Poster 734
Abstract ID: 66682
Category: KO1: Clinical Transplantation: Viral Hepatitis C
Patient Survival and Fibrosis Progression After Liver Retransplantation for Hepatitis Coinfection.
M.
Ghabril, Mayo Clinic Jacksonville, Jacksonville, FL, M. Krishna, Mayo Clinic
Jacksonville, Jacksonville, FL, A. Keaveny, Mayo Clinic Jacksonville, Jacksonville,
FL, J. Aranda-Michel, Mayo Clinic Jacksonville, Jacksonville, FL, B. Rosser,
Mayo Clinic Jacksonville, Jacksonville, FL, D. Harnois, Mayo Clinic
Jacksonville, Jacksonville, FL, R. Satyanarayana, Mayo Clinic Jacksonville,
Jacksonville, FL, H. Grewal, mAYO cLINIC jACKSONVILLE, Jacksonville, FL, D.
Willingham, Mayo Clinic Jacksonville, Jacksonville, FL, W. Hewitt, Mayo Clinic
Jacksonville, Jacksonville, FL, J. Nguyen, Mayo Clinic Jacksonville,
Jacksonville, FL, C. Hughes, Mayo Clinic Jacksonville, Jacksonville, FL, J.
Steers, Mayo Clinic Jacksonville, Jacksonville, FL, R. C. Dickson, Mayo Clinic Jacksonville,
Background
Hepatitis C infection (HCV) is the leading cause of
liver transplantation (LT). However,
retransplantation (RLT) for HCV is controversial due to variable reported
outcomes. Aim: To review outcomes & histologic
progression in pts undergoing RLT for graft failure
secondary to recurrent HCV.
Methods
A retrospective review of all RLT in pts with previous
LT for complications of HCV at a single center between 2/1998-4/2004.Pts undergoing
RLT for recurrence of HCV & non-HCV pts with LT-RLT interval (RI)>90
days (d)
were included. Pt & donor characteristics,
bilirubin (Bili), creatinine (Cr) &
hospitalization status at RLT were collected. MELD
& Childs Pugh score (CPS) at RLT were calculated. A single blinded
pathologist scored HCV pts liver biopsies (Ishak score) at 4 months (mth) &
1 year (yr) post LT & RLT. Results
124 RLT were performed in the study period, including
27 for recurrent HCV (grp1) & 23 RLT for non-HCV pts (grp2) who met the
study criteria. The overall 1yr survival was 74% & 78% respectively. Causes
of death in grp 1 were recurrent HCV(1), biliary
stricture(1),cardiac(2),sepsis(2),& HUS/TTP(1). 3 pts per grp received a
third graft with 2 per grp surviving at follow up (grp1 grafts failed<30 d,
unrelated to HCV). The differences between groups are shown in the table below.
1yr mortality in grps 1 & 2 was associated with pts age>60*(67 &
75%), hospitalized pts (40 & 50%,grp2*) & intensive care at RLT(50
& 33%,grp1*).1yr
mortality was increased in grp1 pts with RI<1yr
*(50%) & donor age>60*(100%). Despite a trend towards increased
mortality with Bili>10(33 & 33%), Cr>2(40 & 25%), MELD>25(36
& 40%) & CPS>9(35 & 50%,grp2*), grp1 pts exceeding these
parameters at RLT had a 60 to 67% 1yr survival with a mean follow up 988 d(373-1874). Grp1 mean grade & stage were similar at
4mth post LT & RLT(4.8 & 1.5 vs 3.6 &
1.1) but decreased at 1yr post RLT**(5.9 & 2.4 vs
2.8 & 0.7).1yr fibrosis
progression was decreased post RLT**(-0.8 vs 2.4
points/yr).
Conclusion
Short term survival & histologic progression after
RLT for HCV recurrence were acceptable in a single center experience in the
last 5 yrs. Mortality was increased with
pt & donor age>60,hospitalization & intensive care
at RLT, & RI of less than 1 year. Mortality was
not related to HCV recurrence. Further study is required to better define
prospective RLT criteria in this pt population.
Poster 735
Abstract ID: 67476
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Non invasive assessment of liver graft fibrosis by transient elastography after liver transplantation.
