Sunday Poster Sessions,
Topic:
Liver Transplantation
Background:
Current guidelines for treatment of chronic HCV utilize EVR
to indicate which patients are likely to achieve an SVR. Reports show a 72% SVR
rate in patients with an EVR. The purpose of this study was to evaluate the
week 12 viral response on SVR rate in chronic HCV post liver transplant
patients.
Methods:
This is a secondary analysis of a multi-center randomized
clinical trial of post OLT patients with recurrent HCV treated with 2 dosages
of PEG IFN alfa-2b plus ribavirin 800 mg/day. PEG IFN dosage began at 0.5 mcg/kg/wk and increased in the high dose group to 1.5
mcg/kg/wk over 6 weeks.
Results:
The total sample contained 59 patients (27 low dose and 32 on
high dose treatment). There were 39 males and 20 females ranging from 37 to 67
years of age (mean 51.4 ± 6.0). Race distribution was White 45 (76%), Black 3
(5%), Hispanic 10 (17%) and Asian 1 (2%). At treatment week 12, 32 (54%)
patients achieved undetectable HCV RNA, 4 (7%) patients had ≥2 log
decrease with positive virus, and 23 (39%) patients had <2 log decrease
(Table 1). There was higher SVR rate in the undetectable virus group at week 12
(23/32, 72%) compared to patients with positive virus and ≥2 log decrease
(1/4, 25%) or <2 log decrease (0/23, 0%). SVR rate was notably higher in
genotype 1 patients with week 12 undetectable virus vs. those with detectable
virus, 13/19 (68%) vs. 0/25 respectively (p=0.001). In genotype 2/3 patients,
SVR was achieved by 10/13 (77%) with week 12 undetectable virus vs. 1/2 (50%)
with detectable virus (p=0.2). 1 patient, a male with genotype 3, stage 1
fibrosis on high dose therapy with detectable virus at week 12, achieved an
SVR.
Conclusions:
·
Slow
viral responders in the post-transplant population, within a ≥ 2 log
decrease but positive virus a week 12, have a significantly reduced chance of
SVR with the standard 48 weeks of treatment than those with undetectable virus
at week 12.
·
Further
investigation is needed to improve SVR rates for slow viral responding
patients.
Number of Patients with Undetectable HCV RNA
|
PEG IFN
Group |
Week 12
Viral Response |
n |
Week 24 |
Week 48 |
SVR |
p Value |
|
Low Dose |
<2 log decrease |
19 |
1 (5%) |
1 (100%) |
0 (0%) |
0.001 |
|
≥2 log decrease but positive |
2 |
0 (0%) |
0 (0%) |
0 (0%) |
||
|
Virus undetectable |
6 |
6 (100%)* |
5 (83%) |
5 (83%) |
||
|
High Dose |
<2 log decrease |
1 |
0 (0%) |
0 (0%) |
0 (0%) |
|
|
≥2 log decrease but positive |
5 |
1 (20%) |
1(20%) |
1 (20%) |
||
|
Virus undetectable |
26 |
26 (100%* |
21 (81%)** |
19 (73%) |
*1 genotype 2/3
patient in each PEG dosing group discontinued at week 24 and subsequently relapsed
**5 patients discontinued prior to week 48 with side effects
521. Chronic
hepatitis E : a new entity
in organ transplant patients
N. Kamar; J. Péron; L. Ouezzani; J. Mansuy; J. Selves;
C. Bureau; J. Guittard; J. Izopet; D. Durand; J. Vinel; L. Rostaing
Introduction:
Hepatitis E virus (HEV) is a RNA virus that causes acute
hepatitis in developing countries, but also sporadic cases in industrialized
countries (non travel associated or autochthonous hepatitis E). Non travel
associated hepatitis E have a predilection for middle aged and elderly males,
are caused by genotype 3 and can carry significant morbidity especially when
seen in the context of chronic liver disease. We describe for the first time a
chronic evolution in organ transplant patients.
Patients:
We identified 14 cases of hepatitis E infection in
Conclusion:
- In organ-transplant patients, HEV should be considered an etiological agent for hepatitis E (HCV RNA in serum and the stools).
- For the first time, we have shown that HEV infection can involve to chronic hepatitis at least in organ-transplant patients.
- A longer follow-up is required to assess the outcome of HEV infection in the setting of organ-transplant receipents.
522.
Post-Liver Transplant Survival in Hepatitis C Patients is Improving, Not
Declining.
