Liver Transplantation – Viral Hepatitis – Saturday Nov 1: 2pm
Liver
Transplantation – General
A. Suddle; V.
Aluvihare; P. Muiesan; M. Foxton; J. G. O'Grady; M. A. Heneghan; M. Rela; N.
Heaton; K. Agarwal
Introduction:
Non-Heart Beating Donors (NHBD) in Liver Transplantation (LT)
are utilized as a strategy to increase the donor pool.
Issues surrounding graft loss and Hepatitis C virus (HCV) recurrence are of
potential concern in this donor group.
Aim:
A retrospective study assessing long term graft outcomes and
HCV recurrence in NHBD and Deceased Brain-stem Donors (
Methods:
Our NHBD program is the largest in
Results:
30 patients with HCV cirrhosis underwent LT with NHBD grafts
between 2001 and 2008, out of a total of 87 NHBD performed (34.5%). A control
group of 48
Conclusions:
Our data suggest no significant difference in outcomes
utilizing NHBD for HCV. NHBD in our experience presents a useful to expand the
donor pool for HCV disease.
Kaplan-Meier Curves for graft
survival in NHB and
Liver Transplantation – HCV Recurrence –
HCV treatment
601.
Incidence of Acute Cellular Rejection During
Interferon-based Therapy for Recurrent Hepatitis C following Liver
Transplantation: A Retrospective Study.
S. A. Gonzalez; A.
Waechter; M. Lee; A. Kamal; E. B. Keeffe; A. Ahmed
Background:
Interferon (IFN)-based therapy may be considered in patients
with recurrent hepatitis C virus (HCV) following liver transplantation (LT).
The potential risk of acute cellular rejection (
Methods:
We performed a retrospective cohort study of all patients
with chronic HCV who underwent LT at our center between 1995 and 2006. All
results from liver biopsies performed during the post-LT follow-up were
reviewed. The presence of
Results:
Two hundred five patients with active HCV infection who
underwent LT were included in this study; 73 patients received at least one
dose of IFN-based therapy. Median post-LT follow-up was 4.0(0-12.3) years.
Overall patient characteristics were as follows: median age 52, 71% male, 66%
HCV genotype 1, 35% hepatocellular carcinoma, 49% alcohol abuse. Treated
patients were more likely to have received IFN-alfa therapy before LT (21% vs.
11%, p=0.05). In treated patients (n=73), 58% received pegylated IFN-alfa and
21% had multiple treatment courses. Median cumulative duration of IFN therapy
was 47(2-284) weeks. Overall, 473 liver biopsies were performed in 162
patients: 97% of treated patients had biopsy-proven HCV recurrence vs. 42% of
untreated patients. IFN-treated patients were more likely to have
immunosuppressive regimens including prednisone (81% vs. 63%, p=0.01) or
tacrolimus (96% vs. 85%, p=0.02). The overall incidence of
Conclusions:
The overall incidence of
Liver Transplantation – General
L. B. VanWagner; J.
Norvell; E. Wang; J. Levitsky
Background:
The number of simultaneous liver-kidney transplants (SLK)
performed has been steadily increasing. Data on outcomes of HCV+ SLK compared
to HCV+ liver transplant alone (LTA) recipients are limited.
Methods:
A case/control study comparing outcomes of all HCV+ SLK
recipients (6/99-1/07) vs. transplant year-matched HCV+ LTA controls (1:1) was
performed (up to 5 year data). Univariate analysis of covariates and Kaplan
Meier and Cox proportional hazard models on overall survival and freedom from
HCV recurrence were conducted.
Results:
38/142 (26.7%) SLK recipients were HCV+. At SLK: Age 53.9±8.1
yrs, 60.5% males, 10.5%
Conclusions:
Our study represents the largest analysis of HCV+ SLK
outcomes and demonstrates a significantly worse survival than LTA, likely due
to higher MELD at transplant and having early complications (infections)
unrelated to HCV. However, long term outcomes, i.e., HCV recurrence, graft and
renal dysfunction, are similar to that of LTA patients. While
Liver Transplantation – General
M. C. Segovia; E. R.
Lyden; T. Bernard; T. M. McCashland
Purpose:
Evaluate a liver fibrosis index score (FIB-4) to predict
stage of fibrosis in patients post liver transplant for hepatitis C (HCV).