C. Barrault, Department of Hepatology Hôpital Henri
Mondor, Créteil, France, F. Medkour, Department of Hepatology Hôpital Henri
Mondor, Créteil, France, C. Atanasiu, Department of Hepatology Hôpital Henri
Mondor, Créteil, France, C. Douvin, Department of Hepatology Hôpital Henri
Mondor, Créteil, France, F. Roudot-Thoraval, Department of Public Health
Hôpital Henri Mondor, Créteil, France, A. Mallat,,Department of Hepatology
Hôpital Henri Mondor, Créteil, France, S. Zafrani, Department of Pathology
Hôpital Henri Mondor, Créteil, France, C. Duvoux, Department of Hepatology
Hôpital Henri Mondor, Créteil, France, J. Tran Van Nhieu, Department of
Pathology Hôpital Henri Mondor, Créteil, France
BACKGROUND
AND AIMS
Transient elastography (TE) (FibroScan, Echosens,
Paris, France), is a validated method of quantification of liver fibrosis in
HCV patients. It may be useful in the follow-up of liver transplant (LT)
recipients, especially in patients with HCV recurrence, because of accelerated
course of the disease. The aim of this study was to assess the diagnosis
accuracy of TE in evaluating liver fibrosis after LT, in patients with or
without recurrent HCV.
METHODS
Thirty patients underwent liver biopsy and TE
concomitantly after LT. Liver fibrosis scoring was assessed on biopsy specimens
by 2 pathologists according to Metavir (F0 to F4), to Ishak (from 0 to 6)
scores, and to a modified Ishak score taking into account septa thickness and
centrilobular perisinusoidal fibrosis (from 0 to 10). Efficiency of transient
elastography and optimal stiffness cut-off values for fibrosis stage assessment
were determined by a receiver-operating characteristics (ROC) curve analysis.
RESULTS
The study population consisted of 83% males and 17%
females. LT indications were HCV cirrhosis in 22 (73.4%), alcoholic cirrhosis
in 5 (16.6%) and miscellaneous in 2 (6.6%). Mean age at elastography was
55.9±9.2 months. Elastography and liver biopsies were performed 57.1±43.3
months after LT. Elastography discriminated well between patients with
significant and non significant fibrosis [median stiffness value in Ishak
scores 0 to 2, vs 3 to 6 : 5.1 (IQR: 4.3-8.3) vs 9.6 (IQR: 7.4-12.1), p=0.007].
Discrimination was better with Ishak score than with METAVIR score. The areas
under ROC curves were 0.80 for Ishak scores > or = 3 (95 % CI, 0.64-0.96)
and 0.77 for modified Ishak score > or = 4 (95 % CI, 0.59-0.94). Optimal
stiffness cut-off value was 7 kPa for Ishak > or = 3 and modified Ishak >
or = 4.
CONCLUSIONS
Transient elastography seems to be efficient to
identify LT recipients with significant graft fibrosis. It is a promising tool
to assess graft fibrosis progression after LT.
Poster 736
Abstract ID: 62520
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Recurrent Hepatitis C Virus Infection after Liver Transplantation and Concurrent Biliary Tract Complications: Poor Outcome.
L. H. Katz, Liver Institute and Department of Medicine
D, Rabin Medical Center, Pe,Givat-Shemuel, Israel, E. Mor, Rabin Medical
Center, Petah Tiqwa, Israel, Petah Tiqwa, Israel, N. Bar-Nathan, Rabin Medical
Center, Petah Tiqwa, Petah Tiqwa, Israel, E. Shaharabani, Rabin Medical Center,
Petah Tiqwa, Petah Tiqwa, Israel, J. Sulkes, Rabin medical center, Petah Tiqwa,
Israel, O. Pappo, Rabin Medical Center, Petah Tiqwa, Petah Tiqwa , Israel, R.
Tur-Kaspa, Rabin Medical Center, Petah Tiqwa and Sackler School of Medicine,,
Petach Tiqwa, Israel, Z. Ben-Ari, Rabin Medical Center, Petah Tiqwa,
Introduction
Recurrent HCV infection is particularly aggressive in the
post-liver-transplantation setting, with rapid progression of liver fibrosis.
