Hepatitis B Community
hbsag clearance switching to interferon after etv responce on hbe+
About This Community:

This forum is an un-mediated, patient-to-patient forum for questions and support regarding Hepatitis B. Topics in this forum include but are not limited to, Causes, Diagnosis, Family and Relationships, Living With Hepatitis B, Research Updates, Treatment, Success Stories, Support, Symptoms.

Font Size:
A
A
A
Background:
Blank
Blank
Blank
Blank Blank

hbsag clearance switching to interferon after etv responce on hbe+

Patients with HBeAg-positive chronic hepatitis B (CHB) with a maintained virological response to entecavir achieved HBsAg clearance when switched to peginterferon alfa-2a therapy (the OSST study)
Q. Ning1; M. Han1; Y. Sun2; J. Jiang3; D. Tan4; J. Hou5; H. Tang6; J. Sheng7; M. Jiang8
1. Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
2. Tangdu Hospital, the Fourth Military Medical University, Xi'an , Shaanxi Province, China.
3. The First Hospital, Fujian Medical University, Fuzhou, Fujian Province, China.
4. Xiangya Hospital, Central South University, Changsha , Hunan Province, China.
5. Nanfang Hospital, Nanfang Medical University, Guangzhou, Guangdong Province, China.
6. Huaxi Hospital, Sichuan University, Chengdu , Sichuan Province, China.
7. The First hospital, Zhejiang University, Hangzhou , Zhejiang Province, China.
8. Shanghai Roche Pharmaceutical Co Ltd, Shanghai, China.

Study purpose: In CHB, nucleos(t)ide analog therapy can result in HBV DNA suppression, but it is difficult to achieve complete serological response and relapse occurs frequently when therapy is stopped. The phase IV Optimizing HBeAg/HBsAg Seroclearance in HBeAg-positive CHB patients with combination and Sequential Treatment of pegylated interferon alpha-2a and entecavir (OSST) study determined whether patients who had maintained HBV DNA suppression with entecavir (ETV) could achieve HBsAg clearance by switching to peginterferon alfa-2a (PEGASYS; PEG-IFN?-2a).
Methods: In the multicenter, randomized, open-label study, HBeAg-positive patients treated with ETV (0.5mg QD) for 1
Related Discussions
29 Comments Post a Comment
Blank
Avatar_m_tn


AASLD 2011 Annual Meeting


You may print by clicking on this  button. To return to the previous page, close this browser window or click the 'X' button in the top right corner of the page.


ID#

1373

Location:

Poster Hall

Time of Presentation:

Nov 07 8:00 AM - 5:30 PM

Category:

SO2. Treatment and Clinical Trials


Patients with HBeAg-positive chronic hepatitis B (CHB) with a maintained virological response to entecavir achieved HBsAg clearance when switched to peginterferon alfa-2a therapy (the OSST study)
Q. Ning1; M. Han1; Y. Sun2; J. Jiang3; D. Tan4; J. Hou5; H. Tang6; J. Sheng7; M. Jiang8
1. Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
2. Tangdu Hospital, the Fourth Military Medical University, Xi'an , Shaanxi Province, China.
3. The First Hospital, Fujian Medical University, Fuzhou, Fujian Province, China.
4. Xiangya Hospital, Central South University, Changsha , Hunan Province, China.
5. Nanfang Hospital, Nanfang Medical University, Guangzhou, Guangdong Province, China.
6. Huaxi Hospital, Sichuan University, Chengdu , Sichuan Province, China.
7. The First hospital, Zhejiang University, Hangzhou , Zhejiang Province, China.
8. Shanghai Roche Pharmaceutical Co Ltd, Shanghai, China.

