Topic: Pathogenesis and Treatment
90. HBV replication can be controlled
through TLR-induced production of IFN-beta by non-parenchymal liver
cells.
J.
Wu; M. Lu; M. Roggendorf; G. Gerken; J. F. Schlaak
Background
and aims:
Recent studies suggested that TLR-based therapies
may represent a promising approach in the treatment of HBV infection.
Therefore, we have studied the role of the local innate immune system of the
liver (Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC)) as
possible mediators of this effect.
Methods:
Murine KC were enriched by counterflow elutriation
and LSEC were isolated by anti-LSEC microbeads to a purity >99% as
controlled by FACS. Dendritic cells were used as controls. Cells were
stimulated by TLR1-9 ligands. The culture supernatants were collected and
tested for their antiviral activity in a viral protection assay. Antibodies to
type I and II IFNs were added to assess the nature of
cytokines produced by activated KC and LSEC. The culture supernatants were
added to differentiated HBV-Met cells, a mouse
hepatocyte line with a stably integrated 1.3 fold HBV genome. HBV gene
expression and replication in treated cells was analyzed by ELISA (HBsAg, HBeAg), southern blot and northern blot.
Results:
Only TLR 3 and 4 ligands were able to stimulate the
production of high amounts of antiviral mediators by KC and LSEC, while, in
contrast to dendritic cells, other TLR ligands failed to show an effect on KC
and LSEC. Using neutralizing antibodies to type I and II IFNs, we could
demonstrate that the TLR-mediated antiviral effect of KC and LSEC is
exclusively mediated through IFN-β. The culture supernatants of KC and
LSEC, when applied on the HBV-met cells, were able to potently suppress HBV gene
expression and replication as assessed by HBsAg and HBeAg ELISA and southern
blot while HBV-RNA levels remained unchanged.
Conclusions:
Our data indicate for the first time that TLR 3 and -4 mediated stimulation of non-parenchymal liver cells leads to the
production of IFN-β which can potently suppress HBV replication and gene
expression. This is of relevance for the local control of HBV infection
by the innate immune system of the liver as well as the use of TLR-based new
therapeutic approaches and sheds new light on the interaction of HCV (TLR 3
stimulator) and HBV.
91. Prognosis following hepatitis B surface antigen seroclearance: a
systematic review of 9 cohort studies and 1398 patients.
A. K. Retana; A. Rajendra; J. B. Wong
Aims:
Seroclearance of hepatitis B surface
antigen (HBsAg) remains the goal of antiviral therapy, but recent reports
suggest continued risk for hepatic complications. Our aim was to quantify
prognosis following seroclearance of HBsAg and identify risk factors for hepatic
progression.
Methods:
In a systematic review of MEDLINE,
Web of Science and bibliographies, we identified 9 retrospective cohort studies
(1398 patients) that reported on clinical course after HBsAg seroclearance. We
extracted data regarding development of hepatocellular carcinoma (HCC), hepatic
decompensation (ascites or varices), and liver-related death. In 4 studies with
controls, we compared outcomes in those who had HBsAg seroclearance with those
who did not. To identify risk factors for progression among those with HBsAg
seroclearance, we compared outcomes of patients with and without cirrhosis and
of co-infected individuals (hepatitis C, D, or HIV) with mono-infected ones.
Data were pooled using the DerSimonian and Laird random effects model.
Results:
Of 9 studies 7 involved Asians. The
mean age 46 (42-51) years; 80% (78-88) were men; 31% (0-100) had evidence of
cirrhosis. The mean length of follow-up was 47 months (19-78). At the end of
follow-up, HBV was detectable in the serum of 32 out of 395 (8%) and in liver
biopsies of 50 out of 62 (81%) patients. When comparing patients with and
without seroclearance, the odds ratios (OR) were 0.6 (95% CI 0.2-1.3) for
developing any liver complication; 0.6 (0.2-1.4) for HCC; 1.1 (0.5-2.6) for
hepatic decompensation; and 0.3 (0.04-2.2) for liver-related mortality. The
risk of complications in patients with HBsAg seroclearance was higher in those
with cirrhosis or with co-infection. Compared to patients without cirrhosis,
those with cirrhosis had OR of 17.0 (2.5-116.6) for developing HCC; 16.8
(0.7-406.6) for liver failure; and 4.8 (0.5-50) for liver-related death. For
patients with any co-infection versus those with mono-infection, the OR were
10.9 (1.3-95.4) for any hepatic complication in patients with cirrhosis and 4.5
(0.06-347.5) in those without cirrhosis. For hepatitis C co-infection, the OR
for developing any hepatic complication was 17.4 (3.9-77.5).