Methods:
The records of all the HCV patients (283 subjects) who
underwent liver transplantation between the years of 1997 and 2007 at the
Results:
The median number of biopsies was 2 per recipient (range
1-12). The mean age at first biopsy was 52.3 years (sd=8.3
years) and 68.95% were male. The main three reasons for liver transplantation
were HCV (53.42%), HCV plus alcohol (25.57%) and HCV plus hepatocellular
carcinoma (12.79%). The distribution of the fibrosis score
for the biopsies were as follows: 44.54%, no fibrosis; 25.56%, stage 1;
15.25%, stage 2; 11.36%, stage 3 and 3.29%, stage 4. The mean FIB-4 index
differed significantly between the fibrosis score groups: The group with no
fibrosis (F0) had a mean FIB-4 of 4.37 (se=0.41); stage 1 (F1), 5.71 (se=
0.52); stage 2 (F2), 6.10 (se= 0.66); stage 3 (F3), 8.56 (se=0.77) and stage 4
(F4), 12.86 (se=1.38) (F0 to F4, p<0.0001). For patients with F4 fibrosis,
the FIB-4 index was significantly larger than for recipients with fibrosis scores
F0 to F3 (p<0.05 for each comparison). The FIB-4 index for patients with F3
fibrosis was also significantly larger than the FIB4-index for recipients with
fibrosis scores F0 and F1 (p<0.05 for each comparison). A threshold
cut-point of 4.09 of the FIB-4 index maximized the sensitivity and specificity
to 80 and 60%. Unfortunately, the negative and positive predictive values for
this cut-point were 94% and 25% respectively.
Conclusions:
FIB-4 is not an accurate test for assessing individual grades
of liver fibrosis in patients post liver transplant for HCV. FIB-4 was able to
differentiate cirrhosis from low-grade fibrosis. Routine use of this
non-invasive marker of liver fibrosis in the post liver transplant setting
remains problematic.
Liver Transplantation – HEV
604.
Incidence and outcomes of acute hepatitis E in a liver transplant unit.
A. Gera;
Background:
Hepatitis E (HEV) infection is rare in Western countries.
Majority of cases are through acquisition in developing countries where the
virus is endemic. However, increasing numbers of indigenous cases are being
reported.
Aim:
To study the incidence, severity and outcome of acute HEV
infection within a large transplant centre.
Method:
A retrospective case note review of all adults testing HEV
IgM positive (MP diagnostic assay) between Jan 2000 and April 2008 was
undertaken. HEV serology was tested on clinical suspicion in acute liver
failure (
Results:
28 adults tested HEV IgM positive: 60.7% male, mean age 34.3
years (range 19-63), mean MELD 24.92 (range 5-40). 15 (53.6%) acquired HEV in
the Indian Sub-Continent, 1 in
Conclusion:
Incidence of HEV in our cohort is low. It is rare for acute
HEV infection to progress to LT. HEV may unmask co-existing liver disease.
Delineation of HEV serology in conjunction with HEV RNA in the context of
Liver
Transplantation – General
606. Impact
of donor age on
V. Aguilera; M. Rodriguez; M. Prieto; C. Ortiz; A.
Palau; F. Gentili; R. Canada; B. Risalde; M. Berenguer
Introduction:
Antiviral therapy post-transplantation has a limited
efficacy. There is an interest in determining factors associated with sustained
virologic response (
Aim:
To assess whether the age of the donor has an impact on
Methods:
96 LT patients (74% men, median age: 56 (37-70)), 87%
genotype 1a or 1b, treated with pegIFN-ribavirin (pegasys: 62%, pegintron 38%)
for a median duration of 356 days (range:16-623 days), at 576 (50 days- 3978)
days from LT. Baseline immunosuppression was tacrolimus in 62%. 19% were
cirrhotic and 68% had advanced fibrosis at baseline. The median donor age was
48 years (range 12-78).
Results:
A
Conclusions:
Aging donors are associated with worse antiviral response
with pegIFN-ribavirin.
Liver Transplantation – HEV
S. Pischke; A. Heim;
P. V. Suneetha; R. Raupach; C. P. Strassburg; M. P. Manns; H. Wedemeyer
Introduction:
Causes of graft hepatitis after liver transplantation are
often difficult to define. Infection with the hepatitis E virus (HEV) causes a
self-limited acute liver disease that usually does not become chronic. However,
investigators from
Methods:
Anti-HEV antibodies were measured by an ELISA assay (Abbott).
