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Journal of Viral Hepatitis, 2012, 19 (Suppl.

3), 530

doi:10.1111/j.1365-2893.2012.01652.x

Poster Sessions
[Correction added after print publication: Poster abstracts P16, P23, P27, P31, P33, P37, P41, P50, P52, P54, P56, P60, P61,
P64 have been withdrawn.]

HEPATITIS C VIRUS
Diagnosis
P1
A novel multiplex diagnostic method for
hepatitis C virus using nanoporous sol-gel based
protein microarray
M Jo1, S Kim2 and H Lee3 1PCL Inc., Korea, 2Dongguk
University, Korea, 3Pohang University of Science and Technology,
Republic of Korea
PURPOSE OF THE STUDY: In the past decade, microarray
technologies have resulted in a paradigm shift in modern
biology. Microarrays enable high-throughput screening
(HTS) of disease-related molecules, including important signaling proteins/peptides and small molecules in low abundance. In this study, we applied nanoporous sol-gel based
protein microarray to multiplex diagnosis for blood screening.
The sol-gel technology has initially been developed to capture
enzymes in their active form for longer period. However, this
technology has not been widely used to capture antigen
markers for antibody detection because of several limitations
such as non-specific interaction between smaller immobilized
antigen and larger interacting antibody. Kim et al. (Anal Chem
2006; 78: 73926) have pioneeringly developed sol-gel
material screening technology to find novel formulation for
optimizing protein-capturing capacity, lower background and
superior protein arrays physical characteristics. Using this
novel formulation, we developed multiplex blood bank
screening platform for simultaneous detection of multiple
markers from hepatitis C virus (HCV) infection.
METHOD: For manufacturing protein microarray of HCV
detection, four different HCV antigens were individually mixed
with sol-gel solution, and spotted onto same well of 96-well
plate along with negative and positive control spots by noncontact type piezo arrayer. About 138 patients serum samples
which had been previously tested by HCV antibody screening
test and HCV Ab RIBA confirmatory test (83 HCV negative and
55 positive) were used. For assay platform, secondary antibody
conjugated with fluorescence (Cy3) was used, and signals
were detected with fluorescence scanner. Cut-off values [signal
to control (background) ratio] for each antigen were determined by a statistical method particle swarm optimization.
RESULTS: The sensitivity and specificity of multiplex detection platform were 100% for both, which is equal or higher
than that of ELISA in HCV diagnosis. Our system also
showed highly reproducible results. Additionally, this plat-

form was compatible with the currently employed automated system used for ELISA-based blood bank screening.
CONCLUSION: We have successfully applied novel screening
technology to multiplex HCV diagnosis with confirmatory testlevel accuracy. We believe that this result will significantly
advance the specificity and sensitivity for multiple disease
diagnostics in high-throughput blood bank screening field.

P2
The evaluation of the new ELISA kit EIA-antiHCV-SPECTRUM-M intended for separate
detection of anti-IgM to different HCV antigens
G Bochkova, S Fomina, V Puzyrev, A Obriadina,
A Burkov and T Ulanova RPC Diagnostic Systems, Russian
Federation
INTRODUCTION: The new kit EIA-anti-HCV-SPECTRUM-M
intended for separate detection of anti-IgM to different HCV
antigens was developed. The recombinant antigens comprising only diagnostically relevant regions of different
variants of native HCV proteins were selected.
AIM: The evaluation of the ELISA kit EIA-anti-HCV-SPECTRUM-M.
OBJECTIVES AND METHODS: The various sequences of recombinant antigens comprising HCV Core, NS3, NS4, NS5
were separately adsorbed on the plate. Diagnostic value of
the assay was studied by testing 205 samples with determined genotype 16; samples of 18 commercial seroconversion panels (BBI Inc., ZeptoMetrix), samples of the AntiHCV Mixed Titer Performance Panel BBI PHV 206 (BBI
Inc.), 190 samples from infants born to HCV-positive
mothers in dynamics, samples from patients with acute
(AHCV) (n = 35) and chronic (CHCV) (n = 439) hepatitis C.
Diagnostic specificity was studied by testing samples of
healthy blood donors (n = 1657), clinical patients
(n = 1278), pregnant women (n = 887).
RESULTS: The testing of the kit EIA-anti-HCV-SPECTRUMM showed that about 86.3% of anti-IgG positive samples of
patients with AHCV and CHCV have anti-IgM to one or more
viral antigens. Good correlation between the presence of
HCV RNA and the detection of anti-HCV IgM was revealed.
About 95.3% samples with the determined genotype have
anti-HCV IgM. More early seroconversion IgM than IgG was
detected for two panels BBI 908 and BBI 916(M). The first
one appeared anti-IgM to NS4. Anti-IgG were detected earlier than anti-IgM in 11 panels. In the rest five panels antiIgG were detected simultaneously with anti-IgM. More than

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

90% of samples from patients with CHCV contain more than


one marker of anti-HCV IgM. About 80% of patients with
CHCV have anti-HCV IgM to three or four antigens. All
samples from babies with AHCV diagnosed in the age of
35 months had anti-Core IgM alone or with anti-NS3 IgM
and were HCV RNA positive. The significant increase of antiCore IgM titers was specified to 910 months and anti-NS
IgM to 918 months and indicated to the development of
CHCV. The study also showed high specificity of the kit EIAanti-HCV-SPECTRUM-M.
CONCLUSION: The measurement of anti-IgM to different
HCV proteins may be important for diagnostics of perinatal
transmitted HCV infection and as a predictive factor of persistent infection.

house real-time PCR, 95% of samples were undetected and


only 5% were positive. Here we obtained 15 positives, 41
negatives and 104 inhibited results with Amplicor Roche
PCR-HCV. In samples analysed by real-time PCR eight results were positives, 0 (zero) inhibited and 152 negatives.
DISCUSSION/CONCLUSION: On the attempt of decreasing
the amount of inhibitors on the semen samples, the procedure of dilution series showed us more efficient results when
compared with Percoll. However, the great amount of
undetected results showed that the viral load might have
been diluted, leading us to the necessity of a more sensitive
technique. There was a significant difference between the
results of the Amplicor Roche PCR and real-time PCR. These
undetected results may have been a consequence of the
absence of the internal control on the real-time PCR reactions.

P3
Serial dilution of semen samples and better
results in HCV-PCR in patients with hepatitis
C infection
N Cavalheiro, A Santos, C Melo, F Tengan, J Levi,
C Rodrigues and A Barone University of Sao Paulo, Brazil
INTRODUCTION: The risk of transmission through seminal
fluid is considered in both the field of assisted reproduction
and STD.
OBJECTIVE: To investigate semen samples from patients infected with HCV and the interference of inhibitors for HCVPCR on the samples.
METHODS: A total of 27 men took part providing samples
and were divided into two groups: (i) 13 semen samples were
processed using a concentration gradient, Percol 90% and
45%, and the semen fractions analyzed were: total semen,
seminal plasma, white cells and sperm. The PCR-HCV
qualitative Amplicor Roche was used. (ii) For 20 patients,
seminal plasma samples were processed after serially diluted
1:2, 1:4 and 1:8 and analyzed by the Roche Amplicor HCVPCR and real-time in house.
RESULTS: All patients were HCV-PCR positive for serum
samples. The mean age was 40.7 years. Ten patients
(37.1%) did not present any apparent epidemiology, eight
(29.6%) reported injection drug use and inhalatory, six
(22.2%) blood transfusion, two (7.4%) had history of drug
use and blood transfusion and one (3.7%) was a health
professional. Genotypes were 1a, 1b, 1, 2b, 3a to 26.0%,
14.8%, 7.4%, 11.1 and 40.7% respectively. In 13 samples
processed with Percoll, 86.5% showed inhibited results. We
had 12 inhibitions and one positive result in the fraction of
the spermatozoa, 12 inhibitions and one negative in leukocytes, and nine inhibited and four negative samples in
seminal plasma. The Amplicor Roche method was used. In
the process of dilution series and PCR amplified by Amplicor
Roche, only 25.62% of samples showed inhibited results,
65% were undetected and 9.38% were positive. For in

P4
Particuliarities of the course of chronic
hepatitises of mixed viral etiology (HBV + HCV)
G Mirojov and A Dustov Institute of Gastroenterology of the
Ministry of Health, Tajikistan
AIM: Specifying

the leading role of HBV, HCV or


HBV + HCV at natural course of chronic hepatitis of mixed
viral etiology.
MATERIALS AND METHODS: Materials included the results
of clinical, biochemical, virology (PCR) and morphological
analyses of 48 patients (36 males and 12 females) with
chronic hepatitis of mixed viral etiology (HBV + HCV). The
average age is 38 years old.
RESULTS: During investigation of the detection ratio of HBV
DNA and HCV RNA in blood sera of 48 patients with
markers of both viruses (HBsAg and anti-HCV) we detected
the following. In 14 patients with presence of markers of
both viruses we detected only replication of HBV (virus
DNA > 100,000 copies/mL) and at the same time there was
no HCV RNA. HBV replication was more frequent (in 10
patients) at presence of HBeAg (wild virus). HCV RNA
detection frequency in patients with mixed infection was
higher and equal to 28 people. In six patients was weak
viremia (up to 30,000 copies/mL); in 12, average viremia
(up to 100,000 copies/mL) and in 10, high viremia (more
than 100,000 copies/mL). In six patients with chronic
hepatitis of mixed viral etiology (HBV + HCV) during PCR
investigation there was neither HBV DNA no HCV RNA. We
did not detect simultaneous replication of both viruses.
Clinical and biochemical features of the process activity
correlated with active replication of viruses and were expressed at chronic HBV (ALT 571.7 109.6) comparing
to HCV (ALT 259.9 42.5).
CONCLUSIONS: Thus, at chronic hepatitis of mixed viral
etiology (HBV + HCV) dominating is HCV, which suppresses
HBV replication and is less severe.

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Poster Sessions

Natural History and Epidemiology


P5

In vitro study of neutrophil apoptosis in chronic


hepatitis C patients
F Essawy1, I Khaled1, M El Ansary2, A Helmy1,
M Moustafa1 and A Ismail1 1Theodor Bilharz Research

P6
Evaluation of inflammatory activity on liver
biopsy of patients with chronic hepatitis C who
have recovered from HBV infection: a case series
study
G Lisboa Neto, N Cavalheiro and A Barone University of
Sao Paulo, Brazil

Institute, Egypt, 2Cairo University, Egypt


INTRODUCTION: Hepatitis C chronic infection is a public

HCV patients manifest with neutropenia and are predisposed to bacterial infections. This study aimed at detection
of neutrophil apoptosis in HCV patients. This study was
carried out on 45 subjects divided into: Group I (15 patients with chronic HCV without neutropenia), Group II
(15 patients with chronic HCV with neutropenia) and 15
normal controls matched for age and sex. Neutrophils were
separated using percoll density and cultured for 24 h to
detect apoptosis by flow cytometry using FITC, Annexin V/
propidium iodide dye(An/PI) to discriminate between normal, early, late apoptotic in addition to necrotic cells. Late
apoptosis was tested by detection of DNA fragmentation
using TUNEL. sFas expression was measured in neutrophil
culture supernatant by ELISA. The morphological features
of cultured neutrophil were examined by light and electron
microscopy. The results obtained showed that the percentage of viable cells (An)ve/PI)ve) was significantly reduced in Group II than the control and Group I, while the
apoptotic cells (An+ve/PI)ve and An+ve/PI+ve) were decreased in both the two patient groups compared to the
control. On the other hand necrotic cells (An)/PI+) were
significantly increased in Group II in comparison to the
control and Group I. The percentage of TUNEL positive cells
was significantly increased in Group I in comparison to
both the control and Group II. sFas was significantly increased in neutropenic as opposed to non neutropenic patients and the control group. LM and EM revealed apoptotic
changes in the control and the studied groups, however the
necrotic changes affected most of the cells in neutropenic
group. It could be concluded that FITC An/PI findings point
to reduction in the number of viable cells, disturbed early
and late apoptotic changes with increased percentages of
necrotic neutrophils. TUNEL test results matched with FITC
An/PI, while sFas being detected in culture supernatant
significantly detected increased neutrophil apoptosis. In
addition the EM findings point to the predominance of
necrotic changes in neutropenic patients. The predominance of the necrotic changes might be related to the
prolonged culture time, which might have caused the cells
to undergo secondary necrosis, thus masking the apoptotic
changes. Accordingly, further researches on larger scale of
patients, with adjustment of culture duration is essential for
more elaborate clarification of the role of neutrophil
apoptosis in HCV-related neutropenia.

health issue worldwide (WHO, www.who.int/mediacentre/


factsheets/fs164/en/index.html). Its clinical course may be
influenced by additional factors (Giannini et al. Liver Int
2003; 23: 1218). It is estimated that 20% of these patients
retain serological markers of previous hepatitis B infection
(Sagnelli et al. J Med Virol 2005; 75: 222226). In fact, HBV
persistence has been recognized even in state of previous and
so-called resolved infection (anti-HBcAg+/HBsAg)) (Sagnelli
et al. J Med Virol 2005; 75: 222226; Missiha et al. Gastroenterology 2008; 134: 1699714). Detectable HBV genome
in episomal form (cccDNA) and in extrahepatic sites supports
this hypothesis. However, its real impact on liver damage
remains unclear (Missiha et al. Gastroenterology 2008; 134:
1699714).
OBJECTIVE: To evaluate the influence of previous HBV
infection on liver necroinflammatory activity in subjects
with chronic hepatitis C, taking into account the estimated
length of HCV infection.
METHODS: This study retrospectively assessed medical records of adult patients with chronic HCV infection, consecutively attended at a hepatitis outpatient clinic over a full
year period (HC-FMUSP, Sao Paulo, Brazil). Subjects in
whom it was possible to determine the time length of HCV
infection to date of liver biopsy were eligible. Interface hepatitis was considered as end-point for analysis of inflammatory activity. Patients were stratified according to serologic
HBV status. HIV-infected patients and chronic active HBV
infection (anti-HBcAg+/HBsAg+) were excluded. Differences
between groups were tested by X2 or Fisher test for categorical data. Survival curves were compared using Mantel
Cox logrank test and Cox regression model for multivariate
analyses. A p-value of 0.05 was considered statistically significant.
RESULTS: Ninety-nine patients were enrolled in the study.
Forty-seven subjects (47.4%) had previous markers of HBV
infection (anti-HBcAg +/HBsAg)) and 23 were male (49%).
The median age was 45 years (IQR: 4154). The estimated
duration of HCV infection was 21.6 years (IQR:15.625.3).
There was no statistically difference between anti-HBcAg (+)
and ()) groups regarding development of interface hepatitis
(p = 0.764). This finding remained not significant after
adjustment for gender, age, insulin resistance and alcohol
intake (HR: 1.11, 95% CI: 0.641.93, p = 0.700).

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Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

CONCLUSION: Previous HBV infection does not appear to


influence liver inflammatory activity in this case series.
Genomic analysis of potential markers of HBV replication,
preferably in situ, may help to elucidate the pathogenesis of
residual HBV infection and its clinical impact in this setting.

