DDW 2007: Sunday Abstracts:
Topic:
Liver Transplantation - General
2. Use of hepatitis C-infected donors in liver
transplantation: a case-control study
P. Kwo; S. Wilson; R.
S. Mangus; A. Tector; J. A. Fridell; R. Vianna; S. Liangpunsakul; V. Misra; S.
Bhardwaj
Background
Hepatitis C is the major reason for the increase in HCC
(Liver Cancer) the need for liver transplantation in the
Methods
Data was extracted from the transplant center registry, UNOS
data, and from the original on-site donor data chart. Thirty percent of all
donors met non-ECD criteria (standard donors) and were included as potential
matches for the case-control study. Each HCV-positive liver donor recipient was
matched to two standard donor recipients as matched standard donor controls
(MSDC) by: recipient age +/- 10 years, primary diagnosis, cancer stage for
those with HCC, recipient MELD +/- 5, and donor age +/- 10 years. Outcomes
included graft and patient survival at 3-months, 1-year and 2-years;
perioperative death; and, HCV recurrence by 4-month and 1-year fibrosis
(F0-F4-Metavir).
Results
The HCV-donor and matched standard donor control groups did
not differ for recipient or donor demographics or in cold and warm ischemia (decrease
in the blood supply) time. Survival results and fibrosis progression are shown
in the table. Median follow- up time was 36 months. Kaplan-Meier actuarial
survival demonstrated improved graft survival for HCV-infected donors with a
trend toward significance (p=0.10).
Conclusions
These preliminary results suggest that HCV-infected liver
transplant recipients receiving livers from HCV-infected donors may have a
slower rate of fibrosis progression at 1-year. A trend was seen in survival
advantage for those receiving HCV-donor grafts compared to standard donor
controls. The use of HCV positive donors may be considered as a first line
therapy to increase the available donor pool of organs in those undergoing
liver transplantation for HCV-related cirrhosis.
Topic:
Liver Transplantation – Recurrence
218 Recurrent Hepatitis C After Liver Transplantation: On-Treatment
Prediction Of Response To Peginterferon Alpha-2a/Ribavirin (Peg/Rbv) Therapy
I. Hanouneh; C. M.
Miller; F. Aucejo; M. Quinn; N. N. Zein
Introduction:
Despite significant progress in the treatment of hepatitis C
(HCV), sustained virologic response (SVR) in liver transplant recipients
remains suboptimal and the clinical utility of SVR predictors during therapy is
unknown.
Aim:
Our Aims were to assess efficacy of peginterferon and
ribavirin combination therapy (Peg/RBV) in liver transplant recipients and to
estimate the predictive value of rapid virological responses (RVR, week 4) and
early virological responses (EVR, week 12) in this population.
Methods:
Retrospective analysis of
prospectively collected data from all patients who were treated with Peg/RBV
using a standardized protocol [28 patients (24 genotype 1 and 4 genotypes 2/3]. According to the protocol, all
patients received 48 weeks of therapy independent of virologic response.
Intention-to-treat analysis was used to measure the primary outcome (SVR).
On-treatment predictors of response were defined as HCV RNA negative or > 2
log10 decrease from pretreatment baseline at 4 weeks (RVR) and 12 weeks (EVR).
Results:
SVR was seen in 9/28 (32%) patients. Patients infected with
genotype 2/3 were more likely to achieve SVR than patients with genotype 1 [4/4
(100%) versus 5/24 (21%) p=0.006]. The highest rate of SVR was seen in patients
with RVR (Specificity and Positive Predictive Value = 100%) while the highest
rate of treatment failure was seen in those who did not have EVR (sensitivity and Negative Predictive Value =
100%, table). The negative predictive value of RVR to identify those who
did not achieve SVR was also very high in this population (92%). EVR had low
specificity (58%) and low positive predictive value (53%) to identify those
with SVR. None of those with detectable HCV RNA at week 24 had SVR while 3/12
(25%) patients who were HCV RNA negative at week 24 did not have SVR due to
breakthrough (1 patient) or relapse (2 patients).
Conclusions:
1. Peg/RBV is effective in the treatment
of post-liver transplant recurrent HCV.
2. On-treatment virologic monitoring is
highly predictive of SVR and may optimize the virologic response and minimize toxicity.
3. Given its high Positive and Negative
Predictive Values, RVR appears to be the most appropriate decision time point
for continuation of therapy.
|
|
|
Sensitivity |
Specificity |
Positive Predictive Value
|
Negative Predictive Value
|
|
RVR |
% |
83 |
100 |
100 |
92 |
|
95% CI |
35.9, 99.6 |
71.5, 100 |
47.8, 100 |
61.5, 99.8 |
|
|
EVR |
% |
100 |
58 |
53 |
100 |
|
95% CI |
66.3, 100 |
33.5, 79.7 |
27.8, 77 |
71.5, 100 |
|
|
Week 24 |
% |
100 |
75 |
77 |
100 |
|
95% CI |
66.3, 100 |
58.6, 96.4 |
42.8, 94.5 |
78.2, 100 |
Topic:
Current Treatment - Pegasys
B. Willems; S. J.
Hadziyannis; T. R. Morgan; M. Diago; P. Marcellin; D. E. Bernstein; P. J.
Pockros; A. LinM. L. Shiffman; S. Zeuzem
Background:
ACCELERATE, a large-scale (n=1469) prospective study recently
showed that, overall, peginterferon alfa-2a (40KD) plus ribavirin (RBV) for
24wks was superior to 16wks in hepatitis C virus (HCV) genotype 2/3 pts (EASL
2006:A734). In this study, two-thirds of pts achieved a rapid virologic
response (RVR; HCV-RNA <50IU/mL at wk 4). These early-responder pts had a
>80% probability of achieving an SVR with 16wks of therapy, suggesting that
this shortened treatment regimen may be a reasonable customized option for RVR
pts who cannot tolerate a full course of therapy. Conversely, pts without an
RVR had an SVR rate of only 49% with 24wks’ treatment, suggesting that these
pts may benefit from more intensive treatment regimens. To determine whether an
intensified regimen of peginterferon alfa-2a plus RBV may be beneficial in
genotype 2/3 pts without an RVR, we retrospectively examined available data
from other pivotal clinical studies.
Methods:
SVR and relapse rates following peginterferon alfa-2a
(PEGASYS®) plus RBV (COPEGUS®) were analyzed in HCV genotype 2/3 pts who did
not achieve RVR in two studies (NV15942, NV15801). In NV15942 (Hadziyannis.
Ann Int Med 2004), pts were randomized to 24 or 48wks of peginterferon alfa-2a
180µg/wk plus RBV 800 or 1000/1200mg/d. In NV15801 (Fried.
NEJM 2002), pts received 48wks of peginterferon alfa-2a plus RBV 1000/1200mg/d.
Results:
·
RVR
was achieved by a high proportion of genotype 2/3 pts (74% and 58% in NV15942
and NV15801).
·
In
pts in NV15942 who did not achieve an RVR, the lowest relapse rate and the
highest SVR rate (76%) was achieved with 48wks of peginterferon alfa-2a plus
RBV 1000/1200mg/d (Table).
·
This
compared with 61% for 48wks’ peginterferon alfa-2a plus RBV 1000/1200mg/d in
NV15801 and 49% for 24wks’ peginterferon alfa-2a plus RBV 800mg/d in
ACCELERATE.
Conclusions:
Genotype 2/3 pts who do not achieve an RVR could receive
added benefit if treated for 48wks with a higher dose of RBV
(1000/1200mg/d).These results merit further investigation in a prospective
controlled study to fully elucidate how treatment customization can benefit pts
before formal recommendations can be made.
|
NV15942 ITT analysis |
24wks |
24wks |
48wks |
48wks |
|
SVR, n/N (%)
[95% CI] |
14/21 (67) |
22/34 (65) |
20/30 (67) |
28/37 (76) |
|
Relapse rates,
n/N (%) [95% CI] |
5/19 (26) |
7/29 (24) |
3/23 (13) |
1/27 (4) |
Pts without follow-up data were
considered not to have achieved an SVR.
Topic:
Disease Progression - General
62. Risk of Hepato-Pancreatico-Biliary Tumors
Following Hepatitis C Virus Infection: a Population-based Study on
H. B. El-Serag; E. A.
Engels; L. Henderson; O. Landgren; T. P. Giordano
Background:
Hepatitis C (HCV) may increase the risk of
hepato-pancreatico-biliary tumors, other than hepatocellular carcinoma.
Previous case-control studies in elderly Medicare recipients indicated a
possible association between HCV and intra hepatic cholangiocarcinoma (ICC).
Little is known about the association between HCV and extra hepatic
cholangiocarcinoma (ECC) or pancreatic cancer.
Methods:
We conducted a cohort study including 146,394 HCV-infected
and 572,293 HCV-uninfected users of U.S. Veterans Affairs healthcare
facilities. We used the inpatient, outpatient, and death files of the national
computerized VA administrative databases. Patients with two visits with a
diagnostic code for HCV infection from 1996-2004 were included, as were up to
four HCV-uninfected subjects for each HCV-infected subject, matched on age,
gender, and baseline visit date. Risks of ICC, ECC, pancreatic cancer, and
hepatocellular carcinoma were assessed using proportional hazards regression,
adjusting for selection factors, race, use of medical services, and potential
confounders. Chart review of 62 ECC and ICC cases indicated a high positive
predictive value for the algorithm used to identify cholangiocarcinoma (85.7%
for ICC, and 73.5% for ECC).