J. G. O'Leary; L. M. Grant; H. Randall; N. Onaca; L.
Jennings; G. Klintmalm; G. L. Davis
Introduction:
Outcomes after orthotopic liver transplant (OLT) for chronic
hepatitis C (HCV) have been reported to be worsening over the last 2 decades.
We analyzed our center’s experience over 15 years to identify trends in
post-OLT survival in patients with and without HCV.
Methods:
Patient and graft survival of adult primary OLT recipients
from January 1991 to June 2006 at Baylor Regional Transplant Institute (n=2051)
were evaluated by Kaplan-Meyer analysis.
Those with or without HCV were analyzed by era:
·
Era
1:1991-1994 (n=509),
·
Era
2:1995-1998 (n=459),
·
Era
3:1999-2002 (n=532), and
·
4:2003-6/2006
(n=551).
Differences in eras with disparate survivals were assessed by
univariate and multivariate analysis.
Results:
Overall, patient and graft survival were significantly lower
among HCV recipients than in others (p<0.0001). This difference was
dependent on the era of transplantation with improvement in HCV patient
(p=0.0015) and graft (p<0.0001) survival in sequential eras: 5-year patient
survival of 61.5%, 62.6%, and 75.6% for eras 1, 2, and 3, respectively (era 4 not
evaluable yet). The change is largely related to changes in listing criteria
for hepatocellular carcinoma (HCC) beginning in era 3. Survival in those
transplanted for HCV with HCC has improved dramatically over time
(p<0.0001). In fact, there was no change in post-OLT patient survival over
time (p=0.19) when those with HCC were excluded from the HCV cohort, while
graft survival still improved in successive eras (p=0.007). There was no change
in survival of non-HCV recipients between eras (p = 0.14), although graft
survival improved after 1994 and has remained stable since (p=0.02). The impact
of potentially detrimental changes in recipient demographics over the eras
including older patients, older donors, and a higher proportion with HCC have
likely been ameliorated by positive trends including shorter cold ischemia
time, fewer retransplants, greater use of tacrolimus and mycophenolate, and
less steroid-resistant rejection.
Conclusion:
1. Post-transplant survival after OLT
for chronic hepatitis C has improved significantly over the last 15 years
despite demographic changes in patients and grafts that have been previously
shown to impair survival.
2. A major reason for this improvement
is better selection of patients with concurrent hepatocellular carcinoma.
3. Risk factors for death in patients
with HCV post-liver transplant are:
a. CMV>3 months post-transplant
b. Recepient age > 60 years
c. Donor age > 50 years
d. Re-operation < 3 months
No donor organs were
obtained from executed prisoners or other institutionalized persons. The
authors have no conflicts of interest.
L. Lilly; N. Girgrah; G. Therapondos
Introduction/Aim:
Successful treatment of chronic hepatitis C virus (HCV)
infection is defined by undetectable serum HCVRNA six months following
cessation of antiviral therapy (sustained virological response; SVR). This
response seems highly durable in immunocompetent HCV patients, with rates
>96% reported after several years of follow-up. However, it is unclear
whether an immunosuppressed patient population will enjoy the same long term
success. We therefore examined our liver transplant patient population with SVR
to assess the durability of their response.
Patients:
Over 150 patients in the liver transplant program at our
institution have been treated for recurrent HCV; to date, 75 have achieved an
SVR. Qualitative HCVRNA determinations were made q3m for one year from cessation
of treatment, and annually thereafter, as well as during any rise in liver
enzymes.
Results:
39/75 patients (52%) were Genotype 1 (G1), and 24 (32%) were
G2 or G3, the remainder were other genotypes or
unknown. Two patients were transplanted for HCV/hepatitis B coinfection, and
had undetectable HBVDNA prior to treating HCV. All patients who had
undetecteable HCVRNA 3m following treatment achieved an SVR. Follow-up from SVR
ranged from 3m to 84m. Two patients died during the follow-up period, one 8m
and the other 22m from end of treatment; both were HCVRNA negative 2m prior to
death. Only one patient relapsed during the observation period. This patient
had received an HCV positive graft, and become HCVRNA negative on combination
therapy, remaining so for 18m after end of treatment. Retransplantation with
combined liver/kidney then took place and, 3m later, serum HCVRNA became
detectable.
Conclusions:
An SVR achieved in liver transplant patients appears to be as
durable as that seen in a non-transplant population, with the only relapse in a
patient who underwent retransplantation and had marked augmentation of
immunosuppression. Further, HCVRNA determination 3m after end of treatment may
suffice to define SVR in this difficult-to-treat population.