P7
Association between monocytic tissue factor
(CD142) expression and diabetes in hepatitis
C-related liver cirrhosis
M Abuelmakarem1, M Eslam1, D Sayed2, M Shawkat1,
N Idriss3, H Abdelhailm1, M Sahrawi1, E Soliman1 and
S Elheney1 1Minia University Hospital, Egypt, 2South Egypt Cancer
Institute, Assuit University, Egypt, 3Assuit University, Egypt
BACKGROUND AND AIM: Both insulin resistance (IR) and
type 2 diabetes mellitus (T2DM) are associated with adverse
outcomes across all stages of chronic hepatitis C (CHC). The
mechanisms by which T2DM may worsen liver function are
not yet established. Immune status plays a pivotal role in
both clearance and progression of hepatitis C virus (HCV)
infection. Tissue factor (TF) is one of the proteins that participate in hemostatic, immune and inflammatory processes.
To test the hypothesis that T2DM contributes to clinical
outcome through changes of TF expression on monocytes in
HCV-related cirrhotic patients with T2DM, this study was
conducted.
METHODS: In HCV-related cirrhotic patients (139 diabetics
and 130 non-diabetics) and 110 controls; the flow cytometric analysis of CD14, TF (CD142), costimulatory molecules; CD86 and HLA-DR on monocytes were determined.
RESULTS: Cirrhotic patients with T2DM have increase in
CD14, the expression of monocytic TF and Cd86 in comparison with cirrhotic non-diabetic patients and healthy
controls. The monocytic expression of TF and CD86 increases significantly with increase of the stage of the childPugh score. The expression of HLA-DR is significantly lower
in cirrhotic patients than controls, while it shows no significant difference between diabetic and non-diabetic patients. Expression of this molecule is not influenced by
advancement of liver cirrhosis.
CONCLUSIONS: The monocytic TF as a significant link
connecting inflammatory and immunological phenomena
can partially explain a lot of events in HCV-related cirrhotic
patients with T2DM. Future target therapy against TF may
be beneficial for T2DM cirrhotic patients.

P8
Prevalence of hepatitis C virus infection in
Mashhad, a north-eastern city of Iran
K Ghazvini1, K Shamsian2, A Rezaee1, A Shamsian2,
H Bidkhori2, M Hedayati-Moghaddam2, S Ahmadi2,
F Fathimoghadam2, H Rafatpanah1, M Dehghan

Nayeri1 and K Ghazvini1 1Mashhad University of Medical


Sciences, Iran, 2Academic Center for Education, Culture & Research
(ACECR), Mashhad Branch, Iran
BACKGROUND: There is no overall estimate of hepatitis C
infection (HCV) in north-east of Iran. We have performed
this research in order to accurately estimate the prevalence
and risk factors of HCV infection among general population
in Mashhad.
METHODS: During 2009, 1678 healthy individuals including
763 men and 915 women with mean age of 29.1 18.5 years
old, were selected randomly by multistage sampling (stratified,
cluster, systematic, simple) from every geographical region of
the city. ELISA was used to screen for antibodies and the positive samples were tested by RT-PCR.
RESULTS: Overall prevalence of HCV infection was 0.4% (six
men and one woman). HCV infection was associated with
sex, age, marital status and history of blood transfusion,
surgery, tattooing and hospitalization.
CONCLUSIONS: In comparison with similar studies, the
prevalence of HCV infection in Mashhad is low. This might
be a result of having prevention programs for high-risk
groups and strict blood-screening programs.

P9
Hepatitis C virus infection in the middle east and
north Africa MENA region: injecting drug users
an under-investigated population
S Ramia, N Melhem and K Kreidieh American University of
Beirut, Lebanon
PURPOSE: Investigation of injecting drug users (IDUs) pop-

ulation is becoming extremely critical and timely in light of


the recent evidence that IDUs now act as the core of hepatitis
C virus (HCV) epidemic in developed countries. The purpose
of this article therefore is not only to review the epidemiology
of HCV in the Middle East and North Africa (MENA) region
but also to see whether IDUs were adequately studied and
whether harm reduction strategies to be applied for their
protection have been set.
METHODS: Literature review was carried out on articles
published within the last decade on HCV infection.
RESULTS: The gathered data showed that the population of
IDUs is severely underinvestigated throughout the whole
region, possibly due to religious and cultural impediments.
CONCLUSION: In order to reduce the risk of HCV infection in
IDUs, a set of recommendations are advanced emphasizing
the urgent need for bio-behavioral studies in this population
to help identify the source and mode of transmission and the
genotypes of HCV involved. These results may allow the
development of effective and yet socially acceptable intervention strategies. We believe that the role IDUs play in
sustaining HCV infection is also an underinvestigated topic
in many developing countries. Similar reviews and hence
interventions should be initiated in these regions.

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Poster Sessions

Treatment and Late-Stage Clinical Trials (Phase


IIb, Phase III and Phase IV)

The study was aimed to evaluate the effect of autologous


transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis
C virus infection. Twenty-five patients with Child C liver
cirrhosis, MELD score >12 were included. They were divided
into two groups. Group I, the MSC group (n = 15); this
group was subdivided into two subgroups: Ia & Ib (undifferentiated and differentiated respectively). Group II (control
group; n = 10) involved patients with cirrhotic liver under
conventional supportive treatment. Ninety mL BM was
aspirated from the iliac bone for separation of MSCs. Surface
expression of CD271, CD29 and CD34 were analyzed using
flow cytometry. Hepatogenesis was assessed by immunohistochemical expression of OV6, AFP and albumin. Finally
approximately 1 million MSCs/kg were suspended in saline
and were placed in blood bag and injected slowly intravenously over 15 min at a rate of 5 drops/min in one session.
Follow-up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin
levels, decline of elevated bilirubin and MELD score in MSCs
group. Statistical comparisons between the two subgroups
(group Ia & Ib) did not merit any significant difference
regarding clinical and laboratory findings.
IN CONCLUSION: Bone marrow MSC transplantation either
undifferentiated or differentiated can be used as a potential
treatment for liver cirrhosis.

diagnostic, treatment and following the treatment response


is a big challenge for Pakistani population where the disease
is highly prevalent in relatively poor class. To estimate the
budget for HCV diagnostic, treatment and its followup, a
study was conducted in different local government hospitals
of Rawalpindi/Islamabad.
METHODS: The expenses for all tests i.e., ELISA-based, PCR
qualitative, PCR quantitative, HCV genotyping, liver function tests, complete blood picture, liver histopathology, liver
biopsy procedures etc were estimated from different hospitals. The data was also collected and budget was estimated
for their single day stay at hospital. The therapy cost was
also calculated for an average quality of interferon (both
standard and pegylated) available in the market.
RESULTS: The average income of a Pakistani is 100400
USD. The data showed that 138 USD is an average cost for
preliminary tests needed to diagnose HCV (i.e., ELISA-based,
PCR qualitative, HCV genotyping, liver function tests and
complete blood picture) and is above 319 USD if the qualitative PCR and histopathology are included. The single-day
stay at hospital costs about 1621 USD and the average stay
of HCV patients is 3 days per every admission. The therapy
costs about 765 USD in case of standard therapy and 3,718
USD for pegylated interferon therapy. Following the treatment response costs ~159213 USD. So a total of 1,381 USD
costs for standard treatment including diagnostic, conventional treatment and hospital admissions and ~4,249 USD in
case of pegylated interferon. Such a high cost of diagnosis
and treatment hinders the people with low monthly income
i.e., 100400 USD per month where mostly the head of the
family is only the supporter for their living. A significant
percentage dies due to either late diagnosis of HCV or failure
to undergo treatment course due to financial constraints.
CONCLUSION: High HCV diagnostic and treatment cost
prevents the low income class to save their lives from a
curable infection. Need is to facilitate the low income nations
to help prevent such infections and also introduce costeffective treatment packages for the poor people who cant
afford the HCV-induced financial burden.

Practical Management Strategies

P12

P10
Phase II trial: undifferentiated versus
differentiated autologous mesenchymal stem cell
transplantation in Egyptians with HCV induced
liver cirrhosis
I Khaled1, M El Ansary2, A Saleh1, S Toema1,
O Hammam1 and S Mogawer2 1Theodor Bilharz Research
Institute, Egypt, 2Cairo University, Egypt

P11
HCV, financial burden and a low income
country: Pakistan
R Khan1, H Bashir2, A Altaf3, I Khawar4, A Gul5 and
Q Bashir6 1Military Hospital, Pakistan, 2Combined Military Hospital,
Pakistan, 3General Headquarters, Pakistan, 4Kampala International

Effects of lidocaine 3% gel delivered rectally in


ano rectal dysfunction induced by telapravir in
chronic hepatitis C. A randomized control study
P Basu1, T Nair1, S Farhat1, L Ang1, M Jafri2 and
N James Shah1 1NS/LIJ Forest Hills, USA, 2New York Medical
College Richmond, USA

University, Uganda, 5Quaid-E-Azam University, Pakistan, 6National

OBJECTIVE: Telapravir is a potent protease inhibitor, which

University of Sciences and Technology, Pakistan

causes anorectal dysfunction (ARD) comprising proctalgia,


rectal ulcers, hemorrhoids and rectal bleeding. Conventional
therapy is suboptimal causing treatment failure. This study
evaluates 3% topical lidocaine gel rectal delivery to abate the
drug related ARD to avoid treatment failure.

PURPOSE OF THE STUDY: Hepatitis C victimized about 4% of

Pakistani population with one quarter population classified


as poor and about 17.2% are living below poverty line and
are facing new challenge i.e., infectious diseases. The HCV

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10

Poster Sessions

METHODS: 52 patients (mean age 51) were recruited


undergoing therapy with telapravir, peginterferon and ribaviran for CHC-C. 45/52 (86%) with rectalgia, 8/52 (15%)
rectal ulcers, hemorrhoids 19/52 (36%) with bleeding 6/19
(31%) without bleeding 13/19 (68%). Group A (n = 17)
placebo Group B (n = 17) hydrocortisone 2.5% cream and
Group C (n = 18) lidocaine 3% gel foam rectally twice daily.
All underwent pre- and post-proctoscopic evaluation and
ano-rectal manometry.
RESULTS: Rectalgia resolved in 3/17 (17%), 8/17 (47%) &
7/18 (94%) for Group A, B & C respectively. Rectal ulcers
healed in 0/2 (0%), 1/3 (33%) & 2/3 (66%) for all the above
groups. Hemorrhoids resolved in 1/6 (16%), 2/6 (33%) & 5/
7 (71%) in all groups. Pre-/post-proctoscopy revealed normal mucosal integrity 4/17 (23%), 7/17 (41%) and 17/18
(94%) above groups. AR manometry results showed pre-/
post-treatment high sphincter tone >4 mm in Group A 2/15
(8%) and no differences in pre- and post-treatment, Group B
7/15(41%), 4/15 (22%) and Group C 5/15 (20%), 2/15
(10%) respectively. Side events: numbness, 4/17(23%) in
lidocaine.
CONCLUSION: Rectally delivered lidocaine 3% gel is efficacious, tolerable compared to the SOC and placebo for ARD
causing treatment failure, retention & SVR. Larger trial
needs to validate this finding.

continuing with PEG/RBV for a total 48 weeks. Chelation


protocols were enhanced for management of increased iron
overload with deferasirox and deferoxamine.
RESULTS: During the course of drug treatment, these notable events occurred: (i) At week 7, GCSF added in response to
absolute neutrophil count 0.2 000/mm3, (ii) At week 8, RBV
was decreased to 80% dose to reduce transfusion requirement, (iii) At week 31, PEG was decreased to 135 mcg for
platelets <50K and (iv) At week 42, PEG was decreased to
90 mcg and Zoloft increased for depression. Chelation was
ongoing with only fair compliance. Anemia and iron overload created concern in these areas: (i) transfusion requirement increased 29%, (ii) liver iron increased sixfold to
25 mg/g dry weight, (iii), cardiac MRI T2* decreased to
12 ms showing increased cardiac iron but LV ejection remained stable at 58% and (iv) Ferritin increased by 30%.
Virus levels declined to undetectable by week 6 and remained undetectable at end of therapy (48 weeks May,
2012).
CONCLUSIONS: Thalassemia major patients with HCV can
be safely treated by triple therapy, Boc/PEG/RBV, with close
monitoring of blood indices, iron overload and cardiac
function. Psychological factors and patient motivations
proved critical to our clinical success, and we recommend
both educational and psychological support.

P13
Practical management of HCV genotype 1a in B
thalassemia major with triple therapy
M Minor, P Harmatz, J Fuentebella, D Haines, A Lal
and E Vichinsky Childrens Hospital & Research Center Oakland,

P14

USA

International University, Uganda, 2Combined Military Hospital,

BACKGROUND: Treatment of hepatitis C virus (HCV) geno-

Pakistan, 3Military Hospital, Pakistan, 4National University of Sciences


and Technology, Pakistan

type 1a with boceprevir (Boc) in combination with peginterferon (PEG) and ribavirin (RBV) yields improved viral
responses and more frequent cures. One of the few drawbacks to Boc use is the higher frequency of associated anemia. Patients with thalassemia major often acquire HCV
through transfusion therapy, and treatment of HCV in
thalassemic patients with PEG/RBV has already been shown
to necessitate an increase in transfusions by 3040% and
requires careful patient management. We report our experience with triple therapy in a thalassemic patient with HCV.
PATIENT

DESCRIPTION

AND

THERAPEUTIC

PROTO-

COL: RA is a 23 year old Iraqi woman with beta thalasse-

mia major, PTSD and transfusion-acquired HCV genotype


1a. Relevant clinical features are HCV 835,000 lU/mL, liver
biopsy grade 23 Stage 3, IL28b haplotypes C/T and T/T,
and iron overload from transfusions, cardiac MRI T2*
16 ms, LV ejection 56%, liver iron 3.9 mg/g dry weight, and
ferritin 2880 ng/mL. The AASLD guidelines for HCV treatment using Boc/PEG/RBV were modified for iron overload
and fibrosis by extending the Boc treatment to 32 weeks and

HCV awareness among new generation in


Uganda: possible risk for HCV high prevalence
I Khawar1, H Bashir2, R Khan3 and Q Bashir4 1Kampala

PURPOSE OF THE STUDY: Hepatitis C virus (HCV) is a global


health issue needs to be addressed in countries like Uganda.
Insufficient awareness and knowledge among young generation is important contributing factor towards rapid viral
spread in Uganda. So to determine the level of awareness
about HCV and its correlation with infection spread an
awareness survey was carried out in young generation of
Kampala, Uganda.
METHODS: A questionnaire-based study was conducted.
Each student was given a HCV awareness brochure which
they returned after filling it. Data was gathered and analyzed
statistically using SPSS.
RESULTS: Study showed insufficient basic knowledge of
HCV. About 50% of the students were not aware of the risk
factors associated with HCV, routes of HCV transmission,
HCV treatment and diagnosis. Students had misconception
regarding vaccination against HCV. They also had significantly insufficient knowledge regarding symptoms associated with HCV.

