Interferon tx for HBV vs. genotype

As a reminder, I have both Hep C & B. I was planning on tx Hep C for 24 weeks and then managing the HBV with an antiviral after that.

Dr. now thinks I should continue on Interferon tx for 48 weeks total (an additional 24 weeks) for HBV because I had such a great initial response to it (UND at 4 weeks) and because of my HBV genotype being “type A”

They said I had a 40% chance of getting rid of HBV with all things considered in my case with IFN. I don’t know where they got this figure from, but if anyone has any insight I would appreciate it.

I know that genotype A can be the easiest to tx, but my main concerns were autoimmune problems developing from the IFN and the way the drug makes me feel. They said that at 24 weeks when I am able to stop taking the Ribavirin for Hep C that my symptoms would improve because the symptoms are more related to the Ribavirin than the IFN.

I could handle an additional 24 weeks of IFN if I truly have a 40% chance of clearing HBV and the symptoms subside after stopping the Riba. I’m just having a hard time figuring out if it is worth it and where they got this figure from. I’m also ready to start feeling better and want my old self back.

Anyone ever heard of a HBV genotype A clearing from IFN mono therapy? Especially when VL was UND after only 4 weeks of tx? Would my chances really go up with 48 weeks of IFN tx versus only 24?

Thoughts anyone?

Anyone currently on or have taken IFN mono therapy? How does the IFN alone make you feel? What was/is your genotype and result?

[cajim]

>>>Anyone ever heard of a HBV genotype A clearing from IFN mono therapy?

Yes, if you have genotype A, low viral activity, and elevated ALT, you have the best chance of clearing HBV once and for all by IFN, the best chance I read was 32%.  Look somewhere in http://www.medhelp.org/posts/show/492008 for details.

[NashPred]

By the way….I think my Dr is pushing for 48 weeks of IFN because the cases of co-infected people he has seen in his office that have cleared HBV (or so they say) had HCV genotype 1 which requires 48 weeks of IFN.

I have HCV genotype 2 and only require 24 weeks of IFN.

[NashPred]

Thanks....I'll see if I can find it in that thread. I searched for "32%" but didn't come up with anything but found a small study from Japan in the thread. It's a long thread to search through but I'll keep looking.

My ALT a start of tx was in the 90's (back in April) and a month into tx had fallen to 62. Just had it checked again today but don't have the results yet.

[stevenNYer]

This is from the URT, posted by cajim:

Interferon

One of the more effective therapies available is treatment with interferon (IFN)-α, a naturally occurring cytokine primarily produced by B lymphocytes, null lymphocytes and macrophages.[103-105] IFN has anti-viral, anti-proliferative and immunomodulatory effects.[106] The molecular virological factors that contribute to the responsiveness of HBV infection to IFN treatment and may play a significant role in predicting whether IFN can be used effectively for treatment are largely unknown. The ability to predict responsiveness is important in the clinical setting, considering the fact that IFN treatment is expensive, is administered by injection, and can have side-effects and be poorly tolerated.

To date, the most important viral factor that has convincingly been shown to determine the response to IFN is the pretreatment HBV-DNA titre, the lower the titre the better the response.[107] Other viral factors that may play a role include the presence of BCP and precore mutations. It has been proposed, although not proven, that the BCP mutations together with a low HBV-DNA level and elevated ALT may be favourable factors of response in IFN-induced anti-HBe seroconversion.[108] The data on the relevance of precore mutants and their influence on the long term response to IFN is also inconclusive. In some studies precore mutants were considered to be necessary for response to IFN.[107,109,110] These data differ from other studies that showed that the precore mutants do not have prognostic value for virus elimination following IFN therapy in HBeAg-positive or -negative patients.[111-113] These differences in responsiveness to IFN treatment may possibly be the result of different genotypes of the virus and therefore an analysis of how various mutations influence the therapeutic response to IFN also requires knowledge about the genotype.[114]