Results:
There were 75 cases of ECC, 37 ICC, 617 pancreatic cancer, and 1679 hepatocellular carcinoma during follow up
that started 6 months following index date. Risk for ICC was elevated with HCV
infection with (Hazard ratio (HR): 2.50 (95% CI: 1.29-4.86)). The adjusted
hazard ratios (aHR) ranged between 2.07 and 2.76 adjusting for cirrhosis,
diabetes, IBD, hepatitis B, alcoholism or alcoholic liver disease (up to 3
covariates at a time).
We found no increased risk for ECC (HR 1.05; 0.60-1.85). The
risk of pancreatic cancer was slightly elevated (HR: 1.23, 1.02-1.49), but was
attenuated when adjusting for acute or chronic pancreatitis or alcoholism (aHR
1.18; 0.97-1.42). As expected, the risk of hepatocellular carcinoma associated with
HCV was very high (HR 14.8; 13.2-15.6).
Conclusions:
·
HCV
infection confers more than two-fold elevated risk of ICC.
·
There
does not appear to be an association between HCV and ECC,
·
The
association with pancreatic cancer needs further study.
S1000. Identification of Novel Biomarker Profiles in
Hepatitis C Positive Liver Cancer Patients.
J. Petersen; K.
Kasturi; C. Elferink; M. Hassan; E. Fung; T. Yip; N. Snyder
Background:
Hepatocellular carcinoma (HCC)in
patients with HCV related cirrhosis occurs with a annual frequency of 1-8%.
Although the prognosis for patients with advanced HCC is poor, if detected
early, successful treatment by transplantation, resection, or radiofrequency
ablation is possible. Currently used biomarkers for HCC are frequently normal
or in the indeterminate range. Thus, the identification of a biomarker or a
series of biomarkers that could identify early stage HCC would be of great
interest. ProteinChip technology (SELDI-TOF) has been used as a profiling
technique to identify potential biomarkers which may represent proteins,
protease-cleavage products, or novel peptides. We used this technology to
investigate differences in the serum profile of patients with chronic HCV from
patients with HCV associated HCC.
Materials and Methods:
With IRB approval we analyzed serum samples from 60 HCV
positive patients, 30 with confirmed HCC and 30 with various stages of fibrosis
(6 each with F0, F1, F2, F3, and F4) without evidence of liver cancer. The
samples were prefractionated using Equalizer® bead protein biomarker discovery
technology and SELDI ProteinChip® array profiling. The fractions were analyzed
on the PCS 4000 time of flight mass spectrometer using CM10, IMAC (pretreated
with Cu), and Q10 chips. Pooled normal human plasma was analyzed concurrently
as controls and to establish criteria for peak magnitude significance. Data of
the proteomic spectra was analyzed by Ciphergen Express Data Manager software
with Pattern Track and Two-way Hierarchical Clustering algorithm.
Results:
We were able to identify 91 peaks of <50 KDa that were
significantly correlated (p<0.05) with the presence of HCC. These peaks were
then analyzed using logistic regression (Insightful Miner v 3.0, Insightful
Corporation Seattle, WA, USA). In this manner we were able to identify 7 peaks
of < 20 KDa that allowed the separation of precancerous HCV-positive
patients from HCV-positive HCC patients. Additional analysis of the profile
revealed that the magnitude of these peaks was greater in the HCV positive patients
without evidence of HCC. The average peak height average for HCV patients
ranged from 2.17 – 17 times greater than that found for the HCC patients. Using
these peaks the sensitivity and specificity for detection of HCC was 100%.
Conclusion:
We were able to identify 7 peaks of <20 KDa that allowed us to separate patients with HCC from HCV positive patients without evidence of HCC. Additional work to identify these putative biomarkers along with the development of assays will be necessary to evaluate their usefulness in the early detection of HCC.
S1004. A Comparison of Alphafetoprotein, AFP-L3% and
Des-Gamma Carboxyprothrombin in Patients with Chronic Hepatitis, Cirrhosis and
Hepatocellular Carcinoma.
F. A. Durazo; M. J.
Tong; L. M. Blatt; W. G. Corey; J. Lin; S. Han; S. Saab; R. W. Busuttil
Background:
Hepatocellular carcinoma (HCC) is a common complication in
patients with cirrhosis of the liver. Detection of HCC at an early stage is
critical for a good clinical outcome. Surveillance of patients at risk to
develop HCC is crucial.
Aims:
a) compare the accuracy of
alphafetoprotein (AFP), AFP-L3% and des-gamma carboxyprothrombin (DCP) in the
diagnosis of HCC in patients with chronic viral hepatitis and with cirrhosis;
b) define the level of each tumor marker with
the best sensitivity, specificity, and positive predictive value (PPV) for the
diagnosis of HCC.
Methods:
243 patients with either chronic hepatitis B (HBV) or chronic
hepatitis C (HCV) were included in the study. Forty eight had stage I-III
fibrosis on liver biopsy, 49 had cirrhosis and 146 had HCC.
Results:
Levels of AFP, AFP-L3% and DCP were significantly higher in
patients with HCC than in patients with chronic hepatitis or cirrhosis
(p=<.0001). ROC curves indicated that the cut-off value with the best
sensitivity and specificity for each test was ≥25 ng/mL for AFP, ≥10%
for AFP L3% and ≥84 mAU/mL for DCP. The sensitivity, specificity and PPV
of AFP was 69%, 87% and 69.8%, of AFP-L3% 56%, 90% and 56.1% and of DCP 87%,
85% and 86.8% respectively. In contrast to AFP and AFP-L3%, DCP levels were
below the ROC cut-off in all patients without HCC. No advantage was observed
when combining two or three of the tumor markers.
Conclusion:
DCP was superior to AFP and AFP-L3% in differentiating
patients with HCC from chronic viral hepatitis and from cirrhosis, and it
should replace AFP as a tumor marker for HCC. The clinical utility of AFP-L3%
is more as a confirmatory test when AFP is elevated.
AFP, AFP-L3% and DCP for the Diagnosis of Hepatocellular Carcinoma
|
|
Sensitivity |
Specificity |
PPV |
NPV |
|
AFP |
69% |
87% |
69.8% |
65.6% |
|
AFP-L3% |
56% |
90% |
56.1% |
57.6% |
|
DCP |
87% |
85% |
86.8% |
81.5% |
AFP= Alpha-fetoprotein DCP= Des-gamma carboxyprothrombin (PIVKA II) PPV= Positive predictive value NPV= Negative predictive value
S1009. Prognosis of Patients with Hepatocellular Carcinoma
Detected by Surveillance Program.
T. Sato; R. Tateishi;
H. Yoshida; T. Ohki; H. Nakagawa; R. Masuzaki; J. Imamura; N. Yamashiki; T.
Goto; H. Yoshida; F. Kanai; S. Shiina; T. Kawabe; M. Omata
Background/Aims:
In
Patients/Methods:
We enrolled consecutive 1431 patients between 1994 and 2004,
who were positive for HCV, negative for HBsAg, and without HCC at the first
visit. We identified HCC among 340 patients during 5.4 yrs of mean follow up
period (AASLD2006). Among these patients with HCC, we analyzed 243 patients who
received all screening (ultrasound and alfa-fetoprotein (AFP)) at our
institution at intervals shorter than 6 months periodically. Diagnosis of HCC
essentially depended on arterial enhancement along with venous washout on
computed tomography (CT) scanning. Hypovascular tumor was followed up, and
pathological diagnosis was provided when the tumor had grown larger. Treatment
procedure was transarterial embolization/surgical resection/percutaneous
transhepatic ablation/best supportive care in 35/18/187/3. Cumulative survival
time was assessed, considering factors including age, sex, albumin, bilirubin, prothrombin time (PT), AFP, platelet count, size and number
of tumors. Kaplan Meier method was used for survival time analysis after the
initial treatments of HCC. Univariate and multivariate Cox proportional hazard
regression analyses were applied to assess the significance of each factor.
Results:
There were 152 men and 91 women with the median age of 67
yrs, Child –Pugh score was A/B/C in 149/85/9. Tumor size was 1.7±0.6cm when
detected, and 2.2±0.9cm when treated. Ninety patients were died during the
observation period (mean 4.9 yrs). Survival at 3 yrs, 5yrs, 8yrs, 10yrs was
74.4%, 51.94%, 42.3%
and 23.2% respectively. Univariate analysis revealed that age, Child-Pugh
classification, AFP, platelet count, and size and number of tumors, and AFP
were statistically-significant independent risk factors for survival.
Conclusion:
HCC was detected early enough for efficient treatment owing to
surveillance program, and patients achieved good survival rates. However, the
survival curve showed an accelerating drop later simulating wearout failure
model. To obtain more than 10 yrs survival, strategies in addition to the
surveillance program for early detection of HCC are strongly required.
S1011. Prognostic indicators of death in patients (pts) with
cirrhosis and hepatocellular carcinoma (HCC) – A systematic review of 64
studies.
