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回复 HBVCURER 的帖子
Oh, I see. You referred to the abstract presented at EASL 2015:
SERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN CHRONIC HEPATITIS B PATIENTS DOSED WITH THE NUCLEIC-ACID POLYMER REP2139-CA
Louis Jansen* 1, 2, Andrew Vaillant3, Femke Stelma1, 2, Neeltje A. Kootstra2, Michel Bazinet3, M. Al-Mahtab4, Hendrik W. Reesink1, 2
1Gastroenterology and Hepatology, 2Experimental Immunology, Academic Medical Centre, University of Amsterdam., Amsterdam, Netherlands, 3REPLICor Inc., Montreal, Canada, 4Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Corresponding author’s email: l.***@****
Background and Aims: Treatment of chronic hepatitis B (CHB) patients with the HBsAg release inhibitor REP2139-Ca may be a promising new option for achieving therapy-induced HBsAg loss (functional cure), however its effect on circulating hepatitis B pregenomic RNA (HBV-RNA) is not known. For this, we determined HBV-RNA levels during treatment with REP2139-Ca and compared these with HBV-DNA and HBsAg levels.
Methods: 12 Patients with HBeAg positive CHB (mean HBV-DNA 8.21 logC/mL) participating in a phase 2 study were dosed with the nucleic-acid based amphipathic polymer REP2139-Ca for 20-38 weeks. Responders to REP2139 (defined as decline in serum HBsAg) were subsequently treated with add-on peginterferon alpha-2a and/or thymosin alpha-1. HBsAg (Architect), HBV-DNA, and HBV-RNA levels were determined in baseline serum samples, after 20-24 weeks of REP2139-Ca monotherapy, and either during a treatment-free follow-up (for responders) or during entecavir treatment (for non-responders). HBV-RNA isolated from 140 µL of plasma was quantified by RT-qPCR using HBV-specific primers. Lower limit of quantification of RNA was set at 3.00 logC/mL. Variables were evaluated with a paired T-test.
Results: HBV-RNA was detectable in all 12 patients before treatment (mean 6.70 (SD 0.83) logC/mL), and was significantly associated with HBsAg (r2 0.33, p=0.049) and HBV-DNA (r2 0.74, p<0.001). After 20-24 weeks of REP2139-Ca treatment, mean HBV-RNA, HBV-DNA, and HBsAg levels declined significantly compared to baseline (-2.54, -3.34, and -3.12 logC or IU/mL, respectively, all p<0.001). At week 20-24, HBV-RNA was undetectable in 8/12 patients. In 7 of these 8 patients, HBV-RNA remained undetectable during the treatment-free follow-up period (mean 21.9 weeks, range 7-27). HBsAg loss and anti-HBs seroconversion was achieved in 4/8 patients during treatment-free follow-up (anti-HBs range 200-766 U/L).
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In 12 HbeAg POSITIVE patients, 20-24 week treatment with REP2139-CA, mean HBV-RNA, HBV-DNA, and HBsAg levels declined significantly compared to baseline. Replicor attributed the decline in HbsAg to REP2139-CA, but they OBSERVED also decline in HBVDNA and HBV-RNA. Replicor offered no explanation, and I of cause cannot offer an explanation.
If you believe it is due to the blocking of release of new viral particles by REP2139-CA, that is your business. If you don't believe REP92139-CA caused decline in HBsAg, that is your business. To me, the decline in both HBVDNA and HBsAg in HBeAg positive patients by REP2139-CA is a very encouraging result if can be repeated in a larger cohart of patients. An explanation of the mechanism that lead to decline in HBVDNA would be nice, but it can wait.
As to masking of HbsAb, it is well known that chronic HBV patients do produce HBsAb(pre-existing) but in far less quantity than HBsAg, hence they are "masked" and cannot be detected .
As to removal of "immunosuppressive" effect, it is believed that the immunosuppressive effect does not have to wait until HBsAg = 0 to be removed, but may start to wane after the decline of HBsAg to a certain threshold level, maybe 1,000 iu/ml.
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楼主: newchinabok
发表于 2015-11-11 14:27