Variables associated with fibrosis progression are under investigation. Biliary
complications remain a significant cause of morbidity following liver
transplantation, despite improved survival. Postcholecystectomy biliary
strictures are associated with advanced hepatic fibrosis.
Aim
The aim of this retrospective study was to determine
whether the presence of biliary complications affects survival in liver
transplant recipients with recurrent HCV infection.
Method
The study group included 56 liver transplant patients
(53.6% male; mean age 52.7 + 10.3 years). The incidence, types and treatment of
biliary complications were documented in those who developed recurrent HCV
infection (n=47) and those who did not (n=9). Outcome was compared between
these two groups and between patients who developed severe recurrence (n=18) or
non-severe recurrence (n=29). The effect of antiviral treatment (peginterferon
and ribavirin; n=25) on outcome was assessed as well.
Results
Twentyone biliary complications developed in 12
transplant recipients with recurrent HCV (25.5%) {anastomotic strictures, n=8;
nonanastomotic strictures, n=2; diffuse biliary strictures, n=3; sludge and
stones, n=6; and biliary leak, n=2). Treatment consisted of endoscopic
retrograde cholangiopancreatography or percutaneous transhepatic
cholangiography balloon dilatation and stent placement or surgical revision and
was successful in 9 patients (75%). In addition, 3 biliary complications
developed in the group with no recurrence (p=NS). There was no statistically
significant association between recurrent HCV infection and biliary
complications (p=NS). However, among those with recurrent disease, the
recurrence was severe in 9 of the 12 recipients with biliary complications
(75%) but in only 9 of the 37 recipients without biliary complications (26%);
this difference was highly significant (p=0.0019). Eight patients with severe
recurrence died (44.4%), including 3 (37.5%) with biliary complications,
compared with 2 patients (7%) with non-severe recurrence, neither of whom had
biliary complications (p=0.003). Antiviral treatment was successful in 9 of the
25 patients (36%) who received it. On multivariate analysis, biliary complications
were a significant predictor of severe recurrence (OR 13.8, CI 2.4-77.9).
Conclusion
Biliary complications of liver transplantation
strongly affect outcome in patients with recurrent HCV infection despite
attempts to relieve the biliary obstruction and to treat the recurrent HCV
infection.
Poster 637
Abstract ID: 63369
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Viral quasispecies and severity of recurrent hepatitis C.
A. Shakil,
University of Pittsburgh School of Medicine, Pittsburgh, PA, L. Wang,
University of Pittsburgh School of Medicine, Pittsburgh, PA, R. Shankarappa,
University of Pittsburgh School of Medicine, Pittsburgh, PA, A. J. Demetris,
University of Pittsburgh School of Medicine, Pittsburgh, PA, C. H. Chang ,
University of Pittsburgh, Pittsburgh, PA, J. J. Fung, Cleveland Clinic
Foundation, Cleveland, OH, A. Marcos, University of Pittsburgh School of
Medicine,
Introduction
Factors that influence the severity of recurrent
hepatitis C in the liver allograft are not well understood. We initiated
prospective follow-up of patients transplanted for HCV cirrhosis, to determine
factors that influence the severity of recurrenthepatitis C.
Methods
Demographic, clinical, radiologic, virologic and
pathologic features were studied. We also determined HCV E2 genomic diversity
pre-transplant and at 3 months post-transplant by heteroduplex mobility assay
using a defined number of viral templates. Our primary endpoint was severity of
fibrosis at one year, with disease categorized as mild (fibrosis stage 0-2) or
severe (fibrosis stage 3-6). Among 230 patients enrolled for prospective follow
up, 50 recipients were included in the current analysis. Eight patients who
died from severe disease before their one year biopsy were assigned a fibrosis
stage of 6. Univariable and multivariable analyses were performed.
Results
The mean age of the recipients and donors was 52 years
and 45 years, respectively. Patients with severe disease were likely to have
received older grafts. Seventy percent of recipients were men and 96% were
white. Fifty percent had donor recipient gender mismatch and 10% had race
mismatch. The meanpre-transplant MELD was 13 with no difference among the two
groups. There was no difference in pre-transplant serum bilirubin, creatinine,
INR, HCV RNA levels and genotype distribution (84% genotype 1) between the
groups. The cold and warm ischemia time and blood product usage was also
similar. Induction T cell depletion (44%) and cumulative tacrolimus and steroid
dosage were similar in the two groups. Thirty-six percent received interferon
therapy during the study period with similar proportions in the two groups.
