Hepatitis B Community
IMPROVED HBsAg LOSS BY 120weeks OF PEGINTF PLUS NUCS
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

IMPROVED HBsAg LOSS BY 120weeks OF PEGINTF PLUS NUCS

http://www.natap.org/2013/EASL/EASL_70.htm

IMPROVED HBsAg LOSS RATE IN CHRONIC HEPATITIS B PATIENTS TREATED WITH PROLONGED PEGINTERFERON α-2A COMBINED WITH NUCLEOS(T)IDE ANALOGUE

Program Abstract

Aims: To investigate the improved HBsAgresponse in chronic hepatitis B (CHB) patients treated with prolonged peginterferon α-2a combined with nucleos(t)ide analogue.

Methods: One hundred and fifty-two CHB patients treated with peginterferon α-2a plus nucleos(t)ide analogue from Jan 2007 to Sep 2012 were retrospectively investigated. The mean treatment duration was 79 weeks (range 24-120 weeks). Serum HBsAglevels at baseline, week 12, 24, 36, 48, 72, 96 and 120 of treatment were detected

Results: The cumulative HBsAgloss rates of patients treated at 48-week, 96-week and 120-week with peginterferon α-2a plus nucleos(t)ide analogue were 8.55% (13/152), 26.97% (41/152) and 29.61% (45/152), respectively. The time to HBsAgloss was 74.93±27.21 weeks. Most HBsAgloss occurred during week 49-96. The HBsAglevel at week 12 of treatment in 45 patients who obtained HBsAgloss was 1.91±1.27log10IU/mL, which was significantly lower than baseline (3.22±0.82log10IU/mL) (t=5.759, P< 0.01). However, the HBsAglevel at baseline in 107 patients who did not obtain HBsAgloss was 3.57±0.96 log10 IU/mL and HBsAglevels reduction at week 12, 24, 48, 96 and 120 were 0.24±0.38, 0.45±0.60, 0.83±0.84, 1.29±1.05 and 1.66±1.66 log10IU/ml, respectively (Figure 1). As expected, the HBsAglevel at week 12 of treatment was not significantly different from that at baseline in this group of patients (t=1.529, P=0.128), while that at week 96 was significantly decreased compared with week 48 (t=2.166, P=0.033).

Conclusion: Prolonged peginterferon α-2a combined with nucleos(t)ide analogue treatment could increase the cumulative HBsAgloss rate. In patients who do not obtain HBsAgloss, prolonged therapy could reduce the HBsAglevel and improve the anti-viral response. The reduction of HBsAglevel of week 12 from baseline could be a predictor of HBsAgclearance
21 Comments Post a Comment
Blank
Avatar_m_tn
as said many times max hbsag clearance by pegintf is between 48 and 96 weeks of therapy, response at 48weeks is very low (about 8% in this study) and at 96weeks  three times more (about 27%), 120 weeks 29.61%
Blank
Avatar_m_tn
Stefan, The Japanese research studies, were suggesting this many years ago.

I think it is not so much nucs, but the effect of interferon itself. Maybe it takes this long to wake the immune system up and balance out things..

Or maybe during the treatment of two years it takes that long for the liver to get rid of infected cells, while interferon blocks hbv replication..

Any way 120 weeks of peg is a torture, most people can barely make 48 weeks..  

And why now? When there is Rep9AC, GS9620, MYR, Zadaxin.. all this is much better to take in a combo..  to lessen the duration of therapy..

I think these researchers are beating a dead bush, with stuff that is being tried.. it is known to work.
Blank
Avatar_m_tn
What is the injection dose for 96 and 120 weeks treatment? Is it always 180 mcg for first 48 weeks followed by 135 mcg for second 48 weeks of treatment? and for third 48 weeks also 135 mcg? Or treatment can be prolonged with 180 mcg for 96 and 120 weeks?
Blank
Avatar_m_tn
interferron-a and interferron-b, whats the difference in structure and efficacy? many places doctors try to confuse people about this.
Blank
Avatar_m_tn
in italy it is routine from many years to have prolonged pegintf, it is also the rule for hdv and other diseases like MS and others, of course at full dose....it is just a matter of sides effects, most patients have no or tollerable sides effects and they can go on whatever.
a trial in china made pegintf mono for 5-6 years, i posted years ago, and they increased response to very high numbers, i dont remember the number but it was in the order of 30-50%

of course this makes sense in responders by 12-24 weeks to go on and all clear hbsag, those not responding are not kept on pegintf because in non responders there is no benefit on prolonged
Blank
Avatar_m_tn
So you mean if you are a responder with no or tolerable sides than treatment can be prolonged with 180 mcg (full dose) for 96 weeks?
Blank
Avatar_m_tn
not 96weeks but 6 years or more like other human trials did, peginterferon is not a poison it is just an immune modulator.....

actually most human trials from drug makers look in the direction of chronic drug managment, stopping all efforts to clear definitively, we have the tolls to clear hbv definitively already, the non response to sequential treatment nuc+peg is 10% on lam plus adv, this is nothing, this is almost close to the nucs non response on hbeag pos
Blank
Avatar_m_tn
Just found an article on interferon use for 12 years with one patient who finally cleared HBV and HDV

Abstract
Chronic delta hepatitis is an uncommon but severe form of chronic viral hepatitis for which there is currently no satisfactory therapy. A patient with chronic delta hepatitis was treated with interferon alfa, 5 million units daily for 12 years. Serial serum samples were tested for routine liver tests and selected samples for quantitative levels of hepatitis B surface antigen (HBsAg) and hepatitis delta virus RNA. Liver biopsies were performed before, during, and after an initial 1-year course of therapy and again after 3 and 10 years of continuous therapy. With initiation of interferon therapy, serum aminotransferase levels decreased to normal range, became abnormal again when the dose was reduced, and increased to pretreatment levels when therapy was stopped. With reinstitution and prolonged therapy, aminotransferase levels became persistently normal; after several years, both hepatitis delta virus RNA and serum HBsAg became undetectable. Liver biopsy, which initially revealed cirrhosis, showed gradual improvement in inflammatory and fibrosis scores and, after 10 years, no abnormalities or fibrosis. Therapy was stopped, and the patient remained free of evidence of infection. In conclusion, long-term therapy with interferon alfa in high doses led to resolution of chronic delta hepatitis, disappearance of hepatitis delta and B virus markers, and improvement in fibrosis.

