Aa
Aa
A
A
A
Close
Avatar universal

Add -on of peg interferon to a stable nucleoside, hbsag loss 40%

Add -on of peg interferon to a stable nucleoside regimen led to loss of HBs Ag in chronic hepatitis HBe Ag negative patients
D. Ouzan1; G. Penaranda2; H. Joly1; H. Khiri2; P. Halfon2
1. Institut Arnault Tzanck, Saint-Laurent du Var, France.
2. Laboratoire ALPHABIO, Marseille, France.

Objectives: Suppression of HBV viral load by nucleoside treatment reduces disease progression but requires indefinite treatment. Hbs Ag loss is a rare event after long term treatment with analogues therapy. In HBe Ag negative patients peg interferon alpha 2a for 96 weeks improved the sustained responses rate versus 48 weeks. It is of interest to know whether the addition of peg interferon for 96 weeks to a stable nucleoside therapy will reduce quantitative HBs-Ag which may follow by HBs Ag loss.
Methods: We analyzed HBs Ag levels of 10 patients who received additional peg
43 Responses
Sort by: Helpful Oldest Newest
Avatar universal
Thanks for the list of clinical trials, most informative. I have posted it to the Chinese Forum.
Helpful - 0
Avatar universal
Different as in different sets of numbers being reported:

1)During add-on therapy, in 2 patients a continuous decline of quantitative HBsAg by -2,6log10 and -3,66 log10 was observed at week 32 and 36, respectively.
2)A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48,
Helpful - 0
Avatar universal

is it add on after long term etv?because that s the only one working with so hi rates
Helpful - 0
Avatar universal
"unfortuantely only gilead is funding very big trials with peginterferon add on that i know of" - looks that also some other look for a combo (Roche or Universitys or BMS)

http://clinicaltrials.gov/ct2/show/NCT01524679

http://clinicaltrials.gov/ct2/show/NCT01220596?term=interferon&recr=Open&cond=Hepatitis+B&rank=8

http://clinicaltrials.gov/ct2/show/NCT01243281?term=interferon&recr=Open&cond=Hepatitis+B&rank=11

http://clinicaltrials.gov/ct2/show/NCT01369212?term=interferon&recr=Open&cond=Hepatitis+B&rank=15

http://clinicaltrials.gov/ct2/show/NCT00597259?term=interferon&recr=Open&cond=Hepatitis+B&rank=24

http://clinicaltrials.gov/ct2/show/NCT01456312?term=interferon&recr=Open&cond=Hepatitis+B&rank=32

I only put this links to be more easy to follow up this, in case that some results will be published later
Helpful - 0
Avatar universal
maybe a statistical analyses (using google excel) of all reported trials results until now will be a god thing to have a more clear overview.

any idea on what we should look ?
Helpful - 0
Avatar universal
I don't think that this was reported on this thread

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06970.x/abstract;jsessionid=2C90371A9FD5EF6A671E355D46E07307.d04t04?userIsAuthenticated=false&deniedAccessCustomisedMessage=

Abstract
Background and Aim:  Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α-interferon (IFN-α) and a nucleos(t)ide analog.

Methods:  This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment.

Results:  A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3–60 months) and 25.5 months (range 9–63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases).

Conclusions:  Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance—the closest outcome to cure.
Helpful - 0
Avatar universal
why you say different numbers ? (do I miss something ?)
Helpful - 0
Avatar universal
Funny, same paper, but different numbers!

J Clin Virol. 2012 Feb 23. [Epub ahead of print]
Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B.
Kittner JM, Sprinzl MF, Grambihler A, Weinmann A, Schattenberg JM, Galle PR, Schuchmann M.
Source

I. Medical Department, University Hospital Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Abstract
BACKGROUND:

Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.
OBJECTIVES:

To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.
STUDY DESIGN:

We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml.
RESULTS:

A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.
DISCUSSION:

We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.
Helpful - 0
Avatar universal
HBsAg by -2,6log10 and -3,66 log10 was observed at week 32 and 36, respectively. = HBsAg by -457 and -4570 was observed at week 32 and 36, respectively.
Helpful - 0
Avatar universal
3.66 log = 10 cube 3.66 (actualy cube is 3 , but i don't know the English term ) = 4570 ~4600
Helpful - 0
Avatar universal
"so 3.66logs should be between 5000 to 9999, may be about 7000iu/ml, i dont now if there is a way to make a precise number from 3.66log, i guess so, anybody expert with maths"

I'm not an math expert but as far as I understand 3.66log = 4 600 UI (log(4600) = 3.66)
Helpful - 0
Avatar universal
i am talking about the german trial with only 2 responding patients which says:
Results: During add-on therapy, in 2 patients a continuous decline of quantitative HBsAg by -2,6log10 and -3,66 log10 was observed at week 32 and 36, respectively.