Study purpose: In CHB, nucleos(t)ide analog therapy can result in HBV DNA suppression, but it is difficult to achieve complete serological response and relapse occurs frequently when therapy is stopped. The phase IV Optimizing HBeAg/HBsAg Seroclearance in HBeAg-positive CHB patients with combination and Sequential Treatment of pegylated interferon alpha-2a and entecavir (OSST) study determined whether patients who had maintained HBV DNA suppression with entecavir (ETV) could achieve HBsAg clearance by switching to peginterferon alfa-2a (PEGASYS; PEG-IFNα-2a).
Methods: In the multicenter, randomized, open-label study, HBeAg-positive patients treated with ETV (0.5mg QD) for 1–3 years with HBV DNA<103 copies/mL and HBsAg<100PEIU/mL either switched to PEG-IFNα-2a (180µg for 48 weeks) or continued ETV for a further 48 weeks. There was an 8-week overlap period in the PEG-IFNα-2a arm. The efficacy endpoints were HBeAg seroconversion and HBsAg clearance at end of treatment (week 48, EOT). Adverse events (AEs) were recorded.
Results: Baseline HBV DNA, HBeAg, ALT and HBsAg levels were low and similar in both arms. At the time of the analysis, 53 PEG-IFNα-2a-treated patients and 49 ETV-treated patients had reached EOT. At EOT, 13% (7/53) of the PEG-IFNα-2a arm had HBsAg clearance (0% in the ETV arm; P<0.05). Similarly, 6% (3/53) of patients in the PEG-IFNα-2a arm achieved HBsAg seroconversion vs none in the ETV arm (P<0.05). Rates of HBeAg loss and HBeAg seroconversion are shown in the table. Patients with HBsAg<3000 IU/mL and negative HBeAg at baseline (HBeAg< 0.2 PEIU/mL) had a high chance of achieving HBsAg clearance at EOT (27%, 4/15). On-treatment HBsAg decline was significantly more pronounced (P<0.001) in the PEG-IFNα-2a arm than in the ETV arm. AEs were higher in the PEG-IFNα-2a arm than in the ETV arm (72% vs 2% for all AEs and 7% vs 0% for serious AEs), but only led to discontinuation in three PEG-IFNα-2a-treated patients.
Conclusion: Patients with a maintained virological response previously treated with ETV can achieve significantly higher rates of HBsAg clearance when switched to a finite course of PEG-IFNα-2a than if they had continued on ETV. Highest rates (27%) of HBsAg clearance were achieved by patients who had HBeAg loss and HBsAg<3000 IU/mL before switching to PEG-IFNα-2a. Response rates for both arms at the end of the post-treatment follow-up period will be described in the final analysis.

PEG-IFNα-2a(N=53) ETV (n=49)
HBsAg loss 13%(n=7) 0%(n=0)
HBsAg seroconversion 6%(n=3) 0%(n=0)
HBeAg loss 72%(n=38) 63%(n=32)
HBeAg seroconversion 15%(n=8) 6%(n=2)
Blank
Avatar_m_tn
This is a good report. I expect similar or even better results for genotype A and D.
Blank
Avatar_m_tn
this study was done for what genotype ?
Blank
Avatar_m_tn
Since it is done in China, you can assume the patients are mostly genotypes B & C.
Blank
Avatar_f_tn
Since I am genotype C this therapy might be one good option.
Blank
Avatar_m_tn
if i remember correct you are HbeAg negative and this study was on HbeAg positive.

anyway, this reports ware on a small number of patients, so the results have to be taken with reservation and clear discuses with the current doctor (maybe the doctor could get in touch with the research team and obtain more details and maybe suggestion on the possible risks ... )
Blank
Avatar_f_tn
Yes, I am HbeAg negative. Thanks for pointing that out!

Blank
Avatar_m_tn

the best approch is tenofovir+vit d3 and keep hbvdna und for 1year at least

than tenofovir+simvastatin 80mg (20mg,  if no sides go to 40mg and then 80mg)+vit d3+alinia  (4-12 weeks)
then you add interferon to the above for 96weeks

simvastatin must be checked for sides like alt and cpk
vit d3 keepin glevels to 50-100ng/ml

i think this is the best now
Blank
Avatar_m_tn

if you go directly to interferon+tnf  your hbv may be too strong and able to suppress interferon, so better weaken hbv first and then add interferon
Blank
Avatar_m_tn
ano po ang ibig sabhin ng SGPT at SGOT,

SGPT 81
SGOT 45

Yang po ang resulta ng test ko last oct 23, im Hep B. Positve.
Blank
Avatar_m_tn
kulang yung data, no HBsAg, HBeAg, Anti-Hbe, Anti-Hbs, HBVDNA & etc.. also, most of the knowledgeable people here aren't filipino. please post in english to get better responses.
Blank
Avatar_m_tn
Hi all,

I always knew first target for eag+ is to serconvert into eag- so tath DNA is almost UND and Hbsag lower than 2500..

