P0635
CHRONIC HEPATITIS B TREATMENT INDIVIDUALIZATION BY
MEANS OF SERUM HBsAg AND MiR-B-INDEX KINETICS
D. Cavallone1, F. Oliveri1, P. Colombatto1, B. Coco1, P. Ciccorossi1,
V. Romagnoli1, B. Cherubini1, F. Moriconi1, B. Ferruccio2,
M.R. Brunetto1. 1Hepatology Unit, Reference Center of the Tuscany
Region for Chronic Liver Disease and Cancer, 2Digestive and Liver
Disease, General Medicine II Unit, University Hospital Pisa, Pisa, Italy
E-mail:
[email protected]
Background and Aims: Non-viral biomarkers of sustained control
of HBV infection are an unmet need for treatment individualization
in Chronic Hepatitis B (CHB). We recently reported that Inactive
Carriers (IC) and patients with sustained-virologic-response (SVR)
to Peg-IFN share a common serum miRNA signature (MiR-B-Index,
MBI). We studied the kinetics of MBI and HBsAg during and after
Peg-IFN.
Methods: 46 CHB patients (11 HBeAg pos, 29 males, median age
48.6 y, range 22.4–64.1 y; genotypes: A 5, D 39, F 2) were treated
with Peg-IFN2a 180 mg/w (median 13.2 months, 8–24 mo): 20 SVR;
17 relapsers (REL) and 9 non-responders (NR). Single RT-q-PCR
for miR-122-5p, miR-99a-5p, miR-192-5p, miR-126-3p, miR-335-5p
and miR-320a were performed using miRCURY RNA Isolation kit,
miRCURY-LNA™ Universal-RT-cDNA-Synthesis and RT-miRNA-PCR
(Exiqon-A/S). HBV-DNA and HBsAg were quantified by COBAS
TaqMan (Roche) and Architect (Abbott). HBsAg and MBI were tested
at baseline (BL), 24–48 wks and end of therapy (EOT) and 24 wks
post treatment (PTFU).
Results: Median HBsAg and MBI values at the different time points
in overall patients, HBeAg pos and neg are reported in the table. MBI
values >−1.7 were found: at BL in 5 HBeAg neg pts (4 SVR, 1 NR);
at EOT in 14/19 (73.7%) SVR (4 HBeAg pos, 10 HBeAg neg) and at
PTFU in all SVR, but in 1 NR and 1 REL only. In HBeAg neg pts at
EOT MBI values ≥−3.0 and HBsAg <1000 IU/mL had 100–93.3% sens.,
94.7–85.0% spec., 93.3–82.4% PPV, 100–94.4% NPV and 97.0–88.6%
DA in identification of SVR (AUROC 0.988 and 0.951 respectively).
Conclusions: Both HBsAg and MBI show good performances in
SVR prediction overall. In HBeAg neg CHB MBI predicts SVR since
therapy beginning and identifies all SVR at EOT qualifying as the
best biomarker for individual therapy monitoring.