All sera from transplanted patients were tested for HEV-RNA by nested
Results:
Antibodies against HEV were detected in a much lower
frequency as reported by Kamar et al. in all groups of patients (see table). We
did not find evidence of graft hepatitis due to hepatitis E in any of the 237
liver transplant recipients studied. None of 145 transplanted patients tested
HEV-RNA positive in a cross-sectional study. Anti-HEV was detected in only two
out of 92 patients specifically admitted for evaluation of elevated
Conclusions:
Chronic hepatitis E is a rather rare event in liver
transplant recipients, at least in
Frequeny of anti-HEV IgG and HEV-RNA in liver transplant recipients and controls
|
|
Number |
Anti-HEV positive |
HEV-RNA positive |
|
Healthy controls |
108 |
1 (0.9) |
not done* |
|
Patients with cryptogenic liver disease |
111 |
5 (4.5) |
not done |
|
Liver transplant recipients |
145 |
6 (4.1) |
0 (0) |
|
Liver transplant recipients |
92 |
2 (2.2) |
0 (0) |
Liver Transplantation – General
L. Lilly; G.
Therapondos; N. Selzner; G. A. Levy; E. L. Renner
Background:
The majority of patients undergoing liver transplant (LT) for
Hepatitis C (HCV) develop histological recurrence, resulting in reduced patient
and graft survival when compared with other indications. Antiviral treatment
with interferon and ribavirin is less effective than in the non-transplant
population, and factors that predict response to treatment, although not fully
characterized, include genotype and, potentially, the calcineurin inhibitor
used. While donor age is an important variable in HCV recurrence following LT,
its impact on response to antiviral therapy has not been widely examined.
Aims:
To determine the effect of donor age on the rate of sustained
virological response (
Results:
134 LT recipients were included. Mean age at transplant was
54.1y, 80% were male, 84% received deceased donor (DD) grafts, and patients
were treated 3-99m following transplant. Overall mean donor age was 44.4y
[10-79]; for DD 46y, and live donors 36y. HCV genotype 1 infection (70%),
recipient age and gender were equally distributed across all donor age groups.
Overall, 75 patients achieved
Conclusions:
In addition to influencing HCV recurrence, donor age appears
to influence the likelihood that antiviral therapy will be successful.
Liver Transplantation – HCV Recurrence
S. K. Satapathy; S. N.
Sclair; J. V.
Backgound:
Recurrent hepatitis C post-liver transplantation (LT) is
universal, and some patients may develop an extremely aggressive course. One
form of severe recurrence is the cholestatic variant, which is characterized by
hyperbilirubinemia and histologically by severe cholestasis accompanied by
prominent pericellular and perisinusoidal fibrosis and few inflammatory
infiltrates. To date, there have only been small case series examining this
entity.
Aim:
Using specific histological criteria, we sought to
systematically characterize the clinical features and outcome in cholestatic
recurrent HCV.
Methods:
The pathology liver database was searched for terms:
cholestasis, fibrosing and hepatitis and cross-referenced with the term “liver
allograft”. There were 973 LT for HCV performed from 1/91-12/07. A total of 50
cases carried a provisional diagnosis of recurrent cholestatic HCV. After
careful histological and clinical review, 21 patients were excluded from the
final analysis (6 had concomitant bile duct problems,12
did not meet strict histological criteria, 3 for other reasons).
Results:
Twenty-five patients (mean age 53+/-7 yrs) were studied;
20(80%) were males; 24 (96%) had deceased donor LT with mean age of 57+/-18 yrs
with 72% of these older than 50 yrs.
Conclusions:
The cholestatic variant of recurrent HCV is an uncommon
complication seen in LT recipients and is seen almost exclusively in older
deceased donor livers. In our study, 36% of biopsies initially diagnosed with
cholestatic recurrent HCV were shown to have an alternative diagnosis after
careful evaluation using specific histological criteria. The majority of these
cases present during the first year post-LT with very high viral loads,
hyperbilirubinemia a poor response to interferon-based regimen and carries an
extremely poor prognosis.
Liver Transplantation – Post Transplant –
HCV Treatment
K. R. Krishnan; K. A.
Brown; S. W. Biggins; F. Yao; J. P. Roberts; D. Moonka; N. Terrault
Introduction:
African Americans (AA), overrepresented among those with
chronic HCV, respond less frequently to pre-transplant
IFN-based antiviral therapy for HCV than Caucasian-Americans (CA). However, the
question remains whether race predicts response to treatment of recurrent HCV
(the leading cause of graft loss) following LT.