Conclusion:
Patients with HBsAg seroclearance had
lower risks of developing complications, but none of these results were
statistically significant. In those with HBsAg seroclearance, the presence of
cirrhosis or co-infection was associated with a statistically significant
increase in HCC or hepatic complications respectively. Additional studies or
longer follow-up in those with HBsAg seroclearance are needed to clarify risks
and identify markers of progression.
93. Genotypic
Analysis of Patients with Evaluable HBV DNA After 1
Year of Telbivudine Therapy in the GLOBE Registration Trial.
M. Seifer; A. Patty; C. Chapron; L. van Doorn; B. Belanger; N. A. Brown; D. N.
Standring
Introduction:
The safety and efficacy of
telbivudine was evaluated in the international GLOBE trial of 1367 patients
with chronic hepatitis B. Here we report the genotypic analysis at week 48 of
165 telbivudine patients with HBV of >1,000 copies per mL.
Methods:
HBV genomes were amplified from sera
of study patients by RT PCR. The entire polymerase RT domain was sequenced to
determine HBV genotypes at screen. For 165 telbivudine patients with HBV DNA
>1,000 copies per mL at week 48 or 52, sera were re-sequenced at week 48 (or
post virologic breakthrough) to identify genotypic mutations. These included
all patients who had met previous virologic breakthrough criteria at week 48.
Results:
Sequences were obtained from 115/165
evaluable patients (with amplifiable HBV DNA and at least 16 weeks on therapy).
RtM204I was the most frequent genotypic change seen (in 46/115 patients,
including 9 mixed mutants) and is the only mutant to date that has been
causally linked to genotypic/phenotypic telbivudine resistance and virologic
rebound: at week 48, M204I was detected in 28 of 32 telbivudine patients
experiencing a 1 log above nadir breakthrough (Standring et al, DDW 2007).
Other genotypic changes among the 115 patients included rtL80 (n=26), rtL180
(4), and rtL229 (6). These were only associated with virologic rebound when
rtM204I was present. There was no evidence for the L180M/M204 resistance
pattern for telbivudine.
The genotypic analysis revealed
rtA181T/S substitutions (n=15/1) that did not co-segregate with M204I or
virologic rebound. These mutants result in a prematurely terminated S protein,
likely ablating viable virus production. The mutation was absent in the 5 A181T
patients who went on to year 2 breakthrough (3 with M204I, 2 with wild-type
M204). Thus, the biological relevance and role in resistance of this variant is
obscure.
Conclusions:
In the large GLOBE study, telbivudine
primarily elicited M204I genotypic changes (n= 46). M204I, with or without
secondary mutation (primarily L80I), is the signature telbivudine mutation
associated with virologic rebound. No L180M/M204V-based resistance/changes were
seen for telbivudine.
94. Presence of
Biopsy-Proven Histologic Damage (Necroinflammation And
Fibrosis) is Common Even When ALT is Less Than 2X ULN in Patients With Chronic
Hepatitis B (CHB).
N. Terrault; W. Kim; S. Lim; G. V.
Papatheodoridis; A. Alberti; M. Yuen; Z. D. Goodman; J. Vaughan; R. Wilber; B.
Kreter
Introduction:
Current treatment guidelines for
chronic hepatitis B recommend initiation in patients with alanine
aminotransferase (ALT) levels ≥2X upper limit of normal (ULN). However,
some patients with ALT below this threshold may have evidence of liver damage
when biopsied and treatment decisions should consider this risk.