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

P16
Detection of HCV RNA in the peripheral blood
mononuclear cells of serum HCV RNA-negative
Egyptian patients under interferon treatment
R Zayed, D Saleh and E Rushdy Faculty of Medicine, Cairo

P15
Intrahepatic expression of interferon alpha
receptor 1 (IFNAR1) in hepatitis C patients
resistant to interferon therapy
Q Bashir1, A Rashid1, A Naveed1, R Khan2, G Trali1
and A Gul3 1National University of Sciences and Technology,
Pakistan, 2Military Hospital, Pakistan, 3Quaid-E-Azam University,
Pakistan
PURPOSE OF THE STUDY: Hepatitis C virus (HCV) has infected >3% of the worlds population and ~4% of the Pakistani population. It is the leading cause of liver cirrhosis and
hepatocellular carcinoma (HCC) if not cured. The only
widely used approved therapy for the disease is pegylated
interferon alpha with response rate in ~50% of the patients.
The disease becomes incurable or resistant because of a
number of factors including both viral and cellular. So a
study was designed to investigate the intrahepatic expression
of one of the cellular factor i.e. interferon alpha receptor 1
(IFNAR1) which is the first molecule to trigger intracellular
cascade to combat the virus.
METHODS: The study was first approved from Institutes
Ethical Committee. Liver biopsies (using ultrasound-guided
liver biopsy technique) and blood from 30 HCV patients
that were resistant to interferon therapy and five patients
who responded to therapy (as control) were taken after
patients informed consent and under sterile conditions.
Blood was used to carry out blood CP (complete picture),
liver function tests (LFTs), viral load determination, HCV
genotyping and pre-biopsy tests. The patients with genotype 3 were selected as it is the most common HCV
genotype that exists in Pakistan. The biopsy sample was
divided into two parts, one was analyzed for liver histopathology and the other part was subjected to PCR-based
detection of IFNAR1 mRNA.
RESULTS: Results showed that about half of the interferon
resistant HCV patients i.e. 46.67% (14 out of 30 nonresponders) lacked the intrahepatic expression of IFNAR1.
CONCLUSIONS: The investigation might prove to be helpful
in developing a predictive assay for interferon resistance and
also a way forward for development of therapeutics to
treat the patients with IFNAR to initiate a natural
signaling cascade to combat virus in IFNAR-deficient HCV
patients.

BACKGROUND: Despite recent success after the introduction


of combination therapy with IFN-a and ribavirin, about 60%
of patients with HCV genotype 4 fail to respond. Resistance
to antiviral therapy remains a serious problem in the management of chronic hepatitis C. In most patients, HCV RNA
could be detected in peripheral blood mononuclear cells
(PBMC).
PURPOSE OF THE STUDY: The aim of this study was to
investigate the predictive value of HCV RNA in PBMC of
patients with chronic hepatitis C after interferon treatment
which may act as the source of HCV re-infection of the hepatic cells.
METHODS: Seventy patients with chronic hepatitis C were
treated with interferon plus ribavirin for 48 weeks, and they
all achieved clearance of HCV RNA from serum. At the end
of treatment, PBMC and serum were examined by real-time
PCR for detection of HCV RNA. Six months later, HCV RNA
in serum was monitored to detect sustained virological response.
RESULTS: Analysis of the PBMC by real-time PCR revealed
the presence of detectable HCV RNA in the PBMC of 27% of
patients in spite of clearance of serum HCV RNA. During
follow up, 80% of the patients who became serum HCV
positive 6 months after the end of treatment had detectable
level of HCV RNA in PBMC at the end of treatment.
CONCLUSIONS: The absence of HCV in the serum of patients
with chronic hepatitis C by the end of treatment does not
exclude viremia. The patient might still be a source of
infection to others. Special considerations should be taken
for the blood transfusion and mother-to-child transmission.
It is thus mandatory to test for HCV in PBMC to detect lack of
response to treatment and persisting infection.

WITH

Treatment Monitoring and Predictors of


Therapeutic Response

D RA W

University, Egypt

CONCLUSION: Insufficient basic knowledge regarding HCV


among young generation is an important contributing risk
factor for HCV prevalence. Need is to educate our young
generation regarding risk factors to help prevent HCV as part
of HCV management strategies.

11

P17
IFN-a receptor 2 (IFNAR2) expression and
interferon resistance in HCV patients
G Trali1, A Naveed1, A Rashid1, A Gul2, R Khan3 and
Q Bashir1 1National University of Sciences and Technology, Pakistan,
2

Quaid-E-Azam University, Pakistan, 3Military Hospital, Pakistan

PURPOSE OF THE STUDY: IFN-a is being used as a thera-

peutic target for viral infections including HCV and HBV for
more than 25 years. Interferon-a/b (IFN-a/b) resist intracellular pathogens by activating innate and adaptive immune response cells involved in infection. IFN-a receptor
(IFNAR) is a heterodimer with two subunits i.e. R1 and R2.
IFN-a receptor dimerizes on interaction with ligand and in

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

12

Poster Sessions

turn activates intracellular cascade (Huber et al. 2011;


Immunology 132: 46674). The mechanism establishes an
antiviral state within virally infected cells which directly
inhibits replication of the virus. The current standard
treatment for HCV has successful rate in ~50% patients
(Vezali et al., 2011, Expert Opin Biol Ther, 11: 30113) due
to a number of viral and cellular factors so we designed a
study to monitor the expression of a cellular factor i.e., IFN-a
receptor 2 in liver biopsies of interferon-resistant HCV patients.
METHODS: Liver biopsies and blood samples were collected
from interferon-resistant HCV patients. Liver histopathology,
HCV load, HCV genotype, liver function tests were monitored. Total mRNA was isolated from the liver biopsies and
subjected to cDNA synthesis. Primers specific to functional
isoform of IFN-a receptor 2 were designed and used for PCRbased detection in liver biopsies.
RESULTS: The IFN-a receptor was detected in 80% of interferon-resistant HCV patients with mild to severe liver histopathology.
CONCLUSIONS: The lack of expression of functional IFN-a
receptor 2 is not the major cause of interferon resistance in
HCV patients.

P18
Interferon therapy shifts natural killer subsets
among Egyptian patients with chronic hepatitis
C
A Fathy1, L Metwally1, M Abdel-Rehim1, G Essmat2,
M Eida3 and M Mohy Eldeen1 1Suez Canal University, Egypt,
2

Cairo University Hospitals, Egypt, 3Taibah University, Saudi Arabia

Natural killer cells can be divided into five subpopulations


based on the relative expression of CD16 and CD56 markers.
The majority of natural killer cells are CD56dim, which are
considered to be the main cytotoxic effectors. A minority of
the natural killer cells are CD56bright, and function as an
important source of immune-regulatory cytokines. Shifts of
these subsets have been reported in patients with chronic
hepatitis C virus infection. We sought to investigate the shift
of natural killer subsets among Egyptian patients with
chronic HCV and to analyze the influence of interferon
therapy on this shift. We applied a flow cytometric analysis
of peripheral blood natural killer subsets for 12 interferonuntreated and 12 interferon-treated patients with chronic
HCV, in comparison to 10 control subjects. Among interferon-untreated patients, there was a significant reduction of
CD56-16+ (immature natural killer) cells. Among interferon-treated patients, the absolute count of natural killer
cells was reduced, with expansion of the CD56bright subset
and reduction of the CD56dim16+ subset. Natural killer

subset counts were not significantly correlated to HCV viral


load and were not significantly different among interferon
responders and non-responders. In conclusion, HCV infection in Egyptian patients has been observed to be statistically
and significantly associated with reduction of the CD5616+NK subset, while a statistically significant expansion of
CD56bright and reduction of CD56dim16+ subsets were
observed after interferon therapy. Further studies are required to delineate the molecular basis of interferon-induced
shift of natural killer subsets among patients with HCV.

P19
Plasma TIMP-1 concentration in patients with
chronic hepatitis C treated with PegIFN and
ribavirin
A Prztbyla Medical University of Lublin, Poland
Literature shows that proteins involved in metabolism of
connective tissue as tissue inhibitor of metalloproteinases 1
(TIMP-1) among others, are detected in circulation and may
be useful as serum markers of fibrosis during chronic HCV
infection. Aim of the study was to assess the impact of
therapy with pegylated interferon alpha and ribavirin on
TIMP-1 concentrations according to achieve a sustained
virological response (SVR) and its usefulness in monitoring
the effects of antiviral treatment. Study group included 54
chronic hepatitis C (chc) patients (25 females, 29 males),
aged from 21 to 57 years (mean 37 years), infected with
genotype 1 and homogenic liver biopsy Metavir results.
Treatment with pegylated IFN alpha and ribavirin according
to guidelines was conducted for 48 weeks. Plasma TIMP-1
concentrations were determined by enzyme immunoassay
method using ready kit Human TIMP-1 Instant ELISA twice
at the beginning of therapy and 6 months after treatment.
Results were analyzed according to of SVR achievement at
6 months after completion of therapy. In the group of 26
(48%) patients with SVR there were no statistically significant differences between TIMP-1 concentrations before and
after treatment. In 28 (52%) patients who did not achieve
SVR, TIMP-1 concentrations obtained after treatment were
significantly higher than the values of TIMP-1 before treatment (p < 0.001) Comparative analysis of results in groups
of patients according to SVR revealed that plasma TIMP-1
concentrations were significantly higher in patients with a
lack of virologic response after treatment (p < 0.001). At
6 months after therapy an increase in concentration of
TIMP-1 in patients who did not receive SVR was noted. The
predominance of inhibiting fibrinolytic activity of TIMP-1
may indicate a progression of liver fibrosis in these patients.
The concentration of plasma TIMP 1 may be useful in
assessing effects of antiviral treatment in patients with chc.

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

P20
ETR and SVR: pegylated interferon versus
standard interferon
R Khan1, H Bashir2, I Khawar3 and Q Bashir4 1Military
Hospital, Pakistan, 2Combined Military Hospital, Pakistan, 3Kampala
International University, Uganda, 4National University of Sciences and
Technology, Pakistan
PURPOSE OF THE STUDY: Hepatitis C virus (HCV) has vic-

timized 10 million Pakistani population and ultimately results


in liver cirrhosis and hepatocellular carcinoma in non-cured
patients. Interferon (IFN) is the main widely used treatment
throughout the world to treat HCV but it fails to produce any
anti-HCV effects in about 50% of the patients because of a
number of viral or host factors. So a study was designed to
determine the response rate to IFN therapy in HCV patients.
METHODS: Patients were included in the study after their
willingness and they signed the consent form. Before starting
treatment, the viral load, HCV genotyping and liver function
tests were done. Therapy was started i.e., both with standard
therapy and pegylated interferon. After interferon therapy
course completion, the patients were followed for at least 6
12 months to check any relapse case.
RESULTS: Results showed that HCV patients treated with
pegylated interferon showed end-of-treatment response
(ETR) about 8290% and sustained virological response
(SVR) 7580%, whereas standard IFN-treated patients
showed ETR 70% and SVR 4555%.
CONCLUSION: Pegylated interferon showed high ETR and
SVR as compared to the standard therapy.

Preclinical and Early Clinical Development


(Phase I and Phase IIa)

13

nate new therapeutic options are needed. The use of fluvastatin (FLV), HMG-CoA reductase inhibitor, has been
proposed to inhibit HCV-RNA replication and improve
therapy outcome. The study aims to assess the impact of
addition of FLV (80 mg/d) to SOC on early viral kinetic response in HCV genotype 4 patients.
METHODS: In a prospective, randomized trial, 30 consecutive patients treatment-nave, non-diabetic CHC genotype
4 patients; receiving either ST (n = 14), or receiving SOC
plus FLV (n = 16). Standard doses of Peg IFN/RBV were
given to all pts. FLV was given simultaneously with SOC
for those assigned to the triple regimen. According to
guidelines, treatment was decided to be stopped in patients
without early virological response (EVR) or HCV-RNA
positive at week 24. HCV RNA level were measured
immediately before first Peg IFN/RBV dose (day 0) then at
days 1, 7, 14, and 28 of therapy. Virological response was
assessed by both intention-to-treat (ITT) and per protocol
analysis.
RESULTS: Demographic, clinical, IL28B genotype and histological characteristics as well as baseline HCV RNA was
comparable in all groups. Patients receiving the triple
regimen had greater log decline at each time point compared to pts on SOC [day 1 (1.6 versus 0.3 log), day 7
(1.72 versus 0.96 log), day 14 (2.5 versus 1.2 log), day
28 (5.6 versus 3.4 log)]. By first week, two pts receiving
ST + FLV cleared HCV RNA completely, while none of pts
receiving ST did that. By the second weeks; 5 pts receiving
ST + FLV cleared HCV RNA completely, while still none of
pts receiving ST did that. Rapid virologic response (RVR)
occurred in 11/16 (68.7%) of pts receiving ST + FLV
while this was found only in 3/14 (21.4%) of pts receiving
ST (p = 0.01). No apparent adverse events associated with

P21
Fluvastatin improves early virologic kinetic
response to PEG IFN/RBV combination therapy
in hepatitis C genotype 4 nave patients: interim
analysis
M Khattab, M Eslam, M Sharawe, S Elheny, A Kamal,
G Elsaghir, H Abd Elhalem, F Mokhtar and O Ashraf
Minia University Hospital, Egypt
BACKGROUND & AIMS: Fewer than half of patients (pts)
infected with hepatitis C virus (HCV) achieve sustained viral
clearance using standard of care therapy for HCV (SOC) with
peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. Alter-

Fig. 1 Rate of negativity of HCV-RNA in both groups


patients.

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

14

Poster Sessions

concomitant FLV occurred. A high LDL level (OR 1.98,


95% CI 1.962.2, p = 0.05) were independently associated with RVR.
CONCLUSIONS: Fluvastatin given adjuvant to SOC in HCV
genotype 4 pts is safe and improves viral kinetic response
during the first 4 weeks of therapy. Baseline elevated LDL
levels were associated with higher RVR rates. These positive
findings led us to expect that addition of fluvastatin to SOC
therapy for HCV may improve SVR rates as well.

Direct-acting Antiviral Combinations

CONCLUSION: This quadruple truncated regimen has excelled the RVR, ETVR over SOC with DAAs over 13%,
without any difference between 24 weeks of NTZ over 12.
Needs a larger trial for validation.

