronic alcoholic hepatitis
within 5 days from cessation of bleeding.
W "13 stopped in 4 pa-
tizs related
with the positivity of at least one marker af llEY infection (chi
rateby
conditions
HBsAg
in 3 patients (5.5% all males) while EL least one
to receive CIS (14) or EIS plus oral Y in doses reducing heart 25%. N ~a$ started in stable haemodinamically
2 DS 52.7~12.!I
dith alcohol induced liver disease. The overall prevalence of
~2s positive
single blind pilot study
ding. Forty-t-o patients vith recent haemorrhagc wre
varices
L.Lindner.
Internal Medicine and Blood Center. Reggia EeilIa naspital. Italy Tte prevalence
about the efficacy of
ter:ing N in :he p-evention of prt-eradication rolled in the study: IL (33.3rl)r.%
CasaIi. E. Carta?trti.
stigated in 55 patients (39 males 16 females. a?
oesophagcal
Ye report the results of a randomized
plockrrr
of Digestive
Italy
fcr a-d conflicting reports are available
H. Bcltraai. 8.
AID HE?AI:TiS B VIRUS
I. Ranghi. P. Rivasi.P. Zanoni- A.C. PIancher 3rd DeFadaent of
E. Ricci. 6. Eedogni
of Internal lledicinr and Department
Endoscopy. Fqgio
TO HEPATITIS C VIRUS (KY)
G. fornaciari.
G. Fornaciari. C. Gumina. 6. Berfoni. C. Barri. R. Conigliaro. Y. GigIioli. G. Giovannini. l.G. Tortilla.
P,
Departmentsof Pharmacology Vanderbilt University. Nashville.
PIC INJtCllOC SCLtRDlHERAPY IESlING NAGOLOL (N)
F.
Branch
PREVEYIION OF VARICEAL PEBLEEOINC DURING THE COUPSf Of ElDOSC~ (LIS): A RA1100lllZEDPILOT IAIAL
OF
SUBJECTSAND CIRRHOTICS.
HC\I positi"itY
liver or oinital chnn-
(IO) wd
cirrhosis
(28).
ras related rith increasing severity of liver di-
tients (28.6Y) for ride effects.
sease (p= 0.0251) while in HBV positive patients .C obsewed
RISULIS: in patients receiving only EIS we observed 4 rebleeding
ly a greater rate of chronic alcohoiic hepatitis
(29.5%) and 3 deaths (21.42) while in the I group there were 1
Only two patients had a positive HC:' result and a noraal liver.
rrbleeding
'de found a very high Prevalence oi anti-XV
(7.1%) and 1 death (7.12); the differences
CONCLUSIONS:
our results indicate a mild beneficial
in the prevention of variceal reblcrding:
uere WS.
effect of N
lack of statistical
II
ents with
alcoholic
gnificancc raY be ascribed to the small number of patients studi
ship between anti-KY se.
In conclusion nadolol
seems of liaittd utility during the course of sclzrltherapy ly for its lor clinical applicabilit)l
mai:
disease
anfib:Cies
as previously
reortrd.
in patiLiver
lesions nay be related to HCV according to the St*ong relation-
cd. N utility ir limited bY high number of non eligible patients and by relevant rate of side effects.
liver
on-
Ic- 0.062).
prevalence and the severity sf liver disea