F. Feitosa; S. Radenne; T. Bizollon; A. dOliveira; P.
Pradat; R. Parana; C. Trepo
Context and objectives:
Liver biopsy is considered the gold standard to evaluate
outcome post liver transplantation. Because of its non invasiveness, hepatic
elasticity measurement (Fibroscan®) has increasingly gained attention for the
evaluation of fibrosis in transplanted patients. Our purpose was therefore to
compare Fibroscan® values with those of liver biopsy in patients transplanted
for HCV cirrhosis.
Patients and methods:
All consecutive patients transplanted for HCV cirrhosis who
underwent a medical visit at
Results:
15 patients (39%) had fibrosis lower than F2 at liver biopsy
and 3 (8%) were F4. For Fibroscan®, these results were 16 (42%) and 9 (24%),
respectively. The mean duration between the transplantation and the biopsy was
76,8 months (3-172) and 3,2 months between the
transplantation and the Fibroscan® (0-9). 17 patients (45%) had cleared HCV
following therapy. At the time of transplantation, 8 patients (21%) presented
already hepatocellular carcinoma on the explanted liver. The observed
concordance between the methods was 0,71 (27 patients)
and the expected concordance was 0,51. The sensibility of Fibroscan® was 0,76 (IC 0,58-0,94) and its specificity, 0,65 (IC 0,53-0,76)
with predictive positive and negative values of 0,72 and 0,65, respectively.
The prevalence and the corrected prevalence was 0,55
and 0,57. The positive likelihood ratio was calculated at 2,2
and the negative as 0,37. Intermethods reliability shows a Kappa index at 0,41 (IC 0,09-0,73; statistical significance> 0,5). The
comparison of all epidemiological and laboratory parameters between the two
groups (concordants and non-concordants) did not show any statistically
significant difference.
Conclusions:
·
Our
data failed to show a close correlation between Fibroscan® and the liver biopsy
in these patients.
·
This
discordance may be in part due to the high proportion of cases with mild
fibrosis that all the more it emphasizes the need for specific validation of
the Metavir Scores with Fibroscan® measurements in the context of
transplantation which warrant further studies.
I. A. Hanouneh; C. M. Miller; A. J. McCullough; R.
Lopez; F. Aucejo; A. E. Feldstein; N. N. Zein
While hyperinsulinemia and its associated metabolic syndrome
(MS) have been implicated in the progression of hepatic fibrosis in HCV
patients, little is known about consequences of MS after LT.
Aim:
Assess the interaction between MS and fibrosis progression in
patients with recurrent HCV after LT using serial liver biopsies.
Methods:
Using electronic pathology database, we identified all LT/HCV
patients with at least two post-transplant liver biopsies (1998–2006). MS was
defined using ATP III criteria at 1 year post LT. Ludwig-Batts scoring system
was used to stage all biopsies (408 biopsies from 95 patients). The first
biopsy that showed progression post LT was used for the time-to-progression
analysis. Univariable and multivariable logistic regression analysis was
performed to identify factors associated with fibrosis progression.
Results:
MS was present in 50% of patients. Median follow-up was 22
(Q25, Q75: 12.0, 31.2) months during which 71% of subjects had fibrosis
progression. Overall median rate of fibrosis progression was 0.08 unites per
month (Q25, Q75: 0.0, 0.17). By unvariate analysis, high HCV RNA at 4 months
post-LT (p<0.001), diabetes (p=0.046), CMV infection (p=0.006) and MS
(p=0.049) were associated with progression of fibrosis. In multivariate
analysis, MS was not associated with fibrosis progression during the first year
post-LT [OR=1.06, 95% CI: 0.49-2.26] but was independently associated with
progression of fibrosis beyond 1 year after LT (OR=6.3, p=0.017). High viral
load at 4 months post-LT (OR=1.1, p=0.004), steroid therapy for acute rejection
(OR=1.9, p = 0.05), and CMV infection (OR=1.9, p=0.01) were independently
associated with fibrosis progression. A Kaplan-Meier plot below outlines the
association between MS and fibrosis progression.
Conclusion:
MS, a potentially modifiable factor, is common and appears to
be strongly associated with long-term fibrosis progression in the setting of
recurrent HCV after LT.
Y. Calmus; C. Duvoux; G. Pageaux; M. Messner; P. Wolf;
L. Rostaing; C. Vanlemmens; D. Botta-Fridlund; S. Dharancy; J. Gugenheim; F.
Durand; M. Neau-Cransac; O. Boillot; O. Chazouillères; I. Lonjon-Domanec; L.
