EASL2015: Some exciting oral presentations

[StephenCastlecrag]

EASL 2015 is being held in Vienna, Aprol 22-26. The program is available:
https://ilc-congress.eu/wp-content/uploads/2014/08/EASL-ILC-2015-Final-programme_bookmarked.pdf

Personally, I am looking forward to the following oral presentations, especially the last one, with some trepidation.

SATURDAY, APRIL 25, 2015
Viral Hepatitis B & D: Clinical
Chairs:
Jerzy Jaroszewicz, Poland
Cihan Yurdaydin, Turkey

ABSTRACT O112
11:30 - 11:45
HBSAG CLEARANCE AFTER ADDITION OF 48 WEEKS
OF PEGIFN IN HBEAG NEGATIVE CHB PATIENTS ON
NUCLEOS(T)IDE THERAPY WITH UNDETECTABLE
HBV DNA FOR AT LEAST ONE YEAR: FINAL RESULTS
FROM ANRS-HB06 PEGAN STUDY: MULTICENTER
RANDOMIZED CONTROLLED PHASE III TRIAL
Marc Bourliere, France

ABSTRACT O113
11:45 - 12:00
HLA DPB1 RS9277535 POLYMORPHISM STRONGLY
PREDICTS HBSAG CLEARANCE IN IFN TREATED
GENOTYPE D HBEAG-NEGATIVE PATIENTS WITH
CHRONIC HEPATITIS B
Pietro Lampertico, Italy

ABSTRACT O114
12:00 - 12:15
SERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN
CHRONIC HEPATITIS B PATIENTS DOSED WITH THE
NUCLEIC-ACID POLYMER REP2139-CA
Louis Jansen, The Netherlands

ABSTRACT O115
12:15 - 12:30
HIGH ANTIVIRAL ACTIVITY OF THE HBV CORE
INHIBITOR NVR 3-778 IN THE HUMANIZED UPA/SCID
MOUSE MODEL
Klaus Klumpp, The United States

ABSTRACT O116
12:30 - 12:45
PREDICTIVE VALUE OF BASELINE AND ON-TREATMENT
QHBSAG LEVEL IN HBEAG POSITIVE CHB PATIENTS
WHO SWITCHED FROM NUCS TO PEGYLATED
INTERFERON A-2A: A FURTHER ANALYSIS FROM NEW
SWITH STUDY
Hong Ren, China

ABSTRACT O117
12:45 - 13:00
PREDICTORS OF CLINICAL RESPONSE: RESULTS FROM
A LARGE, RANDOMIZED CONTROLLED STUDY WITH
TENOFOVIR DISOPROXIL FUMARATE (TDF) PLUS
PEGINTERFERON ALFA-2A (PEG) COMBINATION FOR
CHRONIC HEPATITIS B (CHB)
Henry L. Chan, China

ABSTRACT O118
13:00 - 13:15
OPTIMIZING THE PRENYLATION INHIBITOR
LONAFARNIB USING RITONAVIR BOOSTING IN
PATIENTS WITH CHRONIC DELTA HEPATITIS
Cihan Yurdaydin, Turkey

ABSTRACT O119
13:15 - 13:30
STOPPING TENOFOVIR DISOPROXIL FUMARATE
(TDF) TREATMENT AFTER LONG TERM VIROLOGIC
SUPPRESSION IN HBEAG-NEGATIVE CHB: WEEK 48
INTERIM RESULTS FROM AN ONGOING RANDOMIZED, CONTROLLED TRIAL («FINITE CHB»)
Thomas Berg, Germany

[stef2011]

thank you, we ll keep an eye on the trials on hbv infected hcc patients although data will be presented next years.

the good thing is these drugs are already available off label in germany (expensive though).a guy is using a combo of 3 of these drugs plus many other immune therapies on stage 4 metastatic colorectal cancer.
he s using it while on remission/very small non growing tumors left.he s actually a lab rat (his own words) but little choice for him actually to hal from such advanced disease, it will be useful to see his sides and small dosage (for now no relevant sides)

[StephenCastlecrag]

I want to make a few brief comments.
Several years, we had a very high hope for REP9AC and NUC/PegIFN treatments, based on the observations that reduced exposure to HBV antigens and hbvdna can partially restore HBV T-cell immunity. Fortunately, the science seems to be confirmed, however the progress of development of REP9AC as a widely available drug has been stalled and the finer details of a successful protocol for the use NUC/PegIFN treatment have yet to be elicited.