P. Tandon; G.
Garcia-Tsao
Background:
In the West, HCC occurs mainly in the setting of cirrhosis.
Although there are many studies of predictors of death in HCC, most combine pts
with and without cirrhosis.
Objectiive:
To perform a systematic review of the literature evaluating
predictors of death in pts with cirrhosis and HCC and to evaluate whether
predictors differ between pts with compensated and decompensated cirrhosis.
Methods:
All prognostic studies of HCC were considered eligible if
they met the following criteria:
a) publication in English;
b) inclusion of adult pts;
c) >80% of pts had cirrhosis;
d) follow-up >6 months;
e) multivariable analysis performed.
Quality was based on widely accepted quality criteria for
prognostic studies. Criteria used to select “good” quality studies were:
inclusion of consecutive pts, relevant baseline characteristics and number of
deaths reported, no model overfitting.
Results:
Of 832 references obtained through a MEDLINE search, 726 were
excluded because they were irrelevant or did not meet inclusion criteria (~20%
of relevant articles were excluded because <80% of pts had cirrhosis). A
total of 21,308 patients were included in 64 selected studies (median,
177/study); 77% male; median age was 64; 64% had HCV cirrhosis; 54% were Child
Pugh class A and 52% had an “advanced” tumor (pre-defined criteria). The most
common predictors of death are shown in the Table. Sensitivity analysis using
only 13 “good” studies yielded the same variables. In studies that included
mostly compensated pts, predictors related to liver disease predominated, while
in studies that included mostly decompensated pts, predictors were both liver-
and tumor-related. However, these studies were few and results are not robust.
Conclusions:
·
This
systematic review of 64 studies shows that the most robust predictors of death
in pts with cirrhosis and HCC are liver-related (Child-Pugh class and
bilirubin) and tumor-related (size, AFP, portal vein thrombosis).
·
Multiple
limitations of the analyzed studies were identified:
o
No
trial met all quality and only 13 trial (20%) met the
4 major quality criteria.
o
Inclusion
of both cirrhotic and non-cirrhotic patients.
o
Heterogeneous
inclusion of patients varying level of patients at varying levels of hepatic
decompensation.
·
Future
prognostic studies of HCC:
o
Should
be performed in specific patients populations with a
different overall prognosis.
§
With
or without cirrhosis
§
Compensated
or decompensated cirrhosis.
o
Should
include 6 predictors of death identified in this review.
|
Variable |
N of studies in which
variable was among the first 5 significant variables |
N of studies evaluating the
variable |
% of studies in which
variable was among first 5 / studies that evaluated variable |
|
Portal vein thrombosis |
19 |
29 |
66 |
|
Tumor size |
18 |
31 |
58 |
|
Alfa fetoprotein (AFP) |
18 |
38 |
47 |
|
Child Pugh class |
16 |
31 |
52 |
|
Bilirubin |
14 |
21 |
67 |
|
CLIP score |
8 |
12 |
67 |
CLIP (Cancer of the
Liver Italian Program); consists of portal vein thrombosis, tumor size, AFP and
Child Pugh score
S1016. Changes Of
Cytokines In Liver Cirrhosis Patients With Advanced Hepatocellular Carcinoma
Treated By Combined Intra-Arterial Chemotherapy.
H. Nagai; D. Miyaki;
T. Matsui; M. Kanayama; K. Higami; K. Momiyama; T. Ikehara; K. Matsumaru; M. Watanabe;
K. Ishii; Y. Sumino; K. Miki
Background:
We have reported that combined intra-arterial chemotherapy
prolongs the survival of liver cirrhosis (LC) patients with advanced HCC (aHCC)
(DDW 2007, LA). Tumor necrosis factor (TNF) is known to induce cancer
cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand.
Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on
hepatocytes is also known to induce apoptosis.
Aim:
The aim of this study was to clarify changes of cytokines in
LC patients with aHCC receiving combined intra-arterial chemotherapy.
Patients/Methods:
Nineteen adult Japanese LC patients with aHCC were treated
with combined intra-arterial chemotherapy between 2005 and 2006 at our
hospital. Their tumors were inoperable, as assessed from computed tomography
findings. Continuous infusion chemotherapy (
Results:
Thirteen of the 19 patients (group R) showed a partial
response (5 patients) or stable disease (8 patients), although 6 of the 19
patients (group N) showed no response. The mean age was 69.5 years in group R
and 62.5 years in group N. There were 10 patients with HCV-related LC and 3
patients with alcoholic LC in group R. There were 2 patients with HCV-related
LC and 4 patients with HBV-related LC in group N. The serum level of TNF-alfa
was lower after chemotherapy than before chemotherapy in group N (p<0.05,
Wilcoxon’s test). There was no difference in the serum levels of TNF-R between
before and after chemothrapy. Moreover, there was also no difference between
the 2 groups (Mann-Whitney test). The serum level of Fas was higher after
chemotherapy than before chemotherapy in group N, while there was no difference
of serum Fas ligand levels between before and after chemotherapy. Furthermore,
there was no difference of NK cell activity between before and after
chemotherapy.
Conclusions:
These results indicate that maintenance of a high serum level
of TNF-alfa and Fas expression on HCC in LC patients with aHCC might be
important to achieve success with combined arterial chemotherapy.
S1017. Role of combined Chemoembolisation/ Radiofrequency
Ablation in the treatment of large/ multifocal Hepatocellular.
N. Rajoriya; E. Leen;
M. Neilson; J. Crichton; E. Forrest; J. Morris; A. Stanley
Background:
Hepatocellular Carcinoma (HCC) is the 4th commonest cause of
cancer in the world. Although surgery or radiofrequency ablation (RFA) can be
effective for small tumours, once the size is > 3cm effective therapies are
often limited. Chemoembolisation is often used as palliative therapy for larger
or multiple tumours, but there are limited data on combined chemoembolisation
and RFA as therapy for this patient group.
Aim:
The aim of our audit was to assess the impact/outcome of
combined chemoembolisation and RFA in our centre in the management of patients
with HCC > 3cm or multiple tumours.
Methods:
A retrospective case note analysis was performed of patients
diagnosed with HCC over a 5 year time period (January 2000-2005). Patients
treated with chemoembolisation followed by RFA (combined therapy) were
identified and outcome assessed.
Results:
52 were diagnosed with HCC over the study period. Aetiology
was alcoholic liver disease (ALD) in 45% and 73% patients had Childs C disease.
33% had a single HCC (mean diameter 5.89 +/-2.57 cm). The overall one-year
survival was 35%. 12 were treated with chemoembolisation followed by RFA (11
male; mean age 59.2+/-10.6). Aetiology included: ALD in 6 patients,
Haemochromatosis in 2, Cryptogenic cirrhosis in 2, HCV
in 1 and PBC in 1. The Child Pugh Grades were: 8 grade
A and 4 grade B with 42% having a raised AFP at diagnosis. 50% patients had a
single HCC (median diameter 6cm, range 3.5cm-20cm). None had extra-hepatic
metastasis on CT +/- MR imaging. 50 % were Barcelona Clinic Liver Cancer (BCLC)
Stage A, 17% stage B and 33% stage C. The median no of chemoembolisation
sessions was 2 (range 1-5), followed by a median no of 2 (range 1-6) RFA
sessions. The only complication encountered was a pyrexia
with abnormal LFTs post-procedure in one patient which settled after antibiotic
therapy. The median follow up was 29 (range 9-78) months.Following combination therapy, 75% of patients had complete radiological
resolution of their HCC based on imaging at a median of 6 (range 2-25) months.
25% had a recurrence of ablated HCC and 42% had new HCCs diagnosed on follow up
imaging.Overall one and two-year survival for those treated with combination
therapy was 58%, and 50% respectively. The median survival for patients graded
BCLC stage A, B and C was 33, 20 and 10 months.
Conclusion:
Chemoembolisation followed by RFA therapy results in good
radiological tumour resolution in patients with > 3cm or multiple HCC
without metastatic disease. However recurrence and new HCC occurs frequently on
follow-up. This combination therapy requires further study to clarify its exact
role in the management of HCC.
S1021. Changing Characteristics of Hepatitis C Related
Hepatocellular Carcinoma in
R. Tateishi; S.
Shiina; H. Yoshida; R. Masuzaki; T. Sato; T. Ohki; N. Yamashiki; T. Goto; H.
Yoshida; F. Kanai; T. Kawabe; M. Omata
Background:
Approximately 80% of hepatocellular carcinoma (HCC) in Japan
were due to chronic hepatitis C. Patients with hepatitis C can be considered as
a fixed cohort in Japan where intravenous drug abuse is uncommon and acute
hepatitis C is quite sporadic since 1990’s.
Aim:
To assess the trend in the
hepatocellular carcinoma (HCC) in
Methods:
We analyzed characteristics of 493 patients with naďve HCC
who were diagnosed between 1991 and 2005 at our institution. Patients were
included if they were HCV-Ab positive and HBsAg negative and had a history of
blood transfusion before diagnosis of liver diseases. Trends in age at
diagnosis of HCC, male to female ratio, interval of diagnosis of HCC and blood
transfusion, platelet count and liver function according to Child-Pugh
classification were assessed by linear regression.