Methods:
Retrospective study of consecutive AA and CA patients
undergoing LT for HCV between 1999 and 2006 at two centers, with no donor
organs from executed prisoners or institutionalized persons. 89 patients (18
AA, 71 CA) received ≥1 dose of IFN-α or PegIFN-α ±Ribavirin (
Results:
Treated AA and CA patients were without significant
differences in median age, donor age, or percent males. IFN and
Conclusions:
AA rarely achieved viral clearance with antiviral therapy
and, among treated patients, AA experienced
significantly higher mortality than CA. This study highlights the significant
challenges in management of AA with recurrent disease and the urgent need for
alternative treatment strategies.
Liver Transplantation – HCV Recurrence
J. Carrion; G. Fernandez-Varo;
X. Forns; W. Jiménez; M. Navasa
Introduction:
The presence of significant liver fibrosis (F≥2) and
particularly portal hypertension (hepatic venous pressure gradient, HVPG ≥
6mmHg) one year after liver transplantation (LT) identifies accurately patients
with severe hepatitis C recurrence.
Aim:
The aim of this study was to explore if serum fibrosis
markers are able to discriminate between slow and rapid “fibrosers” during the
first year after LT.
Methods:
Serum levels of Hyaluronic Acid (HA), Amino-Terminal
Propeptide of Type
Results:
Results were correlated with the Scheuer fibrosis stage
(n=135) and HVPG (n=95) one year after LT. Fibrosis stage was: F0-F1 in 85
(63%) and F≥2 in 50 (37%); HVPG was < 6 mmHg in 64 (67%) and ≥ 6
mmHg in 31 (33%). The diagnostic accuracy (AUC-ROC) of the algorithm assessed
12 months after LT was 0.78 for significant fibrosis (F≥ 2) and 0.90 for
portal hypertension (HVPG ≥ 6mmHg). The figures at 3 and 6 months after
transplantation were 0.67 and 0.77 for significant fibrosis (F≥ 2) and
0.75 and 0.87 for portal hypertension (HVPG ≥ 6mmHg).
Using the best cut-off of 3-M-
Conclusion:
Measurements of noninvasive serum markers 12 months after LT
are accurate at identifying patients with severe hepatitis C recurrence. More
importantly, discrimination between slow and rapid fibrosers can be performed
as soon as 6 months after transplantation in a significant proportion of
patients.
Liver Transplantation – Post Transplant –
HCV treatment
614. Early
virological response and absence of diabetes are associated with sustained
virological response to hepatitis C treatment after liver transplantation in
patients with cyclosporine A based
immunosuppression.
M. Hurtova; M. Fourti;
N. Medjahed; D. Samuel; M. Neau-Cransac; Y. Calmus; G. Pageaux; R. Lorho; C.
Vanlemmens; A. Laurent; T. Decaens; C. Duvoux
Introduction:
Antiviral properties of cyclosporine (CsA) might increase the
chance of a sustained virological response (
Aim of the Study:
to evaluate virological response to Peg
Interferon (Peg IFN) and Ribavirin (riba) based therapy of HCV recurrence in
patients on CsA.
Patients and methods:
We retrospectively reviewed charts of 46 patients with proven
recurrent HCV infection of the graft transplanted in 7 French Liver Transplant
centers.
Inclusion criteria were: positive HCV RNA, CsA based
immunosuppression, first antiviral therapy after LT and Peg IFN+riba treatment.
We assessed virological response at Week 12 (EVR), Week 48 (end of treatment
response,
Results:
Patient
Characteristics:
34 men, 12 women, median age at LT
53.5±9years. Mean
post transplant pre-treatment follow-up was 55.5months (3-204), median
pre-treatment viral load was 6.4log. Sixty-eight percent of patients had HCV
genotype 1/4, 32% had G 2/3. Fibrosis was graded using the Metavir score: 60%
of patients were F1-2, 40% were F3-F4. Sixty five percent of patients received
Peg IFN alfa 2a; 35% alfa 2b; mean initial ribavirine dose was 800mg daily
(400-1200). Median treatment period was 12 (4-18) months. EPO and GCSF were
used in 84 % and 13% of patients, respectively. The EVR,
Univariate analysis showed that patients with
Conclusions:
Our study shows that Peg IFN-riba based therapy in CsA
treated liver transplant patients can result in
Liver Transplantation – HCV Recurrence
M. Donato; C.
Rigamonti; F. Agnelli; E. Arosio; E. Melada; G. Rossi; M. Colombo
Background and Aims:
Hepatitis C recurrence (HepC-R) after liver transplantation
(LT) is associated with reduced patients/graft survival. We aimed to define the
survival rate and risk factors of severe fibrosis development in patients with
HepC-R.
