Genotype 1A or 1B - does it matter anymore?

[hepcandme]

My doc says that the new treatment regimens do not differentiate for those with Genotype 1A or 1B. This seems to substantiate that assertion:

http://www.medscape.com/viewarticle/823549#1

I am also wondering why anyone would add Riba to the  ledipasvir and sofosbuvir combination since it doesn't seem to improve outcomes?

And, thoughts on 12 weeks vs 24 weeks?

Looking to begin a new treatment just as soon as the FDA approves this combo

[hepcandme]

Oh Susan

I Really am wishing for this treatment to work for you! I can't imagine what it has been like - all those years of feeling lousy

Hopefully, Interferon is a thing of the past

Best and Be Well !

[susan400]

Hi.  I just wanted to explain to you where I was coming from with my earlier comment.  When I said about not wanting to 'rush out onto the Ledi/Sofi that's coming out, if for some reason, I relapse (which of course, I'm hoping I don't).  For years, I was doing back to back treatments, like practically every 12-15 mon.  This is the 11th time for me, dating back to 1997 being my first treatment.  Every treatment has been with interferon.  My body has been through alot.  It has helped to keep the virus from causing alot of damage, but it has not been without a great cost to the rest of my life and health.  The interferon caused me to have a permanent (no cure) skin disease.  It's wreaked havoc on my personal life from all these treatments and how it's affected moods, etc.  I used to actually be able to work during the earlier treatments, but it got to the point to where I could no longer function with my retaining new directions as far as remembering.  Somebody explains something to me I have to be told 10 times before that 1 direction will retain and if somebody attempting to give me 5 tasks at once, I completely fall apart.  Anyhow, I want to be able to function like a normal person and keep hoping that someday I'll have a NEW normal.  I hope this helps to clarify where I was coming from.  I used to jump right into another treatment, but really can't anymore.  Susan400

[Willy50]

Wishing you success on the next go-round and recovery in between. : )

[hepcandme]

well, now it's just the Sipro (diuretic) 25 mg per day and a Vit B pill 500 mg per day so, I am nearly drug free to take on the next harsh drugs that will rid me of Hep C forever!

Thanks for bringing this issue to my attention Will

[Willy50]

Thank you for identifying why you were on antibiotics in the first place; I wondered.

Every now and then it is worth re-evaluating drugs anyway. I know that they are trying to use cipro less and it has acquired a few warnings latlely.

I hope that making some inquiries and doing some reading helps. Your pharmacist may also be a good reference to ask on additional drugs  you might take, replacement antibiotics, or ....if the  cipro may have contributed to the neuropathy, if there is some course to take to regain what you may have lost?  Do's or don'ts? Probiotics? etc.

Best of luck and I hope things get better.

willy

[hepcandme]

Hi Willy

I sent my concerns to my doc and he said it was OK to stop the Cipro, especially if I thought that my neuropathy had become worse since taking it

I have never believed in over-prescribing antibiotics but I am allergic to some of the others that docs love (can't remember the names at the moment - I'm still at work)

I believe that the reason they consider using an antibiotic as a prophylactic is that one can develop a serious bacteria infection from fluids retained as a result of ascites

since that doesn't seem to be a huge problem for me at the moment, I would rather not take it, or any, antibiotics, unless I have to

Trying to make the old immune system healthy enough to do its job!

Getting rid of Heo C is a nice thing to do for the old immune system

[Willy50]

I have been worrying that I have only had negative things to say.

The answer is that I do not know, and I frankly think that many doctors would argue the point. I have no doubt of it.  But..... it is your body and your life.

Do not just take what I say as fact; run it by a doctor or 3, and ask a few pharmacists and always read up on drugs you take.
To the best of my knowledge one does not take drugs life cipro prophylactically, especially when one has liver disease.
==========

My friend, whose life a floroquinalone basically destroyed only took 2 doses, but (in her case) it is especially counter indicated with steroids. Yes, it was prescribed by a doctor prophylactically.
Somewhere on medhelp there are also a few threads on this very topic.

http://www.medhelp.org/user_journals/show/16135/Fluoroquinolones-increase-risk-of-tendon-rupture-in-elderly--transplant-recipient--steroid-users

If you have neuropathy you might see a neurologist. My neuropathy ramped up with treatment, I felt due to anemia.  My world class doctor argued with me, but the neurologist allowed that I may have been right. Such as it was....one could not prove anything.