Results:
The patients consisted of 280 males and 213 females. Mean age
increased from 59.6 years in 1991 to 71.6 years in 2005 (P < 0.001).
Majority of patients had a history of blood transfusion in 1960's before paid
blood donation was discontinued in
Conclusion:
HCC with blood transfusion related hepatitis C emerges from a
fixed cohort, majority of whom had a history of blood transfusion in 1960’s.
The patients were getting older rapidly reflecting the aging of background
population. Duration of infection tends to be longer with increasing number of
patients with less advanced disease or non-cirrhotic liver.
Topic:
Disease Progression
- General
S1055 Comorbid Medical and Psychiatric Illness and Substance Abuse
in HCV-Infected and Uninfected Veterans
U. A. Khan; K.
McGinnis; M. Skanderson; A. Butt
Background:
We undertook this study to determine the prevalence of comorbidities
(secondary diagnoses for specific complications) in HCV infected and uninfected
persons.
Methods:
Demographic/comorbidity data for HCV infected persons and
age, race and gender matched HCV uninfected controls were retrieved from the VA
National Patient Care Database using ICD-9 codes. We used logistic regression
to determine the odds of comorbidities in HCV infected subjects.
Results:
We identified 126,926
HCV infected subjects and 126,926
controls. HCV infected subjects had a higher prevalence of diabetes,
anemia, hypertension, COPD/asthma, cirrhosis, HBV, cancer, psychiatric
comorbidities and substance abuse but a lower prevalence of coronary artery
disease (CAD) and stroke.
In HCV infected persons, the odds of being diagnosed with
congestive heart failure, diabetes, anemia, hypertension, COPD/asthma,
cirrhosis, HBV and cancer were higher, but lower for CAD and stroke. After
adjusting for substance abuse, the odds of psychiatric comorbidities were not
higher in HCV infected persons. (see table)
Conclusions:
·
The
prevalence of comorbidities differs in HCV infected and uninfected veterans.
·
The
association between HCV and psychiatric diagnoses is partially attributable to
substance abuse.
·
These
factors should be considered when evaluating patients for treatment and
designing new intervention strategies.
Odds of co-morbid diagnoses in HCV-infected veterans compared with HCV uninfected veterans.
|
|
Unadjusted OR (95% CI)* |
Adjusted OR (95% CI)†|
|
Medical Comorbidities |
|
|
|
Coronary artery disease |
0.75 (0.73-0.77) |
0.74 (0.71-0.760 |
|
Stroke |
0.90 (0.86-0.95) |
0.86 (0.82-0.90) |
|
Peripheral Vascular Disease |
0.97 (0.92-1.02) |
0.95 (0.90-1.00) |
|
Cancer |
1.09 (1.05-1.13) |
1.15 (1.10-1.20) |
|
Diabetes |
1.10 (1.08-1.13) |
1.20 (1.17-1.23) |
|
COPD/Asthma |
1.26 (1.23-1.30) |
1.05 (1.02-1.08) |
|
Anemia |
1.83 (1.76-1.90) |
1.53 (1.47-1.60) |
|
ESLD/Cirrhosis |
12.0 (11.04-13.12) |
8.24 (7.54-9.00) |
|
Hepatitis B |
21.58 (17.31-26.89) |
13.34 (10.67-16.67) |
|
Psychiatric Comorbidities |
|
|
|
Schizophrenia |
1.24 (1.20-1.28) |
0.80 (0.77-0.82) |
|
PTSD |
1.58 (1.54-1.62) |
1.05 (1.02-1.08) |
|
Major Depression |
1.62 (1.57-1.66) |
0.93 (0.90-0.96) |
|
Mild Depression |
1.73 (1.69-1.77) |
1.03 (1.01-1.06) |
|
Bipolar Disorder |
1.85 (1.79-1.92) |
0.96 (0.92-1.00) |
|
Alcohol and Drug Use |
|
|
|
Drug Use Disorder |
4.71 (4.60-4.82) |
--- |
|
Alcohol Use Disorder |
3.92 (3.84-4.00) |
--- |
*The two groups were matched
for age (5 year blocks), race and gender. – Adjusted for age, race, gender,
drug use and alcohol use.
Topic:
Diagnostic Tools – Biochemical/Imaging
Y. Bujanover; R. Klar;
M. Kori; E. Granot; R. Shoul; V. Nachmias
Background:
In the past several noninvasive laboratory methods were
suggested as an alternative to liver biopsy.
Recently a panel of six serum markers -Fibro test(FT)
– Actitest (AT) was validated in the prediction of liver fibrosis and
inflammatory activity in adult patients with liver disease.
Aim:
The aim of the present study was to assess the diagnostic
utility of the Fibrotest – Actitest in pediatric patients with viral and
autoimmune hepatitis.
Subjects and methods:
Twenty four patients were studied, 14 female, 10 male, age range 2-18 yr (m-12.4yr).
Diagnosis : HCV-13; HBV-3;HCV+HBV-1; HCV+HIV-1;Autoimmune hepatitis-4. Liver biopsy was
performed in 23 patients.
Six biochemical markers were evaluated using commercial kits:
Total bilirubin, GGT, alfa2 macroglobulin, haptoglobin, apolipoprotein A1, ALT.
Those parameters were used for the calculation of the FT-AT scores according to
the patent algorithm of Biopredictive (France) ranging from 0-1. Liver biopsy
was compared to the results of the FT and AT using AUROC statistical analysis.
Results:
·
FT-
75% of the patients were F0;
·
F0-F1
12%,
·
F1-
4%,
·
F1-F2-
8%,
AT-A0 41%, A0- A1
-20%, A1- 12%, A1-A2 -20%, A3 – 4%.
The AUROC comparing FT with the liver
biopsy results were:
·
0.85
for F0,
·
0.87
for F0-F1,
·
0.88
for F1-F2.
FT yielded a higher AUROC than AT .85 VS .70 respectively.
Conclusions:
·
Fibrotest
– Actitest is a simple and effective method to assess fibrosis and inflammation
in pediatric patients with liver disease.
·
The
correlation with liver histology was high.
·
The
biochemical markers may serve as an alternative to liver biopsy in pediatric
patients
Topic:
Epidemiology
S 1227 Prevalence and risk factors associated with hepatitis B and
hepatitis C virus infections among healthy population in an urban community in
Dhaka,
H. Ashraf; C.
Rothermundt; N. H. Alam; P. K. Bardhan; A. Brooks; S. Hassan; N. Gyr
Introduction:
Prevalence data of hepatitis B virus (HBV) and hepatitis C
virus (HCV) infections among healthy population in
Methods:
Asymptomatic subjects of either gender of all ages residing
at an urban community of Kamalapur,
Results:
From June 2005-April 2006, 1844 healthy subjects were
enrolled, 37% males, 22% gave previous history of jaundice.
·
HBsAg
was positive in 121 (6.6%) subjects: 14 (0.8%) were only HBsAg positive and 107
(5.8%) were both HBsAg and Anti-HBc positive. Only Anti-HBc was positive in 420
(23%) subjects and,
·
HCV
was positive in 9 (0.5%) subjects: 4 (0.2%) were only
Anti-HCV positive and 5 (0.3%) were both Anti-HCV and Anti-HBc positive.
·
About
half of the HBV positive subjects were between ages 20-40 years, which was rare
(4%) among under-5 children.
Some factors such as were significantly
associated with HBV infection:
·
previous jaundice (OR 1.33; p=0.01),
·
exposure
to a community barber for shaving (OR 2.29; p=0.00),
·
received
treatment from unregistered health care providers (OR 1.44; p=0.005),
·
received
treatment for sexually transmitted diseases (OR 1.77; p=0.002),
·
being
married (OR 2.23; p=0.00), and
·
multiple
sex partners (OR 2.57; p=0.00)
Some additional factors such as were
significantly associated with HBV infection:
·
receiving
illicit drug injections (OR 11.86; p=0.01),
·
needle-stick
injuries (OR 2.11; p=0.001),
·
needle
piercing of ear, nose and body (OR 1.3; p=0.01),
·
surgical
operation (OR 1.3; p=0.02),
·
circumcision
(OR 1.47; p=0.00) and
·
animal
bites (OR 1.68; p=0.00) like dog, cat, monkey-bites
Conclusion:
·
The
finding of the study demonstrates a high endemicity of HBV infection in an
urban community in
·
However,
HCV infection is rare.
·
Prevention
of HBV infection in
Topic:
Treatment – General
S1231
Peginterferon Alfa 2a /
Ribavirin Versus Peginterferon Alfa 2b / Ribavirin Combination Therapy In
Chronic Hepatitis C Genotype 3
A. Q. Khan; A. Awan ; S. Shahbuddin ; Q. Iqbal
Editor’s note:
This is an interesting study, but the patient population is too small to
draw any conclusions about the efficacy of either product.
Introduction:
Hepatitis C virus (HCV) genotype 3
account for up to 80% of HCV infection in
Material and Methods:
In an open randomized controlled trial 66 naďve Chronic
Hepatitis C genotype 3 patients were randomized to receive Peginterferon Alfa
2a 180 ug/weekly plus Ribavirin 800 mg/day (33 pt group I) or Peginterferon
Alfa 2b 1ug/kg/body wt/weekly plus Ribavirin 800 mg/day (33 pt group II) for 24
weeks. Both groups were comparable for age, sex, baseline ALT level, albumin
level, viral load, and genotype 3 subtypes. Primary end point was loss of HCV
RNA at 24 weeks after stopping the treatment (SVR).