Other
P23
Envelope protein 2 phosphorylation sites (S75
and S277): a possible site for resistance to HCV
interferon therapy
S Afzal and M Idrees University of the Punjab, Pakistan
PURPOSE OF STUDY: Hepatitis C is a major health problem

NS/LIJ Forest Hills, USA

OBJECTIVES: Chronic hepatitis C is a global challenge with


end-stage liver disease and rising hepatocellular carcinoma.
Peginterferon alfa and ribavirin was the backbone of therapy. Recently introduced directly acting antivirals (DAAs)
protease inhibitor has a promising role in escalating sustained viral response (SVR) in response guided therapy in
non-responders, partial and relapses. This study utilized nitazoxanide (NTZ) and telapravir, with SOC for 24 weeks in
treatment experienced patients.
METHODS: Fifty (n = 50) patients were divided into Group
A (n = 12) NTZ 500 mg three times for 12 weeks, Group B
(n = 12) NTZ 500 mg twice daily for 24 weeks, Group C
(n = 26) control. All received peginterferon alfa 2a 180 mcg
SQ QOW with fixed dose of ribavirin 1200 mg daily for
24 weeks with telapravir 750 mg three times daily for
12 weeks. Viral load was obtained at day 0, 7th day, 14th
day, 4 weeks, 12th week and 24 weeks. Viral kinetics was
analyzed. In Group A: 5/12 (42%) non-responder, 6/12
(50%) partial responder, 2/12 (16%) relapsers. In Group B:
5/12 (42%) non-responders, 6/12 (50%) partial responder,
1/12 relapsers (8%). In Group C: 10/26 (38%) non-responder, 10/26 (38%) partial responder, 4/26 (15%)
relapsers, 2/26 (8%) unknown. Exclusion: decompensated
cirrhotic, HCC, poor DM, hemolytic anemia, severe coronary
artery disease, major depression, renal failure, Prior severe
skin rash, active drug and alcohol abuse. Side effects: anemia
28/50 (56%), neutropenia 14/50 (28%), thrombocytopenia
8/50 (16%), fatigue 34/50 (68%), depression 10/50 (20%),
mild skin rash 22/50 (44%), severe skin rash 1/50 (2%). Use
of growth factors: Epogen 12/50 (24%), Neupogen 8/50
(16%), eltrombopag 5/50(10%).

affecting more than 200 million individuals in world including Pakistan. The mechanism how HCV induces interferon
resistance is still indefinable. HCV genotype 1a shows greater
hindrance to treatment than genptype 3a. One of the mechanisms by which virus evades the antiviral effect of interferon
alpha involves that HCV envelope protein 2 (E2) interacts with
PKR which is the interferon-inducible protein kinase and
which in turn blocks the activity of its target molecule called
eukaryotic translation initiation factor elF2a. Sequence
analysis of E2 of HCV genotype 1a reveals it contains a domain
known as PePHD domain. This domain in genotype 1 strains is
reportedly homologous to PKR and its target eIF2a. Thus
envelope protein competes for phosphorylation with PKR. By
binding to PKR, PePHD inhibits its activity and therefore cause
virus to evade antiviral activity of interferon (IFN). In present
study the possible role of phosphorylation was investigated in
E2 protein for interferon resistance.
METHODS: Envelope protein coding genes were isolated from
local HCV isolates, cloned and sequenced. Tertiary structure
of E2 gene was predicted. These were analyzed by Scansite
and finally six sites were predicted by both servers. An online
server NetSurfP was used to find the surface accessibility of
local envelope sequence. Discovery Studio and SWISS PDB
Viewer were applied to visualize 3D protein structure of the
putative sites. PDB structure was built up by using the server
I-TASEER (Ab-initio protein structure predictor).
RESULTS: Insilico phosphorylation of tertiary structures revealed that two residues 75 and 277 of E2 gene are surfaceexposed at cytoplasmic domain and can compete with the
phosphorylation of PKR protein. This brings forward a possible relation of E2 and PKR through a mechanism via
which HCV evades the antiviral effect of IFN. A hybrid insilico and wet laboratory approach of motif prediction, evolutionary and structural analysis has pointed out serine 75
and 277 of the HCV E2 gene as a promising candidate for the
serine phosphorylation.
CONCLUSION: It is proposed that serine phosphorylation of
HCV E2 gene has significant role in interferon resistance.
Recognition of these nucleotide variations can help out to
suggest genotype-specific therapy to avoid and resolve HCV

D RA W

Peginterferon alfa, nitazoxanide, telapravir,


ribavirin, in genotype 1 prior experienced
chronic hepatitis C patients a randomized
clinical pilot trial
M Jafri1, P Basu2, T Nair2, S Farhat2, N James Shah2
and K Mittimani2 1New York Medical College Richmond, USA,

WITH

P22

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

15

infections. This work will also help to identify factors that


favor a successful innate immune response against HCV
infections.

CONCLUSION: It is concluded that serum RL may be considered an additional useful parameter for monitoring hepatic fibrosis progression in HCV infected patients.

P24

P25

Value of reelin as parameter for monitoring


hepatic fibrogenesis in a group of Egyptian
HCV-infected patients
S Mansy, M Nosseir, M Zoheiry, M Othman,
M Hassanein, M Guda, H Yehia and H Abotaleb Theodor

Protective effect of HCV infection on renal


anemia
Z Dimitrijevic, K Paunovic and B Mitic Clinical Center Nis,

Bilharz Research Institute, Egypt


PURPOSE: Chronic hepatitis C is characterized by significant

liver fibrosis which progress to cirrhosis. Non invasive


techniques for the prediction of the different stages of fibrosis
are important for monitoring hepatic fibrogenesis especially
for the evaluation of antifibrotic treatment. The present work
investigates the value of reelin (RL) which is an extracellular
matrix protein secreted by stellate cells (SC) as marker for
monitoring hepatic fibrogenesis in comparison with the
readily available non-invasive biomarkers: aspartate aminotransferase (AST) to platelet ratio (APRI), AST to alanine
aminotransferase ratio (AAR), FIB-4 and serum hyaluronic
acid (HA).
METHODS: 74 cases positive for serum HCV RNA and
hadnt any additional cause of chronic liver or organic diseases were enrolled in this study. They were subjected to
blood and liver biopsies collection according the rules of
Declaration of Helsinki. Fifteen healthy volunteers constituting the control group were subjected only to blood sample
collection. The collected samples were subjected to: quantitative measurement and the semi-quantitative immunohistochemical assessment of human RL in the harvested serum
and the corresponding liver sections respectively; study the
distribution of SC at an ultrastructural level; staging of
fibrosis using Metavir scoring system; morphometric image
analysis of hepatic fibrosis; quantitative measurement of
serum HA, AST, ALT and platelet count. Also the sensitivity,
specificity, negative predictive value (NPV), positive predictive value (PPV), the receiver operating characteristic curve
(AUROC) are statistically calculated to evaluate the performance of the serum RL as a diagnostic test for the discrimination between mild (F0-F1), significant (F2-F3) and
cirrhosis F4, versus Fib-4, APRI, AAR and HA.
RESULTS: The quantitative values of serum RL correlated
significantly with: the corresponding semi-quantitative
assessment of RL immunoreactive cells, the stage of fibrosis,
the morphometric image analysis of liver fibrosis, and serum
HA. The sensitivity, specificity and PPV of RL at a cutoff
value 0.21, AUROC 0.57 for predicting mild stage of
fibrosis (F0-F1) were 83%, 59% and 84% respectively. While
for predicting significant fibrosis (F2-F3) was 80%, 65% and
84% respectively.

Serbia and Montenegro


BACKGROUND: Hepatitis C virus (HCV) infection is major

cause of chronic liver disease among patients on chronic


hemodialysis (HD), despite the important reduction in risks
obtained by use of recombinant erythropoietin (rHuEPO)
instead of blood transfusions to treat anemia. However,
studies regarding effects of HCV infections on anemia in
these patients remain inconclusive. The aim of our investigation was to evaluate the effect of HCV infection on anemia
in our HD population.
PATIENTS AND METHODS: Retrospective study was carried
out from January 2005 to December 2011. Forty-six HCVpositive patients and 58 hemodialysis patients without
hepatitis C were assessed for a 12-month period by monthly
lab results for the hemoglobin levels, iron stores, and
transaminase levels. Their requirements for rHuEPO and
intravenous iron were also analyzed monthly.
RESULTS: There was no difference in age, sex, time on
dialysis, distribution of primary renal diseases, albumin and
parathormone levels between HCV(+) and HCV()) patients.
Anti-HCV-positive patients required significantly lower
rHuEPO doses (14,287 11,304 U/month) in comparison
with the HCV()) group, which required 27,114 18,266
U/month (p < 0.001). The similar observation was found for
the parenteral iron supplementation (102.8 10.2 mg
versus 250 32.5 mg/month, p < 0.001). The mean
hemoglobin level in hepatitis patients (10.24 1.03 g/dL)
and control group (10.06 1.12 g/dL) did not differ significantly (p = 0.24).
CONCLUSION: The patients with HCV have lower requirement for exogenous erythropoietin replacement compared
with HCV-negative patients. Greater erythropoietin production by HCV-infected liver could be a possible explanation.

P26
Producing of HCV-like particles in alphaviral
expression systems
E Aleksejeva, I Sominskaya, J Jansons, K Spunde and
T Kozlovska Latvian Biomedical Research and Study Centre, Latvia
Effective therapeutic and prophylactic anti-HCV vaccines do
not exist until now due to the genetic variability of HCV and
its ability to adapt to selective pressure, such as immunological recognition and antiviral treatment. Unfortunately,
investigation of HCV biology has been hampered by the lack

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

P27

AWN

Tissue factor expression on blood monocytes in


patients with chronic liver disease
L El Messery1, R Zayed1, N El Bassiouny2 and O Badr2
Faculty of Medicine, Cairo University, Egypt, 2Theodor Bilharz

Research Institute, Egypt

BACKGROUND: Monocytes play a crucial role in the path-

WITH
DR

ogenesis of inflammation and fibrosis in chronic liver diseases. Activated monocytes increase expression of TF that
participate in haemostatic and inflammatory processes.
PURPOSE OF THE STUDY: To assess the expression of tissue
factor on activated peripheral blood monocytes in patients
with HCV induced chronic liver disease and its relation to
the degree of hepatic insufficiency and haemostatic imbalance.
METHODS: The study was conducted on 60 patients classified according to Child Pugh classification into Child A (15
patients), B (15 patients), C (15 patients) and Child C during
acute attack of haematemesis (15 patients). Fifteen healthy
subjects served as normal controls. Immunophenotype

characterization was carried out by flow cytometric analysis


for identification of monocyte tissue factor expression
(CD142) on activated blood monocyte population (CD11b
and CD14) in different groups studied.
RESULTS: Data demonstrated significant increase in the
expression of each of CD11b, CD14 and CD142 revealing
monocyte activation and increased expression of tissue factor on peripheral blood monocytes in different groups of
patients compared to healthy subjects, especially cases during acute attack of haematemesis.
CONCLUSION: Increased monocyte tissue factor expression
in patients with chronic liver may play a key role in the
intensification of the inflammatory and immunological processes in conjunction with activation of the coagulation
mechanisms. The interaction of all these phenomena may
trigger bleeding by perturbing the unstable haemostasis in
frail patients with chronic liver disease.

DRAW
N

of efficient and reliable in vitro systems for virus propagation.


The alphaviruses, due to high level expression, broad host
range, and cytoplasmic replication provide an opportunity to
develop a model system for HCV investigation in cell
cultures. Semliki Forest virus (SFV) (Liljestrom and Garof.
Biotechnology (NY) 1991;12:135661) and Sindbis virus
(Xiong et al. Science 1989; 243:118891) are alphavirus
expression species that are most commonly used for developing of already existing genetic vaccines, which have
greater efficacy than conventional genetic vaccines. The aim
of our research is the development of the newer types of HCV
vaccine candidates, based on the general concept that one or
several structural genes of the HCV are incorporated into the
genome of a viral carrier (in our case, SFV and Sindbis) for
amplification and expression of immunogenic proteins. For
this purpose in earlier works HCV core protein, E2 protein
genes, and genome fragment coding polyP (combined coreE1-E2-p7) genes were inserted into expression vectors and
high levels of authentic, posttranslationally processed proteins have been provided in cell culture by using recombinant alphaviruses. The formation of homogeneous
HCV core-like particles of 3537 nm in diameter and HCVlike particles of 60 nm in diameter also were shown, but the
number of such particles in cell lysates was low. In this work
besides core-E1-E2-p7 proteins genes the gene of protein NS2
was cloned into expression vectors. We suppose, that
amount of formed and realised HCV-like particles should
increased at the use of such combination of genes. Thus,
HCV-like particles obtained in alphaviral expression system
may serve as a useful tool for a better understanding of the
mechanism of HCV assembly, and for the study of HCV
morphogenesis.

WITH

16

P28
Analysis of different anti-HCV vaccine
prototypes
G Sudmale, I Petrovskis, D Skrastina, J Jansons,
I Stahovska, I Akopjana, Z Kushnere, P Pumpens and
I Sominskaya Latvian Biomedical Research and Study Centre, Latvia
The aim of the study was to develop of a new anti-HCV
therapeutic vaccine prototype, based on combination of the
HCV variable structural part and conservative non-structural regions. This type of vaccine could be especially effective for chronic infections. High genetic variability of HCV
HVR1 region demands, from our point of view, an urgent
need to elaborate personalized, or individual, vaccines to be
effective against a particular patients hepatitis C virus. The
vaccine variable structural part is represented by highly
variable region of virus envelope protein E2 (HVR1). HVR1
regions of HCV genome form selected sera samples of chronic
HCV patients were amplified, cloned and sequenced.
Obtained sequences were cloned into the HBcAg vectors and
expressed in Escherichia coli cells. Chimeric VLPs were
purified by gel filtration and the best ones were used for
immunization of Balb/c mice. The titers of anti-HBc and antiHVR1 were detected. Mice sera with highest antibody
response were chosen for virus neutralization test against
HCVpps with as specific HVR1 as well as unrelated HVR1
sequences. The highest virus neutralizing effect was
observed in case of HCVpps HVR sequences identical to sequences used for immunization. In case of using unrelated
HCVpps, neutralization effect was lower, but induced antibodies still were able to neutralize unrelated HCVpps. The
second part of vaccine is represented by highly conservative
non-structural protein NS3/4a designed on the basis of
consensus sequences representing combination of Latvian
major subtype 1b HCV isolates. For this purpose NS3/4a
regions of HCV genome form selected chronic HCV patients

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions
sera samples were amplified, cloned and sequenced. Nucleotide and protein consensus sequences of NS3/4a region that
are typical for HCV genotype 1b viruses circulating in Latvia
were created. NS3/4a nucleotide consensus sequence was
optimized for expression in the mice and human cell cultures. In the nearest future we plan to perform co-immunization experiments.
Study was carried with the financial support of the New
Visby program of the Swedish Institute; ERAF 2010/0224/
2DP/2.1.1.1.0/10/APIA/VIAA/164; LZP grant 10.1290;
ERAF 2DP/2.1.1.2.0/10/APIA/VIAA/004

17

CONCLUSION: PLA may play a role in the unique PVT


outcome of the haemostatic balance in a group of patients
whose credentials of hyperdynamic portal circulation predispose them to bleeding rather than thrombosis. Consequently, P-selectin targeted therapy may be used to prevent
this complication.

P32
P32 Abstract withdrawn

HEPATITIS B VIRUS
P29

Diagnosis and Monitoring

P29 Abstract withdrawn

P33
P30

Abstract withdrawn

P30 Abstract withdrawn

P34
P31
Portal vein thrombosis and haematemesis in
chronic liver disease. Are P-selectin and PSGL-1
clues?
B Madkour1, H Sadek2, I Shaheen2, A Saleh1,
R Yaseen1, E Bayoumi1 and S Toima1 1Theodor Bilharz
Research Institute (TBRI), Egypt, 2Cairo University, Egypt
BACKGROUND AND STUDY AIMS: Bleeding and thrombotic

W IT H
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complications are common problems in patients with


chronic liver disease (CLD). The aim of the present study was
to evaluate the level of soluble P(sP)-selectin, and P-selectin
glycoprotein ligand-1 (PSGL-1) (CD162) expression on
neutrophils among patients with CLD and to clarify the role
of their interaction, by measuring the platelet leucocyte
aggregates, on the clinical outcome of the haemostatic balance in those patients. We also investigated the hypothesis
that the balance between platelet activation and endothelial
biological function is impaired.
PATIENTS AND METHODS: sP-selectin and thrombomodulin
(TM) levels were measured by enzyme-linked immunosorbent assay (ELISA) and flowcytometric detection of CD162
was performed. Platelet-leucocyte aggregation (PLA) in
whole blood was measured as positive for CD41a and CD45
in 66 CLD patients divided into the portal vein thrombosis
group (PVT) (n = 25), the haematemesis group (n = 21)
and the haemostatically stable group (n = 20).
RESULTS: sP-selectin was significantly elevated in all patient
groups. Decreased surface expression of CD162 on neutrophils was detected in all patients groups. PLA was statistically significantly increased in the PVT group. TM was
statistically significantly increased in the PVT, haematemesis
and haemostatically stable groups.