Pre-transplant and 3 month post-transplant HCV viral diversity was
significantly higher among patients with mild disease compared to those with
severe disease. However, viral genomic complexity (entropy) was similar. On
logistic regression analysis, pre-transplant HCV diversity and donor age were
associated with severity of disease posttransplant (ROC AUC: 0.76).
Conclusions
Among transplant recipients with HCV, donor age and
pretransplant HCV diversity are associated with the severity of recurrent
disease at one year post-transplant. Further studies are needed to determine
the utility of pre-transplant HCV diversity as a prognostic tool in transplant
decision making.
Poster 738
Abstract ID: 64223
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Predictive factors of early and sustained viral response in patients with recurrent hepatitis C after liver transplantation treated with combined therapy (IFN-alpha and ribavirin).
T.
Casanovas-Taltavull, Hospital Universitari de Bellvitge, Liver Transplant Unit,
Hospitalet de Llobregat, Spain, M. Llobet, Hospital Universitari de Bellvitge,
Liver Transplant Unit, Hospitalet de LLobregat, Spain, A. Casanova, Hospital
Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat,
Spain, J. Niubó, Hospital Universitari de Bellvitge, Liver Transplant Unit,
Hospitalet de Llobregat, Spain, T. Serrano, Hospital Universitari de Bellvitge,
Liver Transplant Unit, Hospitalet de Llobregat, Spain, C. Baliellas, Hospital
Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat,
Spain, N. Chahri, Hospital Universitari de Bellvitge, Hospitalet de Llobregat,
Spain, B. Verdura, Hospital Universitari de Bellvitge, Hospitalet de Llobregat,
Spain, R. Ballester, Hospital Universitari de Bellvitge, Hospitalet de
Llobregat, Spain, E. de Lama, Hospital Universitari de Bellvitge, Hospitalet de
Llobregat, Spain, C. Cañas, Hospital Universitari de Bellvitge, Hospitalet de
Llobregat, Spain, J. Fabregat, Hospital Universitari de Bellvitge, Hospitalet
de Llobregat, Spain The aim of the study is to investigate hepatitis C viral
response in the liver transplantation
Introduction
(LT) population to help selection of appropriate
candidates for treatment and/or therapies in the future.
Method
A prospective, observational study is currently
ongoing, with the inclusion of all LT patients with histological diagnosis of
recurrent hepatitis C, at any stage of fibrosis, who start combined therapy
with IFN-alpha and ribavirin at our center.
Scheduled doses are: standard (STD) IFN-alpha-2a (3 MU thrice weekly) or
pegylated (PEG) IFN-alpha (180 ìg weekly) plus ribavirin 600-1200 mg/day during
12 months (except for patients with histological cholestatic features and/or
early severe recurrence, who receive 50-75% of antiviral doses). During
antiviral therapy patients only receive
one immunosuppressive agent (anticalcineurin
inhibitor). 52 patients (64% men, 55±10 years –mean±SD-, 92% genotype 1) have
been included in the study of early virological response (EVR) (HCV-RNA
negativity at 12 weeks after therapy initiation), with data on sustained
virological response (SVR) (24 weeks after treatment) for 36 of them. Mean
post-LT time is 4.5±3 years, and indication for LT was: 55% chronic liver
disease, 39%
hepatocellular carcinoma, and 5% retransplantation.
48% received PEG-IFN and 52% STD-IFN, 44% of patients presented cholestatic
features in the liver biopsy and/or early severe recurrence.
Results
There were 25% (13/52) of treatment
discontinuations. EVR was achieved in
36.5% of patients, and SVR in 47.2%, in an intention-to-treat analysis.