Results:
Of these 66 patients: 60 patients (30 in each group) completed
the trial (2 patients (1 in each group) were lost to follow up, 1 patient in
group I developed hyperthyroidism, 2 patients (1 in each group) developed
severe thrombocytopenia and one patient in group II developed severe
neutropenia).
Reduction of peginterferon dosage
were required in
4 patient (2 in each group) and reduction of ribavirin dosage were required in
3 patients (2 in group I and 1 in group II).
End of treatment response (ETR) in group I and II was 26
(86.6%) and 27 (90%) patients respectively. Sustained virologic response (SVR)
in group I and II was 26 (86.6%) and 27(90%) patients respectively.
Conclusion:
Both Peginterferon Alfa 2a / Ribavirin and
Peginterferon Alfa 2b / Ribavirin regimens were similar in efficacy and safety
in Chronic HCV genotype 3 patients.
Topic:
Treatment – General
S1232 Efficacy of a 72-week course of treatment for previous
relapsers to PEG/ribavirin therapy
J. McMahon; S. C.
Gordon
Editor’s note:
This study is interesting because it attempts to individualize
treatment, but there is too small of a patient population to draw conclusions.
Background/Aims:
Patients who relapse after 48 weeks of PEG/ribavirin
treatment represent a difficult therapeutic challenge. No guidelines exist
concerning the proper management of these individuals. Two recent studies
showed lower relapse rates following 72 vs. 48 weeks of therapy among treatment
naďve candidates. It is unknown, however, whether a longer duration of
re-treatment will achieve SVR among previous relapsers. We assessed our
preliminary experience using a repeat course of extended PEG/ribavirin in
patients who previously relapsed after 48 weeks of PEG/ribavirin.
Methods:
Four consecutively evaluated HCV patients
(3 genotype 1, 1 genotype 2), who relapsed following an initial 48-week course
of PEG/ribavirin, underwent re-treatment for 72 weeks. During their initial
therapy, 3 of 4 patients became negative within the first 16 weeks, and all
four patients maintained >80/80/80 adherence. None of the patients required
growth factors at any time. Following initial therapy, all 4 relapsed within 12
weeks of their last dose. Each was then re-treated with PEG-IFN alfa 2a 180 mcg
once weekly plus ribavirin (>13.3 mg/kg/day) for 72 weeks. We assessed HCV
RNA using Amplicor 2.0 quantitative and reflex TMA qualitative testing.
Results:
During re-treatment, each patient became HCV RNA negative by
treatment week 12, and maintained viral negativity for the duration of
treatment. Six months after completing re-treatment, each patient remained HCV
RNA negative, thus now achieving a recognized SVR. Extended duration therapy
was well tolerated; 2 of the 4 patients received higher doses of ribavirin
based on weight, and no patient required dose reductions due to adverse events.
Conclusions:
1. SVR is attainable among patients who
relapse following 48 weeks of PEG/ribavirin therapy.
2. 72 weeks of re-treatment was well
tolerated in this group of motivated patients.
3. Two of these patients received higher
doses of ribavirin during re-treatment, thus ribavirin dosing may affect the
ability to achieve SVR.
4. Each patient remained adherent during both
regimens, thus the duration of viral negativity appears to represent a pivotal
goal.
5. Patients who relapse after 48 weeks of
PEG/ribavirin should be considered for re-treatment with a longer duration
regimen.
|
Age |
Gender |
Weight(Kg) |
Fibrosis |
Genotype |
Previous Treatment |
Re-Treatment Baseline Viral Load |
|
39 |
F |
68 |
1 |
1 |
Peg2b/riba 800mg |
1,840,000 |
|
47 |
M |
85 |
3 |
1 |
Peg2b/riba 800mg |
245,000 |
|
52 |
F |
89 |
2 |
1 |
Peg2a/riba 1200mg |
1,200,000 |
|
50 |
M |
80 |
4 |
2 |
Peg2b/riba 1200mg |
3,450,000 |
D. Tanioka, Y. Iwasaki, K. Takaguchi, H. Ikeda, R.
Okamoto, Y. Araki, M. Ando, T. Shimoe, N. Hashimoto, K. Kita, M. Tomita, Y.
Makino, H. Kobashi, K. Sakaguchi, Y. Shiratori1
Background/Aims: A combination therapy of interferon
(IFN) or pegylated IFN plus ribavirin achieves higher rate of sustained
virologic response than IFN monotherapy. However, poor adherence is one of the
most important problems, especially in older patients. In this study, we
analyzed factors that might have effect on adherence to therapy in patients who
had initial or re-treatment of IFN therapy.
Patients/Methods:
We consecutively enrolled 363 patients (221 were IFN naďve
and 142 were undergoing re-treatment) with chronic hepatitis C. Mean age of
naďve and re-treatment groups were 54.8 and 55.7 years, respectively. IFN
alpha-2b was administered daily for two weeks, followed by three times per week
for 22 weeks, while ribavirin was administered daily. We evaluated tolerability
in terms of treatment adherence to the 80/80/80 rule. Logistic regression
analysis was performed to analyze the factors associated with adherence to
combination therapy.
Results:
Of 363 patients, 189 (52%) achieved 80% adherence.
Multivariate logistic regression analysis revealed that re-treatment, center
with more patients (>=30 cases) enrolled, patients age (<55 years), body
weight (<60 kg), genotype 2, hemoglobin concentration (>=14 g/dL), and
dosage of IFN per weight (<0.13 MIU/kg) were associated with achievement of
80% adherence to combination therapy. Accordingly, the achievement of 80%
adherence was more frequent in re-treatment (61%) than in naďve group (46%)
(p<0.01), in centers with more patients enrolled (57%) than in less patients
enrolled (46%) (p=0.03).
Conclusion:
·
Retreatment
group and patients treated in center with more patiens tested had different
background from others.
·
In
these groups, dose reduction and discontinuation rate of interferon and
ribavirin were lower and adherence was higher.
·
There
was no significant difference in SVR rate in spite of different background.
Topic:
Treatment—Disease Progression
H. Miyatake; Y.
Kobayashi; Y. Iwasaki; S. Nakamura; R. Terada; K. Miyoshi; H. Ohnishi; S.
Iwadou; B. Shoji; K. Kuwaki; J. Toshimori; T. Yasunaka; H. Hagihara; K.
Sakaguchi
Background and Aims:
It has been reported that interferon (IFN) treatment for
chronic hepatitis C could prevent the development of hepatocellular carcinoma
(HCC).
HCC are liable to recur frequently even after curative therapy
mainly because of multi-centric occurrence. The purpose of this study was to
clarify the effect of previous IFN treatment before the development of HCC on
the recurrence and survival of HCC patients.
Methods:
Three hundred and eighty-two out of 897 patients with HCC
diagnosed at
Results:
Mean follow-up period of all patients was 6.2 years. IFN
treated group comprised 70 men and 48 women, and mean age at IFN therapy and
development of HCC was 58 and 65 years old, respectively.
One hundred out of 118 patients (85 %) were classified into
Child-Pugh classification A. IFN untreated group comprised 182 men and 82
women, and mean age at development of HCC was 67 years old. Survival rate of
SVR was higher than that of non-SVR and IFN untreated patients (p=.010).
The 1st HCC recurrence rate was similar between SVR and
non-SVR. However, the 2nd HCC recurrence rate in SVR at 2 years was
significantly lower than that in non-SVR (0% vs. 68%, p=.006). There were no
significant difference in the survival rate and the 1st and 2nd recurrence rate
between SVR and non-SVR.
In multivariate analysis, the age at the time of IFN therapy
(p=.043) and tumor number at HCC development (p=.044) were independent factors
related to 1st HCC recurrence, while sustained virologic response (p=.057) were
related to 2nd HCC recurrence.
Conclusions:
Sustained virologic response to previous interferon treatment
in patients with hepatitis C may reduce the risk for the second recurrence of
HCC and improve survival.
Topic:
Treatment—Disease Progression
S1728 The Prevalence and
Significance of Occult Hepatitis B In A Liver Transplant population with
Chronic Hepatitis C
K. Shetty; M. T. Hussain; L. Nei4; K. Reddy;
A. Lok
Background:
Occult hepatitis B virus(HBV)is
defined as the detection of HBV DNA in the serum or liver of those who test
negative for hepatitis B surface antigen (HBsAg).It has been implicated in HBV
reactivation within immunosuppressed populations, and in the development of
hepatitis C virus (HCV)-associated cirrhosis and hepatocellular carcinoma (HCC)
in non-transplant settings. The significance of occult HBV following orthotopic
liver transplantation (OLT) is incompletely understood.
Aims:
1.
Determine the prevalence of occult HBV in a
HCV-infected transplant population
2.
Examine the course of occult HBV post- orthotopic
liver transplantation
3.
Assess the effect of occult HBV on the histological
recurrence rate of post- orthotopic liver transplantation HCV
Methods:
Those with HCV cirrhosis listed for
orthotopic liver transplantation were prospectively followed. PCR techniques were utilized to test for
serum HBV DNA at enrollment, within the explant and at 8 and 24 weeks post-
orthotopic liver transplantation.