Samelson; D. Samuel
Aim:
The aim of this randomized, double-blind study was to
determine the effect of placebo or maintenance therapy with ribavirin (RBV)
monotherapy, after a year of combination therapy with peginterferon-alfa 2a
(PEG-IFNα-2a) and RBV, on continued eradication of HCV after liver
transplantation (LT).
Methods:
The study enrolled 100 patients (age 53.2 ± 8.3; male 73.3%;
time since transplant 1.2 ± 118.0; Geno 1, 73.4%, Geno 2, 2.1%, Geno 3 5.9%,
Geno 4 2.0%) with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR
scoring) on a liver biopsy obtained 1–5 years after LT. At inclusion, the
activity and fibrosis scores (METAVIR) were 1.67 ± 0.76 and 1.47 ± 0.70,
respectively. PEG-IFNα-2a and RBV were initiated at 90 µg/wk and 600 mg/d,
respectively, and increased to 180 µg/wk and 1000 mg/d or adjusted as a
function of hematological tolerance. At week 52, combination therapy was
discontinued and patients were randomized to RBV alone or placebo for a further
48 weeks (blinded). 75% of patients received tacrolimus and 25% cyclosporine.
Growth factor use was permitted.
Results:
After one year of combined therapy, 63 patients were negative
by PCR and randomized between RBV alone or placebo. At
78 weeks (6 months after combined therapy), a sustained virological response
(SVR) was obtained in 40% of ITT patients (40/100). At 30 months (M30) (6
months after the end of the maintenance period), 47% of the patients randomized
to RBV (16/34) and 55% of those randomized to placebo (16/29) had undetectable
HCV-RNA (NS). At M30, the histological activity score was 1.52 ± 1.08 (vs 1.63
± 0.74 at M12) in the RBV group and 1.72 ± 0.84 (vs 1.51 ± 0.88 at M12) in the
placebo group (NS). At M30, the fibrosis score was 1.52 ± 1.08 (vs 1.63 ± 0.91
at M12) in the RBV group and 1.72 ± 1.07 (vs 1.51 ±1.09 at M12) in the placebo
group (NS).
The fibrosis score marginally improved in the RBV group between
M12 and M30 (-0.14 [CI : -0.5;-0.22]), whereas it
worsened in the placebo group (+0.26 [CI : -0.02;+0.54])(p=0.07).
Conclusion:
·
After
1 year’s combination therapy with peginterferon alfa-2a plus ribavirin, a SVR
was achieved in 40% of patients following liver transplantation in ITT
analysis.
·
A
maintenance therapy with one year of ribavirin does not improve long-term
virological response, but may lead to an improvement in fibrosis score.
M. Orrego; R. Restrepo; B. Aguilar; V. Araya; K. D.
Rothstein; C. Manzarbeitia; D. J. Reich; S. Munoz
Introduction:
Hepatitis B reinfection (HBVr) occurs with a variable
frequency after receiving a HBcAb+ liver donor.
However, there is little data on clinical, serological and virological factors
associated with HBVr after LT.
Aim:
To determine the incidence of HBVr in LT recipients and to
identify clinical, serological and virological factors associated with HBVr.
Methods:
Retrospective analysis of our LT
population from June 1995 to May 2007. Non-HBV infected recipients with complete laboratory
data post LT were studied. HBVr was defined as a positive HBsAg or HBV DNA
>20,000 IU/ml post LT. Fisher’s exact test was used for group comparisons.
Results:
60 of 550 LT recipients (10.9%) received HBcAb+ donors. 42 of
60 patients met inclusion criteria. 6 of 42 (14%) LT recipients had HBVr.
Lamivudine prophylaxis was used post LT in 6% of the recipients. 74% of the
recipients had HCV infection. Median time for HBVr was 20.7 (5.8 to 110)
months. 76% were male. Mean age was 54.3 years.
We identified three different groups for HBV (table1). Of the
26 patients in the MG, one (4%) patient had HBVr. In the UG, 4 of 12 (33%)
patients developed HBVr. The UG had 8.7 (95%CI, 1.1 to 69) times the risk of
HBVr compared to the MG after LT (p=0.03). The remaining 4 patients were
vaccinated and one (25%) patient had HBVr.