Evaluation of the VERSANT HBV DNA 1.0 assay


(kPCR)
A Lachaud1, E Meteau1, S Tronchet1, J Turczyn2, J
Chen2, L Fisher2, V Nguyen2, J Surtihadi2 and M
Hennig2 1Biomnis, France, 2Siemens Healthcare Diagnostics, USA
PURPOSE OF THE STUDY: The VERSANT HBV DNA 1.0

assay (kPCR)* is a kinetic polymerase chain reaction (kPCR)


method for quantifying hepatitis B virus (HBV) DNA in
human plasma and serum, using the VERSANT kPCR
Molecular System.This system combines a fully automated
sample preparation module and a fully automated amplification and detection module. This study evaluated the
reproducibility of the VERSANT assay and compared its
performance to the Roche COBAS AmpliPrep/COBAS TaqMan HBV Test, v. 2 (COBAS assay), a CE-marked method.
METHODS: Assay reproducibility (precision) was evaluated
at two laboratory sites using two assay reagent lots and four
VERSANT kPCR Molecular Systems. Reproducibility was
assessed using a 10-member panel prepared by diluting
high-titer HBV DNA viral stock (genotype A) in human
plasma and serum to five HBV DNA concentrations. The
concentrations of the plasma and serum members ranged
from 171 to 21,365,955 IU/mL and from 196 to
24,558,927 IU/mL, respectively. The VERSANT and COBAS
assays were compared using 209 paired HBV DNA-positive
clinical samples across the quantification range, with HBV
genotypes A to H represented.
SUMMARY OF RESULTS: Using this panel, the VERSANT
assay showed good reproducibility (total log SD range: 0.11
0.15). Deming regression analysis of log quantitative results
obtained from the VERSANT assay versus the COBAS assay
showed good correlation (Y = 0.09 + 1.01; R = 0.97). On

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

average, the VERSANT assay quantified 0.14 log IU/mL


higher than the COBAS assay, with 95% of the differences
falling within the range of )0.721.00 log IU/mL.
CONCLUSIONS: The VERSANT HBV DNA 1.0 assay (kPCR)
using the VERSANT kPCR Molecular System is a reliable and
accurate assay for the quantification of HBV DNA in plasma
and serum from HBV-infected individuals.
*Currently not commercially available.

Not available for sale in the U.S.


This study was sponsored by Siemens.

P35
Prevalence of HBV genotypes among hepatitis
patients in Egypt
I Khaled, O Mahmoud, M Zahran and E Baioumi
Theodor Bilharz Research Institute, Egypt

Evaluation of the DiaSorin LIAISON XL system


vs. Abbott Architect for determination of viral
hepatitis markers
R Adler, R Barsuk and R Safadi Hadassah University Hospital,
Israel
AIMS: Assays for hepatitis markers are used to determine

exposure, infection and status of immunity to viral hepatitis.


These tests must be highly sensitive, specific and accurate.
The objective of the evaluation was to compare hepatitis
marker determination capabilities of the DiaSorin LIAISON
XL (LXL) system to the Abbott AxSYM and Architect (Arch)
systems.
METHODS: Commercial seroconversion panels for HBsAg
and anti-HCV were tested on both systems. Sensitivity and
specificity for detection of HBsAg mutants were assessed on
the LXL and Arch analyzers. Serum samples positive for
hepatitis markers were serially diluted and tested in order to
define sensitivity and LOD. Linearity of quantitative HBsAg
and anti-HBs was determined using WHO international
standards. Problematic samples (dialysis patients, pregnant
women) were assayed on all systems.
RESULTS: LXL and Arch systems were equally sensitive to
seroconversion panels. The LXL HBsAg Quant was reactive for
all mutants while Arch failed to detect one. LXL anti-HBs II
was linear through 51000 mIU/mL anti-HBs (r2 = 0.994).
Problematic anti-HCV samples were compared and INNO-LIA
was used to determine specificity for each method 23/15
results were not confirmed by INNO-LIA. Sensitivity determined by serial dilution was equal for all markers assayed. LXL
anti-HBc IgM was more sensitive than Arch.
IN CONCLUSION: The DiaSorin LIAISON XL is equally
sensitive, specific and accurate as the Abbott Architect
system.

P37
The potential function of APOBEC3G for limited
replication of hepatitis B virus: report of case
series and review of literature
A Mohamadkhani1, F Mohammadkhani2, H Poustchi1
and G Montazeri1 1Shariati Hospital, Tehran University of Medical
Sciences, Iran, 2Amirkabir University of Technology, Iran
BACKGROUND AND STUDY AIMS: Recent findings introduced APOBEC3G (A3G) as a host factor that blocks viral
replication. It induces G to A hypermutations in viral DNA at
the step of reverse transcription and in response to interferon. The aim of this study was to investigate the expression
of liver A3G protein in association with both replication of
HBV and frequency of G to A mutations in basal core promoter (BCP)- pre-core (PC) region.

WITH

Phylogenetic analysis has led to the classification of hepatitis


B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show
heterogeneity in their global distribution. These attributes of
the genotypes may account not only for differences in the
prevalence of hepatitis B virus mutants in various geographic regions, but also makes them responsible for differences in the clinical outcome and response to antiviral
treatment in different population groups. Africa is one of the
highly endemic regions of HBV with five genotypes (AE)
identified. Almost all patients in the Mediterranean area are
infected with genotype D. However, there is little information
of genotype distribution in Egypt. A total of 140 Egyptian
patients with hepatitis B surface antigen (HBsAg) positive
were enrolled in this study. Of the 140 patients, only 100
patients were HBV DNA positive and only these were included in the study. They were classified into 20 patients
with acute hepatitis (AH), 75 patients with chronic active
hepatitis (CAH) and five patients with hepatocellular carcinoma (HCC). HBV genotypes were determined using INNOLiPA methodology which is based on the reversed hybridization principle.
RESULTS: This study showed that genotype D constituted
87% of the total infections (75% CAH, 7% AH and 5% HCC).
The other 13% showed mixed infections of D/F.
CONCLUSION: These findings show that the most prevalent
genotype in Egypt is genotype D especially in CAH and HCC
patients while the mixed type D/F is mostly encountered in
AH.

P36

DRAW
N

18

 2012 The Authors


Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions

19

of 283 seroconversion samples respectively. About 181


samples were detected as HBV DNA positive. The detection of
HBsAg by DS-EIA-HBsAg-0.01 and HBV DNA ranged within
0133 days with the delay means of 21.85 days and
24.48 days respectively. The detection of HBsAg by other
best EIA assays ranged within 0142 days with the delay
means of 28.52 days. DS-EIA-HBsAg-0.01 detected HBsAg
in the specimens of eight panels by one bleed earlier and in
the specimens of four panels by 25 bleeds earlier than the
initial detection of HBV DNA (100400 copies/mL) occurred. The moments of detection of HBsAg by DS-EIAHBsAg-0.01 and initial detection of HBV DNA coincided at
evaluation of the specimens of 13 panels.
CONCLUSION: The assay with highest level of sensitivity is
the most effective both for detection of different HBsAg
subtypes and mutants and for early detection of HBV infection. DS-EIA-HBsAg-0.01 allows reducing diagnostic window by 2.63 days in comparison to the HBV DNA assay and
6.67 days in comparison to other best EIA assays.

P38

P39

Evaluation of diagnostic efficiency of the highly


sensitive enzyme immunoassay for HBsAg
detection
N Egorova, S Igolkina, I Pyrenkova, I Sharipova,
V Puzyrev, A Obriadina, A Burkov and T Ulanova RPC

Prevalence of HBV genotypes in Egypt among


hepatitis patients
I Khaled, O Mahmoud, A Saleh and E Baioumi Theodor

WITH

DRAW
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PATIENTS AND METHODS: Fifty-one liver biopsies of nave


chronic hepatitis B (CHB) patients enrolled for the expression
of A3G by immunohistochemistry (IHC) standard method.
The presence of HBV DNA and sequences of BCP-PC region
in the time of liver biopsy were investigated in all patients.
RESULTS: Among 34 patients with detectable HBV DNA, 31
carried a range of 15 G to A mutations in BCP-PC region.
IHC results showed that the expression level of A3G in CHB
patients liver was very low. Of all patients, A3G expressed in
three undetectable HBV DNA subjects and a patient with
2.24 104 copies/mL of HBV DNA. G to A mutated residues
were indicated at position 1727, 1757, and 1896 of HBV
genome of this patient.
CONCLUSION: This study indicates that despite achieving
very low levels of A3G in liver and positive subjects, A3G has
potential role to restrict in vivo replication of HBV. However
the innate antiviral activity of A3G that might be directed by
interferon or viral proteins needs to be unraveled in chronic
hepatitis B.

Diagnostic Systems, Russian Federation


OBJECTIVES: The early stage of HBV infection with HBsAg

below the detection limit of the best available EIA kits (0.05
0.1 IU/mL) is one of the main reasons of transfusion-associated hepatitis B. The aim of the study was to evaluate the
advantage of highly sensitive (0.01 IU/mL Second International Standard for HBsAg) NIBSC code number: 00/588)
assay DS-EIA-HBsAg-0.01 (CE0483) intended for detection
and confirmation of HBsAg.
METHODS: The panel of HBV-genotyped/subtyped samples
(n = 16) (Paul-Ehrlich-Institut, Germany), the panel of
samples containing mutant variants of HBsAg subtypes
ayw1 and adw2 (n = 13) (RPC Diagnostic Systems, Russia),
seroconversion panels (n = 28) (Boston Biomedica Inc. and
ZeptoMetrix Corp.) were used. The total number of reactive
specimens in all seroconversion panels was calculated as
well as the mean number of days of delay in detection of
HBsAg and HBV DNA.
RESULTS: All 16 HBV genotyped/subtyped specimens (A/
adw2, B/ayw1, B/adw2, C/adr, D/ayw2, D/ayw3, E/ayw4,
F/adw4, G/adw2) highly diluted (concentration of HBsAg
equal to 0.031 IU/mL or 0.010 ng/mL) were detected as
positive by the DS-EIA-HBsAg-0.01. Data on investigation of
mutant variants of HBsAg showed that DS-EIA-HBsAg-0.01
has higher sensitivity in comparison to other CE-marked
assay. DS-EIA-HBsAg-0.01 and other most sensitive EIA
assays detected 203 and 152 samples as HBsAg positive out

Bilharz Research Institute, Egypt

Phylogenetic analysis has led to the classification of hepatitis B


virus into eight genotypes, designated A to H. The genotypes
have differences in biological properties and show heterogeneity in their global distribution. These attributes of the
genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also makes them responsible for differences in the
clinical outcome and response to antiviral treatment in different population groups. Africa is one of the highly endemic
regions of HBV with five genotypes (AE) identified. Almost all
patients in the Mediterranean area are infected with genotype
D. However, there is little information of genotype distribution
in Egypt. A total of 140 Egyptian patients with hepatitis B
surface antigen (HBsAg) positive were enrolled in this study.
Of the 140 patients, only 100 patients were HBV DNA positive
and only these were included in the study. They were classified
into 20 patients with acute hepatitis (AH), 75 patients with
chronic active hepatitis (CAH) and five patients with hepatocellular carcinoma (HCC)]. HBV genotypes were determined
using INNO-LiPA methodology which is based on the reversed
hybridization principle.
RESULTS: This study showed that genotype D constituted
87% of the total infections (75% CAH, 7% AH & 5% HCC).
The other 13% showed mixed infections of D/F.
CONCLUSION: These findings show that the most prevalent
genotype in Egypt is genotype D especially in CAH and HCC
patients while the mixed type D/F is mostly encountered in
AH.

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Poster Sessions

P40
Humanizing viral hepatitis case detection and
treatment in two provinces of Afghanistan
(Wardak and Sar-e-Pul)
N Noor, C Hamidi and S Shams Swedish Committee for
Afghanistan, Afghanistan
BACKGROUND: One million people are living in Sar-e-Pul

and Wardak provinces in rural areas with high social stigma, overcrowding, population density, poor sanitary facilities, limited access to health services (66%) and, thus Viral
Hepatitis become of the major cause of death in these
provinces.
METHODS: I along with SCA Health Management Teams
visited 44 health centers from JanuaryMarch 2012. We
conducted 44 supervisory visits and collect data from
January 2010 to December 2011 through national recording/reporting checklist, structured questioners, and medical
records and register book in health centers1.
RESULTS: In 2010, 98 health facilities, one mobile team and
497 health posts were involved as a diagnostic and treatment centers which covered 48% of population, while it
increased to 106 health centers, two mobile team and 515
health posts that covered 66% of population with free access
to services. In 2010, 850 viral hepatitis cases detected from
which 349 people died (41%), while it increase to 924 cases
and 435 (47%) death in 2011. Most of the cases were
accidentally diagnosed during examination or blood test for
other conditions.
CONCLUSION: The main routes of transmission for viral
hepatitis in these two provinces were due to high usage of
injection and high usage of infected dental equipment by nonprofessional people. Health education for both professional
staff and public people will play significant role in case notification, increase treatment success rate and decrease death
rate, thus, we would recommend health education and
awareness programs for people who are living in rural areas as
well as we recommend to extend safe injection programs.
1. Health Management Information System (HMIS) 2012

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P41
Association of TLR2 protein with serum ALT in
chronic hepatitis B patients harboring pre-core
mutant
A Mohamadkhani1, F Mohammadkhani2, H Poustchi1
and G Montazeri1 1Shariati Hospital, Tehran University of Medical

WITH

Sciences, Iran, 2Amirkabir University of Technology, Iran


BACKGROUND: Chronic hepatitis B patients harboring pre-

core mutant variants of hepatitis B virus (HBV) may show


fluctuating of ALT levels with histologic activity on biopsies
indicative of inflammation and injury. Toll-like receptor 2

(TLR2), as a mediator of microbial pattern recognition has


important role in elimination of pathogens. The aim of this
study was to investigate the association of serum TLR2 with
clinical findings of HBeAg negative chronic hepatitis B patients.
METHODS: Fifty one HBeAg negative patients with detectable HBV DNA were examined for the presence of mutations
in pre-core region of HBV genome. Concentration of serum
TLR2 was measured by enzyme-linked immunoassays.
Interaction of tertiary structure of truncated HBeAg and
TLR2 (2Z80 A) was evaluated with molecular docking.
RESULTS: Patients with G1896A mutation had higher
concentration of serum TLR2 compared to patients without
this mutation (4.8 2.9 versus 3.4 2.2 ng/mL,
p = 0.03). Estimating regression equations in pre-core mutant patients showed with increasing serum TLR2 concentration bigger than 6, serum ALT raises sharply.
Computational molecular docking studies showed an interaction between truncated HBeAg and TLR2.
CONCLUSION: Present results suggest that serum TLR2 level
might reflect higher expression of membrane-bound TLR2
and its pro-inflammatory results in liver damage and serum
ALT elevation.

W IT H
DRAW
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20

P42
Detection of occult hepatitis B virus infection
and prevalence of hepatitis B and hepatitis C
infection among blood donors in South Egypt
H Hamed and R Bakry South Egypt Cancer Institute, Egypt
BACKGROUND: Occult HBV infection is defined as the presence of hepatitis B virus (HBV) DNA in blood or liver tissues
in patients negative for Hepatitis B surface Antigen (HBsAg)
who may or may not be positive for HBV antibodies. The aim
of this study is determination of presence or absence of HBV
DNA in the serum samples from HBsAg negative blood donors by polymerase chain reaction (PCR) method to assess
the magnitude of occult HBV infection and to reduce the risk
of HBV infection.
MATERIALS AND METHODS: Over a period of 1 year
(December 2010November 2011), a total of 7340 blood
units were collected at blood bank of South Egypt Cancer
Institute, Assiut University, Assiut, Egypt for the incidence of
HCV and HBV infection and 180 HBsAg negative blood
specimens were collected from randomly selected blood
donors for anti-HBcIgM, anti-HBs antibody and HBV DNA.
RESULTS: One hundred and seventy one blood units from
the total 7340 units were positive for anti-HCV (2.3%) and
97 were positive for HbsAg (1.3%). Donors who were positive for antiHBcIgM and anti-HBs were 7/180 (3.8%) and
34/180 (18.8%) respectively. From the seven positive for
anti-HBc IgM, four of them are also positive for anti-HBs, 2/
180 (1.1%) specimens only were positive for HBV DNA by
PCR.