Results:
56 patients with HCV cirrhosis were
enrolled, 44 underwent OLT. The overall
prevalence of occult HBV based on positive serum HBV DNA was 8/56(14%) and
based on positive hepatic HBV DNA was 19/44(43%). The presence of serum
hepatitis B core antibody (anti-HBc) and a history of injection drug use
correlated with occult HBV. Explant-proven HCC was found in 63% of patients with
occult HBV compared to 32% of those without occult HBV (p = 0.02, odds ratio
4.3)(table 1). An overall histological HCV recurrence
rate of 51% was noted, with no significant difference between groups. Multivariate analysis showed HCV recurrence
to be associated with donor age, and HCV viral load. No detectable serum or
explant HBsAg was noted at 8 or 24 weeks in any patient.
Conclusion:
Occult HBV is far more prevalent in
patients with end-stage HCV than would be expected from its prevalence in the general
population. It is strongly associated with the presence of anti-HBc, history of
injection drug use and explant-proven HCC. No effect of occult HBV is noted on
HBV reactivation, HCV recurrence or post- orthotopic liver transplantation
patient survival.
Comparison of demographics/HCV recurrence
|
Variable |
Occult HBV |
Standard |
No Occult HBV |
SD |
p Value |
|
Mean age |
52.7 |
5.4 |
51.9 |
6.3 |
NS |
|
MELD at OLT |
19.7 |
10.6 |
20.6 |
7.9 |
NS |
|
IVDA(%) |
72 |
|
56 |
|
0.03* |
|
Anti-HBc positive(%) |
12(63) |
|
6(24) |
|
0.01* |
|
Anti HBs positive(%) |
7(36) |
|
8(32) |
|
0.6 |
|
ACR(%) |
6(32) |
|
2(8) |
|
0.04* |
|
HCC (%) |
12(63) |
|
8(32) |
|
0.02 |
|
Recurrent HCV(%) |
11(56) |
|
13(51) |
|
0.9 |
IVDA
: intravenous drug abuse;ACR : acute cellular
rejection.* p = significant
Topic:
Liver Transplantation –Liver Transplantation - General
S1729. Effect
of Pre-Transplant Hepatitis C Virus RNA Status on Post-Transplant Outcome.
C. G. Nudo; R. Cortez; D. Wepler; A. G.
Tzakis; A. Regev View Pres.
Background:
Low or undetectable hepatitis C
virus (HCV) RNA before liver transplant (OLT) have been shown to lead to
decreased rate of HCV recurrence after orthotopic liver transplantation.
Aim:
To
determine whether patients with undetectable HCV RNA (RNA-) or detectable HCV
RNA (RNA+) at the time of orthotopic liver transplantation differ in HCV recurrence,
graft or overall survival.
Methods:
A retrospective chart review of
patients transplanted for HCV cirrhosis was performed. Data collected
included: MELD score, recipient/donor
age, recipient/donor sex, pre-transplant HCV RNA, post-transplant HCV
recurrence (viral/histological), patient and graft survival.
Results:
Between July 1995 to July 2004, 49
patients were HCV RNA- at orthotopic liver transplantation. 48 HCV RNA+ patients at the time of
orthotopic liver transplantation were analyzed as a control group. All HCV RNA- patients were negative as a
result of combination therapy with interferon/pegylated interferon and
ribavirin, which was discontinued before orthotopic liver transplantation.
There was no difference in recipient gender (male 63% vs 62.5%), recipient age
(51.6+/-9.9 vs 53+/-8.45), donor gender-male (67% vs 50%), or donor age
(40.7+/-13.7 vs 41.9+/-18.6) between the HCV RNA- and HCV RNA+ groups
respectively. The mean duration of follow-up after orthotopic liver
transplantation was 50.6+/-36.9 vs 40.8+/-18.7 months for the HCV RNA- and HCV
RNA+ groups. 69% of patients in the HCV RNA- group developed virological
recurrence during follow-up. There was no difference in the incidence of
histological recurrent hepatitis C between the HCV RNA- and HCV RNA+ groups
(55.6% vs 56%). However, the HCV RNA+ group had a lower time to histological
recurrence (8.45+/-8.6 vs 18+/-19 months, p=0.02). There was no difference in
rate of death (20.8% vs 28.6%), but there was a trend toward a higher rate of
graft failure in the HCV RNA+ group (12.5% vs 2%, p=0.059). In the HCV RNA-
group 31 of the 49 subjects received a graft from a same gender donor.
The patients who received an
opposite gender graft had a higher rate of histological recurrence of hepatitis
C (72.2% vs 38.7%, p=0.038). In the HCV RNA+ group there was no difference in
rate of histological recurrence between gender mismatched and matched groups
(59% vs 53.8%, p=0.78). In the combined group of HCV RNA+ and HCV RNA-, there
was a trend towards a higher rate of histological recurrence in the gender
mismatched group when compared to the matched group (65% vs 45.6%, p=0.067).
Conclusions:
·
Patients transplanted for HCV cirrhosis with
undetectable HCV RNA (HCV RNA -) had lower rate of virologic recurrence (55%
vs. 100%, p=0.0001), a trend toward a lower rate of histological recurrence
(36.7% vs. 56.3%, p=0.068), and longer time to development of histological
recurrence (medium 11 vs. 5.6 months, p=0.03), when compared to patients with
detectable HCV RNA (HCV RNA +). These
results were unrelated to SVR.
·
Patients with SVR had a statistically lower rate of
virolgoical recurrence and histological recurrence when compared to patients
with no SVR/RNA (-) or RNA (+). All
patients with SVR had no virological recurrence or histological recurrence post
transplantation.
·
All HCV RNA negative subjects who received a liver
graft from donors of the same gender had a trend toward a higher histological
ree survival (logrank p=0.051)
·
Furthers studies are needed to evaluate these
findings.
Liver Transplantation – General
I. J. Lo; C. Kin; B. Alkofer; J. V. Guarrera;
B. Samstein; L. Ratner; D. Jan; S. Bellemare; M. Kinkhabwala; J. C. Emond; J.
F. Renz.
Introduction:
Liver transplantation (LTX) is
limited by a donor shortage. Utilization of allografts that do not meet
traditional criteria (extended donor criteria [EDC]) offers immediate expansion
of the donor pool. EDC allografts are allocated by transplant center rather
than wait-list priority (UNOS).
Methods:
To maximize access to LTX, 200 EDC
allografts were systematically applied to an adult wait-list population from
04/01 through 01/06 while 130 patients received a UNOS allograft (mean
follow-up:3.2yr). EDC allografts
included: age>65years, donation after cardiac death, hepatitis C positive
(HCV), hepatitis B core antibody positive, human T-cell lymphotrophic virus
positive, split-liver allograft, serum [Na]>155meq/dl, history of carcinoma,
macrovesicular steatosis>40%, and behavioral high-risk donors. EDC
recipients demonstrated a higher incidence of HCV liver disease, hepatocellular
carcinoma (HCC), and significantly lower (p<0.01) model for end stage liver
disease (MELD) score at LTX (Table #1).
Results:
Over half of EDC recipients
admitted from home for LTX had been hospitalized within the preceeding 90days for
complications of liver failure. Wait-time between groups was significantly
lower for EDC (p<0.01).
No significant difference in the
incidence of complications categorized as biliary, vascular, wound, and delayed
or primary graft nonfunction was observed. Log-Rank analysis of Kaplan-Meier
survival estimates demonstrated no significant difference in patient or graft
survival at 6months; however, EDC death secondary to recurrent HCV, HCC or
co-morbidities contributed to lower one-year survival. Length of stay was
significantly lower for EDC recipients. Of 543 listings during the study
period, EDC increased patient access by 77%. Allocation of EDC by our
transplant center reduced patient wait-list removals secondary to death by over
50% compared to regional data for each year of the study (p<0.01).
Conclusion:
In conclusion, EDC liver allografts
maximize utility of the existing donor pool and increase access to LTX while
providing satisfactory results to select recipients.
TABLE #1
|
|
EDC |
UNOS |
|
MELD +/- S.D. |
22 +/- 11 |
25 +/- 12* |
|
LOS +/- S.D. (d) |
12 +/- 9 |
27 +/- 31 |
|
KAPLAN-MEIER |
|
|
|
GRAFT SURVIVAL |
|
|
|
1 MONTH (%) |
94 |
91 |
|
6 MONTH (%) |
84 |
91 |
|
12 MONTH (%) |
75 |
85 |
|
PATIENT SURVIVAL |
|
|
|
1 MONTH (%) |
97 |
98 |
|
6 MONTH (%) |
90 |
95 |
|
12 MONTH (%) |
81 |
81 |
*p<0.05
Topic:
Liver Transplantation –Race/ Ethnicity
S1732.
Blacks have worse graft and overall survival at 2 years after OLT in the MELD
era.
A. N. Ananthakrishnan; K. Saeian.
Background / Aims:
Beginning
Methods:
We analyzed the United Network for
Organ Sharing (UNOS) database for adult liver transplants performed between
Results:
There were 13,891whites, 1,557
blacks, 2,198 Hispanics, and 1,038 transplant recipients belonging to the other
races. Patients in the age group 50-64 years formed just over half the study
population with more males than females in each racial subgroup.