GASTROENTEROLOGY 1999;117:1229-1233
http://www.sciencedirect.com/science/article/pii/S0016508599704099
Blank
Avatar_m_tn
thanks very interesting, i do believe it is more the cost and the advantage of keeping most patients infected to drive the small and short use of pegintf than the real fact of sides.and all these long studies confirm this

among my relatives only old age had sides (i person) while all the others had no sides effects (i mean really minor sides)
Blank
Avatar_m_tn
is there a big risk for developing autoimmine disease while on interferon therapy? and does this risk become raise with prolonged theraphy?
Blank
Avatar_m_tn
is there a big risk for developing autoimmune disease while on interferon therapy?

i dont think so because only patients already having problems like worsened and they were not put on high blood levels of vit d which manages autoimmunity.if we go on high d blood levels we improve pegintf response and prevent any autoimmune disease
i ve also seen vitd levels increase ip10 production studies but i have not checked them fully.vit d increase ip 10 and ip10 increases pegintf response because it increases when intf increases to manage the autoimmnity

those on prolong therapy never developped any different sides than those on 24 weeks, i dont think it has any risk.if one has sides he will fell them alreay at 24 weeks and choose if to stop
Blank
Avatar_m_tn
" A patient with chronic delta hepatitis was treated with interferon alfa, 5 million units daily for 12 years." Does any one know how to covert 5 million units of interferon daily in terms of pegasys dose? 5 million daily x 7 days = 35 million units per week does it equal 180 mcg weekly of pegasys dose?
Blank
Avatar_m_tn
5million units of ifn alpha per day will result in a zigag curve of actual ifn concentrations , due to the short half life.
But it amounts in the average to a very high concentration, possibly equivalent to a double dose of 40 kilodalton pegasys per week. that is 360 mcg.
Blank
Avatar_m_tn
Thanks for reply. I can not find studies for prolonged treatments with 180 mcg for another 48 weeks. All studies I found say 180 mcg for first 48 weeks then reduced dose to 135 mcg next 48 weeks. Do you presonally think it safe to prolong with 180 mcg for next 48 weeks or dose must be reduced?
Blank
Avatar_m_tn
the reaction to ifn is quite different between patients. Prolonged ifn therapy is frequently used at full dose for 72 weeks in partial responders in HCV. They also sometimes use double dosing for the 48 or even 72 weeks in repeat treatments to achieve SVR. Autoimmune reactions and long term sequelae are frequent among those treated in that way, even longtime after svr.
The patient in that paper was. quite unique in that he tolerated ifn so well. I had a discussion about him with dr. lau long time ago and she told me that he almost refused to get off ifn.
a person calling himself double dose often discussed the aspects of this treatment on the hcv board. Go and check his posts.
Blank
Avatar_m_tn
Next week will be my 48th week of interferon I will have to make decision on which dose to prolong my treatment. I will insist on full dose with Dr for at least 72 weeks. Thanks for sharing your experience with us.
Blank
Avatar_m_tn
do you know your vit d25oh level?it would be interesting to see members experience on vit d and pegintf and see if vitd25oh 80-90ng/ml has influence on sides effects, no autoimmune reactions in prolonged or double dose and increased respose
Blank
Avatar_m_tn
I have tested vitd once and it was 57 ng/ml I never took vit d vitamins before test. I have no side effects from interferon.
Blank
Avatar_m_tn
that s very good level we just need to see other members with sides and their vit d levels and if they are responding or not
Blank
Avatar_m_tn
we do not know the HBsag kinetics of the guy who took interferon for 10 years.  is it worth continuing HBSag for more than two year if there is no significant drop?
Blank
Avatar_m_tn
no i think that if there is no response by the 12th or 24th week it doesn t worth to  do intf, it is best to take tdf or etv for a couple of years and then retry pegintf
Blank
Post a Comment
To
Blank
Weight Tracker
Weight Tracker
Start Tracking Now
Hepatitis B Community Resources
RSS Expert Activity
233488_tn?1310696703
Blank
New Cannabis Article from NORTH Mag...
Jul 20 by John C Hagan III, MD, FACS, FAAOBlank
242532_tn?1269553979
Blank
3 Reasons Why You are Still Binge E...
Jul 14 by Roger Gould, M.D.Blank
242532_tn?1269553979
Blank
Emotional Eating: What Your Closet ...
Jul 09 by Roger Gould, M.D.Blank
Top Hepatitis Answerers
Avatar_m_tn
Blank
stef2011
Italy
Avatar_m_tn
Blank
StephenCastlecrag
Australia
Avatar_m_tn
Blank
Rome70
Moscow, Russia
Avatar_m_tn
Blank
andrey19
Russia
Avatar_m_tn
Blank
mer971
Avatar_m_tn
Blank
makeadifferencenow