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Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions
CONCLUSION: Anti-HBc antibody should be tested routinely
on blood donor and if they found positive (regardless of antiHBs titre), the blood should be discarded. Also HBV DNA by
PCR is preferable to be done to all blood donors to reach
100% safe blood transfusion.

P43
A case of HBV infection in a previously
vaccinated blood donor
P Clerici, B Brando, M De Paschale and S Latella Legnano
Hospital, Italy

In the medical literature just a few reports are available on


the serologic behaviour of HBV-vaccinated subjects without
anti-HBs antibodies, who undergo a new HBV infection.
A case of a vaccinated blood donor with a documented HBV
infection is reported here. A 40 year-old male was vaccinated against HBV in 1990. The early serologic response
was not documented, and anti-HBs antibodies were tested as
negative at least from 2001 on, when he enrolled as a regular blood donor. The evidence of a new HBV infection was
recorded in a blood donation on June 2011. At that time the
HBV screening results were: HBsAg neg, HBeAg neg, antiHBe neg, anti-HBc neg, anti-HBs positive (205 mUI/mL),
with normal ALT. HBV-DNA testing was positive. The donated unit was discarded, and the donor was investigated for
risk factors for HBV transmission, with no clear evidences. A
follow-up program was initiated. After 1 week total anti-HBc
and IgM anti-HBc gave grey-zone readings by chemiluminescence, with HBsAg neg, HBV-DNA neg, HBeAg neg, antiHBe neg, anti-HBs positive (477 mUI/mL) and normal ALT.
After 1 month both total anti-HBc and IgM anti-HBc IgM
were intensely positive; anti-HBs was positive (517 mUI/
mL), whereas HBsAg, HbeAg and anti-HBe remained negative, always with normal ALT. No further changes were
recorded after 2 months (positive anti-HBs at159 mUI/mL)
and later on. In conclusion, our case report documents a
new HBV infection in a vaccinated subject, with early antiHBs production, quick and transient appearance of HBVDNA and slow anti-HBc production. We dont know whether
the donor has successfully seroconverted for anti-HBs at the
time of vaccination or whether anti-HBs antibodies have
faded away subsequently. Anyway, the HBV memory state
induced by vaccination seemed effective, since a good antiHBs recall response was obtained shortly after exposure. The
systematic nucleic acid testing for HBV on all donated blood
units allows to identify efficiently unusual occurrences like
the one described here, and to discard potentially infected
blood units.

21

Natural History and Epidemiology


P44
Difference in the characteristics of HBV
infection in Italian and non-Italian patients in
northern Italy
M De Paschale, M Manco, L Belvisi, C Magnani, T Re,
P Vigano`, S Biagiotti, F Capelli, A Mazzone,
M Baldacci, A Ferrara, A Neri, C Guastoni,
R Bonazzina, B Brando and P Clerici Legano Hospital, Italy
The introduction of vaccination against HBV in Italy has led
to a reduction in both the incidence and the prevalence of
HBV infection. However, an increasing immigration from
countries where HBV is highly endemic has led to a wave of
new HBsAg positive subjects. The aim of our study was to
compare the serological, clinical and epidemiological data
among subjects of Italian and foreign origin in a hospital of
Northern Italy. We examined 488 subjects, of which 107
(21.9%) were of foreign origin [41 males (38.3%) and 66
females (61.7%), mean age 32.2 years (range: 159)] and
381 (78.1%) were of Italian origin [242 males (63.5%) and
139 females (36.5%), mean age: 56.9 years (range: 23
93)]. Databases of laboratory and clinical records were
analyzed retrospectively to search for information about
possible routes of infection, clinical diagnosis and search for
anti-HIV, anti-HCV and anti-HDV antibodies. The incident
cases (patients who have been diagnosed as having chronic
hepatitis for the first time during the study) and the prevalent cases (patients whose diagnosis of chronic hepatitis
was made before the study) were identified whenever possible. There were no significant differences between foreign
and Italian patients in the prevalence of HIV (7.5% versus
6.1%), HCV (2.9% versus 3.7%) and HDV (4.7% versus
5.0%) coinfection or in the presence of HBeAg (9.7% versus
5.3%). There were no differences in rates of acute (3.3%
versus 5.1%) or chronic (96.7% versus 94.9%) infections,
while the differences were statistically significant (p < 0.01)
among prevalent cases (54.5% versus 85.3%) and incident
cases (45.5% versus 14.7%). Even the differences between
asymptomatic (70.6% versus 34.9%) and symptomatic
(29.4% versus 65.1%) patients were statistically significant
(p < 0.01). Regarding the risk factors the only significant
differences were identified between community-acquired
(33.9% versus 53.6%, p < 0.05) and perinatal transmission
(44.1% versus 6.8%). In conclusion, the HBsAg positive
subjects of foreign origin are mostly women, younger than
their Italian counterparts and with a recent diagnosis. They
have predominantly asymptomatic infection probably because they consider themselves healthy, and fit to embark
into emigration. Among foreigners, perinatal transmission is
still an important risk factor that reflects the epidemiological
situation of the countries of origin.

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22

Poster Sessions

P45
Screening for HBsAg, anti-HCV and anti-HIV in
pregnant women in a rural area of north Benin
M De Paschale1, C Ceriani1, T Cerulli1, D Cagnin1,
S Cavallari1, K Diombo2, J Ndayake2, G Aouanou2,
D Zaongo2, G Priuli2, P Vigano`3 and P Clerici3 1Legnano
Hospital, Italy, 2Hopital Saint Jean de Dieu, Benin, 3Legano Hospital, Italy

In African countries the prevalence of HBV, HCV and HIV


infection is considered high. Among the transmission routes,
in addition to sexual and family contacts (especially for
HBV), it is important the perinatal transmission. Screening
in pregnancy is a valid tool to prevent the infection. The aim
of this study was to evaluate the prevalence of markers of
HBV, HCV and HIV infection in pregnant women at the
Saint Jean de Dieu Hospital of Tanguie`ta, Benin. Therefore
the sera of 283 women (mean age 26.2 years, range 1541)
were examined. HBsAg (confirmed by neutralization method), total anti-HBc, anti-HCV (confirmed by immunoblotting
method) and anti-HIV 1/2 (confirmed by Western Blot) were
searched by screening enzyme-linked immunosorbent assays. Forty-eight samples (17.0%) were positive for HBsAg
screening test, of which 44 (15.5%) were confirmed at
neutralization test. Two hundred thirty-four (82.7%) were
positive for anti-HBc antibodies, of which 190 (79.5%)
among HBsAg negative samples. Twenty-eight samples
(9.9%) were positive for anti-HCV screening test, of which
22 (7.8%) confirmed positive and four (1.4%) indeterminate
at immunoblotting. Twelve (4.2%) were positive for anti-HIV
1/2, of which nine (3.2%) confirmed positive and two (0.7%)
indeterminate at Western blot. The differences in anti-HBc,
anti-HCV and anti-HIV by age classes (1520, 2130,
>30 years) were not statistically significant, while the
prevalence of HBsAg increased from 6.4% in the lower age
class to 24.0% in the higher class. Of the nine confirmed
HIV-positive women, four were positive for HBsAg and two
for anti-HCV. In conclusion, our data confirm a high prevalence of HBV and HCV infection in the study area. The prevalence of HIV infection is similar to that reported by WHO in
2009 in the same region. Saint Jean de Dieu Hospital currently
applies HIV screening for all pregnant women, while not for the
HBsAg and anti-HCV. Our data support the implementation of
screening in pregnancy for these latter two markers.

available for Tajikistan. The present study was to investigate


the genotypic prevalence and clinical significance of HCV,
HBV, and/or HDV among chronic hepatitis patients with and
without liver cirrhosis and/or HCC in Tajikistan.
METHODS: Sera were obtained from 124 consecutive cases
of chronic liver diseases. Patients in this study were classified
into two clinical groups: (i) chronic hepatitis and (ii) liver
cirrhosis. Genotyping of hepatitis C virus (HCV) was performed, and total RNA was extracted from serum, reverse
transcribed into cDNA using random hexamer primers as
described previously (Ohno. J Clin Microbiol 1997; 35: 201
7). All of the HBsAg-positive samples were subjected to
genotyping by commercial EIA kit (Institute of Immunology
Co., Ltd, Tokyo, Japan).
RESULTS: Genotypes of HBV, HCV, and HDV were determined by genetic sequencing. The overall prevalence of antiHCV, HCV core antigen (HCVcAg) and HBsAg was 46% (57/
124) and 41.1% (51/124), respectively. Co-infection of
HCV/HBV, HBV/HDV, and HCV/HBV/HDV was found in
4.8% (6/124), 11.2% (12/124), and 0.8% (1/124) of cases,
respectively. HDV genotype 1 was found in 19.6% (10/51) of
HBsAg-positive patients. The HBV/HDV co-infection was
relatively high in group 2 compared with group 1 (15%
versus 7.1%). HCV/1b was detected in 84.6% (44/52) of
HCV RNA-positive patients, followed by 3a (7.6%), 2a
(5.7%), and 2c (1.9%). HBV/D was detected in 94.1% (48/
51) of HBsAg-positive patients, followed by HBV/A (5.8%, 3/
51). T1762/A1764 double mutation was associated with
liver cirrhosis in HBV-infected patients (p < 0.001). We
found correlation between HBV-infected patients, the
T1762/A1764 mutation and hepatocellular carcinoma.
CONCLUSION: Among HBV-infected patients, the T1762/
A1764 mutation was associated with liver cirrhosis and
hepatocellular carcinoma.

Treatment and Late-Stage Clinical Trials (Phase


IIb, Phase III and Phase IV)
P47
Stopping TDF treatment after long term virologic
suppression in HBeAg-negative CHB: two cases
from an ongoing randomized, controlled trial
T Berg1, E Schott2, G Felten3, C Eisenbach4, T Welzel5,
T Warger6, L Gallo6, E Martins7 and M Biermer8
1

P46

Universitatsklinikum Leipzig, Germany, 2Charite-CVK, Germany,


Gastroenterologische Gemeinschaftspraxis, Germany, 4Medizinische

Hepatitis B, C, and HCC viruses in Tajikistan


A Dustov Institute of Gastroenterology of the Ministry of Health,

Universitatsklinik Heidelberg, Germany, 5J.W. Goethe Universitat,

Tajikistan

Moeller, Heyne, Biermer, Germany

AIM: The implication of genotypes is increasingly recognized

PURPOSE: Recent data suggest that long term suppression of

in the clinical course of HBV treatments and in response to


antiviral drugs of HCV. Genotypic prevalence of both
etiological agents varies geographically, and no data are

HBV DNA may lead to a reconstitution of the immune response to HBV in some patients after stopping adefovir therapy
in HBeAg-negative patients (Hadziyannis et al. 44th Annual

Germany, 6Gilead Sciences, Germany, 7Gilead Sciences, USA, 8Drs

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Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

Poster Sessions
(a)

(b)

23

enrolling patients at 15 sites in Germany (ClinicalTrials.gov: NCT01320943). The study aims to enroll 90
HBeAg-negative patients in total.
RESULTS: Initial data from two subjects who stopped TDF
and have reached study visit Week 40 and Week 32,
respectively, are presented here. One study subject (Case A)
is currently maintaining HBV replication at low levels (Week
34: 24 IU/mL, Week 36: 34 IU/mL, Week 40: 182 IU/mL)
without TDF while having achieved normal ALT levels
(<45 IU/mL). The expected HBV flare had peaked at Week 6.
Notably HBsAg levels have been decreasing ()1.5 log); with
the sharpest drop occurring immediately post ALT-peak (Fig.
1A). In contrast, the second subject (B), after having flared
at study visit Week 8, demonstrated slow decline of HBV
DNA which turned into an increase and a second peak at the
Week 28 visit. TDF therapy was restarted and subsequently
HBV DNA fell rapidly while ALT levels normalized (Fig. 1B).
HBsAg levels had remained constant in this subject. Patients
who were randomised to the continuous TDF arm remain on
TDF therapy without any issues.
CONCLUSION: These two initial cases support the validity of
this investigational approach. While stopping TDF may induce a flare and subsequent viral control, it also appears that
TDF can potentially be safely and effectively re-introduced if
required. This clinical trial will allow the study of the long
term outcome of patients and the investigation of prognostic
factors associated with off-therapy response.

Practical Management Strategies


P48
Fig. 1 Both study subjects stopped TDF at baseline, HBV
DNA and ALT flared subsequently. Subject A) continues
without TDF having low level HBV DNA, normal ALT and
declining HBsAg while in subject B) TDF has been restarted
after a second flare which quickly reduced HBV DNA and
normalized ALT.

Multivariate Cox analysis on chronic hepatitis B


treatment initiation based on a 2-year
prospective study in five European countries
H Leblebicioglu1, S Zeuzem2, J Zarski3, K Simon4,
I Klauck5, E Morais5, B Lescrauwaet6, D Kamar7 and
V Arama8 1Ondokuz Mavis University, Turkey, 2Klinikum der
Johann-Wolfgang Goethe Universitat, Germany, 3CHU de Grenoble,

Meeting of the European Association for the Study of the Liver


2009, April 2226; p. S30, abstract 18). The viral relapse
seemed to boost immune response to HBV which was followed
by HBsAg clearance in approximately 1/3 of patients. The
FINITE CHB Study evaluates the controlled stopping of long
term tenofovir DF (TDF) therapy in virologically suppressed
HBeAg-negative patients to assess this concept.
METHODS: Eligible study subjects who had been on
effective TDF-containing therapy (TDF mono or TDF+LAM
or TDF+FTC) for at least 4 years are randomized to either
stop TDF at baseline or to continue TDF therapy. All
subjects will be followed for 144 weeks. Primary study
endpoint is HBsAg loss at Week 144. The protocol defines
criteria for restarting TDF in case the HBV relapse exceeds
acceptable limits. This open-label study is currently

France, 4Klinika Chorob, Poland, 5Bristol-Myers Squibb, France,


6

Independent Consultant, Belgium, 7Docs, France, 8Carol Davila

University of Medicine and Pharmacy, Romania


PURPOSE OF THE STUDY: The aim of this analysis was to

explore the major determinants associated with the initiation


of treatment in nave chronic hepatitis B (CHB) patients from
a cohort across five European (EU) countries.
METHODS: A multivariate Cox proportional hazard regression model was used to analyze the determinants of treatment initiation by a backward selection. The data analyzed
were derived from an observational cohort study, consisting
of diagnosed adult CHB patients managed in outpatient
clinics, prospectively enrolled from March 2008 to October
2009, in France, Germany, Poland, Romania and Turkey.
Patients with HIV and/or HCV co-infection and evidence of

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Poster Sessions

P49
Impact of healthcare policies on the clinical
management of chronic hepatitis B: analysis of
real-world data from five European countries
K Simon1, V Arama2, J Zarski3, S Zeuzem4,
B Lescrauwaet5, D Kamar6, I Klauck7, E Morais7 and
H Leblebicioglu8 1Wroclaw University of Medicine, Poland, 2Carol
Davila University of Medicine and Pharmacy and Prof. Dr. M. Bals
3

National Institute of Infectious Diseases, Bucharest, Romania, CHU de


Grenoble, France, 4Klinikum der Johann-Wolfgang Goethe-Universitat,
Germany, 5Independent Consultant, Belgium, 6Docs, France,
7

Bristol-Myers Squibb, France, 8Ondokuz Mayis University, Turkey

PURPOSE: In Europe, healthcare policies and reimbursement decisions are determined at a national level, differing
between countries. This analysis from a prospective, longitudinal, non-interventional study aimed to describe the impact of local healthcare policy on the management of
patients with CHB in five European countries.