Patients with HCV formed the
largest proportion of subjects undergoing liver transplantation in each racial subgroup
(range 22.3-40.8%). Compared to whites, blacks had a higher proportion of
patients undergoing transplantation for acute liver failure (12.3% vs. 6.7%,
p<0.05) and HCV (37.6% vs. 34.3%, p <0.05).
On multivariate analysis, blacks
had lower overall (HR 1.22, 95% CI 1.02-1.44) and graft survival (HR 1.27, 95%
CI 1.11-1.46) compared to whites. This disparity in outcomes persisted after
inclusion of either the MELD score at listing or at transplant in our final
model. There was no significant difference in overall or graft survival between
blacks and whites at 3 months and 12 months. Compared to whites, blacks
transplanted for hepatitis C (0.72 vs. 0.80, p=0.02) or hepatocellular
carcinoma (0.60 vs. 0.76, p=0.02) had significantly lower survival rates at 2
years.
Conclusion:
·
In the MELD era, black patients have survival rates
similar to whites in the first year after orthotopic liver transplantation, but
have significantly lower survival at two years, especially for hepatitis C and
hepatocellular carcinoma.
·
This disparity is unlikely to be attributable to
severity of liver disease at the time of listing or transplant as persists
after adjustment for the MELD score and medical condition at the time of
transplant.
·
Thus other factors contributing to these
differences, whether biologic or socioeconomic, require further investigation.
Topic:
Liver Transplantation – General
S1735.
Distinct Differences in Global Immune Cell Function Profiles Between HCV(+) and HCV(-)
Post-liver Transplant Patients..
H. Kwok; N. Chang; J. Weissman; E. S. Franco;
Z. Kayali; P. W. Baron; O. Ojogho; M. H. Mendler.
Background/Aim:
We hypothesized that global
cellular immune function (ImmuKnow®(I), Cylex®
Immune Cell Function Assay measuring serum CD4+ ATP activity) differs according
to cause of pre-liver transplantation disease and changes over time after liver
transplantation.
Methods:
We reviewed a single center liver
transplant cohort where I was performed from 2/05 to 7/06. Data included:
demographics and liver disease; and for each I level (event), time from
Liver transplant (TFT), immunosuppressants and diagnosis.
Results:
114/196 (58.2%) patients were
included; 69% males; 37% Caucasians, 4% Asians, and 54% Hispanics; liver transplant
at age 51yo (4-71); for HCV(58%), alcoholic liver
disease (41%), HCC/liver cancer (16%), and others(33%). 477 events were
obtained; 3 (1-17) per patient, 25m (4d-19y) TFT.
Diagnoses were:
·
normal allograft
function (n=166, 35%),
·
recurrent disease
(n=199, 42%),
·
septic event
(n=34, 7%),
·
undetermined (n=27, 6%) and
·
other (n=51,
11%).
HCV led to 188/199 (94%) of cases
of recurrent disease; 188/281 (67%) of HCV patients developed recurrent
disease. The I distribution was non-Caucasian
with a median of 162 (1-761). As shown below, the range of I levels in HCV (+)
patients were constant over TFT, but levels in HCV (-) patients were initially
high and later decreased to similar levels as HCV(+)
patients.
Those with recurrent HCV on
treatment had lower levels [n=10; 63.5(3-146)] as compared to those
off-treatment [n=178; 147(1-563), p=0.0036] or without recurrence [n=58;
155(7-563), p=0.0034]. Also, similar TFT-dependent profiles were observed for
the ratio of I/Lymphocytes (L) 103/µL [I/L ρgATP/103cells,
113.5(0.53-2012), and I/L was significantly lower in patients with recurrent
HCV.
Conclusion:
Global cellular immune function
(ImmuKnow®) post-liver transplant appears depressed at baseline in HCV(+)
patients as compared to other liver diseases, and even more so in HCV(+) with
recurrent disease and on treatment. These differences narrow with increased
time from transplantation.
Topic:
Liver Transplantation—Allocation - General
S1736. Impact
of Extended Criteria Donor Livers on Survival of Patients with Hepatocellular
Carcinoma.
A. Cooper; R. S. Mangus; M. Maluccio; R.
Vianna; J. A. Fridell; A. Tector.
Introduction/Aim:
Liver transplantation is the most
effective treatment for patients with hepatocellular carcinoma (HCC), with
optimal outcomes in those meeting
Methods:
Records from 698 consecutive adult
liver transplants from July 2001 to June 2006 were reviewed. Of these patients,
138 (19.8%) had HCC and 489 (70%) received ECD livers. Primary ECD criteria
included: age ≥ 60, BMI ≥ 35, maximum AST or ALT > 500, maximum
bilirubin > 2.0, peak serum sodium > 170, HBV/HCV/HTLV reactive,
non-heart beating donor, cold ischemia time > 12 hours, ICU stay > 5
days, ≥ 3 pressors simultaneously, and extensive chronic alcohol abuse. Outcomes
included 1- and 2-year survival and HCC recurrence. Kaplan-Meier estimates of
survival time for ECD vs. standard donor (SD) groups were compared using the
log-rank test. The simultaneous impact of MELD score, primary diagnosis,
recipient age, transplant year and
Results:
Median follow-up for the entire
population was 25.4 months from the date of transplantation. Medican follow-up for survivors was 31.8 months. Of the 138 patients, 31 (22.5%) have died: 10
(7%) died of cancer, 4 (3%) died of recurrent hepatitis C and liver failure,
7(5%) died of other or unknown causes.
There are 107 (77.5%) patients who are currently alive, 6 (4.3%) with and
101 (73.2%) without evidence of disease recurrence. No patients were lost to follow-up.
The estimated mean survival from
the date of transplant was 52.4 months for patients in the DS group and 54.8
months in patients receiving ECD (p=0.61 by unpaired t-test with Welch’s
correction). Overall actuarial survival
at 1 year was 85% (ECD 83.6%, SD 87.5%), and 77% at 2-years (ECD 77.3%, SD
76.9%).
Conclusion:
The use of extended criteria donor
livers increases organ availability for patients with liver disease and provides
acceptable survival in patients with HCC.
In this cohort of patients transplanted with HCC, there was not
significant difference in overall survival between those receiving a standard
donor liver and those receiving an ECD liver.
Additionally, tumor recurrence rates did not differ between the ECD and
SD groups. Thus, transplantation with
ECD livers does not appear to impart any oncologic detriment for patients with
HCC. These results suggest that ECD
livers represent a viable avenue for expanding the opportunity to offer
transplant to patients with CCC, even those who are not typically considered
acceptable candidates.
There was no difference between the
ECD and SD groups in tumor recurrence. Overall survival was also the same
regardless of
Topic:
Liver Transplantation –General
M. Lee; A. Kamal; A.
Lapasaran; E. B. Keeffe; C. O. Esquivel; A. Ahmed.
Introduction:
Previous studies suggest that liver
transplant patients with diabetes mellitus have increased risk of death up to 6
years following transplant, but these studies did not control for MELD score.
Aim:
We studied our patient population
to determine if diabetes mellitus was a predictor of late mortality independent
of MELD score.
Method:
We conducted a retrospective
analysis of all adult patients undergoing liver transplantation at
Results:
Of 530 patients identified,
information regarding diabetes mellitus was available for 431. Patients with
acute liver failure (n=17), undergoing kidney-liver transplant (n=28), and
dying prior to discharge (n=51) were excluded.
Of the remaining 370 patients,
diabetes mellitus was present in 62 (Table 1). Over a mean follow-up of 4.46
years, survival was 81% in the diabetic group and 94% among controls (Figure
1). In the diabetic group, the most common causes of death were unknown (30%),
metastatic cancer (20%), and graft failure (20%); among non-diabetics, common
causes of death were multiorgan failure (33%), gastrointestinal bleeding (20%),
and metastatic cancer (20%). Diabetes
mellitus remained a significant predictor of death (HR 3.11, p = 0.01), even
after controlling for MELD score, age, BMI and presence of HCV.
Conclusion:
Diabetes mellitus is an independent
risk factor for mortality following liver transplantation. Future research is needed to study
accelerated atherosclerosis in the setting of immune suppression among diabetics and
the effects of diabetes-related systemic metabolic derangements on allograft
function as an explanation for this finding.
Demographic Characteristics
|
|
Diabetes |
No diabetes |
p
value |
|
Number of patients |
62 |
308 |
N/A |
|
Mean age (years) |
54.4 |
50.1 |
0.002 |
|
Mean BMI (kg/m2) |
28.6 |
27.1 |
NS |
|
Presence of HCV |
56% |
45% |
NS |
|
Mean follow-up |
3.7 |
4.7 |
0.01 |
|
Mean MELD score |
17 |
19 |
NS |
Topic: Liver
Transplantation—Post
T. Serrano; A. Garcia-Gil; J. Arenas; Y. Ber;
C. Valiente; R. Sainz.
Introduction:
The impact of donor age on liver
transplantation has been analysed by several studies, but all of them are
retrospective, and the results are contradictory.
Aim:
To evaluate
graft survival and complications of liver transplantation with old donors in
the first year after transplantation.