In a study of German patients a higher rate of HBeAg seroconversion following IFN treatment was found in those infected with genotype A than those with genotype D (37%vs 6%).[115] The rate of HBeAg loss was also significantly higher in patients with genotype B compared with those with genotype C in a Taiwanese study (41%vs 15%).[60] In the former study, additional factors besides genotype, including the number of BCP mutations and low DNA levels, were found to be related to a better response and in the latter study; young age was found to be an additional positive predictive factor. Because genotype B-infected patients have a high HBeAg seroconversion rate, Wai et al.[116] compared treated and untreated Chinese patients with chronic hepatitis B. They showed that, in addition to low pre-treatment HBV-DNA levels and elevated ALT levels, genotype B was associated with a higher antiviral response to IFN treatment. The response to IFN treatment of genotype A-infected Chinese patients was found to be better than those infected with genotype D/E (70%vs 40%).[117] In contrast, in a study performed in Japan, IFN was given to seven patients with chronic HBV infection. Of the four responders, one was infected with HBV genotype B and three with genotype C. HBsAg persisted in the remaining three patients, all of whom were infected with genotype A, and HBeAg remained positive in one of them.[118] In a longitudinal study, no difference was reported in the rates of sustained seroconversion to anti-HBe in IFN-treated patients compared with those that were untreated, and this was not affected by the HBV genotype with which the patient was infected. However, the cumulative probability of HBsAg clearance was greater in patients infected with genotype A than those infected with genotype D.[96] These studies involved a small number of patients, which may be the reason for the conflicting observations.

Genotype switching has also been observed after IFN treatment indicating infection with a mixture of genotypes prior to treatment.[65,119,120] The minor populations, however, were not detected by either standard genotyping assays or direct sequencing and were detected using either a genotype-specific PCR plus RFLP or cloning.

Thus the results of studies from one geographical region cannot be extrapolated to other regions, without a thorough knowledge of the HBV strains circulating in each of the regions.

[NashPred]

Thanks guys….

I just noticed that the URT thread has 2 different sections now…..one for posts 1-200 and another for posts 201-229.

Since I have the pre core and BCP mutations, I guess this works in my favor for IFN tx coupled with GT A.

I may have to give it a shot (pun intended) a stay on the IFN then see how my symptoms improve after I am able to stop the Ribavirin for the Hep C.

I want to give myself the best chance but also don’t want to sacrifice my health. IFN can sometimes do more harm than good in other areas of the body. I have many pros and cons yet to consider.

I am going to ask my Dr if he can cite any cases of 24 vs 48 weeks when I see him in a month.
I did have them check my HBsAg again today just out of curiosity.

[cajim]

Would appreciate your recording and posting your experience during the course of  your IFN treatment.

[NashPred]

No problem cajim….I will defiantly keep everyone posted.

When someone spontaneously clears or clears from IFN tx, does surface antigen just go away or do they actually build up surface antibodies and become immune?

If only HBsAg goes away, are you then able to get vaccinated in order to build up HBsAb?  

[cajim]

Once you have been exposed to HBV, you don't clear the virus without developing the antibody against it, I think.

[NashPred]

Thanks again, cajim. Hopefully one day we will all get the chance to find out through real life experience.

I don’t know why it is that every time I go to the Dr and think I have my treatment course all planned out, they throw something new at me and I get home with even more questions than I had before.

I’ve been trying not to obsess about all of this lately and concentrate on the power of positive thinking and keeping my mind, soul and spirit well centered. Then I go to the Dr and they get me thinking about it too much again. It can be hard enough to remain in a positive state of mind as it is while on the combo tx that I am on.

Thanks for all the help. This board has been a fantastic source of information for me and I will keep everyone posted on my progress to hopefully add to the information source.

[zellyf]

NashPred, my understanding is that interferon increases your chances of clearing the surface antigen even a few years from treatment.  I certainly understand not wanting to over TX.

The vaccination is unnecessary if you develop antibodies.

Best of luck and keep us up to date.

[NashPred]

Zelly, I guess the reasoning behind that is that he IFN will for the most part be out of my system within a couple of weeks of stopping, but the boost to my immune system could last a few years. (I guess)

I just read on older post by Peteshine where he said that when he was on IFN mono therapy, his only real sx was itching. That is encouraging and I can deal with that if it helps my chances.