METHODS: Country-specific cohorts of adult patients with


compensated CHB managed in outpatient clinics in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years between March 2008 and
December 2010.
RESULTS: Data were collected for 1,267 patients from 34
sites. Baseline age and gender distribution differed between
untreated and treated cohorts but were similar across
countries for both cohorts. Differences between countries,
and between patients treated and untreated, were observed
in the 12 months pre-baseline and during follow-up, in
terms of tests ordered, clinic visits, hospitalisations and
treatment choice. Reasons for clinical management decisions, along with the pattern of tests ordered during followup, showed differences between the countries in variables
used to monitor and modify treatment. Hospitalisations
during follow-up were more frequent in Romania (1.45
hospital days/patient-year) and Poland (1.81 days/patientyear) than in Turkey, France and Germany (0.00, 0.05 and
0.10 days/patient-year, respectively). Clinic visits were more
frequent in Poland (3.19 visits/patient-year versus 0.30
1.78 across other countries). Choice of therapy was influenced by approval and reimbursement status during the
study period (tenofovir and telbivudine unavailable/not
reimbursed in Poland and Romania; telbivudine not reimbursed in Turkey). EASL treatment guidelines were updated
in October 2008; their influence on patient management
remains unclear. The most frequently prescribed monotherapies were entecavir and tenofovir in Germany and
France; lamivudine, entecavir and pegylated interferon in
Poland and Romania; tenofovir, entecavir and lamivudine in
Turkey.
CONCLUSIONS: This observational study in five European
countries showed that country specific healthcare infrastructure and reimbursement policies have an impact on
CHB patient management. Observed differences in monitoring patterns, hospitalization rates and other healthcare utilization can be related to cost and reimbursement issues. The
impact of local versus EASL treatment guidelines on treatment choice needs further investigation.

P50
Health providers knowledge, attitude and
practice about hepatitis B & C transmission in
Iran
E Eftekhar Ardebili Tehran University of Medical Sciences, Iran

decompensated cirrhosis (Child-Pugh score 7), hepatocellular carcinoma or liver failure at baseline were excluded.
Factors considered candidates to enter the multivariate
model (with univariate test at a p-value < 0.20) were:
country, pre-treatment alanine aminotransferase (ALT) level, pre-treatment viral load (VL), liver biopsy, hepatitis B eantigen status (HBeAg) and age. The statistical criteria for
exclusion at each step of the model building process is pvalue > 0.05. Results are presented as hazard ratio (95%
confidence interval) and p-value.
SUMMARY OF RESULTS: Data were collected for 1267 patients followed for up to 2 years between March 2008 and
December 2010, with a median (months) ranging from 12.5
(Poland) to 14.5 (Romania). A total of 646 nave patients
were included in the model. Patients were 54.2% male, aged
(years) 1878 and median (years) time since CHB diagnosis
is 2.6 (037.7). There is a higher probability to initiate a
treatment in Germany (7.04 [2.3321.33]; p = 0.0006),
Poland (8.48 [3.7219.36]; p < 0.0001) and Romania
(4.52 [1.9510.46]; p = 0.0004) compared to Turkey.
There is a higher probability to initiate a treatment when
1ULN<ALT&LE;2&TIMES;ULN ALT and p=0.0580)
[0.982.57]; (1.59>2ULN (1.81 [0.993.29]; p = 0.0523)
compared to ALT 1 ULN. There is a higher probability to
initiate a treatment when VL2000 IU/mL (6.23 [3.53
11.60]; p < 0.0001) compared to Undetectable and
VL<2000 IU/mL.
CONCLUSIONS: This observational cohort, conducted in five
EU countries identified VL and ALT level as the two major
clinical outcomes driving the treatment initiation decision in
CHB-nave patients. Results were also statistically different
across EU countries, possibly due to different patient characteristics and different health care policies.

W IT H
DRAW

24

PURPOSE OF STUDY: Hepatitis B and C are among the


threatening conditions for health care providers. These types
of hepatitis are commonly transmitted by blood or its products in health and medical staff. Since the last three decades,
these diseases are now known as occupational diseases. In
order to obtain the knowledge, attitude, and performance of

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Poster Sessions

WITH

DRA W

health staff in the city of Karaj (a metropolitan city in the


West of Tehran) about preventing of any further spread of
hepatitis B and C, a cross sectional study was conducted
from April to July of 2011.
METHODS: Sampling done by census of staff who were
expertise as health workers including health care providers
in urban health centers, nurses and nurse-aids, technicians
of the laboratory, family health and dental health providers
were enrolled, which have been 651 persons. A selfadministered questionnaire been completed by the respondents including seven questions measuring demographic
characteristics, 20 selective questions asking about knowledge, 16 questions of attitude was ordered by Likert scale.
Five interpretive questions showed qualification of performance, two questions were about the incidental puncturing
of the contaminated needles or sharp objects in the body,
and a text box prepared at the bottom of page for the
respondents comments for presentation of any revising
suggestion.
RESULTS: Overall, studied population had good knowledge,
excellent attitude, and moderate performance (53.5%,
89.4% and 62.2%) respectively. All of three KAP domains
between together had a linear and straight correlation.
Young staff had more knowledge than the aged ones.
Favorite KAP observed in the age group of 3140 years.
Knowledge of women was a little bit less than the men.
About 210 people (32.3%) had needle stick puncture along
the past year.
Conclusion: 220 persons had renovating comments about
the optimization of the field immunity and health promotion.
Some of the suggestions were very primitive and marvelous,
so the compiling of a curriculum for reeducation of personnel may be necessitated.

Preclinical and Early Clinical Development


(Phase I and Phase IIa)
P51

25

Module. Purified DNA targets were amplified and detected by


real-time PCR on the VERSANT Amplification/Detection
(AD) Module. A noncompetitive internal control was added
to monitor extraction, target amplification, and detection.
Uracil DNA glycosylase was used for chemical contamination control. The assay was standardized with 2nd WHO
HBV International Standard (NIBSC code 97/750). Analytical sensitivity (limit of detection [LoD]), defined as the lowest
concentration with a 95% detection rate, was determined
using 2nd WHO HBV International Standard dilution panels.
Twenty runs were assessed using two kit lots. Reproducibility, linearity, accuracy, and quantitation range were
evaluated with two 12-member panels (serially diluted HBV
genotype A live virus in HBV-negative plasma and serum)
with levels of 5 to 8.0E + 08 IU/mL. Each panel was tested
in 36 runs using three kit lots. Clinical specificity was
determined using 1,230 unique HBsAg-negative normal
blood donor specimens (600 plasmas and 630 sera). Fifteen
plasmid samples for HBV genotypes AH were also tested.
SUMMARY OF RESULTS: Assay LoD was 13 IU/mL. Lower
limit of quantitation (LLoQ) was 13 IU/mL and upper limit of
quantitation (ULoQ), 7.0E + 08 IU/mL. All panel levels
showed a linear response and good reproducibility: total CV
of quantitation <35% above 100 IU/mL. The accuracy of all
panel levels within quantitation range was <0.16 log.
Clinical specificity was 100% (1230/1230; 95% lower-end
one-sided confidence limit, 99.8%). The assay detected and
quantified HBV genotypes AH equivalently.
CONCLUSION: The VERSANT HBV DNA 1.0 assay (kPCR)
together with the VERSANT kPCR Molecular System is
highly sensitive and specific with a wide dynamic quantitation range. There are no significant differences in assay
sensitivity, reproducibility, linearity, or accuracy across kit
lots, instruments, and sample matrices.
*Currently not commercially available.

Not available for sale in the US.

Other
P52

Diagnostics Inc., USA

Kaohsiung Medical University Hospital, Taiwan

PURPOSE OF THE STUDY: The VERSANT HBV DNA 1.0

PURPOSE OF THE STUDY: Nucleos(t)ide analogues are

assay (kPCR)* is a real-time kinetic PCR-based quantitative


test for human hepatitis B virus DNA in plasma and serum.
This study evaluated the analytical performance of the
VERSANT HBV DNA 1.0 Assay (kPCR) on the VERSANT
kPCR Molecular System.
METHODS: Viral DNA was extracted from panels or patient
specimens using VERSANT Sample Preparation 1.0 Reagents on the VERSANT kPCR Sample Preparation (SP)

effective treatment for chronic hepatitis B (CHB) patients.


Entecavir (ETV) is a potent inhibitor for hepatitis B virus
(HBV) replication and shown to be effective and safe. The
aim of the present study was to evaluate the effectiveness in
Taiwanese treatment-nave patients with chronic hepatitis B
(CHB).

DRAW
N

Performance evaluation of the VERSANT HBV


DNA 1.0 assay (kPCR)
C Wong, C Cadwell, L Grewal, D Monga, C Wong,
U Vajapey, S Aung, P Swiatkowski, L Cheng, C
Cosenza, J Surtihadi and Q Meng Siemens Healthcare

WITH

Entecavir therapy for treatment-nave chronic


hepatitis B patients in Taiwan
C Dai, M Yeh, C Huang, C Huang, N Hou, M Hsieh,
J Huang, Z Lin, S Chen, J Tsai, M Yu and W Chuang

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Poster Sessions

WITH

DRA W

METHODS: Total 501 patients [150 hepatitis B e antigen


(HBeAg) positive] treated with ETV 0.5 mg/day were
enrolled. All patients were treatment-nave and positive for
HBV DNA by PCR method before ETV treatment and
treated for more than 3 months. The rate of undetectable
HBV DNA, defined as virological response (VR), were
evaluated.
SUMMARY OF RESULTS: The mean HBV DNA level was
7.2 1.1 log IU/mL and 5.4 1.4 log IU/mL for HBeAg (+)
and HBeAg ()) patients, respectively. For HBeAg (+) patients, the rates of undetectable HBV DNA at month 3,
month 6, year 1, year 2 and year 3 were 27.4%, 60.0%,
83.9%, 89.8% and 94.7%. The rates of ALT normalization at
month 3, month 6, year 1, year 2 and year 3 were 59.1%,
70.8%, 78.3%, 87.5% and 84.2%, respectively. The cumulative rate of HBeAg seroconversion after 3 years of ETV
treatment was 35.1%. Age <30 years old and baseline ALT
>10 ULN were the independent factors associated with
HBeAg seroconversion. Baseline ALT > 5 ULN and HBV
DNA < 7 log IU/mL were independent factors associated
with undetectable HBV DNA. For HBeAg ()) patients, the
rates of VR were 72.1%, 92.5%, 98.7%, 100% and 100% at
month 3, and month 6, year 1, year 2 and year 3, respectively. The ALT normalization rates were 54.6%, 67.9%,
75.2%, 75.0% and 89.3% at month 3, month 6, year 1, year
2 and year 3, respectively. Baseline HBV DNA < 6 log IU/
mL was the only independent factors associated with VR at
month 3 and month 6.
CONCLUSION: The virological response rates achieve 90% or
more when treatment-nave Taiwanese patients receive ETV
therapy for more than 6 months in HBeAg ()) and 2 years in
HBeAg (+) patients. Pretreatment HBV DNA level was the
most important factor associated with the initial VR.

P53
P53 Abstract withdrawn

DRAW
N

P54
Influence of immunosuppresive therapy on HBV
mutations among renal transplantation
recipients
M Vaezjalali, P Ahmadpour, H Rezaee, M Rostami and
H Goodarzi Shahid Beheshti University of Medical Sciences, Iran
OBJECTIVES: One idea about high mortality of HBV-positive

WITH

renal transplantation recipients (RTR) is the influence of


immunosuppressive medications on hepatitis B behavior.
The aim of this study was to define hepatitis B virus (HBV)
mutational patterns among these immune-compromised
patients in Iran.
METHODS: Nucleotide sequences obtained from chronic
hepatitis B patients and encompassing the precore, basal
core promoter (BCP) and surface (S) regions, were compared.
The patients were grouped as case (renal transplant

recipients = 10) and control (immunocompetent patients = 74). Genotypes and mutations were determined by
sequencing and phylogenetic analysis.
RESULTS: All strains belonged to genotype D, subgenotype
D1 and subtype ayw2 and ayw3. Six RTR patients infected
by strains with the basal core promoter (T1762A1764/
T1764G1766) and two strains had shown precore (A1896)
mutations. However among immunocompetent patients, 44
strains had basal core promoter and 20 strains specified
precore mutations.
CONCLUSION: Previous studies have shown more rapid progression of HBV infection in RTRs. Host- and virus-related
factors are possibly associated with liver disease. In this study
there was no difference between existence of core promoter
and precore mutations among RTR and immunosuppressant
therapy. It seems that other factors such as high viral load may
play important role among HBV-infected RTRs.

W IT H
DRAW
N

26

P55
Hepatitis B vaccination in renal dialysis patients:
an audit and subsequent revision of the hospital
protocol
R Gupta, J Nicholas and D Dobie Royal Wolverhampton
Hospital, UK

Hepatitis B vaccination commenced at our hospital (Royal


Wolverhampton Hospitals NHS trust) in 2002. Since the
start, the programme had been seen to conform with
national guidelines published by the Renal Association
(http://www.renal.org/Clinical/GuidelinesSection/BloodBorneVirusInfection.aspx); however no formal audit was ever
conducted. Huge variations also existed between different
members of the renal team. The purpose of the study was to
ensure that all patients who were eligible for vaccination
were vaccinated appropriately, and that all practices were in
keeping with the national guidance. Additionally an aim
was to review the hospital renal IT system to assist with
quality control and thus patient care. For the study a sample
of 92 patients was randomly selected from a total population
of 278 patients receiving renal replacement therapy at the
hospital dialysis unit. Immunisation data, including the date
of immunisation together with the result and date of result,
was tabulated. The data showed that 62 out of 92 patients
mounted a suitable response from the immunisation programme. Significant discrepancies were unearthed as 32
patients were eligible for a booster dose, but only 11 received
them. A total of 22 boosters were given in the chosen
sample. The conclusions drawn from the study were that
due to discrepancies in the booster programme some patients
were being missed out from receiving the best possible care
while others were being receiving boosters inappropriately.
This has both financial and ethical implications and the
mismatch stems from a lack of uniformity of practice. The
recommendations from the audit were to devise the hospital

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Poster Sessions
protocol according to national guidance, so that all renal
physicians could maintain standard practice, and to increase
the use of IT in the renal department to further assist with
monitoring and immunisation of patients.

27

CONCLUSIONS: Re-education of medical staff, vaccination of


high-risk people, appraising of community about the tattoo
and leeching for declining of HBV infection prevalence is
recommended.