Methods:
From January 2000 through October 2007, 104 patients
transplanted for HCV-related cirrhosis (38 with
Results:
68 (76%) were males, 62 (69%) infected with genotype 1.
Median recipient age at LT was 55 yrs (range 20-66), median donor age 51 yrs
(range 15-78). 311 liver biopsies were available for histological study (mean
3.5/patient). 27 patients (30%) developed acute rejection and 22 (24%)
experienced acute HepC-R. Overall, 22 (24%) developed S≥4 during
follow-up: 11 (50%) within first year, the remaining 11 during second-fourth
year. Thirty-nine patient (43%) underwent combined
antiviral therapy (15 with pre-therapy S≥4). Patient survival was similar
in patients who developed S≥4 with respect to those who did not (5 yr
survival: 83% vs 81%); however, survival was significantly better in treated
patients (N=39) or untreated ones with mild disease (N=23) compared to those
with contraindications to antiviral treatment (N=28) (5 yr survival: 94% vs 89%
vs 56%; p=0.001). Female gender (p=0.02; OR=3.76; 95%IC 1.18-12) and acute
HepC-R (p=0.002; OR=5.72; 95%IC 1.85-17.62) were significantly associated with
S≥4 development at multivariate logistic regression analysis. Cox
proportional analysis showed that acute HepC-R (p=0.0002; HR=5.17; 95%CI
2.20-12.10) and >50 yrs donor age (p=0.01; HR=3.08; 95%CI 1.26-7.56)
significantly increased the risk of severe fibrosis post-LT.
Conclusions:
Recipients of an aged liver who experienced acute HepC-R
should be prioritized to receive antiviral therapy with Interferon/Ribavirin.
Liver Transplantation – HIV/HCV
Coinfection
T. Antonini; A.
Roque-Afonso; M. Sebagh; B. Roche; R. Sobesky; C. Guettier; D. Samuel; J.
Duclos-Vallee
Introduction:
Fibrosing cholestatic hepatitis (
Patients and Methods:
Between December 1999 and January 2008, 61 HIV-positive
patients underwent LT because of end stage liver disease due to HCV, 13 of them
with hepatocellular carcinoma (
Results:
The median age of recipients and donors was 42.6 (38-46) and
50 (29-64) years respectively, predominantly male (78%). 7 patients received
cadaveric LT while 2 received domino LT (using liver from familial amyloid
polyneuropathy patients). Before LT median CD4 count was 299 cells/mm3
(603-140), HIV RNA was <12 cp/mL, HCV genotype was 1, 3a, and 4a for 6, 2
and 1 patient respectively. Immunosuppression included steroids in all
patients, cyclosporine (n=4) or tacrolimus (n=5) and mycophenolate mofetil
(n=5). After LT, mild (N=2) and severe (n=2) acute rejection was observed
respectively, 2 patients have been treated by increasing immunosuppressive
therapy and 2 by steroids bolus. The mean delay for diagnosis of
Conclusion:
In our cohort of 61 liver transplanted HIV-HCV coinfected
recipients
Liver Transplantation – HCV Recurrence –
HCV Treatment
E. De Martin; A.
Gobbo; M. Senzolo; S. Boninsegna; M. Guido; M. Gambato; A. Masier; G. Germani;
F. P. Russo; G. Zanus; U. Cillo; P. Burra
Background:
Few patients with histological HCV recurrence following LT may
be selected for antiviral therapy mainly due to post-LT complications and risk
of side effects. Whether antiviral therapy is worthy in terms of histological
benefit is still open to debate.
Aim:
To asses the effect of antiviral
therapy on fibrosis progression due to HCV recurrence after LT.
Methods:
All consecutive LT-HCV+ patients followed up at the
Gastroenterology Unit undergoing Peg-IFN/Ribavirin therapy for HCV histological
recurrence (Scheuer’s stage of fibrosis (S) >=1), with per protocol liver
biopsies (LB) performed before and after antiviral treatment (AT), were
included in this study. The fibrosis progression rate (FPR) was expressed as
fibrosis unit per month (FU/mo). Patients were stratified in 3 categories based
on when LB was performed: 0-24; 25-48; 49-72 months after LT, respectively, at
6-12 months after AT.
Results:
27 patients (16 M, 11 F, mean age 54 (39-66 years), follow-up
12-95 months) underwent AT. 25 patients were genotype 1b, 1 2b and 1 2a/2c. 19
(70%) were on tacrolimus, while 8 (30%) were on cyclosporin. The mean time of
starting AT since the transplant was 25 months (3-98). 15/27 (55.5%) patients
withdrawn from AT due to side effects before the end of treatment (12 months).