Point is..... why risk it?

I know very very little of your case, so don't trust me, just follow up on a few things I'm asking and see where it takes you.

If you have neuropathy you might also look at my old threads; there is one called something like Vitamins and Micronutrient Testing. There are some you tube links which demonstrate some of what I am referring to; drug interactions and the gut.

http://www.medhelp.org/posts/Hepatitis-Social/Vitamin-and-Micronutrient--Testing/show/2027720#post_9603214

This should keep you busy for a while.

Take care and I hope this has been of some benefit to your situation.

willy

[hepcandme]

Wow

The Cipro I take is intended as a prophylactic antibiotic but it is really frightening to think that taking it once a week could actually be Causing my neuropathy to worsen

Geesh, why don't the docs consider these factors?

I do know that others in this group have been prescribed Cipro and in much higher doses so I think it is part of the standard of care for cirrhotics

My Vitamin B level is fine. It was on the low side before but never out of the normal range and now it is in the high normal range

Magnesium - I will ask for them to throw that test on in the next labs in a few weeks

thanks Willy for all the great input

[Willy50]

Here is another idea for your next TX;
Sovaldi and Daclatasvir (also currently in trials; they may be looking for TX failures to PI's)

This treatment might not need ribavirin

http://www.natap.org/2013/EASL/EASL_106.htm
(scoll down to figure 23 and read)

"Apparently the combination of DCV + SOF is so potent that it even works without additional ribavirin. These findings are very helpful as they help to envision that there will be potent salvage regimens even in patients failing previous DAA therapy and resistance development. "

~W

[Willy50]

http://www.fda.gov/Drugs/DrugSafety/ucm365050.htm

Safety Announcement

[8-15-2013]  The U.S. Food and Drug Administration (FDA) has required the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy. This serious nerve damage potentially caused by fluoroquinolones (see Table for a list) may occur soon after these drugs are taken and may be permanent.

The risk of peripheral neuropathy occurs only with fluoroquinolones that are taken by mouth or by injection.  Approved fluoroquinolone drugs include levofloxacin (Levaquin), ciprofloxacin (Cipro), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), and gemifloxacin (Factive).  The topical formulations of fluoroquinolones, applied to the ears or eyes, are not known to be associated with this risk.

If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped, and the patient should be switched to another, non-fluoroquinolone antibacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk. Peripheral neuropathy is a nerve disorder occurring in the arms or legs. Symptoms include pain, burning, tingling, numbness, weakness, or a change in sensation to light touch, pain or temperature, or the sense of body position.  It can occur at any time during treatment with fluoroquinolones and can last for months to years after the drug is stopped or be permanent.  Patients using fluoroquinolones who develop any symptoms of peripheral neuropathy should tell their health care professionals right away.

[Willy50]

Yes, it is good news and it bodes well for your future treatment.

If you want to treat as soon as possible it looks to me like the gilead (sov/ledi) treatment will be what you need, but I would consider adding RBV.

============================
"I am not taking many meds now - Spiro 25 mg (diuretic), Vitamin B 500 mg and a once a week antibiotic - Cipro "
=============================

It seems to me that you are on meds if you are taking cipro. I also don't understand; there is a once per week antibiotic? Is that according to recommended dosing? Or is it being used prophylactically?

Cipro is a pretty serious antibiotic. Read up on it; the floroquinalone group is getting a lot of scrutiny lately. I have a friend who took only two doses whose life has been destroyed. I'm in no position to question suitability, but I wonder if you might review your usage of this drug with your doctor and perhaps moreso your pharmacist. Please also read up on it.

I am afraid that some of these hi powered antibiotics have been prescribed improperly.

Far be it from me to diagnose, but this blog contains some concepts, that you may want to run down;
http://www.survivingcipro.com/articles-authored-by-you/gut-health/

My concern is that if drugs damage your gut flora, then the nutrients you need for your nerves get destroyed. In short- could the cipro be causing or contributing to your neuropathy?