Now this seems to be any longer sufficient for a healty life..,correct?
Blank
Avatar_m_tn

no not correct, until hbsag is >1500iu/ml or even better 500iu/ml you have cronic (chronic) hbv, use of antioxidants and helathy life might prevent liver damage but this ca happen also with higher hbsag

hbeag and hbvdna und have very poor meaning in term of hbv clearance but liver damage is none as long as hbvdna  is und
Blank
Avatar_m_tn
I think that getting HbeAg negative from HbeAg positive was considered a end point of treatment are related to the fact the the negativation of the HbeAg is correlated to the reduce of HBV DNA (in most of the cases). So, as Stefa 2011 specified, HBV DNA und it means no liver damage.

But all of this are to manage and not to cure, and to manage imply to have a small risk.

if we are discussing about curing, we look at HBsAg (at least in present) and try to lower down until as much as possible until one point were we can use interferon to have a good chance to seroconvert.

Now the questions are:
- why not everybody is responsive to interferon?
- all patients that have HbsAg under a threshold are responsive ?
- do we have to look for other things in order to be more responsive (e.g. vit D, hdl/ldl, interferon gamma ...)
- how will act interferon lambda on HbsAg?
- how we can lowdown HbsAg without interferon (for reaching the point from where it is considered to have a chance to clear hbsAg using interferon )
- what is the value from were we can consider to add interferon (now is somewhere around 1500 ui/ml)
- how can we increase body interferon (vitamin c ? sport ? .... )
Blank
Avatar_m_tn

why not everybody is responsive to interferon?

the main way hbv can remain cronic (chronic) is by blocking interferons and citokines, even if we inject them in high quantity hbv blocks them anyway.
we do know we can preent his by making hbv weak and we know interferon can be henanced by this:

simvastatin 80mg (monitoring carefully for sides, otherwise 40mg), interferon works by lowering intracellular cholesterol that is used by viruses to make antigens and virions.
if we lower cholesterol we act the same way as interferon but interferon can lower much more than simvastatin does, anyway simvastatin can help improve interferon response, nucs response.
trials are checking if simvastatin alone or combo with nucs can improve response, too bad we dont have a combo interferon+sim but anyway we do know from other human trials that sim lowers hcc risk and prevents fibrosis/cirrhosis, so it makes sense to use it off label anyway

vitamin d3, we do know vitamin d3>ng/ml improve immune response and interferon response both monoterapy and combo and in any case vit d3>ng/ml is a must for anybody hbv infected or not since it has only pro

alinia is known to heance interferon response a great deal acting on interferon pathways

vitamin c is known to lower cholesterol henancing interferon production, this is one of the ways vit c improve immune response, but not oral vitamin c which is not absorbed.
only IV vitmin c or liposomal vitamin c can have this effect.the doses to be used are from 2g to 10g liposomal or IV.do not even consider normal ascorbic acid because it is not absorbed and makes diarrea (diarrhea)



Blank
Avatar_m_tn
- all patients that have HbsAg under a threshold are responsive ?

under 1500iu/ml yes, altough clearance may take years.hbsag at -iu/ml means there is already natural interferon production and active immune system on hbcag and hbsag.but we have little studies on this, as usual drug makers do not fund studies or trials to clear hbv but only studies and trial to keep life long cronic (chronic) infection controlled by drugs


- do we have to look for other things in order to be more responsive (e.g. vit D, hdl/ldl, interferon gamma ...)

yes but hbsag quant monitoring can reflect that, i think not needed

- what is the value from were we can consider to add interferon (now is somewhere around 1500 ui/ml)

i know researcher here in italy clear hbsag by interferon courses of 96 weeks repeted many times when there is hbsag lowering during the years.nobody has checked if vit d, statins etc can help lower hbsag with nucs combo

moderate sport increase interferon production, but intense sport lowers int and immune response.
it was found about 40-45min per day increases interferon
Blank
Avatar_m_tn
"it was found about 40-45min per day increases interferon" - how can we measure interferon ?

for sport and hbv i will open a new thread.
Blank
Avatar_m_tn
regarding sports and HBV we can discuss on http://www.medhelp.org/posts/Hepatitis-B/Sport-and-HBV/show/1617515
Blank
Avatar_m_tn
regarding simvastatin  - one word, this drug has to be carefuly taken by the people that have low cholesterol (below 140 - 150)
Blank
Avatar_m_tn

forgot also 4-5cups of   coffee increase interferon response, lower hcc risk and fibrosis
Blank
Avatar_m_tn
"Interferon works by lowering intracellular cholesterol that is used by viruses to make antigens and virions."