9/27 patients (33.4%) were
Conclusion:
The progression of fibrosis due to HCV recurrence following
LT is seen despite the antiviral therapy, faster in the long-term compared to
the early period after surgery whereas slower in patients with virological
response.
Liver Transplantation – Live Liver Donation
S. K. Satapathy; T. D.
Schiano; J. V.
Background:
Long-term outcome of recurrent hepatitis C after living donor
liver transplant (LDLT) and its rate of fibrosis progression have not been well
characterized. Initial studies suggested that HCV patients did poorly after
LDLT. Biliary complications are common in this group and could contribute to
fibrosis progression.
Aims:
We sought to determine the prevalence of histological HCV
recurrence, rate of fibrosis progression and associated factors such as
steatosis, biliary complications and response to interferon treatment as well
as long-term graft survival in HCV recipients who underwent LDLT.
Methods:
Forty-six HCV recipients (mean 52±9 yrs) underwent LDLT from
1/99-2/05. All liver biopsies with both H&E and trichrome slides were
assessed for all patients. Biopsies were performed only when clinically indicated.
Fibrosis progression rate per year (FPR) was defined as the ratio between the
fibrosis stage in Ishak units (0-6) and duration in months since LDLT.
Results:
Histological HCV recurrence was noted in 39(84.8%) recipients
after a mean interval of 36 wks (3-221 wks).
Conclusions:
Histological recurrent HCV in recipients of LDLT is
associated with accelerated fibrosis progression during the first year, especially
in those who have concurrent bile duct problems. The presence of significant
ductular reaction on histology potentially may be playing a significant role in
fibrosis progression in recipients with recurrent HCV.
Liver Transplantation – General
P. Manousou; D. N.
Samonakis; E. Cholongitas; E. Xirouchakis; V. Calvaruso; V. A. Arvaniti; A.
Sigalas; M. Pleguezuelo; F. Grillo; I. Giamalis; D. W. Patch; J. O'Beirne; A.
P. Dhillon; A. Burroughs
Introduction:
Post-transplant recurrence of HCV is a universal phenomenon
with a cumulative probability of developing graft cirrhosis of about 30% at 5
years.
Aim:
Evaluate impact of immunosuppression and other factors on
survival and progression of significant fibrosis in a consecutive series of
patients transplanted for HCV cirrhosis.
Methods:
We evaluated survival, time to reaching fibrosis Ishak stage≥4
(F4) (with time to last biopsy for all patients who did not reach this stage)
and HVPG (Hepatic Venous Pressure Gradient) ≥10mmHg and analysed
independently associated risk factors with Cox regression analysis. Recipient
age/gender, donor age/gender, pretransplant
Results:
246 transplanted patients with cadaveric donors, median age
51.6 years (21-66) and median follow-up of 51.6 months (1-216).
Concomitant
56 patients reached F4 or more. Cox regression revealed that
absence of steroids (OR.4.8, 95%CI: 1.7-6.2) and episodes of
Conclusion:
Maintenance of steroids and use of azathioprine were
associated with better survival and less severe fibrosis. Development of severe
fibrosis was also related to a hepatitis flare.
Liver Transplantation – General
P. Lampertico; M. Viganò; S. Bhoori; F. Agnelli; M.
Donato; M. Bongini; M. Iavarone; C. Cotsoglou; A. Russo; L. Caccamo; G. Rossi;
M. Colombo; V. Mazzaferro
Background and Aim:
The long-term outcome of hepatitis B virus (HBV) infected
patients who underwent liver transplantation (LT) because of hepatocellular
carcinoma (
Patients and Methods:
We retrospectively reviewed all patients consecutively
transplanted between January 1999 and September 2007 for
Results:
78 patients were followed-up for a median of 48 (2-110)
months. Five patients (6%) showed
Conclusions:
Cirrhotic patients undergoing liver transplantation for
HBV-related
Liver Transplantation – HCV Recurrence –
HCV Treatment
E. Xirouchakis; C. K.
Triantos; P. Manousou; A. Sigalas; V. Calvaruso; A. Corbani; D. W. Patch; A. K.
Burroughs
Background and Aim:
Pegylated interferon with ribavirin (Peg/R) is the most
effective therapy for chronic hepatitis C (HCV) but its utility and
effectiveness after liver transplantation has been difficult to assess. We
evaluated efficacy, tolerability, and safety of Peg/R in liver transplant
candidates and recipients with HCV cirrhosis.