In the last year or so, thanks to research in cancer immunotherapy, we saw the emergence of anti immune checkpoint and C-ART therapies, both seem to hold great promise not just for cancer but also for HBV. Of course, we also saw the arrival of CRISP-Cas9 technology, who knows what and where this technology can lead to.

In the meantime, we await results from early clinical trials of ARC520, GS9620, Birinapant, SB1900, Novira's capsid inhibitor, ABX203, and GS4774.

So we remain hopeful, but the wait seems to be longer.

Now the latest research from Bertoletti is truly amazing.

[StephenCastlecrag]

Thank you for the insight, very much appreciated.

[studyforhope]

addition of anti pd1 agents might well help the intensity of  of the hbsag clearance and push it into seroconversion.

but this therapy activates t cells all scross the spectrum and its proper extent is hard to titrate. so it is quite dangerous. Obtaining approval for hbv clearance trials will be difficult.

here is an example:

We report the acute onset of polyarticular inflammatory arthritis in 2 patients receiving the immune check-point inhibitor, pembrolizumab (MK-3475), anti-PD1 drug for metastatic melanoma after 14 and 11 months therapy, respectively. The first patient had severe tenosynovitis, synovitis, bone marrow edema, and myositis, whereas the second patient had predominantly synovitis and tenosynovitis. Good symptomatic control was obtained with bisphosphonates and salazopyrin, avoiding the use of T-cell immunosuppressants. These cases raise important questions on whether anti-PD1 therapy allows preexisting autoimmune T-cell clones to escape tolerance by suppressing regulatory T cells or whether they allow autoimmunity to develop de novo. These conditions heighten our awareness of complications associated with the clinical use of these agents, and provide a prototypical model for future research into the understanding of autoimmunity.

in comparison, replicors side effects are quite mild.

[stef2011]

what about pd1 nivolumab after achieving peginterferon response with peg add on sequential with nucs and of course with baseline hbsag much less than 1000iu/ml (nivolumab+tdf after 6 months of peg+tdf)

we should have some ideas about possible liver damage from the hcc hbv infected trials

[studyforhope]

the problem with therapeutic vaccines is that at best they will elicit a t cell response agsinst the epitopes in the vaccine proteins or peptides.

if immune adaptive mutations in the patients hbv genome exist, these t cells will not work.

nevertheless the cuban core/hbsag combo vaccine worked about as good as interferon. The abivax trial will hopefully confirm that. But that is not enough to produce a permanent hbsag seroconversion.

These therapeutic vaccines might have a role to solidify svrs like the ones achieved with replicor plus immuntherapy.

[Scaredpreg]

Thabk you' for the info. Although new in this forum and some terminology, if I am understanding this right... The percentage of cure with current strategy still have a low percentage with lengthy treatment.  I hope they find something soon to cure this complex virus. Praying to God for all of us.

[sorte]

How about therapeutic vaccacines ? There are some trials

[studyforhope]

the current approaches with nuc/interferon , as has again been shown, will only lead to a small perecentage of stable seroconversion. if many years of nuc pretreatment would improve this disapointing percentage remains to be seen.

replicors results as recently shown in the ots presentation teach a big lesson regsrding the effectiveness of hbsag reduction to almost nothing. Additional immune stimulation is needed and might have to be more specific and prolonged and combined with post treatment svr stability monitoring to achieve a true permanent svr status.

the lack of success in functional cures is both a result of low quality t cells as well as multiple immune resistance mutations in the targeted hbv genomes.
most of these adaptive immune escape mutations are located in the critical high efficiency epitopes, especially in the core and e antigen genes and their promotor regions.

some lower quality epitopes always remain, but their tcell engagement does not lead to killing and cytokine responses of sufficient strength. the use of birinapant might help to overcome this relative weakness and restore effectiveness.

most likely only a combination of these concepts will lead to svr rates of over 50%.

YET ANOTHER APPROACH is the direct improvement of tcell weakness using engineered tcells tailored to hbv class i epitopes by electroporative introduction of  EPITOPE SPECIFIC T CELL RECEPTOR MESSENGER RNA into lymphocytes in a large scale and adoptively transferring those into patients...