Significant predictive factors of EVR were: PEG-IFN
(52% EVR vs. 22% for STD-IFN, p=0.02), high receptor weight (p=0.02), low donor
BMI (p=0.02), non infiltration of polymorphonuclear leukocytes at post-reperfusion
biopsy (p=0.02) and non histological cholestatic features (48% EVR vs. 22% for
cholestatic hepatitis and/or early severe recurrence, p=0.04). Significant
predictive factors of SVR were: EVR (p=0.01) and detection of autoantibodies
detection during treatment (p=0.02). Subgroup of patients treated with
cyclosporine (86%) displayed higher EVR (42%) and SVR (51%) rates than global
sample, but a randomized controlled study would be necessary to investigate
this finding.
Conclusion
A good viral response may be achieved with combined
therapy for hepatitis
C recurrence in immunosuppressed patients, specially
with PEG-IFN. It is important to evaluate EVR in order to predict SVR.
Poster 739
Abstract ID: 65959
Category: KO1: Clinical Transplantation: Viral Hepatitis
C
MULTICENTER RANDOMIZED TRIAL OF HCV TREATMENT WITH PEGINTERFERON-ALFA 2A AND RIBAVIRIN AFTER LIVER TRANSPLANTATION:ONE-YEAR REPORT.
Y.
Calmus, Service de Chirurgie, Hopital Cochin, APHP, Paris, France, C. Duvoux,
Hopital Henri Mondor, Créteil, France, D. Samuel, Hopital Paul Brousse,
Villejuif, France, G. P. Pageaux, Hopital Saint-Eloi, Montpellier, France, M.
Messner, Hopital Pontchaillou, Rennes, France, P. Wolf, Hopital Hautepierre,
Strasbourg, France, L. Rostaing, Hopital Rangueil, Toulouse, France, C.
Vanlemmens, Hopital Minjoz, Besancon, France, Y. LeTreut, Hopital Conception,
Marseille, France, S. Dharancy, Hopital Huriez, Lille, France, J. Guguenheim,
Hopital de l'Archet, Nice, France, F. Durand, Hopital Beaujon, Clichy, France,
M. Neau-Cransac, Hopital Pellegrin, Bordeaux, France, O. Boillot, Hopital
Edouard Herriot, Lyon, France, L. Samelson, Laboratoires Roche, Neuilly,
France, K. Boudjema, Hopital Pontchaillou, Rennes,
Aim
The aim of this randomized, double blind study was to
determine whether maintenance therapy
for one year with ribavirin (RBV) alone after a year of bitherapy with
peginterferon-alfa 2a (PEG2A) and RBV, enhanced the eradication of HCV after
liver transplantation (LT). Primary endpoints were the virological response at
12 (end of bitherapy) and 30 months (6 months after one year of maintenance
therapy with RBV or placebo).
Results
We report here the results of the first year of
treatment. Methods: 97 patients were included, with recurrent HCV and a minimum
of stage 1 fibrosis (METAVIR scoring) on a liver biopsy obtained 1 to 5 years
after LT. 75% of patients received tacrolimus and 25% cyclosporine. PEG2A was
initiated at 90 ug/wk and RBV at 600 mg/d, then increased to 180 ug/wk and 1000
mg/d or adjusted as a function of hematological tolerance. Growth factor use
was permitted. Therapy was stopped for intolerable side effects or cytopenia
(hemoglobin < 8g/dl, PMN < 750/ul, platelets <30,000/ul). Results: At
52 weeks, HCV-PCR was negative in 62 % of patients(60/97), and in 75 %
(58/77)of those who had completed 52 weeks of therapy (21% of patients did not
complete the 52-week course of therapy). Viral response was 100 % in patients
with genotype 2 or 3 and 65 % in patients with genotype 1 or 4 (p = 0.004).
There was no correlation between viral response and histological score,
biological parameters at inclusion or the type of calcineurin inhibitor. ALT
transaminases were 133 ± 120 IU/l (SD) before therapy, and 52 ± 38 IU/l after
one year (p = 0.001). Histological activity was 1.68 ± 0.77 before, and 1.11 ±
0.767 after therapy (p = 0.0001), whereas fibrosis remained unchanged (1.47 ±
0.71 and 1.61 ± 0.99, respectively, p = 0.06). 37% of patients required
erythropoietin (EPO) support and 12% also required G-CSF. Globally, hemoglobin
levels decreased from 13.7 ± 1.5 to 11.3 ± 1.5 g/dl. Serious antiviral-related
adverse effects were observed in 15 patients: acute rejection was observed in
2, severe cytopenia requiring the discontinuation of antiviral therapy in 7,
acute renal failure in 2, ischemic cardiopathy in 2, psychiatric disorders in
2, diabetes in 2.