Methods:
We searched medical databases and conference proceedings
between January 1999 to January 2008 selecting randomized and non randomized
studies. Primary end points meta-analytically were: 1) sustained viral response
(
Results:
Peg interferons using 1-1.5mcg/Kg (alpha-2b) or 180ug
(alpha-2a) combined with ribavirin 800-1200mg/day were the most effective
compared to any other regimen or no therapy. In 3 pretransplant studies (n=355
pts) the median
Conclusion:
Liver Transplantation – General
N. S. Becker; J. M.
Vierling; N. L. Sussman; R. Stribling; C. A. O'Mahony; J. A. Goss; P. K. Jalal
Background:
HCV cirrhosis, the most frequent indication for OLT in the
Aim:
To compare patient and graft survivals for: 1) HCV cirrhosis
patients in the pre-MELD and MELD eras and 2) patients transplanted for HCV and
non-HCV indications.
Methods:
The UNOS database for adults (>18 yrs) undergoing OLT was
used to compare patient and graft survival rates for patients transplanted in 2
eras: pre-MELD (1992-2001) and MELD (2002-2007). Patients requiring
retransplantion or multi-organ transplantion were excluded. Survivals were
determined using Kaplan-Meier analysis and compared using a log-rank test.
Results:
Of 59,605 adult OLT recipients included in the study, 25,052
(42%) had HCV. HCV significantly increased as an indication for OLT from the
pre-MELD to MELD era: 40% vs. 45%, p<0.001. There was no difference in HCV
patient survival between the two eras: 87% vs. 87% at yr 1 and 77% vs. 76% at
yr 3. Similarly, there was no difference in HCV graft survival between the two
eras: 81% vs. 82% at 1 yr and 70% for both at 3 yrs. There was a significant
reduction in mortality within 30 days of OLT in the MELD era: 2.85% vs. 4.40%,
p<0.001. The primary causes of mortality 30 or more days post-OLT were
similar in both eras: graft failure (25%), infection (20%), malignancy (14%),
multiorgan failure (14%) and cardiovascular causes (12%). Patient survival at 3
yrs was significantly decreased for HCV compared to non-HCV in both eras:
pre-MELD 77% vs. 81%, p<0.001 and MELD 76% vs. 80%, p<0.001. Similarly, 3
yr graft survival was also significantly decreased in HCV compared to non-HCV
in both eras (p<0.001). Patient survivals did not differ for non-HCV
patients in either era.
Conclusions:
Neither patient nor graft survivals for HCV patients
undergoing OLT have improved from the pre-MELD to MELD era. In both eras, patient and graft survival rates were
significantly lower in HCV patients compared to non-HCV patients. It is
imperative that all modifiable risk factors for poorer outcomes in HCV patients
be identified and ameliorated to improve long-term outcomes.
Liver Transplantation – HCV Recurrence –
HCV Treatment
626.
PegIFN-ribavirin for recurrent hepatitis C: worse efficacy in recent years.
M. Berenguer; V.
Aguilera; C. Ortiz; M. Rodriguez; F. Gentili; A. Palau; R. Canada; B. Risalde;
M. Prieto
Introduction:
Antiviral therapy post-transplantation has a limited
efficacy. Results have however improved over time with the introduction of
ribavirin and pegylation of interferon (IFN).
Hypothesis:
Improved efficacy (higher sustained
virologic response-
Aim:
To assess whether the efficacy of
pegIFN-ribavirin has improved over time.
Methods:
96 LT patients (74% men, median age: 56 (37-70)), 87%
genotype 1a or 1b, treated with pegIFN-ribavirin (pegasys: 62%, pegintron 38%)
for a median duration of 356 days (range:16-623 days), at 576 (50 days- 3978)
days from LT. Baseline immunosuppression was tacrolimus in 62%. 19% were
cirrhotic and 68% had advanced fibrosis at baseline. The median donor age was
48 years (range 12-78).
Results:
A
Conclusions:
The efficacy of antiviral therapy with pegIFN-ribavirin has
worsened over time, at least in our center. The increase in donor age and a
greater proportion of cirrhotics may be potential causes. Further analysis is
underway to understand the reasons for this negative trend.
Liver Transplantation – HCV Recurrence
627. Severe
HCV infection recurence on the liver graft of patient transplanted for HCV
related cirrhosis : Is
retransplantation feasible?
R. Sobesky; P.
Carrier; B. Roche; T. Antonini; M. Sebagh; A. Roque-Afonso; C. Guettier; F.