ENGINEERED HBV-SPECIFIC T CELLS: DISENTANGLING ANTIVIRAL FROM KILLING CAPACITY
Sarene Koh* 1, Christine Y. L. Tham2, Anthony Tanoto Tan2, Andrea Pavesi3, Roger D. Kamm4, Antonio Bertoletti2
1Singapore Institute for Clinical Sciences A*STAR, 2Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, 3Singapore MIT Alliance - SMART, Singapore, Singapore, 4Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States

Corresponding author’s email: sarene_koh***@****-star.edu.sg

Background and Aims: We have recently demonstrated that adoptive transfer of engineered HBV-specific T cells in a patient with HBsAg-productive HCC cause a profound inhbition of HBsAg production (J Hepatology 2014. doi: 10.1016/j.jhep.2014.10.001.). The difficulty to disentangle the antiviral effect of HBV T cells from their killing ability constitutes a barrier to the application of this immunotherapeutic approach in chronic HBV patients. Therefore, our aim was to produce HBV-specific T cells that can inhibit virus replication without hepatotoxicity and analyzed the antiviral mechanism mediated by these engineered T cells.
Methods: Using messenger RNA electroporation of HBV-T cell receptor in human lymphocytes, we produced HBV-specific T cells characterized by different activation and maturation stages. These distinct HBV-specific T cell populations were tested in 2 dimensional (2D) and 3D in vitro assays for their ability to inhibit HBV replication and/or lyse target cells.
Results: Among different engineered HBV-specific T cell populations, we selected a perforin/granzymelow HBV-specific T cells able to induce 50% drop in HBV viral load in HepG2.2.15 without causing detectable hepatotoxicity at an effector to target ratio of 1:3 (both in 2D and 3D models). After HBV-specific recognition, these resting naïve (CD28+CD27+) T cells produced a large range of cytokines (IFN-gamma, TNF-alpha, GM-CSF and lymphotoxin-alpha and -beta. Analysis of the specific antiviral mechanisms indicated that a specific synergy between classical antiviral cytokines (IFN-gamma, TNF-alpha, GM-CSF) and activator of lymphotoxin-β receptor (LTβR) pathway mediate the antiviral but non-cythopathic effect.
Conclusions: It is possible to produce HBV-specific T cells able to efficiently inhibit HBV replication without causing direct hepatocytes killing. This represents an attractive cell population for adoptive T cell therapy of chronic hepatitis B. The relative contribution of antiviral cytokines and/or LTβR activation to antiviral activity can lead to the development of new targeted combinatorial therapy in HBV infection.

Disclosure of Interest: None Declared


European Association for the Study of the Liver C/O EASL - The Home of Hepatology - 7 rue Daubin - 1203 Geneva - Switzerland
Phone: [phone] - Fax: [phone] - Email: [email protected]

[StephenCastlecrag]

Many thanks for the abstracts!

I guess a lot to ponder over.The results are not as good as we hope, but they are not bad either. It seems there is not quick way to a cure using NUC/Interferon combination. What is next?

Your comments will be appreciated.

[Royal36]

Thank you studyforhope

[studyforhope]


RS-4263
Viral hepatitis
Hepatitis B & D - clinical (Therapy, new compounds, resistance)