I will more than likely try to stay on IFN for at least a month after stopping the Riba, see how I feel, and then go from there. Time will tell. I have 10 or 11 more weeks left on Ribavirin. I just took shot #14 of IFN tonight.

[meki]

OK - let me check this...
OK - so HCV IFN/Combo Riba ---- poss with Alinia or any PI?

And HBV - possible clearance too?

40%? That's comparable to HCV 1a --- correct?

Is it monotherapy only with HBV --- or have there been no studies to include the RIBA plus or minus a PI?

[NashPred]

Meki,

Just to clarify, I am on Pegasys/Riba at the moment for HCV GT2. No Alinia.

They tell me I have as much as a 40% chance of clearing HBV but I think a lot of stars have to align in order for this to happen. Of course I do have some things working in my favor i.e. HBV GT “A” and HBV DNA and HCV RNA both being UND at 4 weeks into tx.

Yes this figure can be considered comparable to HCV GT1 but as Zellyf had mentioned, I don’t think clearance immediately happens when tx stops. My chances go up with each passing year and I think; only if I remain HBV DNA UND after stopping tx. So many more factors come into play to achieve this 40% figure than would have to happen for someone with HCV GT1.

This is part of my dilemma….when you consider that my chance will go up with each year, is the additional 24 weeks of PEG IFN really going to make a difference? Maybe the additional 24 weeks of Pegasys will help me to stay UND and thus give me a better chance. I just don’t know at this point. I have not really found any studies to support or contradict this.

Once I’m done with HCV tx, then HBV tx will be mono therapy of Pegasys. I don’t know of any studies on the effects of Ribavirin on HBV and don’t believe Riba plays any role as far as HBV goes. Also studies I’ve seen with PEG IFN coupled with an HBV antiviral don’t seem to make any difference either.

Know if I could only find a study of the effect of PEG IFN on HBV genotype “A” that were UND at 4 weeks….. then I would be set. I think the problem is that there are not enough genotype A’s as compared to the other genotypes so studies usually include all GT’s lumped together and most people don’t go UND so quickly, if at all. Even when reading studies of PEG IFN tx for HBV, they usually don’t take into account an HCV/HBV co-infection. So in a way, I’m am kind of my own study with my own unique situation.

It’s crazy and keeps getting crazier. Lucky for me, my sx on tx have improved a lot over the last month or so. I contribute a lot of it to a new way of positive thinking and not dwelling on the negatives of Hepatitis like I did in the beginning and that has helped tremendously. I learn what I NEED to know and try to block out the negatives.

[NashPred]

Here are some results from section 991 of the following article:

http://www.hbvadvocate.org/news/reports/HBV_AASLD_2007/Abstracts/interferon.htm

It says:

The cumulative incidence of HBsAg seroconversion was significantly higher in patients who developed SVR compared with those who failed interferon treatment during the whole follow-up period (40% vs. 8% at year 5, and 60% vs. 18% at year 10 and 80% vs. 30% at year 15).

So it looks like the key is for me to first obtain the SVR of which I have anywhere from a 4 to 11% chance with PEG IFN and THEN I have a 40% chance of HBsAg seroconversion after 5 years or 60% after 10 years. Does this sound right?

Still this isn’t specific to my particular case.

[cajim]

>>>Know if I could only find a study of the effect of PEG IFN on HBV genotype “A” that were UND at 4 weeks….. then I would be set.

Somewhere here:  http://www.medhelp.org/posts/show/492008, it was stated that speedy VL suppresion within 24 weeks is the optimal treatment result.  Yours was 4 weeks, even better than optimal.  Somewhere there too it was stated that genotypes A and B respond better to IFN than C and D.

Hopefully you have time to leaf through the studies and find them.

Best.

[meki]

See - now --- I'm learning something here.

Thanks Nash... Good information.

[NashPred]

Cajim….first of all, thank you for all the research articles you have posted. You’re a great asset to the forum.

I don’t think I have found the one you have referenced but I have found many informative articles about IFN tx for HBV and have learned a lot.  Many point to IFN being first line therapy for certain genotypes.