Saliba; P. Ichai; D. Azoulay; R. Adam; D. X. Castaing; D. Samuel; J.
Duclos-Vallee
Background:
HCV-related cirrhosis is one of the most common indications for
liver transplantation (LT). However, almost all patients have post-LT
recurrence, with a significantly negative outcome on long term graft and
patient survival. The natural history of HCV liver graft infection is faster
than in immunocompetent patients and the question of the retransplantation
(reLT) is discussed.
Aim:
To study the outcome of HCV infected patients retransplanted
for severe recurrence of HCV infection on the liver graft.
Methods:
An indication of reLT was proposed in 28 patients with a mean
age of 45 (± 8) years in a monocentric population of 504 HCV infected patients
transplanted for end stage liver cirrhosis or hepatocellular carcinoma. The
indication of reLT was proposed in 11 patients for surgical complication
(primary non function or hepatic artery thrombosis), in 11 patients for severe
complications of HCV related liver graft infection and in 6 patients because of
chronic rejection or alloimmune hepatitis.
Results:
Among the 11 patients transplanted for severe HCV reinfection
on the liver graft, the mean interval between the 2 LT was 92 (± 62) months.
The mean MELD score before reLT was 22.5 (± 6.2). Three patients had renal
insufficiency related to calcineurin inhibitors and had a combined kidney and
liver transplantation. Four of the 11 patients deceased after reLT, three
within 10 months because of infectious complications after a prolonged stay in
intensive care unit. One of the 4 patients who had combined kidney and liver
transplantation died because of a septic shock 6 months after reLT. One patient
died 2 years after reLT because of severe HCV recurrence on the liver graft
with severe hepatic insufficiency and renal failure. Survival after reLT was
7/11 (63%) at 1 year, 5/9 (55%) at 2 years and 3/7 (42%) at 5 years respectively.
A severe liver fibrosis progression (upper 1 point of Metavir unit per year)
was observed in 20% of patients after reLT while it was observed in 36% of
patients after the first LT.
Conclusion:
In this study, liver fibrosis progression was not more severe
after reLT than after the first LT. A combined kidney
transplantation was performed in 27% of the cases of reLT.
The survival of patients retransplanted for severe HCV
recurrence on the liver graft was at 63% at 1 year and 42% at 5 years.
Liver Transplantation – General
C. Aloman; M. Fiel; C.
Chang; S. N. Sclair; P. Grewal; L. U. Liu; K. Iyer; G. Rodriguez-Laiz; M. L.
Sturdevant; J. V. del Rio Martin; T. D. Schiano
Background:
Patients with liver cirrhosis have an increased incidence of
immune abnormalities represented by (+)rheumatoid
factor(RF) but also by non-organ specific autoantibodies. The prognostic
significance of these markers regarding the development of allograft
dysfunction is unknown.
Aim:
To evaluate the incidence of immune abnormalities in patients
undergoing liver transplantation (LT) and correlate their presence with abnormal
liver chemistry tests 3 months post-LT and histological severity of recurrent
HCV.
Methods:
Cirrhotic patients undergoing LT at The Mount Sinai Hospital
between 10/07 and 4/08 were studied. Patients with autoimmune hepatitis were
excluded. All patients had an immune panel drawn right before LT, consisting of
RF, IgA, IgG, IgM,
Results:
We evaluated 45 patients, average age 56; 73% had HCV
infection. Both HCV and non-HCV patients had increased prevalence of immune
abnormalities before LT-See Table(*p<.05). Only one case (+) for LKM-1 and LC-1 were detected. Graft
dysfunction defined by abnormal laboratory tests at 3 months does not correlate
with the presence of Ig abnormalities, RF or autoantibodies before LT. Severe
recurrent HCV correlated with a high titer RF (>100 IU/ml) pre-LT.
Conclusion:
The presence of immunological abnormalities before LT may be
helpful in determining the development of graft dysfunction or recurrent HCV in
the first 3 months after liver transplantation. Rheumatoid factor before LT
predicts the severity of HCV recurrence. Further prospective studies are
necessary to define better patterns of association.
|
|
HCV vs Non-HCV |
|
(+)RF, ns |
96 vs 78% |
|
IgG>2200 mg/dL, ns |
42 vs 35% |
|
IgA>400 mg/dL, ns |
67 vs 64% |
|
IgM>300 mg/dL, ns |
29 vs 36% |
|
(+)SMA,* |
29 vs 0% |
|
(+) |
61 vs 14% |
|
(+) |
58 vs 42% |
|
(+) |
22 vs 14% |