Conclusions
Using PEG2A and RBV associated with a liberal use of
EPO, a viral response was achieved in 74% of patients, with a low rate of side
effects, including 2% of acute rejection and 2% of renal failure.
Poster 742
Abstract ID: 67071
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Long term results after therapy with pegylated interferon alpha 2a in HCV positive liver transplant recipients
M. Bahra, Charité - Campus Virchow, Dep. of Surgery,
Berlin, Germany, U. P. Neumann, Charité - Campus Virchow, Dep. of Surgery,
Berlin, Germany, D. Jacob, Charité - Campus Virchow, Dep. of Surgery, 13353
Berlin, Germany, J. M. Langrehr, Charité - Campus Virchow, Dep. of Surgery,
Berlin, Germany, R. Neuhaus, Charité, Campus - Virchow, Dept. of Surgery,
Berlin, Germany, P. Neuhaus, Charité – Campus Virchow,
Background
Hepatitis C reinfection after orthotopic liver
transplantation (OLT) is a
major cause of graft loss in HCV positive liver graft
recipients. We evaluated the efficacy and safety of pegylated interferon
alfa-2a and ribavirin treatment for recurrent HCV after OLT.
Methods
60 patients with recurrent HCV received peginterferon alpha
2a (0.5 -
1.5g/kg per week) and ribavirin
(400-800mg/ day) for a minimum of 48 weeks. Including criteria were: positive
test for anti-HCV and HCV RNA by RT-PCR, >2-3 times elevated serum alanine
aminotransferase (ALT) levels before initiation of treatment, and a liver
biopsy showing recurrent hepatitis C. Endpoint of the study was defined by undetectable serum HCV-RNA 6
months after end of treatment (sustained
virologic response). Furthermore protocol biopsies
were accomplished to evaluate the influence of pegylated interferon on fibrosis
progression. Mean follow-up was 96 weeks.
Results
28/60 patients became HCV-RNA-negative after 48 weeks
of treatment (46,6%). Sustained
virologic response (SVR) was achieved in 20/60 (33,3%) patients. Liver specimen
showed increase of fibrosis from 0.8 to 1.25 (Metavir-Score). Side effects like
neutropenia (51,6%) and anemia (38.3%) were treated with G-CSF,
erythropoietine, and dose reduction of peginterferon and ribavirin. 12/20
patients with SVR received supportive treatment with growth hormones (4/20
G-CSF alone, 2/20 erythropoietine
alone and 6/30 G-CSF and erythropoietine). In five
patients complete cessation of the pegylated interferon/ribavirin treatment was
indispensable (8.3%).
Conclusion
The use of peginterferon alpha 2a is safe and
effective in patients with
hepatitis C reinfection after OLT. The yearly fibrosis
progression rate during interferon therapy tended to be decelerated. Treatment
of neutropenia and anemia helped to maintain antiviral therapy and seemed to
play a role to increase SVR rates.
Poster 743
Abstract ID: 67221
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
Antiviral therapy for HCV-1b liver transplant recipients: better results with younger grafts.
S. Benlloch, La Fe Hospital, Valencia, Spain, M.
Berenguer, La Fe Hospital, Valencia, Spain, A. Fernández, La Fe Hospital,
Valencia, Spain, A. Palau, La Fe Hospital, Valencia, Spain, V. Aguilera, La Fe
Hospital, Valencia, Spain, M. Prieto, La Fe Hospital, Valencia, Spain, J. Berenguer,
La Fe Hospital, Valencia, Spain
Introduction
With the introduction of pegylated interferon and
ribavirin, improvements have been made in the treatment of post-transplantation
chronic hepatitis C. Results though are worse than those obtained in non-transplant
patients. Aims: to analyse whether the outcome of anti-HCV therapy is
influenced by the age of the graft.
