studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 991A
(95%CI 1.01 − 1.09), p=0.0018), AFP > 20 ng/mL (HR 3.2
(95%CI 1.01 − 9.99), p=0.049), WFA(+)-M2BP (per 1 COI)
(HR 1.3 (95%CI 1.01 – 1.63), p=0.039) as independent risk
factors for the development of HCC. Conclusion: WFA(+)-M2BP
can be applied as a simple and reliable surrogate marker for
the risk of HCC development, in addition to liver fibrosis stage
as determined by liver biopsy.
Disclosures:
Seigo Abiru - Grant/Research Support: CHUGAI PHARMACEUTICAL CO.,LTD
The following authors have nothing to disclose: Kazumi Yamasaki, Shigemune
Bekki, Yuki Kugiyama, Shinjiro Uchida, Akira Saeki, Satoru Hashimoto, Shinya
Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi
1601
Identification of a non-invasive model based on serum
levels of miR-122 and miR-222 to predict severe fibrosis
and cirrhosis in patients with chronic hepatitis B
Kevin Appourchaux 5,2 , Emilie Estrabaud 5,2 , Matthieu Resche-Rigon
3,4 , Martine Lapalus 5,2 , Michelle Martinot-Peignoux 5,2 , Nathalie
Boyer 2 , Michel Vidaud 6 , Pierre Bedossa 7,1 , Patrick Marcellin 5,2 ,
Tarik Asselah 5,2 ; 1 INSERM, Paris, France; 2 Hepatology, Beaujon
Hospital, Clichy, France; 3 Service de Biostatistique et information
médicale, Saint-Louis Hospital, Paris, France; 4 INSERM UMR1153,
Paris, France; 5 INSERM UMR1149, Paris, France; 6 INSERM
UMR745, Paris, France; 7 Service d’Anatomie Pathologique, Beaujon
Hospital, Clichy, France
Background and aims Patients with chronic hepatitis B (CHB)
are at high risk to develop cirrhosis and hepatocellular carcinoma
(HCC). Staging fibrosis is mandatory, for both the prognosis
and the need for treatment. The liver-enriched miR-122
has been suggested to inhibit HBV replication. MicroRNAs are
increasingly investigated as biomarkers because of their high
stability. We aimed to identify miRNAs differentially expressed
during fibrosis in patients with CHB. Patients and Methods A
total of 103 patients with CHB were consecutively enrolled. All
the patients had at least one biopsy to determine the stage of
fibrosis (METAVIR scoring system) and no HCC. 85,4% of the
patients were males, the mean age was 41.8 years. The mean
HBV DNA level was 5.74 logUI/mL and 60.2% of the patients
were negative for HBe antigen. Serums and biopsies were
available for respectively 88 and 83 patients (69 paired liver/
serum). Among patients with available serums 2.3%, 26.4%,
27.6%, 24.1% and 19.6% had respectively F0, F1, F2, F3
and F4 ; and among patients with available biopsies, 2.4%,
27.7%, 27.7%, 20.5% and 21.7% had respectively F0, F1,
F2, F3 and F4. The expression of miR-27b, -29a, -92a, -122,
-146a, -222 and -224 which are related to liver fibrosis was
assessed by RT-qPCR. Results A reduced expression of hepatic
miR-122 (p=0.004) and miR-27b (p=0.038) was observed in
patients with severe fibrosis and cirrhosis (F3-F4) compared
to those with no, mild and moderate fibrosis (F0-F1-F2). An
increased expression of hepatic miR-222 (p=0,018) and
miR-224 (p=0.0001) was observed in patients with F3-F4
compared to those with F0-F1-F2. A reduced expression of
circulating miR-122 (p=0.049), miR-92a (p=0.031), and miR-
29a (p=0.048) was observed in patients with F3-F4 compared
to those with F0-F1-F2. An increased expression of circulating
miR-146a (p=0.015) and miR-222 (p=0.040) was observed
in patients with F3-F4 compared to those with F0-F1-F2. The
multivariate analysis of clinical data and circulating miRNAs,
allowed us to build a model combining circulating miR-122
and miR-222, platelets count and alkaline phosphatase (ALP).