all the other cells use the same cholesterol, so  going to low is not an option.
Another question when you spoke about cholesterol you refer to the LDL or HDL or VHDL or do not matter, we spoke about total cholesterol.
Blank
Avatar_m_tn
"forgot also 4-5cups of   coffee increase interferon response, lower hcc risk and fibrosis" - Italian cups or American cups ? (Italian are small, "strong" and aromate, American are big, "diluated" and not so aromate :) )
Blank
Avatar_m_tn
http://www.ncbi.nlm.nih.gov/pubmed/21462335 - regarding coffee
Blank
Avatar_m_tn
wow, well done study

.......of brew from a special Arabica coffee

is there any expert in coffee?lately i bought the coffee beans directly and just powder it before making coffee.....but we need an expert to tell us which is the best coffe and the richest as antioxidants


Antioxidant-rich coffee reduces DNA damage, elevates glutathione status and contributes to weight control: results from an intervention study.
Bakuradze T, Boehm N, Janzowski C, Lang R, Hofmann T, Stockis JP, Albert FW, Stiebitz H, Bytof G, Lantz I, Baum M, Eisenbrand G.
Source
Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
Abstract
Epidemiological and experimental evidence increasingly suggests coffee consumption to be correlated to prevention or delay of degenerative diseases connected with oxidative cellular stress. In an intervention study comprising 33 healthy volunteers, we examined DNA-protective and antioxidative effects exerted in vivo by daily ingestion of 750 mL of freshly brewed coffee rich in both green coffee bean constituents as well as roast products. The study design encompassed an initial 4 wk of wash-out, followed by 4 wk of coffee intake and 4 wk of second wash-out. At the start and after each study phase blood samples were taken to monitor biomarkers of oxidative stress response. In addition, body weight/composition and intake of energy/nutrients were recorded. In the coffee ingestion period, the primary endpoint, oxidative DNA damage as measured by the Comet assay (± FPG), was markedly reduced (p<0.001). Glutathione level (p<0.05) and GSR-activity (p<0.01) were elevated. Body weight (p<0.01)/body fat (p<0.05) and energy (p<0.001)/nutrient (p<0.001-0.05) intake were reduced. Our results allow to conclude that daily consumption of 3-4 cups of brew from a special Arabica coffee exerts health beneficial effects, as evidenced by reduced oxidative damage, body fat mass and energy/nutrient uptake.
Blank
Avatar_m_tn
we can try to ask one of the researchers about the coffee. (maybe somebody from Germany has more chance to a email answer  (?))
Blank
Avatar_f_tn
I see your point and I'll probably go for it. Thanks.
Blank
Avatar_m_tn
http://www.coffeeandhealth.org/

maybe keep an eye on this, i have no time to check now if that's a reliable website
Blank
Avatar_m_tn
Well. I am a Chinese in US. I would put the reservation of this research until it is published in a international journal paper. I believe that many chinese researchers are not honest with their research data.

Dan
Blank
Avatar_m_tn

we have already tons of studies on coffee, not a problem, we already know 4-5 cups per day is the best but we dont know which is the best brand or if any coffee has the same antiox potency
Blank
Post a Comment
To
Blank
Weight Tracker
Weight Tracker
Start Tracking Now
Hepatitis B Community Resources
RSS Expert Activity
242532_tn?1269553979
Blank
Control Emotional Eating with this ...
Sep 04 by Roger Gould, M.D.Blank
242532_tn?1269553979
Blank
Emotional Eating Control: How to St...
Aug 28 by Roger Gould, M.D.Blank
233488_tn?1310696703
Blank
New Cannabis Article from NORTH Mag...
Jul 20 by John C Hagan III, MD, FACS, FAAOBlank
Top Hepatitis Answerers
Avatar_m_tn
Blank
stef2011
Italy
Avatar_m_tn
Blank
StephenCastlecrag
Australia
Avatar_m_tn
Blank
veteranB
CA
7951432_tn?1400922437
Blank
flyinsky
paris, France
Avatar_m_tn
Blank
makeadifferencenow
Avatar_m_tn
Blank
andrey19
Russia