they just say the hbsag quantity baseline on the guy with low hbsag on etv, about 16iu/ml which should be closer to 2logs so i think the 3.66log  is about the only other patient on tdf+etv

i have to say many researchers are so bad at reporting, it is so easy to be precise on the numbers, on the contrary some of them are so confusing on the most important tests
another thing i do hate is the old way to report alt levels as ULN when they dont even say what they consider as normal alt
Helpful - 0
Avatar universal

yes they are very confusing and should not be used, at least for the hbsag which has small numbers.
2 logs is from 10 to 99iu/ml
3logs is from 1000 to 9999iu/ml
4logs is from 10.000iu/ml to 99999iu/ml

so 3.66logs should be between 5000 to 9999, may be about 7000iu/ml, i dont now if there is a way to make a precise number from 3.66log, i guess so, anybody expert with maths
Helpful - 0
Avatar universal
I thought the figures were 2.90 log (10) fold and 4.25 log (10) fold which I took to mean reduction to 1/794 and 1/17782 - I am a bit confused about these log number.
Helpful - 0
Avatar universal

the combo of tdf+etv makes me think this combo is more potent than tdf or etv alone since  this patient had prior interferon non-response and only 10months from hbvdna und, she also had anti-hbs fast development and hbsag was high before peg addon:
During add-on therapy, in 2 patients a continuous decline of quantitative HBsAg by -2,6log10 (etv patient with hbsag 16iu/ml baseline) and -3,66 log10 (tdf+etv patient, high hbsag almost 4logs) was observed at week 32 and 36, respectively.

too bad they just say hbsag 3.66 logs which is between little lower than 10.000iu/ml and higher than 5000iu/ml.so definitely the combo of the most potent antivirals may have a relevance confirmed in bigger trials
Helpful - 0
Avatar universal
I don't know what of antivirals was used.

I think that a wide range of antivirals was used. In text they say about the 2 patients one on entecavir plus tenofovir and the second one on entecavir.
Helpful - 0
Avatar universal
"unfortuantely only gilead is funding very big trials with peginterferon add on that i know of" - is that so ?  I'm surprise that Gilead funding trials with peginterferon, because as I know  peginterferon is not a Gilead drug.

(maybe Gilead look for a compartation viread + peginterferon vs viread + GS 9620 or vs viread + Gilead vaccine )
Helpful - 0
Avatar universal
We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial........

i think so too, they just tried nas in general and even stopped too early in non responders, as they say in the conclusion they should have kept peginterferon for longer and use stronger tdf.another limit is they made tdf add-on too early.the french trial was made better reaching 40% response but also in that case they used adv and lam while the use of tdf or tdf+etv could have reached much higher rates already in 48weeks of combo

the new trials with tdf and peg add on have much better design but i think it is better not to wait for those results because in any case tdf and peg add on is the most potent therapy we have
Helpful - 0
Avatar universal
Do you have any info what oral nucleoside was used? Because i think if all were priorily treated with tnf before peg add-on response rates would have been higher.
Helpful - 0
Avatar universal
http://www.ncbi.nlm.nih.gov/pubmed/22365367

- just a link for already presented case
Helpful - 0
Avatar universal

i think the we can have response from entecavir or tenofovir on hbsag as high as 1700-8000iu/ml but we need more data and bigger trials on use of tenofovir and entecavir and on hbsag at those ranges

unfortuantely only gilead is funding very big trials with peginterferon add on that i know of
Helpful - 0
Avatar universal
as calmama notice a big difference in terms of HbsAg can be notice in this two studys. 4,695  IU/ml (range 16-15,120) vs  660 IU/ml (range 50-1754) and iIwas wandering if the HbsAg level was a entry criteria for  the second case or if they use a different technology to measure.

somehow I think that the difference is to big
Helpful - 0
Avatar universal

these are my observation, weak antivirals like lam and adv take about 7 years to make interferon response work and 1 patient did not respond, these weak antivirals worked only with low hbsag less than 1000iu/ml

potent antivirals like entecavir and tenofovir worked even if treatment was short:
1 patient etv 3 years with very high hbsag about 8000iu/ml
1 patient tdf+etv 10 months hbsag not known
1 patient tdf 3 years, high hbsag around 1400iu/ml

so my guess is tenofovir is the most potent, etv+tdf even more potent and may shorten the time needed to get peginterferon response.etv and tdf can get peginterferon response even with high hbsag

what makes interferon response?i guess cccdna+intrahepatic hbvdna suppression because the longer you treat the lower cccdna, and also etv and tdf have little more decline on cccdna+intrahepatic hbvdna, combo etv+tdf even more cccdna+intrahepatic hbvdna suppression

we also know intrahepatic hbvdna suppress immune system, i think tests in serum are not reliable for this type of studies they should biopsy these patients to see hbsag quant, hbcag quant and cccdna hbvdna in the liver, i know it is difficult to obtain biopsy from patients but we do know serum tests dont show real status of the liver

as regards my treatment i will make tdf+etv+peg for sure, since this ******* virus doesn t respond so easily to treatment we must throw at him all we can, we do know all these combos have no sides....just expensive for insurance
Helpful - 0
Avatar universal
A big difference between these two studies is their mean baseline HbsAg.  This one is 4,695 (range 16-15,120) IU/ml, while the previous study is 660 IU/ml range (50-1754).  About 10-fold difference there.  If the baseline HbsAg is a predicting factor of interferon treatment response (ie. HbsAg < 1500 iu/ml means more likely to respond), the results make sense.  

I just wonder how much HbsAg reduction would tenofovir or entecavir (or combo of the two) make after 3 years of antiviral treatment?  Is there such data published somewhere?
Helpful - 0
2
Have an Answer?

You are reading content posted in the Hepatitis B Community

Didn't find the answer you were looking for?
Ask a question
Popular Resources
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.