Methods
Analysis of efficacy (rate of end-of-treatment and
sustained biochemical and virological responses) and tolerance (rate of treatment
discontinuation, interferon and/or ribavirin reduction, use of growth factors)
following antiviral therapy in a cohort of 66 HCV-1b infected recipients
treated with standard (n=30) or pegylated (n=36) + ribavirin.
Results
An end-of-treatment (EOT VR) and sustained virological
responses (SVR) were obtained in 45% and 30%, respectively. Of potential
predictors of SVR analysed (gender, age, pretransplantation antiviral therapy,
induction immunosuppression, history of significant alcohol, Child-Pugh and
hepatocellular carcinoma at transplantation, rejection, rejection therapy,
disease severity at initiation of therapy, laboratory tests – body mass index
and viral load pre-antiviral therapy, type and duration of antiviral therapy,
time from transplantation to therapy, interferon and/or ribavirin reductions,
use of growth factors), both type of antiviral therapy (13% with standard
IFN+Rbv vs 45% with pegylated IFN + Rbv; p=.02) and viral load at initiation of
therapy (p=.05) were predictive of response. A trend was observed with regards
to age of the donor with a median age of 37 years (17-69) in those achieving a
SVR vs 48.5 (16-76) in non-responders (p=.056).
Conclusions
HCV clearance is achieved in a significantly higher proportion
of HCV-1b infected liver transplant recipients treated with pegylated
interferon-ribavirin compared to standard interferon-ribavirin. The age of the
donor, variable known to influence disease progression, is also involved in the
response to antiviral therapy.
Poster 744
Abstract ID: 67596
Category: KO1: Clinical Transplantation: Viral
Hepatitis C
On treatment virological response of 70% in 100 patients treated with combination antiviral therapy for recurrent HCV following liver transplantation.
L.
Lilly, University Health Network, Toronto, Canada, N. Girgrah, University
Health Network, Toronto, Canada, A. Al Alwan, University Health Network,
Toronto, Canada, B. McQuarrie, University Health Network, Toronto, Canada, P.
Wong, University Health Network, Toronto, M. Cattral, University Health
Network, Toronto, Canada, P. Greig, University Health Network, Toronto, Canada,
I. McGilvray, University Health Network, Toronto, Canada, G. Levy, University
Health Network,
BACKGROUND:
Chronic liver failure due to HCV infection is the
leading indication for liver transplantation worldwide; disease recurrence
after transplantation is inevitable. Short-term patient and graft survival
following liver transplantation for hepatitis C are similar to other
indications; long-term results are inferior. Response rates of recurrence to
antiviral therapy are reported to be significantly lower than those seen in
non-transplanted patients. A large single center experience is reported here.
PATIENTS
& METHODS
100 patients (73% Genotype 1) with
histologically-proven recurrent HCV received at least three months of
combination therapy with Interferon/PEG-Interferon and Ribavirin between Jan 98
and Jan 05. Serum aminotransferases, HCV-RNA and histology were followed.
RESULTS
Seventy patients (70%) achieved an on-treatment
virological response (OTVR) at a mean of 5m on treatment; 65 of these have
become HCV-RNA negative. 12/30 non-responders remain on treatment (mean 13m);
therapy was discontinued in 18/30, 4 for side effects and 14 for lack of
response to >12m of therapy; two of these patients died of decompensated
cirrhosis. 49 patients have achieved an end of treatment response (ETR)
following a mean of 15m of therapy; of the remaining 21 OTVR pts, 20 remain on
treatment while one has stopped due to adverse effects. Of the 49 ETR patients,
24 have achieved an SVR, 7 have relapsed and 18 are <6m post treatment
discontinuation. 61% of patients have required growth factors. Rejection rate
was 7%. Three patients who developed fibrosing cholestatic HCV within a year of
tx are included, with 1 SVR, one OTVR still on treatment, and one non-responder
who currently has decompensated cirrhosis 4y after transplant.
CONCLUSIONS
Combination therapy yields virological response in 70%
of treated patients, similar to that described in non-transplant patients;
requirements for growth factors are common. The optimal duration of therapy is
unclear, although likely longer than in the non-transplant setting.