PREDICTORS OF CLINICAL RESPONSE: RESULTS FROM A LARGE, RANDOMIZED CONTROLLED STUDY WITH TENOFOVIR DISOPROXIL FUMARATE (TDF) PLUS PEGINTERFERON ALFA-2A (PEG) COMBINATION FOR CHRONIC HEPATITIS B (CHB)
Henry L. Chan* 1, SH. Ahn2, WL. Chuang3, Aric J. Hui4, F. Tabak5, R. Mehta6, J. Petersen7, Chuan-Mo Lee8, Xiaoli Ma9, Florin A. Caruntu10, Won Y. Tak11, Magdy Elkhashab12, L. Lin13, P. Dinh13, EB Martins13, P. Charuworn13, JG Mc Hutchinson13, GM Subramanian13, SG Lim14, GR Foster15, Scott Fung16, Luis Morano17, Didier Samuel18, Kosh Agarwal19, Ramazan Idilman20, Simone Strasser21, M. Buti22, GB. Gaeta23, AJ. Hui24, George Papatheodoridis25, R. Flisiak26, P. Marcellin27
1The Chinese University of Hong Kong, Hong Kong, China, 2Yonsei University College of Medicine, Seoul, Korea, South, 3Kaohsiung Medical University, Kaohsiung, , 4Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China, 5Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, , 6Liver Clinic, Surat, India, 7University of Hamburg, Hamburg, Germany, 8Kaohsiung Chang Gung Memorial Hospital , University College of Medicine, Kaohsiung, Taiwan, 9Drexel University College of Medicine, Philadelphia, United States, 10National Institute for Infectious Diseases “ Matei Bals”, Bucharest, Romania, 11Kyungpook National University Hospital, Daegu, Korea, South, 12Toronto Liver Center, Toronto, Canada, 13Gilead Sciences, Inc., Foster City, United States, 14Yong Loo Lin School of Medicine, Singapore, Singapore, 15Queen Marys University of London, London, United Kingdom, 16University of Toronto, Toronto General Hospital, Toronto, Canada, 17Hospital de Meixoeiro, Pontevedra, Spain, 18Hôpital Paul Brousse, Villejuif, , 19King's College Hospital, London, United Kingdom, 20Ankara University School of Medicine, Ankara, , 21Royal Prince Alfred Hospital, Sydney, Australia, 22Hospital Universitari Vall d'Hebron, Barcelona, Spain, 23Second University of Naples, Naples, Italy, 24The Chinese University of Hong Kong, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong, , 25Athens University Medical School, “Laiko” General Hospital of Athens, Athens, Greece, 26Medical University of Bialystok, Bialystok, Poland, 27Hôpital Beaujon, Paris, France

Corresponding author’s email: ***@****

Background and Aims: There are scarce on-treatment data on HBsAg and HBV DNA kinetics with concomitant nucleos(t)ide analog and immunomodulator HBV therapy. Predictors of clinical response may help manage patients on combination therapy.
Methods: From study GS-US-174-0149, 740 CHB patients without advanced disease were randomized 1:1:1:1 to receive (TDF+PEG) x48 weeks (arm A); (TDF+PEG) x16 weeks followed by TDFx32 weeks (arm B); continuous TDF (arm C); PEGx48 weeks (arm D). Associations between baseline and on-treatment variables with change in HBV DNA (log10 IU/ml) or HBsAg (log10 IU/ml) levels from baseline to week 48 or HBsAg loss at Week 72 were examined via linear regression or Cox regression analyses, respectively, in univariate models as well as multivariate models.
Results: In a multivariate analysis, treatment arms A, B, and C compared to arm D, baseline HBeAg-negative status, higher baseline HBV DNA, and lower baseline HBsAg levels were associated with greater HBV DNA decline at Week 48. For every 1 log10 IU/ml increase in baseline HBV DNA or 1 log10 IU/ml decrease in baseline HBsAg, there is an expected greater HBV DNA decline by 0.85 or 0.31 log10 IU/mL, respectively, at Week 48. On multivariate analysis, achieving HBsAg loss was associated with treatment Arm A, GT A, early ALT flare on treatment, and, at Week 12, with HBsAg decline from baseline >1 log10 IU/ml (table). The positive predictive values for achieving HBsAg loss at week 72 with (TDF+PEG)x 48 weeks with either 1 log10 IU/ml decline or HBsAg < 100 IU/ml at week 12 were 43% and 50%, respectively, and the negative predictive values (NPV) were 97% and 95%, respectively. TDF+ PEG combination for 48 weeks exhibited the largest HBsAg decline (log10 IU/ml) as compared to other treatment arms (Arm A: -1.1, B: -0.5, C: -0.3, D: -0.8; p < 0.01 for all comparisons of arm A versus others). Similar levels of HBsAg decline were observed in genotypes (GT) A and B (mean log10 IU/ml ± SD: -1.2±2.0 and -1.1±1.2, respectively), both of which exhibited a greater decline than GT C and D (-0.5±0.9 and-0.4±1.0, respectively) (p < 0.05).
Conclusions: Higher baseline HBsAg levels appear to impact negatively on-treatment HBV DNA response. HBsAg decline on TDF plus PEG combination therapy x48weeks was synergistically greater than on either TDF or PEG monotherapy. HBsAg decline appears to favor HBV GT A and B. Moreover, HBsAg decline at week 12 shows high NPV for week 72 HBsAg loss and may provide a valuable tool for response-guided therapy in PEG+TDF combination treatment.