Methods:
Prospective analysis of 181
consecutive L liver transplantations performed between February 2000 and June
2005. Patients who died with normal liver function before 1 year after liver
transplantation, patients with ABO incompatible donors, and those who were lost
in the follow-up were excluded (n=29). liver
transplantations were divided into two groups depending on donor age:
A.
Less than 60 years old (n=104);
B.
≥60 years old (n=48).
Results:
During the follow-up period, 13 out
of 48 grafts in the group of older donors were lost (27.1%), and 14 out of 104
(13.5%) were lost in the other group (OR 2.4; 95%CI: 1.06-5.58; p=0.04). The
incidence of acute and chronic rejection, infection and arterial complications
was similar in both groups, but biliary complications were higher in the older
donor group (31.3% vs 14.4%, OR 2.7; 95%CI:1.2-6.1;
p<0.05).
The incidence of anastomotic
biliary strictures was similar in both groups (7.7% group A vs 8.3%), but the
incidence of non-anastomotic biliary stenosis NABS was clearly higher in the
older donor group (18.8% versus 5.8%; OR 3.8; 95%CI: 1.26-11.30; p<0.05).
The main cause of graft loss in the
older donor group was NABS. In almost half of patients with NABS, no hepatic
arterial complications were found. Protocol biopsies done at the end of the
first year in 80% of HCV infected livers (n=34) showed that patients included
in group B had more severe fibrosis (stage 3 or 4 )
than younger donor recipients (58.3% vs4.5%; OR=29.4; 95%CI: 2.9-296.5;
p<0.001.
Graft survival 12 months after LT
was higher in younger donors (86.5% vs 72.9%; p<0.05).
Conclusion:
The use of grafts from donors ≥60
years increases the incidence of biliary complications, severity VCH reinfection
and is related to a increase in graft loss in the first year after liver
transplantation mainly because of NABS.
Topic:
Liver Transplantation - Post
H. Yang; C. Chen; C. Jen; U.
H. Iloeje; J. Su; S. You.
Background and Aims:
Chronic infections with hepatitis B
virus (HBV) or hepatitis C virus (HCV) are well-documented risk factors for
cirrhosis and hepatocellular carcinoma (HCC). We aimed to investigate mortality
associated with the viruses in this study.
Methods:
The mortality of this cohort was
follow-up between
Results:
Among a
total of 23,186 cohort members (290872.7 person-years of follow-up), the number
(prevalence) of HBV, HCV, HBV/HCV co-infection and neither HBV nor HCV
infections was 3,895 (16.8%), 1040 (4.5%), 215 (0.9%) and 18,036 (77.8%),
respectively.
The all causes mortality per
100,000 person-years was 877.1, 1248.7, 1179.9, and 595.1 for HBV, HCV
infections, HBV/HCV co-infection and neither HBV nor HCV infection,
respectively (liver cancer mortality: 284.1, 257.6, 228.4, 12.3; mortality of
chronic liver disease and cirrhosis: 85.0, 93.7, 152.2, 16.7; non-liver-related
mortality: 508.0, 897.5, 799.3, 566.0).
Taking those with neither HBV nor
HCV infection as referent, the RRadj (95% CI) of all cause mortality adjusted
for gender, age, cigarette smoking and alcohol consumption was 1.7 (1.5-1.9),
1.8 (1.6-2.2), and 1.9 (1.3-2.6) for HBV, HCV infections, and HBV/HCV
co-infection, respectively [liver cancer mortality: 25.2 (16.8-37.9), 19.6
(11.8-32.5), 17.4 (7.2-42.1); mortality of chronic liver disease and cirrhosis:
5.5 (3.5-8.6), 5.3 (2.8-10.2), 9.0 (3.2-25.1); non-liver-related mortality: 1.1
(0.9-1.2), 1.4 (1.1-1.7), 1.3 (0.9-2.0)]. Subjects infected with HCV only had
significantly higher risk of dying from cerebrovascular disease and renal
failure with RRadj (95% CI), 2.2 (1.4-3.6) and 2.9 (1.3-6.1), respectively.
Conclusions:
HBV, HCV infections and HBV/HCV
co-infection had elevated risk of liver-related mortality compared with neither
HBV nor HCV infection. HCV infection may be associated with death from several
extra-hepatic manifestations such as cerebrovascular disease and renal failure.
Hepatitis B:
Diagnostic Tools
C. Chen; M. Lee; W. Lee; C. Jen; H. Yang; U.
H. Iloeje; J. Su; S. Lu; S. You; C. Chen
Background:
Serum ALT is a marker of hepatocyte
damage in chronic hepatitis.
Aim:
·
evaluate the relationship between ALT changes over
time and HCC risk;
·
examine the baseline
factors associated with ALT changes over time.
Methods:
A subgroup of the R.E.V.E.A.L.–HBV
cohort of HBsAg-seropositive and anti-HCV-seronegative participants, with ≥5
ALT measurements, was used in the analyses. The outcome was new liver cancer (HCC)
cases. We defined low, medium, and high
ALT as <20 U/L, ≥20 U/L but <45 U/L, and ≥45 U/L,
respectively. A semi-parametric group-based modeling was used to determine
major classes of ALT trajectories. Associations between baseline risk factors
and the ALT trajectories were examined using polytomous logistic regression.
Cox proportional hazards modeling was used to analyze the associations between
the ALT trajectory classes and HCC risk.
Results:
A total of 1712 subjects with 61
new HCC cases contributed 21,225 person-years of follow-up. Four ALT trajectory
classes were identified:
·
class I persistently low (n=551);
·
class II low-to-medium (n=808);
·
class III high-to-medium (n=99);
·
class IV
medium-to-high (n=254).
Of the baseline risk factors, gender,
age, HBeAg status, serum HBV DNA levels, and alcohol consumption were
significantly associated with the ALT trajectory. With class I subjects as the
reference group, the adjusted hazard ratio [HRadj (95% CI)] of developing HCC
was 4.0 (1.2-13.4) for class II subjects; 4.6 (1.1-18.9) for class III
subjects; and 7.4 (2.1-25.9) for class IV subjects after adjustment for gender,
age, HBeAg status, HBV DNA levels, cigarette smoking, and alcohol consumption.
With HBV DNA <300 c/mL as reference, the HRadj (95% CI) of developing HCC
associated with baseline HBV DNA level was 1.8 (0.5-7.4) for HBV DNA 300 to
<104 c/mL; 4.0 (1.1-14.8) for HBV DNA ≥104 to <105 c/mL; 7.1
(2-25.6) for HBV DNA ≥105 to <106; and 9.6 (2.5-36.2) for HBV DNA ≥106
c/mL.
Conclusions:
Serum ALT changes over time is a
strong independent predictor of HCC. Baseline HBV DNA was a significant
predictor of the ALT trajectory over time and remained an important risk factor
for HCC development after adjusting for the ALT trajectories.
Topic: Disease
Progression---Metabolic
A. Colecchia; A. Vestito; E. Petracci; M.
Bacchi-Reggiani; A. Morselli-Labate; A. Di Biase; G. Mazzella; F. Lodato; M.
Montagnani; F. Pasqui; D. Festi
Nonalcoholic fatty liver disease ( NAFLD) and metabolic syndrome ( MS) are considered closely
related diseases, having insulin resistance as common pathogenetic mechianism.
A few studies, however, have simultaneously assessed NAFLD and MS prevalence
and associated factors in a general population.
Aim:
To evaluate
by means of a cross-sectional study prevalence and associate factors of NAFLD
and metabolic syndrome.
Material and Methods:
The cross sectional study was
performed on a general population, aged 28-84 yrs; 1534 out of 1646 ( 93%) subjects agreed to participate to the study. All
subjects underwent abdominal ultrasound (
Results:
479 out of 1534 (31.2%) subjects
were excluded because they presented other liver diseases (391 alcohol, 20 HBV,
63 HCV and 5 autoimmune).
382 out of 1055 subjects ( 36.1%) ( males 57.8%, mean age:
52.1 ± 12.7) had NAFLD, while 240 out of 1055 ( 22.7%) subjects had metabolic
syndrome ( males 45.8%,mean age 55.5 ± 12.6).
In NAFLD, metabolic syndrome prevalence was 41.6% (159
out of 382 subjects); at multivariate analysis, associate factors resulted: sex
male (OR:1.89), systolic hypertension (OR:1.9), hyperglicemia (OR:1.9),
visceral obesity (OR:4.9), Tg/HDL ratio (OR:2.9), ALT (OR:2,5), gGT (OR:1.8).
NAFLD was present in 66.2% (159 out 240 subjects) of metabolic syndrome subjects: at multivariate analysis associated
factors resulted: increasing age (OR:1.5); female sex (OR:1.05); fatty liver (
OR:5.22); Tg/Hdl ratio ( OR: 23.04).
Conclusions:
The present study confirms the
strong association between NAFLD and metabolic syndrome; although NAFLD
prevalence is higher. Subjects with NAFLD had higher risk (OR: 13.5) to have
metabolic syndrome than vice-versa (OR: 5.22); this observation suggest that
NAFLD could play an early role in the development of metabolic syndrome.
Further epidemiological and pathophysiological studies are needed to better
define which is the killer or the victim.