Methods:
We determined the distribution of
Knodell necroinflammatory (NI) and Ishak fibrosis (IF) scores within groups
determined by current breakpoints of baseline ALT categories (<2X; 2-5X;
>5X ULN) in 1253 patients from Phase III studies of nucleoside- naïve
HBeAg-positive (ETV-022) and HBeAg-negative (ETV-027) CHB. The patients’ mean
viral loads at baseline met the criteria for treatment according to current
treatment guidelines: 9.6 log10(ETV-022) and 7.6
log10(ETV-027). Association of histologic scores with viral load was not
performed due to study inclusion criteria which constrained enrollment to
patients with elevated HBV DNA.
Results: See table
Conclusions:
Over two-thirds of nucleoside-naïve
HB patients with elevated VL demonstrate clinically significant (NI >7)
necroinflammation, despite ALT values <2X ULN. Consistent with the natural
history of CHB in this population, fewer patients demonstrate advanced fibrosis
or cirrhosis than elevated NI scores, but advanced fibrosis is common even when
ALT is <2X ULN. Patients with elevated VL frequently demonstrate clinically
relevant changes in histopathology which merit treatment even when ALT values
are not elevated >2X ULN.
Frequency of Baseline NI and IF Thresholds by ALT Categories
|
|
ALT
<2 ULN |
ALT
2-5 ULN |
ALT
>5 ULN |
All
patients |
|
ETV- 022
(HBeAg(+)) |
n=234 |
n=305 |
n=113 |
n=652 |
|
NI≥7 |
68% |
80% |
95% |
78% |
|
IF≥4 |
11% |
15% |
20% |
14% |
|
ETV- 027
(HBeAg(-)) |
n=217 |
n=283 |
n=101 |
n=601 |
|
NI≥7 |
75% |
83% |
81% |
80% |
|
IF≥4 |
17% |
17% |
21% |
18% |
95. Tenofovir
(TDF) monotherapy is effective in suppressing serum HBV DNA in chronic
hepatitis B (CHB) patients with primary nonresponse to adefovir (ADV) but not
those with ADV-resistant HBV.
J. Tan; S. N.
Wong; M. T. Hussain; K. Oberhelman; A. Lok
Background:
Adefovir (ADV) results in primary
non-response in as many as 50% of patients (pts) with CHB. Tenofovir (TDF), a
nucleotide analogue closely related and with equimolar potency as ADV, may
result in more marked viral suppression as it is administered at a dosage that
is 30 times that of ADV.
Aims:
To determine viral
response to TDF or TDF+emtricitabine (FTC) therapy in pts with suboptimal
response to ADV.
Methods:
Pts with suboptimal virological
response (HBV DNA >4 log10 c/mL after > 6 months of treatment) to ADV
were switched to TDF (n=9) or TDF+FTC (n=2). HBV DNA by PCR and liver
chemistries were monitored every 3-6 months. Viral resistant mutations were
determined using direct sequencing. Cloning of serial samples was performed for
pts with known ADV-resistance and pts with a suboptimal virological response to
TDF.
Results:
At the start of TDF, median age was
51 years (35-72), 9 were HBeAg+ve. Two pts had viral breakthrough and genotypic
resistance (rtA181V) to ADV. Pt #1 had an initial decrease in HBV DNA from 7.6
to 5.1 log10 c/mL after 3 months of TDF, HBV DNA levels plateaued for the next
11 months and then decreased to 3.7 log10 c/mL, 4
months after the addition of FTC. The percentage of clones with rtA181V and
rtN236T mutations was 100% and 3% at the start of TDF and 100% and 8% after 13
months of TDF. Pt #2 had decrease in HBV DNA from 7.3 log10 c/mL to 2.6 log10
c/mL after 9 months of TDF+FTC. The percentage of clones bearing the rtA181V
mutants was 100% at the start of TDF and 96 % after 3 months of TDF; rtN236T
was not detected in any of the clones. Nine pts did not have ADV-resistant
mutations, and median HBV DNA at the start of TDF was 6.8
log10 c/mL. After a median of 13 months on TDF, 6 had undetectable HBV
DNA, 2 had HBV DNA of 2.5 log10 c/mL. The remaining pt had suboptimal
virological response on TDF, with HBV DNA decreasing from 7.6 to 5.1 log10 c/mL
after 21 months treatment. None of the clones had any ADV-resistant mutation at
baseline, but 17% of the clones had rtA181T mutation at the last visit.