Disclosure of Interest: None Declared

[studyforhope]

RS-2857
Viral hepatitis
Hepatitis B & D - clinical (Therapy, new compounds, resistance)


PREDICTIVE VALUE OF BASELINE AND ON-TREATMENT QHBSAG LEVEL IN HBEAG POSITIVE CHB PATIENTS WHO SWITCHED FROM NUCS TO PEGYLATED INTERFERON A-2A: A FURTHER ANALYSIS FROM NEW SWITH STUDY
Peng Hu1, Jia Shang2, Wenhong Zhang3, Guozhong Gong4, Yongguo Li 5, Xinyue Chen6, Jianning Jiang7, Qing Xie8, Xiaoguang Dou9, Yongtao Sun10, Yufang Li11, Yingxia liu12, Guozhen Liu13, Dewen Mao14, Xiaoling Chi15, Hong Tang16, Xiao Ou Li17, Yao Xie18, Xiaoping Chen19, Jiaji Jiang20, Ping Zhao21, Jinlin Hou22, Zhiliang Gao23, Huimin Fan24, Jiguang Ding25, Hong Ren* 1
1Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Infectious Diseases, Henan Provincial People’s hospital, Zhengzhou, 3Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 4 Department of Infectious Diseases, The Second Xiangya Hospital of South University, Changsha, 5Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, 6International Medical Department, Beijing YouAn Hospital, Capital Medical University, Beijing, 7Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 8Department of Infectious Diseases, Jiaotong University School of Medicine, Shanghai Ruijin Hospital, Shanghai, 9Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, 10Department of Infectious Diseases, he Second Affiliated Hospital of the Fourth Military Medical University, XiAn, 11Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, 12Liver Disease Department, Shenzhen Third People’s Hospital, Shenzhen, 13Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha, 14Liver Disease Department, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 15Liver Disease Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou , 16Center of Liver Diseases, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 17Liver Disease Department, Hangzhou Sixth People’s Hospital, Hangzhou, 18Liver Disease Department, Beijing Ditan Hospital, Beijing, 19 Liver Disease Department, Guangdong General Hospital, Guangzhou, 20Center of Liver Diseases, First Affiliated Hospital of Fujian Medical University, Fuzhou, 21Liver Disease Department, 302 Military Hospital of China, Beijing, 22Hepatology Unit, Nanfang Hospital, Southern Medical University, 23Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, 24Hepatology Unit, Guangzhou Eighth People’s Hospital, Guangzhou, 25Hepatology Unit, Ruian People’s Hospital, Ruian, China

Corresponding author’s email: hp_cq***@****

Background and Aims: Background and aim: qHBsAg level, which has been used to predict IFN response in treatment naïve patients, is rarely studied in NUC-treated CHB patients. Aim of this study is to investigate the predictive value of baseline and on-treatment qHBsAg levels on treatment response in patients who switched from a long-term treatment of NUC to pegylated interferon a-2a (PEG-IFN a-2a).
Methods: Method: HBeAg positive CHB patients who achieved partial responses (defined as HBV DNA<200IU/ml and HBeAg loss) with a prior NUC history for 1-3 years were included in NEW SWITCH study. All participants were switched to PEG-IFN a-2a treatment for either 48 or 96 weeks (with the first 12 weeks overlapping NUC therapy) at a randomization ratio of 1:1 and followed-up to 48 weeks after the discontinuation of PEG-IFN a-2a. The predictive values of qHBsAg levels at baseline, 12wks and 24wks on treatment response (defined as HBsAg loss at week 48) were analyzed in the retrospective analysis.
Results: Results: 271 patients, who had completed 48wks of treatment, were recruited in this analysis, including 47(17.3%) patients achieved HBsAg loss at week 48. Significantly lower qHBsAg levels at baseline (720.97IU/ml vs 5456.16IU/ml, P<0.001) and reduction of qHBsAg during treatment (P<0.001) were observed in patients with HBsAg loss comparing with those without.
Patients with qHBsAg<1500IU/ml at baseline achieved higher HBsAg loss rate than those with qHBsAg≥1500IU/ml (33.3% vs 4.1%, P<0.0001). Similarly, those with qHBsAg levels <200IU/ml at week 24 achieved higher HBsAg loss rate than those with qHBsAg≥200IU/ml (48.4% vs 0.6%, P<0.0001).
Analysis of the combinative prediction value of baseline and on-treatment qHBsAg levels has shown that patients with qHBsAg<1500IU/ml at baseline and qHBsAg <200IU/ml at week 24 had the highest response rate (PPV 51.35%), while those with qHBsAg≥1500IU/ml at baseline and qHBsAg≥200IU/ml at week 24 had the lowest response rate (NPV 100%, Fig.1).
Conclusions: Conclusion: Combination of qHBsAg levels at baseline and week 24 might be able to predict HBsAg loss at week 48 in HBeAg positive CHB patients who switched to PEG-IFN a-2a after achieving partial responses in NUC treatment.
Figure:




