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COMBINATION OF PEGYLATED
INTERFERON AND LAMIVUDINE IS SUPERIOR TO LAMIVUDINE MONOTHERAPY IN THE
TREATMENT OF CHRONIC HEPATITIS B - A RANDOMIZED TRIAL
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J.J.Y. Sung*, H.L.Y. Chan, A.Y. Hui, F.K.L.
Chan, A.M.L. Chim, M.L. Wong, N.W.Y. Leung, *Presenting Author
Department Of Medicine & Therapeutics, Chinese University Of Hong Kong,
Hong Kong
Background: Previous studies combining interferon with lamivudine failed
to prove additional benefit in clearance of HBV infection. We aimed to
study the anti-viral effects of pegylated interferon (Peg-IFN) and
lamivudine combination. Patients and Methods: Treatment-naive chronic
hepatitis B patients who had positive HBeAg, HBV DNA >1, 000, 000
copies/ml and ALT 1.3-5X upper limit of normal were recruited into an
open-labeled, randomized study. Patients received either combination
treatment (Combo group) with Peg-IFN 1.5 mcg/kg for 8 weeks, then Peg-IFN
plus lamivudine 100mg daily for 24 weeks followed by lamivudine alone
for 28 weeks, or lamivudine monotherapy 100mg daily for 52 weeks (Lam
group). End-of-treatment and sustained (24-week post-treatment)
virological response (VR, defined as HBeAg seroconversion and
undetectable HBV DNA) and biochemical response (BR, defined as
normalization of ALT) were analyzed. Results: The interim results of
first 40 patients who finished treatment and follow-up were analyzed.
There was no difference in the gender, age and ALT levels between the
two groups. The proportion of patients achieving end-of-treatment and
sustained VR in Combo group was significantly higher than that of Lam
group (75% vs 25%, p=0.0005 and 50% vs 10%, p=0.02 respectively). There
was no significant difference in the end-of-treatment and sustained BR
between the Combo and Lam groups (95% vs 70%, p=0.1 and 50% vs 30%,
p=0.3 respectively). Four patients receiving Peg-IFN had premature
termination of treatment due to serious adverse events. Conclusion:
Combination of Peg-IFN and lamivudine has superior anti-viral effect to
lamivudine monotherapy in the treatment of chronic hepatitis B
infection. |
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PREDICTORS OF VIROLOGIC
RESPONSE IN COMBINATION THERAPY WITH INTERFERON (IFN) ALFA 2B PLUS
RIBAVIRIN OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION (LT)
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B. Lavezzo*, 1 A. Franchello, 2 A. Smedile,
1 D. Cocchis, 2 E. David, 3 A. Barbui, 4 A. Ottobrelli, 1 M. Fadda, 5 A.
Brunati, 2 M. Salizzoni, 2 M. Rizzetto, 1 *Presenting Author 1Dept Of
Gastroenterology, 2Dept Of Liver Transplant Surgery, 3Dept Of Pathology
Division, 4Dept Of Virology Division, 5Dept Of Clinical Nutrition
Service, Molinette Hospital, Turin, Italy
Background: combination treatment (CT) with IFN plus ribavirin is
efficacious in small group of patients (pts) with recurrent hepatitis C
after LT. Predictor factors of response are lacking. Aim: to evaluate
pre-treatment predictors of virologic response (negative HCV-RNA by PCR,
Monitor Roche) at end of treatment (ETVR) and at 6 months (mo) of
follow-up (SVR) in pts treated with CT for recurrent hepatitis C.
Methods: we evaluated 108 pts, mean age 53 yr (29-65), 77% males76%
genotype 1, with recurrent hepatitis C after LT, histology at baseline:
20 pts acute hepatitis, 88 pts chronic hepatitis with mean grading score
of 5/18 (4-11) and mean staging score 2/6 (1-5). They were treated with
IFN alfa 2b 3 MU x 3 weekly plus ribavirin 800 mg/die for 6 or 12 mo.