P57
P56
Predisposing factors of chronic hepatitis B virus
(HBV) infection in the north of Iran, 2011
H Eftekhar, F Akbari Haghighi, A Movahedi and
A Batebi School of Public Health, Tehran Medical Sciences University,

Prevalence of anti-HDV antibodies in HBsAg


negative subjects
M De Paschale, M Manco, L Belvisi, C Magnani, T Re,
P Vigano`, C Agrappi, P Mirri, A Gatti, B Banfi and
P Clerici Legnano Hospital, Italy

Iran
PURPOSE OF THE STUDY: Hepatitis B is an infectious and

WITH

D RA W

inflammatory illness of the liver caused by the hepatitis B


virus (HBV) that affects humans. The disease has caused
epidemics in parts of Asia and Africa (Williams. Hepatology
2006; 44: 521526). About a third of the world population
has been infected at one point in their lives, including 350
million who are chronic carriers. The overall HBsAg prevalence rates declined from 1.79% (1789/100,000 donations)
in 1998 to 0.41% (409/100,000 donations) in 2007 in
Iran. The frequency of HBV infection entering the blood
supply has decreased over this period as a result of
improvement in donor recruitment and selection, and universal vaccination of newborn since 1993, possibly
decreasing HBV infection prevalence in the general population (Kafi-abad et al. Tranfus Med 2009; 19: 189194). In
the province of Golestan which has second prevalence of
HbsAg (6.3%), between donor in Iran, we conducted a
survey for identifying of predisposing factors of HBV infection
in the north districts of Iran in 2011.
METHODS: This case-control study comprises of 200 individuals as case who referred to the Central Blood Bank of the
Province to donate blood and then, explicated they are
HBsAg carriers. About 402 donors who were HbsAg negative and referring before or after cases selected as control.
A questionnaire included demographic, and HBV risk factors
variables such as house causal contacts, sexual partnering,
travel to abroad, surgery, leeching, tattoo, phlebotomy
completed by the respondents. After collection of data, they
were analyzed by SPSS an ordinary descriptive statistical
package.
SUMMARY OF THE RESULTS: Between 200 HbsAg positive
donors 176 (88%) persons were male and 24 (12%) were
female. The most prevalent carriers were in the age groups of
2030 year (37.5%). There was a prominent significance
relations between chronic HBV and independents variables
such as house causal contacts, sexual partnering, travel to
abroad, surgery, leeching, tattoo, phlebotomy (p < 0.0001).
Therefore, variables such as marriage, and age of the
respondents had a significant relation with HBV infection
(p < 0.05), but it had not enough power in compare with
the previous variables.

The presence of anti-HDV antibodies is commonly found in


HBsAg positive subjects, and their presence indicates a HBVHDV co-infection. After recovery, the anti-HDV (with the
disappearance of HBsAg) may persist for years. On the other
hand, in the active infections, the competition between HBV
and HDV in some cases can lead to a decrease in the HBsAg
production. The aim of our study was to determine the
prevalence of these antibodies in HBsAg negative subjects,
but with the presence of other markers of HBV infection.
About 485 serum samples from HBsAg-negative subjects
(288 males, 197 females, mean age: 65.6 years, range
1896 years) who had sequentially come to our laboratory for the detection of markers of HBV, were investigated
for anti-HDV. Of these, 352 were anti-HBs positive/antiHBc positive (group A), 92 anti-HBs negative/anti-HBe
negative/anti-HBc positive (group B) and 41 anti-HBs
negative/anti-HBe positive/anti-HBc positive (group C). In
case of positivity for anti-HDV, HBV-DNA was researched,
and, where possible, also HDV-RNA. A total of four samples (0.8%) were anti-HDV positive: 1 (0.3%) in group A,
1 (1.1%) in group B and 2 (4.9%) in group C. All were
negative for HBV-DNA. Of the four samples, the one of
group A (HDV-RNA not tested) belongs to a woman of
foreign origin without biochemical signs of liver disease
(anti-HIV and anti-HCV negative). The sample of the
group B belongs to a patient with HCV liver disease (antiHIV and HDV-RNA negative). The samples of group C
belonged to two individuals, one of which died of septic
shock without any biochemical signs of liver disease (antiHIV and anti-HCV negative, HDV-RNA not tested) and one
with cirrhosis awaiting transplantation, not treated, with
anti-HCV positive and anti-HIV, HCV-RNA and HDV RNAnegative. In conclusions, in our area, the prevalence of
positive anti-HDV in HBsAg positive subjects had already
been estimated to be 4.9% (De Paschale M et al. Infection
2012, in press). In comparison, the percentage of 0.3% in
HBsAg-negative subjects with a past HBV infection (antiHBs and anti-HBc positive) is much lower. On the other
hand, the prevalence of anti-HDV positive among subjects
without anti-HBs antibodies, but with the presence of antiHBe and anti-HBc (4.9%) is equal to that found in the
HBsAg-positive subjects and suggests the search of anti-

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28

Poster Sessions

HDV in this group. The observed negativity for HDV-RNA,


however, raises questions that should be further investigated especially in the presence of markers of HCV infection.

P59

P58

HEPATOCELLULAR CARCINOMA

Hepatitis B virus genome asymmetry in


hepatocellular carcinoma: a case-series study
A Mohamadkhani Tehran University of Medical Sciences, Shariati
Hospital, Iran

D R AW

PURPOSE OF THE STUDY: The aim of this study was to


analysis complete genome sequence and compositional
asymmetry of HBV in different stage of hepatitis B.
METHODS: Full genome sequencing of 24 patients with
chronic hepatitis B, some of whom were complicated by
cirrhosis and hepatocellular carcinoma (HCC) was
performed. Mutations analysis was implemented in
comparison with HBV genotype D reference from the international DNA database. CpGProD, a web-based application,
were used for evaluating CG contents and predicting CpG
islands.
SUMMARY OF RESULTS: All strains had a length of 3182
base pairs except for two cases of HCC in which nine and 21
nucleotides, respectively, were deleted in preS2. The genetic
relatedness of these isolates was 97100%. There was a
common CpG-rich regions in all 24 isolated full genome
sequence, however comparatively compositional asymmetry
exhibit a strong negative GC skew for forming a CpG island
in minus strand in overlap with enhancer I and X-protein
gene promoter in three HCC patients, the cirrhotic patient
and three chronic hepatitis.
CONCLUSION: The high percentage of sequence identity
between HBV isolates in our patients demonstrates that
genomic factors except genotype are involved in hepatocarcinogenesis. Variation in GC content which is caused by a
different spectrum of mutations may have effect on DNA
compositional asymmetry and epigenetic modification of
HBV DNA in HCC.

W IT H

P61

BACKGROUND AND OBJECTIVES: Hepatitis B is a disease


caused by the hepatitis B virus, which is transmitted through
percutaneous or mucosal exposure to infectious blood or
body fluids. From prevention to treatment nurse have
functions as counselor, educator, advocate, case manager,
and primary care provider. Aim of the study was to find out
the effect of an educational program on nurses knowledge
and practices concerning hepatitis B virus.
METHODS: A quasi-experimental study was conducted in
50 nurses in emergency hospitals, Erbil City, from 15th of
January to 15th of June 2012. Assessment of the knowledge
and practices of nurses was carried out by using a questionnaire designed by the researchers. An educational program was designed, constructed and oriented in order to
improve the nurses knowledge and practices towards hepatitis B virus. Post-test was carried out after the educational
program using the same (pre program) questionnaire. Data
were analyzed using the Statistical Package for Social Sciences (SPSS) version 18).
RESULTS: The mean (SD) score of pre test knowledge was
6.96 1.6, while the mean (SD) score of post test
knowledge was 8.4 1.5 (p < 0.001). The educational
program has significant effects on nurses knowledge about
agent of hepatitis B virus (p < 0.001), complications of renal
failure (p = 0.002), and avoiding sharing needles and
syringes (p = 0.013).The post test mean scores for practice
(47 2.46) was significantly higher than the pre-test mean
score (43.7 5.16). The educational program had effects on
advising practice of hand washing before and post using
gloves (p = 0.01) using solution for hand washing
(p = 0.003), risk of contamination with patients bloods and
fluids (p = 0.04), removing of gown and washing hands
(p = 0.012).
CONCLUSION: The educational program played a significant
role in raising the level of knowledge and practice toward
prevention of hepatitis B virus.

P60

Seroprevalence of hepatitis E among Iranian


renal transplant recipients
Z Rostamzadeh, N Sepehrvand and Z Shirmohamadi

W IT H
DRAW

Effect of an educational program on nurses


knowledge and practices toward hepatitis B
virus in emergency hospitals in Erbil City
S Kurdy Hawler Medical University, Iraq

Abstract withdrawn

Virology Department, Urmia University of Medical Sciences, Iran


BACKGROUND: Renal transplant recipients are known to be
susceptible for viral infections with more severe clinical
presentations compared to healthy persons. Hepatitis E is
generally a self-limited disease which is caused by hepatitis E
virus. Recently, Hepatitis E becomes more important in organ transplant recipients, because of new findings regarding

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Poster Sessions

WITH

DRA W

the chronicity potential in this patient group. This study was


aimed to evaluate the seroprevalence of anti-HEV IgG among
kidney transplant recipients of Urmia in the north-west region of Iran.
METHODS: Ninety one patients were selected randomly
among patients who underwent kidney transplantation in
Urmia, Iran. Each patient was experimented for anti-HEV
IgG using ELISA method (Diapro, Italy).
RESULTS: Twenty eight subjects (30.8%) were seropositive
for anti-HEV IgG. Seropositive cases are generally older than
seronegative cases (p = 0.009). There was no correlation
between HEV infection and the level of education
(p = 0.206), the history of blood transfusion (p = 0.164),
history of pre-transplantation hemodialysis (p = 0.228).
There was not significant difference among the serum ALT
level of anti-HEV seropositive and seronegative cases. Multinomial logistic regression indicated no significant relationship between HEV infection and increase in ALT levels,
even when controlled for the treatment with azathioprine
(p = 0.79, OR=1.12; 95% CI: 0.452.76).
CONCLUSION: The anti-HEV IgG has a high prevalence in
Iranian kidney transplant recipients, and it is significantly
higher in comparison with previous studies in general population or HD patients. This could be of great clinical
importance considering the probable persistent HEV infection in the setting of graft recipients suggested in the literature.

29

HIV-1 (HIV-RNA > 500,000 copies/mL) with anti-HCV


negative yet. After 2 weeks the anti-HCV were still negative.
The patient started antiretroviral therapy with TVD + LPV.
At 6 weeks from time 0, the search for anti-HCV was still
negative, but the search for HCV-RNA was positive
(3.78 million IU/mL, genotype 3a). The subsequent search
of HCV-RNA on samples at one and 2 weeks from the time 0
gave values 100,615 and 1.50 million IU/mL. One week
later the patient started a treatment with 1000 mg peginterferon + 180 mg ribavirin. Only after 3 months from the
time 0, the search for anti-HCV was positive both at ELISA
and at immunoblotting (LIA) and HCV-RNA was negative.
After 11 and 13 months from time 0, the search for antiHCV at ELISA was weak positive (ratio sample/cutoff: 1.9
and 1.4 respectively) and negative at LIA. (HCV-RNA negative). The patient ended therapy for HCV and after
2 months (15 months from time 0) the detection of antiHCV was still weak positive at ELISA and negative at LIA
(HCV-RNA = negative). After 17 months from time 0 even
the detection of antibodies at ELISA was negative. Subsequent samples up to year 6 from time 0 were always
negative for HCV-RNA and anti-HCV at ELISA and LIA. In
conclusion, a patient with double acute infection HIV/HCV
subjected to early antiviral therapy for both viruses, can
develop a modest response in anti-HCV antibodies both in
the titer and in duration (14 months).

TRANSPLANTATION AND VIRAL HEPATITIS


HIV CO-INFECTION AND VIRAL HEPATITIS
P63
P62
Limited presence of anti-HCV antibodies in a
patient with contemporary HIV/HCV acute
infection: case report
M De Paschale, M Mena, M Manco, P Vigano` and
P Clerici Legnano Hospital, Italy

Phase II trial: Undifferentiated versus


differentiated autologous MSC transplantation
in Egyptian patients with HCV-induced liver
cirrhosis
I Khaled, A Saleh, S Toema, E Baioumi, O Hammam
and M Wahdan Theodor Bilharz Research Institute, Egypt

The loss of anti-HCV antibodies after recovering has been


reported in the literature, but little is known about the
antibody behavior during therapy begun in the acute phase
in a subject with concomitant acute HIV infection. We describe a case of concurrent HCV and HIV acute infection,
promptly treated with antiviral drugs, followed serologically
for 6 years. A 28-year-old Italian male patient presented
himself in October 2005 to our hospital for febrile lymphadenopathy. In anamnesis, a tattoo, undergone about
2 months before, was reported. The patient was subjected to
laboratory examination including the detection of antibodies
anti-HIV1/2 ELISA with a borderline positive result (ratio
sample/cutoff = 1.00) and negative Western blot 1/2. The
research of HIV-RNA was positive (10,620 copies/mL, subtype F1). The search for anti-HCV, anti-HBc and HBsAg was
negative (ALT: 298 U/L) (time 0). After 1 week, the detection of anti-HIV 1/2 was positive by ELISA and Western Blot

The study was aimed to evaluate the effect of autologous


transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis
C virus infection. Twenty-five patients with Child C liver
cirrhosis, MELD score >12 were included. They divided into
two groups. Group I, the MSCs group (n = 15), this group
was subdivided into two subgroups: Ia & Ib (undifferentiated
and differentiated respectively). Group II (control group;
n = 10) involved patients with cirrhotic liver under conventional supportive treatment. Ninety mL BM was aspirated
from the iliac bone for separation of MSCs. Surface expression of CD271, CD29 and CD34 were analyzed using flow
cytometry. Hepatogenesis was assessed by immunohistochemical expression of OV6, AFP and albumin. Finally
approximately 1 million MSCs/mL were suspended in saline
and were placed in blood bag and injected slowly intrave-

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Poster Sessions

nously over 15 min at a rate of 5 drops/min in one session.


Follow-up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin
levels, decline of elevated bilirubin and MELD score in MSCs
group. Statistical comparisons between the two subgroups
(Groups Ia & Ib) did not merit any significant difference
regarding clinical and laboratory findings.
IN CONCLUSION: Bone marrow MSCs transplantation either
undifferentiated or differentiated can be used as a potential
treatment for liver cirrhosis.

DRA W
N

P64
Chronic liver failure treated by liver
transplantation for patients with hepatitis C
virus. An overview of the past 12 years
M Maza Marques, E Chaib, A Lopes Lipolis, A Ramires
Hoshino, D Gianuzzi and C Soares Schmidt University of

patients with chronic HCV infection, and cirrhosis develops in


as many as 20% of patients within 1020 years of HCV infection. Our aim is to analyze both patient and graft survival rate
over the past 12 years.
MATERIAL AND METHODS: We have reviewed 35 articles
published between 2000 and 2011. A total of 122,763
patients have undergone liver transplantation for HCV
infection. The patient and graft survival rates in 13 years,
46 years and 710 years were analyzed.
RESULTS: Overall patient survival rates were 13 years
(76%), 46 years (20.44%), 710 years (19.3%). The graft
survival rates were 13 years (48.76%), 46 years
(17.95%), 710 years (22.24%).
CONCLUSION: Virtually all patients become reinfected with
HCV after transplantation, and histologic evidence of
chronic hepatitis develops in about half of them within a few
months. A recurrent liver failure appear to occur between 4
and 6 years with patient and graft survival rates of 20.44%
and 17.95% respectively.

W IT H
DRAW
N

30

WITH

Sao Paulo School of Medicine, Brazil

BACKGROUND: Hepatitis C virus (HCV) leads to chronic

inflammation of the liver in about 85% of infected individuals.


Histologic features of chronic hepatitis develop in virtually all

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Journal of Viral Hepatitis  2012 Blackwell Publishing Ltd, 19 (Suppl. 3), 530

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