studies

974A AASLD ABSTRACTS HEPATOLOGY, October, 2015
and more inflammation or significant fibrosis. Methods: One
hundred and seventy-three patients with chronic hepatitis B
virus (HBV) infection, whose treatment decisions depended on
liver biopsies, were enrolled in the study (NCT01962155 and
ChiCTR-DDT-13003724). The levels of serum angptl2 were
detected by Human ANGPTL2 Assay kit (Immuno-Biological
Laboratories Co., Japan). Liver biopsies were performed in
all patients. Histological Activity Index (HAI) and Liver fibrosis
stage were assessed according to Ishak criteria independently
by 2 pathologists. Results: 1) Serum Angptl2 levels were significantly
associated with not only HAI scores (p=0.000, spearman
rho=0.327) but also the liver fibrosis stages (P=0.000,
spearman rho=0.318). 2) Patients with moderate and more
inflammation or significant fibrosis (HAI>=5 or F>=3)who
should be treated immediatelyhad higher serum angptl2 (5.76
± 2.62 vs 4.31±1.82 ug/ml), AST, GGT and lower platelet
counts, HBsAg. Multivariate analysis confirmed that only
serum angptl2 level could independently predict urgent antiviral
therapy. 3) Angptl2 showed areas under the receiver
operating characteristics curve of 0.69 (95% CI: 0.60, 0.76)
for indicating moderate and more inflammation or significant
fibrosis. Leave-one-out cross-validation showed 64% cross-validation
grouped cases correctly classified. Using a cutoff value
of ≥7.36ug/ml, moderate and more inflammation or significant
fibrosis could be correctly identified with 91.76% specificity
and 72.0% PPV. Similarly, a lower angptl2 level (3.95 ug/
ml) could excluded urgent therapy with 78.41% specificity
and 70.8% PPV. Conclusion: Serum angptl2, a novel single
biomarker, independently predict moderate and more inflammation
or significant fibrosis, saving half of patients from liver
biopsies.
Disclosures:
The following authors have nothing to disclose: Hong Zhao, Yong-Qiong Deng,
Gui-Qiang Wang
1565
PreS mutations analyzed by deep sequencing are
correlated with the progression of liver diseases and
HBsAg production.
Yuichiro Suzuki, Shinya Maekawa, Nobutoshi Komatsu, Mitsuaki
Sato, Masaru Muraoka, Shuya Matsuda, Mika Miura, Yasuhiro
Nakayama, Taisuke Inoue, Minoru Sakamoto, Nobuyuki Enomoto;
University of Yamanashi, Chuo, Japan
Background and Aim: Recently, it is considered that achieving
HBsAg seroclearance is the ultimate therapeutic goal in
the treatment of chronic hepatitis B since serum HBsAg titer
is suspected to reflect HBV-cccDNA titer in the liver. On the
other hand, preS region of HBV genome responsible for HBsAg
production was reported to be often mutated in advanced liver
disease by direct sequencing. However, the interrelationship
among HBsAg, preS mutation and liver disease progression is
complicated and remains unclear. In the present study, to clarify
the interrelationship among HBsAg titer, preS mutation and
disease progression, we performed deep sequencing study
for preS mutations. Methods: A total of 96 patients including
32 inactive carriers (IC), 28 with chronic hepatitis (CH) and
36 with cirrhosis or hepatocellular carcinoma (LC/HCC) were
analyzed. All of inactive carriers were HBeAg negative, and
22 patients were with HCC. They were all nucleotide analogue
naïve. Deep sequencing was performed targeting 522nt in the
preS region from patient serum, and proportion of preS1 and
preS2 start codon mutations, preS1 and preS2 deletions was
determined in each patient. Results: In IC group, CH group,
and LC/HCC group, median HBsAg was respectively 688 IU/
ml, 2075 IU/ml, and 1065IU/ml. HBsAg level