Median time LT to treatment was 10 mo (2-86) Immunosuppressive therapy
was cyclosporine in 63%, FK in 37% of pts. Mean ALT levels pre-treatment
was 238 UI/L (50-1000), mean HCV-RNA level 38 MEq/ml (0, 7-120). Age,
gender, immunosuppression, baseline ALT and HCV-RNA levels, histological
grading and staging pre-treatment duration of therapy, time interval
from LT to start of therapy, genotype were evaluated by linear
multivariate regression analysis. Results: ETVR was obtained in 29, 6%
of pts, SVR in 23%. HCV genotype non-1 responded better than genotype 1
(SVR 46% vs 16%, p: 0, 001). Age and baseline HCV-RNA were predictors of
ETVR (p < 0.05), but not SVR (age p: 0, 07). Duration of therapy was
correlated with SVR, but virologic relapse occurred only in genotype-1
pts. In relapsed pts serum HCV-RNA became negative just before the end
of therapy. Conclusions: in LT genotype non-1 is predictor of SVR. In
genotype-1 duration of therapy should be personalized to obtain a better
and stable efficacy of treatment. |
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PREDCTIVE
FACTORS OF HCC RECURRENCE AFTER LIVER TRANSPLANTATION (OLT)
: AN INTERIM ANALYSIS
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S. Gianni*, 1, 2 F.V. Mirante,
2 R. Fassati, 2 D. Forti, 2 V. Mazzaferro, 2 U. Cillo, 1, 2
A. Maffei Faccioli, 2 G.L. Grazi, 2 M. Salizzoni, 2 F.
Filipponi, 2 M. Castagneto, 2 G. Tisone, 2 U. Valente, 2 F.
Farinati, 1, 2 M. Pompili, 2 G. Gasbarrini, 2 R. Naccarato,
1, 2 S. Fagiuoli, 1, 2 *Presenting Author 1Department Of
Surgical And Gastroentrological Sciences, Padua, Italy
2Monotematica 2000 AISF OLT Study Group, Padua, Italy
Background: HCC represents a frequent indication for OLT,
however recurrence is common in advanced neoplasms. Aim: To
evaluate potential predictive factors of HCC recurrence
after OLT. Methods: We evaluated the role of hypothesized
predictive factors of recurrence in a large series of
transplants (587) in HCC, performed between '86 and '99 in
Italy. Results: HCC recurrence occurred in 11.1% of the
patients and represents the major cause of death (83, 7%).
Mean time of HCC recurrence was 16, 75±13, 9 (median 12 m.).
Morpho-biological parameters that significantly related with
recurrence were: tumor bilobarity (p=0, 006), number of
nodules (>3; p<0, 0001), size of nodules (>5cm; p<0, 0001),
absence of Milano's selection criteria (p=0, 0004),
non-incidental diagnosis (p=0, 01), high levels of _FP (p=0,
02). Hystological parameters significantly related with
recurrence were: microvascular invasion (p=0, 004),
satellitosis (p<0, 0001). When all the above parameters were
introduced in a multiple regression analysis, the following
variables were selected as independent predictor of
recurrence: size and number of nodules (p<0, 0001 and p=0,
05, respectively), incidental diagnosis (p=0, 013),
satellitosis (p=0, 008), _FP levels (p=0, 008),
microvascular invasion (p=0, 019) and thrombosis (p=0, 05).
Pre-OLT neoadjuvant treatment significantly prolonged post-OLTdisease-free
survival. Conclusions: HCC recurrence rate was 11, 1% at
median time of 1 year after OLT, HCC being the main cause of
death. The strongest predictive factors of post-transplant
HCC recurrence are: size and number of nodules,
non-incidental diagnosis, satellitosis, micro/macrovascular
invasion and high AFP levels. These data suggest that the
expansion of size criteria could negatively affect
recurrence rates. Further investigations based on
prospective studies are required. |
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Factors Associated With recurrence After Liver transplantation For
Hepatocellular Carcinoma
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T. Decaens, 1 F. Roudot-Thoraval, 1 S.
Hadni-Bresson, 2 P. Wolf, 3 J. Gugenheim, 4 F. Durand, 5 M.
Neau-Cransac, 6 O. Boillot, 7 K. Boudjema, 8 Y. Calmus, 9 J.
Hardwigsen, 10 C. Ducerf, 11 G. Pageaux, 12 S. Dharancy, 13 O.