Disclosure of Interest: None Declared

[studyforhope]

This a follow up analysis of replicors second trial.

RS-3322
Viral hepatitis
Hepatitis B & D - clinical (Therapy, new compounds, resistance)


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).

[sorte]

http://www.businesswire.com/news/home/20150408005174/en/Replicor-Presentations-EASL-2015#.VSVqfRebNEQ

[studyforhope]

This is abstract 0112 peg add on after tenofovir.
Not much different than the AASLD results.

Background and Aims: Uncontrolled studies suggest that addition of PEGIFN in CHB patients receiving NUCs with undetectable serum HBV DNA may increase HBsAg clearance. We conducted a multicenter randomized controlled study to evaluate this strategy.
Methods: The key inclusion criteria were: HBeAg negative CHB and documented negative HBV DNA while on stable NUC regimens for at least 1 year. Patients with PEGIFN contra-indications were excluded.
From Jan 2011 to July 2012, 183 patients (86% male, mean age 47.6 years range 28-74, HBV DNA undetectable for 198 weeks range (13-1074), were randomized to receive a 48 weeks course of 180 µg/w PEGIFN-alfa-2a (Pegasys) in addition to the backbone NUC regimens (Group 1: n=90) or no additional therapy (Group 2: n=93). Patients were stratified according to the HBsAg titers (< or ≥ 2.25 log IU/ml). NUC regimens remained unchanged during the study period up to week 144. Treatments discontinuation was allowed if HBsAg clearance was sustained for 24 weeks. Patients were seen monthly during the first 48 weeks, then every 3 months.
The primary end point was the proportion of patients with serum HBsAg clearance at week 96. Secondary endpoints included HBsAg clearance at Week 48.
Results: 85 patients initiated PEGIFN in group 1, 17 patients discontinued prematurely PEGIFN due to adverse events, and 4 patients had a dose reduction to 135μg/w or 90µg/w. There was no discontinuation of the NUC regimens in group 1 and only one patient in group 2. At week 48, 7 patients had an HBsAg clearance in group 1 and 1 in group 2 (p= 0.032).  Demographic and baseline characteristics, CHB history and history of anti-HBV therapies were studied. HBsAg clearance at the end of PEGIFN treatment (W48) was associated with (1) baseline HBsAg titer (p= 0.020) and (2) history of HBeAg seroconversion prior to randomization (4/19 (21%) vs 3/64(4.6%))(p=0.038).
Final results regarding primary end point at week 96 will be presented in this meeting.
Conclusions: Addition of a 48 weeks course of PEGIFN alfa-2a to oral anti-HBV therapy in HBeAg negative CHB patients with undetectable serum HBV DNA for at least 1 year: (1) Results in a low rate of HBsAg clearance (7/90 (8%)) and (2) Suggests that low baseline HBs Ag titers and a history of HBeAg seroconversion either spontaneaously or under HBV therapy may increase HBsAg clearance rate.

Disclosure of Interest: None Declared

[mer971]

Thanks Stephen for this info

[StephenCastlecrag]

Not yet. I am sure it would be free. Lampertico also has a late poster, I think.

[stef2011]

did you check if they are available online by the 9th of april like posters?

maybe it worths paying for the videos of oral presentations this year if not available free, so much results from the pgintf add ons or switch