Here is just a sample of some of the articles in the URT relating to HBV and IFN for anyone interested, and also for my future reference:

Jun 12, 2008 06:07PM
Jun 14, 2008 01:32PM
Jun 14, 2008 01:46PM
Jun 22, 2008 04:41PM
Jul 06, 2008 10:09AM

[cajim]

>>>it was stated that speedy VL suppresion within 24 weeks is the optimal treatment result.

Apr 19, 2008 05:13PM, Notes on "Treatment of the HBV-Infected Patient: When to Start, When to Stop, and When to Change Therapy," Keeffe, E.B.  March 5, 2008.

Sadly, their tables are easier to see but there is no way to post graphs in threads, so you have to get their message through words.

>>>it was stated that genotypes A and B respond better to IFN than C and D

Jun 14, 2008 01:32PM, Notes on “Should Treatment of Hepatitis B Depend on HBV Genotypes? – A Hypothesis Generated from an Explorative Analysis of Published Evidence,” Wiegand, Jet al., AASLD 2006, #1009.

Best.

[NashPred]

Being able to post charts and graphs would be a nice feature to have on these forums sometimes.

So far, it looks like my chances are about the best anyone could hope for with current tx options and all things considered in my case.

The post from April says:

>>>>> Patients who are treated with peginterferon alfa-2a receive therapy for a fixed duration of 1 year, but it is possible that a shorter duration of therapy may achieve the same outcomes.<<<

Wish I knew if the additional 24 weeks would make any difference. I guess that’s what I’ll have to decide when the time comes. I may just take it a week at the time and see how I feel or just split the difference and tx for 36 weeks. Either way I’ll keep you posted as to my progress.

14 shots down and who knows how many more to go.?

Thanks again for all your help.

[cajim]

>>>Wish I knew if the additional 24 weeks would make any difference.

There were one or two studies that did say prolonged IFN treatment strengthened/improved the good results.

Best.

[NashPred]

Just a quick update…..I got my lab results from last week back this morning.

VL still UND. (Thank you PEG IFN)

HBsAg still reactive (no big surprise…just had it checked out of curiosity)

ALT is now down to 26. This is probably the lowest it has been in over 20 years (guessing)

ALT was in the 90’s at start of PEG IFN tx back in April.

[cajim]

Yeah, your treatment is showing optimal result.

Best.

[zellyf]

26...I'm positively jealous!

So happy for you!

[NashPred]

WOW! It’s been a while since I’ve checked in. Hope everyone is doing well.

Zelly, I thought the nurse had my labs (ALT) mixed up with a healthy female for awhile after she called with the results. I don’t think I really believed it until I got my hands on the hard copies of my labs and saw it for myself. I might have to have it framed…ha ha.

Just wanted to update everyone even though there really isn’t much to update at this point.

I have 5 more weeks of Peg IFN and Ribavirin tx to go for HCV and then I will continue with Peg IFN mono therapy for HBV for up to 6 more months and see what happens. I am hopeful that I will start to feel at least a little better after I am able to stop taking the pills for HCV in 5 more weeks.

Last Dr appointment was 8-8-08 and they ran what seemed like every HBV test available. I expect the nurse to call this week with the results. Hope my ALT is still normal and VL still UND. I know they also tested HBeAg, sAg, and I think sAb. I’ll hope for the best and remain positive no matter what.

I’ll keep ya’ll posted.

[cajim]

Glad to hear from you and hope good results are coming.

Best.

[NashPred]

Thanks Jim....looks like you've been busy. Lots of questions asked on the forum lately. I have some catching up to do.

[zellyf]

Thanks for the update, NashPred.  Make sure you tell us your results!

[NashPred]

Finally got the results of my lastest lab work:

HBsAg - still positive (I'll see what I can do about converting that for next month)

VL - still UND (Everything is good there)

ALT - 27 (Only up 1 point from last month so it is holding steady.)

I got this info over the phone from the nurse so I don't have the hard copy yet, but I didn't ask about eAg or eAb but I would guess eAg still Neg and eAb still Pos.

Looking forward to coming off the Ribavirin that I take for HCV to see if some of my CBC's return to normal. Just 1 more month of those pills.

Tune in next month for exciting adventures.

[cajim]

Good results.  For HBsAg to turn negative, I have read it may take years.

Best.