There was no difference in HBVr in the vaccinated group
compared to the MG and the UG. To investigate HBVr by LT recipient diagnosis,
we compared HCV infected recipients (74%) to non-HCV recipients (26%). Of the
31 HCV infected recipients, 2 (6.4%, 95% CI, 0% to 21%) developed HBVr. In
contrast, 4 (36%, 95% CI, 10% to 69%) of the non-HCV recipients had HBVr. The
non-HCV recipients had 5.6 (95% CI, 1.2 to 27) times the risk for HBVr in
comparison with HCV infected recipients (p=0.03). Since both HCV infected
recipients and MG recipients appeared to be protected against HBVr, we tested
if the combination was also protective. 3 (60%) of the 5 recipients in the UG
with non-HCV diagnosis had HBVr compared to 0 of 22 recipients in the MG with
HCV infection (p=0.003).
Conclusions.
·
Serological
and virological characteristics have important implications to allocate HBcAb +
livers. Recipients in the matched group with HCV infection appear to be
protected from HBV reactivation after LT.
·
The
unmatched group and non-HCV recipients have higher risk of HBV reactivation and
therefore, HBV antiviral prophylaxis should be strongly considered.
·
HBVr
in the vaccinated group may have been explained for low HBsAb titers in the
recipient.
Table 1
|
Groups |
Matched
group (MG) |
Unmatched
group(UG) |
Vaccinated
group |
|
Donor |
HBcAb+ / HBsAb+ or - |
HBcAb+ / HBsAb+ or - |
HBcAb+ / HBsAb+ or - |
|
Recipient |
HBcAb+ / HBsAb+ or - |
HBcAb- / HBsAb - |
HBcAb– / HBsAb + |
533. High
Prevalence of Glomerulonephritis in Patients with End-stage HCV-induced
Cirrhosis
B. McGuire; B. A. Julian; J. Novak; S. Bynon; W. J.
Cook; S. Eddleman; D. E. Eckhoff
Introduction:
Patients undergoing liver transplantation for cirrhosis due
to hepatitis C virus (HCV) infection have a greater frequency of renal
insufficiency after liver transplantation compared to patients without HCV. It
is speculated that there is a greater prevalence of glomerulonephritis (GN) at
the time of liver transplantation, but there are no data to support this
postulate. The aims of this study were to determine the prevalence and type of
renal pathology with HCV-induced and nonviral-induced cirrhosis and to correlate
renal pathology with serum and urinary markers of renal disease.
Methods:
Forty adult patients undergoing liver transplantation for
cirrhosis (including 30 patients with HCV-induced cirrhosis previously
reported) were evaluated prior to liver transplantation for renal dysfunction
(serum creatinine), hematuria (dipstick > trace blood), and proteinuria
(urinary protein/creatinine ratio >0.3). At the end of transplantation, a
needle biopsy of the right kidney was done.
Results:
The clinical data for the six patients with nonviral-induced
cirrhosis included: mean age 55 yr (44-68), 5 men, and cause of liver disease
was 2 non-alcoholic steatohepatitis, 2 alcohol, 1 primary sclerosing
cholangitis and 1 cryptogenic. Hepatoma was present in 1 patient, diabetes in 3
and hypertension in 4. The mean calculated MELD score was 23. Preoperatively, 5
patients had one or more abnormal noninvasive study (3
elevated serum creatinine, 2 hematuria, and 2 proteinuria); 1 patient
had normal studies. Kidney biopsy showed 3 patients with IgA nephropathy (IgAN)
and 3 without GN. The clinical data for the 34 patients with HCV-induced
cirrhosis included: mean age 52 yr (41-73), 23 men, 13 hypertensive, 8
diabetic, and 2 had hepatorenal syndrome at engraftment requiring hemodialysis.
Mean calculated MELD score was 24.
Preoperatively, 19 patients had at least one abnormal
noninvasive study (13 elevated serum creatinine, 12
hematuria, and 7 proteinuria); 15 patients had normal studies. Kidney biopsy
showed 29 patients with an immune-complex GN (14 membranoproliferative GN, 9
IgAN, and 6 mesangial GN). No patient in either group had cryoglobulins by
electronmicroscopy or serum measurement. At liver engraftment, histologically
recognizable glomerular disease affected 29/34 (85%) of patients with end-stage
HCV cirrhosis versus 3/6 (50%) of patients with nonviral-induced cirrhosis (p =
0.05).
Conclusion:
·
Patients
with HCV-induced cirrhosis have a higher prevalence of immune-complex GN
compared to patients with nonviral-induced cirrhosis at the time of
engraftment.
·
These
findings may explain the decline in renal function that commonly occurs after
liver engraftment for HCV.