Conclusions:
TDF is effective in suppressing HBV
replication in most patients with suboptimal response to ADV. However, TDF
alone may be less effective in pts with ADV resistance as ADV-resistant
mutations persist and are further selected. Our data suggest that mutations
resistant to ADV are cross resistant to TDF.
Session Title: Clinical: Hepatocellular Carcinoma and Cholangiocarcinoma
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
S1013. Blood Folate
Levels And Risk Of Liver Damage And Hepatocellular
Carcinoma: A Prospective Study In A Chinese High Risk Cohort.
T. M. Welzel;
H. A. Katki; L. Sakoda; A. A. Evans; A. A. Evans; W. London; G. Chen; S.
O'Broin; F. Chen; W. Lin; K. A. McGlynn
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
S1022. Outcome Of
Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation
.
I. W. Graziadei;
G. Millonig; M. Kern; W. Mark; R. Margreiter; W. Vogel
Clinical Epidemiology I
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 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. (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.
|
|
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. â€Adjusted for age,
race, gender, drug use and alcohol use.
Clinical Hepatitis
S1226. Diagnostic value of biochemical markers for prediction of liver
fibrosis and inflammation in pediatric patients.
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
S1227. Prevalence
and risk factors associated with hepatitis B and hepatitis C virus infections
among healthy population in an urban community in
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 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) were significantly associated with HBV
infection. Similarly, 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 were
associated with HBV infection.
Conclusion:
The finding of the study demonstrates
a high endemicity of HBV infection in an urban community in
S1230. Sequential
Treatment With Lamivudine And Alpha-Interferon In
Chronic Hepatitis B: A Pilot Study.
G. A. Niro; R. Fontana; D. Gioffreda; S. Fiorella; A. Iacobellis; P. Conoscitore; A. Andriulli
Background:
Monotherapy with alpha interferon
(α-IFN), effective in a small subset of patients with chronic hepatitis B
(CHB), is limited by relevant side effects. Long-term treatment with
nucleosides/nucleotides analogues is burdened by drug-resistant mutants occurrence. Sequential therapy of IFN with nucleos(t)ide analogues might represent a strategy to delay
emergence of drug resistance.
Aim:
To evaluate the efficacy of
sequential lamivudine and IFNα 2b monotherapies in preventing the
occurrence of YMDD mutants and in achieving a virologic and biochemical
response at the end of therapy and at the end of 12-month follow up.
Methods:
Fifteen patients with HBsAg, anti-HBe
positive chronic hepatitis, HBV-DNA > 100.000 copies/ml, and ALT > 2x ULN
received 4 consecutive courses, each lasting for 6 months, of monotherapy with
lamivudine (100 mg/day), followed by IFN α 2b (5 MU/tiw), lamivudine (100
mg/day) and IFNα 2b (5 MU/tiw). At the end of the 24 months of therapy
patients were followed up for 12 months. Quantitative HBV-DNA was evaluated
during and off treatment, and, whenever positive, HBV polymerase and
precore/core regions sequenced.
Results:
All patients completed the 24 month
treatment period. End of treatment response was achieved in 10 patients (67%).
One pt did not respond to therapy although viremia levels declined in respect
to baseline, and a second pt with undetectable viremia at week 16 experienced a
genotypic resistance at week 24 and a phenotypic resistance at week 72. A
rebound of viremia occurred in the remaining three pts at week 48, that was followed by self-limiting acute hepatitis in a
single pt. At the end of follow up six pts (40%) remained sustained responders.