The AUC of the model was 0,86 while FIB-4 and APRI had
an AUC of 0,81 and 0,70, respectively. Conclusions Hepatic
miR-27b, -122, -222 and -224 were differentially expressed in
patients with F0-F1-F2 and in those with F3-F4. The increased
expression of miR-222 in patients with F3-F4 might suggest
a premalignant condition to HCC. The model combining the
assessment of the following non-invasive biomarkers, circulating
miR-122 and miR-222, platelets count and ALP was more
accurate than FIB-4 and APRI to distinguish patients with F3-F4
from those with F0-F1-F2.
Disclosures:
Nathalie Boyer - Board Membership: MSD, JANSSEN, Gilead, Abbvie; Speaking
and Teaching: BMS
Patrick Marcellin - Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen,
MSD, Abbvie, Alios BioPharma, Idenix, Akron; Grant/Research Support: Roche,
Gilead, BMS, Novartis, Janssen, MSD, Alios BioPharma; Speaking and Teaching:
Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Boehringer, Pfizer,
Abbvie
Tarik Asselah - Advisory Committees or Review Panels: AbbVie, Merck, Gilead,
BMS, Roche, Janssen
The following authors have nothing to disclose: Kevin Appourchaux, Emilie
Estrabaud, Matthieu Resche-Rigon, Martine Lapalus, Michelle Martinot-Peignoux,
Michel Vidaud, Pierre Bedossa
1602
Interleukin-2 Receptor and Transforming Growth Factor
Alpha Independently Predict Significant Fibrosis in
Chronic Hepatitis B Patients with Normal or Mildly Elevated
Alanine Aminotransferase
Gui-Qiang Wang, Yong-Qiong Deng, Hong Zhao; Department of
infectious disease, Peking University First Hospital, Beijing, China
Background: Patients with normal or mildly elevated serum alanine
aminotransferase (ALT) are not guaranteed to be free from
liver damage. Invasive liver biopsy is the current gold standard
for assessing histological liver injury. There is an increasing
demand for developing a noninvasive marker or index for diagnosis
of liver inflammation and fibrosis in patients with normal
or mildly elevated ALT.Aim: The aim of this study was to investigate
the association of circulating cytokines and chemokines
with liver inflammation and fibrosis, and to deeply assess their
diagnostic value in CHB patients with ALT less than 2 times of
upper limit of normal(ULN).Methods: Two hundred and twenty
seven CHB patients with qualified biopsy were prospectively
enrolled. There were 151 patients with ALT≥2×ULN and 76
persons with ALT 2×ULN. All patients underwent liver biopsy.
The serum levels of cytokines and chemokines were determined
by simultaneous multianalyte detection methods. Histological
Activity Index (HAI) and Liver fibrosis stage were assessed
according to Ishak criteria.Results: Patients with moderate and
more inflammation showed significantly higher levels of CXCL-
11, CXCL-10 and interlerkin-2 receptor(IL-2 R)than the opposite
(P0.001). Patients with significant fibrosis had higher levels of
interleukin-8(IL-8) (P=0.027), Transforming growth factor alpha
(TGF-a) (P=0.011), IL-2R (P=0.002) and CXCL-11(P=0.032)
than no significant fibrosis. In 151 patients with ALT≤2×ULN,
31.8% and 29.1% showed moderate and more inflammation
and significant fibrosis respectively. Multivariate analysis indicated
CXCL-11 independently associated with moderate and
more inflammation, and TGF-a, L-2R with significant fibrosis
in patients with ALT≤2×ULN. Based on CXCL-11, TGF-a, L-2R
and clinical parameters, we developed inflammation-index
and fib-index which showed areas under the receiver operating
characteristics curve (AUROC) of 0.75 (95% CI 0.66-
0.84) for moderate and more inflammation, and 0.82(95% CI
0.75, 0.90) for significant fibrosis respectively in patients with
ALT≤2×ULN. Leave-one out cross-validation showed 74.5%
and 81.3% cases correctly classified by inflammation-index
and fib-index. Compared to existing scores, fib-index was
significantly superior to aspartate aminotransferase (AST) to
platelet ratio index (APRI) and FIB-4 score for significant fibro-