studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 911A
no change after treatment. All patients were divided equally
into training and testing cohorts. The fibrosis scoring index for
CHC was analyzed against Ishak staging system as the gold
standard. Results: 27 out of 100 parameters showed high-level
correlation with Ishak staging, mainly in the portal and total
collagen compartments. Systematic area under curve (AUC)
optimization analysis further identified 6 parameters with the
highest correlation out of the 27. These 6 parameters were as
efficient (AUC: 0.86–0.94) in identifying differences between
all Ishak brosis stages as using all 27 parameters (AUC: 0.85–
0.94). Systematic analysis performed for the 39 paired biopsies
identified 8, 1 and 2 parameters for the respective Ishak
staging decrease, increase, and no change groups. These 11
parameters from the paired biopsies comprised 7 which were
already identified in the 27 parameters, and 4 new ones. Taking
the best correlating parameter from these 4 new ones with
Ishak staging, and adding it to the 6 highest correlation parameters,
we developed a 7-parameter indexing model (comprising
Strlength, Portal, NoShortStrP, NoStrPA, NoLongStrPA,
StrLengthPA, NoXlinkP). This model can faithfully and reliably
recapitulate Ishak brosis scores in CHC patients, including the
paired pre- and post-treatment biopsies. Conclusions: A modified
qFibrosis model was developed and validated for CHC
patients and for treatment response assessment. An indexing
system with 7 parameters was shown to be highly accurate
and reproducible for the objective and quantitative analysis of
fibrosis progression and/or regression in CHC patients.
Disclosures:
Lai Wei - Advisory Committees or Review Panels: Gilead, AbbVie; Grant/
Research Support: BMS
The following authors have nothing to disclose: Huiying Rao, Feng Liu, Aileen -.
Wee, Bo Feng, Ming Yang
1437
Collagen and tissue turnover as function of age – implications
for fibrosis
Morten A. Karsdal 1 , Federica Genovese 1 , Emilie A. Madsen 1 ,
Tina Manon-Jensen 1 , Detlef Schuppan 2,3 ; 1 Nordic Bioscience, Herlev,
Denmark; 2 Institute of Translational Immunology and Research
Center for Immunotherapy, University Medical Center, Mainz,
Germany; 3 Division of Gastroenterology, Beth Israel Deaconess
Medical Center, Harvard Medical School, Boston, MA
Background: The extracellular matrix (ECM) is the backbone of
all tissues. It is a complex grid consisting of multiple structural
proteins which each play a vital role for the function and maintenance
of normal tissue function. In development and growth,
tissue is being formed and elaborated (tissue modeling), while
in adult life, tissues are being maintained and remodeled.
These processes involve likely different mechanisms. During
tissue modeling and remodeling, small fragments of proteins
are released into the circulation, where they may be used as
biomarkers of tissue turnover. Aim: The aim of the study was
to investigate ECM turnover in rodents as a function of age.
Materials and Methods: Serum of rats of 1, 2, 3, 4, 5, 6,
10 and 12 months of age was profiled for 15 markers of
ECM turnover, including: fragments of type I, II, III, IV, V and
VI collagen formation (P1NP, Pro-C3, P4NP_7S, Pro-C5, Pro-
C6) and degradation (C1M, C2M, C2M-beta, C3M, C4M,
C5M, C6M); biglycan (BGM) and elastin (ELM7) degradation;
and the type I and II collagen telopeptides CTX-I and CTX-II.
Results: Type I and II collagen turnover was up to 93% and
97% downregulated in old (one year) compared to young (one
month) old animals (p