At baseline the precore stop codon mutation (G1896A) was found in 80% of
patients and was equally distributed between responders and non responders. The
A1762T mutation was observed in 8 patients (53%), 4 responders (40%) and 4
(80%) non responders, while the G1764A mutation was detected in 9 patients
(60%), 5 responders (50%) and 4 non responders (80%). When taken collectively,
the group of triple promoter mutations at nucleotide 1762-1764-1896 prevailed
in non responders (60% vs 20%). Mutations L180M and M204V were identified in
the single pt with breakthrough.
Conclusion:
Sequential therapy with
lamivudine/interferon was efficacious in maintaining virological response in
40% of patients and capable of inhibiting the emergence of resistance to
lamivudine. Genetic alterations of the HBV genome within the basic core
promoter influenced response to therapy.
Esophagus
S1340. Clinical Predictors for Recurrence of Esophageal Varices after
Obliteration by Endoscopic Band Ligation.
V. Chandrasekhara; J. Yepuri; J. Sreenarasimhaiah
Background:
There is no universal standard of
care for endoscopic follow-up after obliteration of esophageal varices by
esophageal variceal ligation (EVL).
AIM: Identify clinical predictive
factors and rate of varices recurrence following EVL.
Methods:
All patients presenting to
Results:
Of 31 patients enrolled to date, 35%
were Caucasian and 65% were Hispanic. 71% of patients were male and 29% female
with mean age of 48 years. At the initial time of EVL, 39% were still consuming
alcohol. The cause of cirrhosis was alcohol alone (26%), hepatitis C (HCV)
alone (26%), combined HCV and alcohol (23%), cryptogenic (9%), nonalcoholic
fatty liver (3.2%), primary biliary cirrhosis (3.2%), combined hepatitis B
(HBV)/HCV (3.2%), and combined alcohol/HBV/HCV (3.2%). Noncompliance with the
EVL protocol was noted in 10/31 (32%) patients. Of these, 4/10 (40%)were Caucasian, 6/10 (60%) were Hispanic, 3/10 (30%) were
non-English speaking, and 8/10 (80%)were actively consuming alcohol. Variceal
rebleeding was noted in 8/31 (26%) within 1 year of initial EVL. Of these, 4/8
(50%) were non-compliant with the EVL protocol. Alcoholic cirrhosis was noted
in 5 of 8 (62.5%) patients. Moreover, 4/5 (80%) were still actively drinking.
For all 31 patients, the mean MELD score was 13.3 and the mean CPT score was
8.1. The mean MELD score was 16.1 for those with variceal rebleeding and 12.3
for those without rebleeding (p=0.013). The mean INR in the rebleeding group
was 1.64 and in the non-rebleeding group was 1.37 (p=0.017). The average age
for the two groups was 49.2 and 47.5 years, respectively. There has been one
death thus far due to a bleeding gastric lesion.
Conclusions:
Recurrence of variceal bleeding after
EVL obliteration occurred in those patients with a higher MELD score and
specifically a higher INR level when compared to those who did not bleed.
Patients with alcoholic cirrhosis had a higher rate of rebleeding. There was no
correlation with patient age. Rebleeding was higher in those who were
noncompliant with the EVL protocol including patients who were non-English
speaking as well as those with active alcohol consumption. Therefore, efforts
needed to be directed to facilitating patient compliance with medical care and
abstinence from alcohol.
ALF/Experimental and Clinical Liver Transplantation
S1728. The
Prevalence and Significance of Occult Hepatitis B In A
Liver Transplant population with Chronic Hepatitis C.
K. Shetty; M.
T. Hussain; L. Nei; 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-OLT
3. Assess the effect of occult HBV on
the histological recurrence rate of post-OLT HCV.
Methods:
Those with HCV cirrhosis listed for
OLT 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-OLT.
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-OLT patient survival.
|
Variable
|
Occult
HBV |
Standard
|
No
Occult HBV |
SD |
p
Value |
|
Mean age |
52.7 |