Chazoullieres, 14 D. Dhumeaux, 1 D. Cherqui, 1 C. Duvoux*, 1
*Presenting Author 1Liver Transplantation Units of 1Hopital Henri
Mondor, Creteil, 2Hopital Jean Minjoz, Besancon, 3Hopital
Hautepierre, Strasbourg, 4Hopital L'archet 2, Nice, 5Hopital Beaujon,
Clichy, 6Hopital Pellegrin, Bordeux, 7Hopital Edouard Herriot, Lyon,
8Hopital Ponchaillou, Rennes, 9Hopital Cochin, Paris, 10Hopital La
Conception, Marseille, France
Aim: The aim of this study was to assess factors associated with HCC
recurrence and disease-free survival after liver transplantation
(LT).
Patients and Methods: 412 patients transplanted for HCC between 1985
and 1998 in 14 French centers, who had not died postoperatively were
studied. Kaplan Meier estimates were calculated for 40 variables
with potential association with recurrence. A uni- and multivariate
analysis was conducted to identified independent predictors of
recurrence.
Results: Overall 5-year disease-free survival was 55%. By univariate
analysis, variables associated with disease-free survival were:
etiology of liver disease (p=0.03), presence of cirrhosis (p=0.001),
alfa foeto-protein level ( p=0.001), _GT activity (p=0.02), the
number of nodules (1, 2-3 or >=4; p=0.03), maximal diameter of the
largest nodule (<3 cm, 3 to 5 cm or >5 cm; p<0.0001), the sum of the
diameter of the nodules (p<0.0001), bi-lobar location (p=0.01),
preoperative portal thrombosis (p<0.0001), pre- or post-LT treatment
(p=0.006), tumor differentiation (p=0.007), the use of
antilymphocyte antibodies (p=0.009), rejection episodes (p=0.003)
and time of LT (p<0.0001). By multivariate analysis, 6 variables
were independently associated with HCC recurrence: maximal diameter
of the largest nodule (p<0.0001), time of LT (p<0.0001), the tumor
differentiation (p<0.0001), the use of ATG or OKT3 (p=0.005),
preoperative portal thrombosis (p=0.08) and the number of nodules
(p=0.06) .
Conclusion: This study a) confirms the prognostic value of tumour
differentiation, b) does not confirm the prognostic value of
bi-lobar distribution of the tumor, c) identifies the use of ATG or
OKT3 as a new predictive factor of tumor recurrence. |
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A
STUDY OF THE PRESENCE OF HCV RNA IN SEMEN OF PATIENTS WITH
CHRONIC HCV INFECTION
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M.A. El Guinaidy*, 1 M.F.
Abdellatif, 2 H.M. Amin, 2 S. Ahmed, 2 *Presenting Author
1Gastroenterology & Hepatology Department, Faculty Of
Medicine, Ain Shams University, Cairo, EGYPT 2Dermatology &
Venereology Department, Faculty Of Medicine, Ain Shams
University, Cairo, EGYPT
Introduction: HCV is a worldwide problem. The prevalence in
Egypt approximates 12%. The role of sexual route in
transmitting HCV remains controversial. The aim of the study
was to detect HCV RNA in semen of chronic HCV infected
patients. Patients and methods: Seminal plasma was tested
for HCV RNA in 40 married patients with chronic HCV
infection (all have positive HCV RNA in their sera) using a
nested reverse transcription PCR assay with commercial kits
for amplification and detection of HCV RNA (Purescript,
Gentra Systems, Minneapolis, USA). Semen was tested for the
presence of PCR inhibitors to identify patients with false
negative results. Results: 10 patients (25%) had HCV RNA in
their semen (seminal plasma was +ve while round cells and
motile spermatozoa were Šve for HCV RNA). Three out of the
10 wives of these 10 patients had HCV RNA in serum. Duration
of marriage was significantly longer in HCV positive wives
compared to non-infected wives. Serum HCV RNA levels were
significantly higher in patients with +ve semen samples than
in patients with Šve semen samples (mean±SD 1, 695, 539±1,
348, 002 vs 241, 860±338, 504 copies /ml, P<0.001).
Conclusion: HCV RNA can be detected in semen of patients
with high blood viral load. They may transmit the infection
to their wives and the risk of transmission increases
proportionately with duration of marriage. |
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