This is also why I recommended getting your levels checked; B-vitamins and magnesium. If you are seeing a neurologist for your neuropathy you might ask them. If you are not, perhaps you should.
IF you are vitamin B deficient, you need to run that down before you start on ribavirin, sine that could contribute to the neuropathy issues you already have.

In the meanwhile..... do some reading....  : )

You have a lot to digest now, and I hope that this has helped in some ways and I hope I have not seemed too critical; the intention was to help.

willy

[hepcandme]

OK

You're right. I am not a null responder:

Null Responder: A null responder is someone who achieves little or no decrease in hepatitis C viral load during HCV treatment. Null responders are highly unlikely to respond to re-treatment with an interferon-based regimen.

Non-responder: Often referred to as a "treatment failure," a non-responder is someone who does not have an EVR or, if they stay on treatment for 24 weeks, does not ever have a 2-log (99%) drop in hepatitis C viral load or undetectable HCV RNA during hepatitis C treatment.

Partial Responder: A partial responder is someone who experiences at least a 2-log decrease in hepatitis C viral load during HCV treatment. Partial responders are more likely to respond to re-treatment than non-responders or null responders.

Relapser: The term relapser refers to someone who has had an EVR or ETR, but whose virus rebounded after they completed HCV treatment. People who had a relapse after completing HCV treatment are more likely to achieve SVR after re-treatment than partial responders, non-responders, or null responders.

but, this is good news that I am a relapser since it improves my chances of achieving SVR, it seems

[hepcandme]

Everyone on the new regimens becomes "undetected"

Viral Load was about 7 million at start of treatment
57 at 3 weeks
undetected at 8 weeks and 12 weeks

then, relapsed when tested 4 weeks after EOT

So, maybe I am using the term null responder incorrectly or they need to reconsider the term since everyone will be undetected during treatment?

I have a MELD score because I needed to be "listed" in order to begin treatment that most likely would include Interferon and there is a danger (slight) that Interferon can actually cause decompensation for cirrhotics

I am not taking many meds now - Spiro 25 mg (diuretic), Vitamin B 500 mg and a once a week antibiotic - Cipro

I calculate my MELD score every time I get lab results using this calculator:
http://optn.transplant.hrsa.gov/resources/MeldPeldCalculator.asp?index=98

But honestly, I can calculate it now in my head as soon as I get the numbers

I know that I should be patient but I feel like I am getting more ill, certainly more anxious about my prognosis

I will certainly pay attention to the data coming out the conference and I Really hope that I can start the new treatment soon. For those who have gone through many, many attempts to conquer this disease, I am in awe of your courage and resiliency

I need a treatment option with a start and finish day in my future that I can hang my hope on

[Willy50]

are you sure you are a null responder?
==========
http://www.medscape.com/viewarticle/713174_2

Definition of Relapse and Nonresponse
Relapse and nonresponse are defined on the basis of the virological response to treatment (Fig. 1). A patient is said to have experienced a virological relapse if HCV RNA decreases and remains below the limit of detection (<50 IU/mL) during treatment but becomes detectable after cessation of treatment. If HCV RNA rebounds and becomes detectable in such a patient before treatment is completed, this is referred to as virological breakthrough. Virological nonresponse is evident when the serum HCV RNA level remains above the limit of detection throughout treatment and is formally defined as less than 2 log10 decline in HCV RNA between baseline and week ...............................................................................12. A patient who has less than 1 log10 reduction in serum HCV RNA at week 12 of treatment is said to have had a null response.....................

(my emphasis-~W)
===============

So...like I say...I am in the dark here, but if you relapsed by week 4 EOT, I'm guessing that you cleared earlier at one point. I'm also guessing you had a viral load drop greater than a one log drop.
Therefore, I'm guessing you are NOT a null responder.

Can you list your starting VL, any PCR data along the way?
I would guess you are a responder.
I would guess that a longer duration may have worked,
or that adding riba may have taken you over the hump.
I'm also guessing that either new treatment may work for you (whether Gilead or Abbvie) but that you may need to do riba to make sure things work this time.

This is not the ONLY way, but it is *one* way.
=========

I understand your reticence. I have been there myself.
I treated last year and ended up with some neuropathy myself; the possible result of anemia. (possibly compounded by riba induced anemia)

If you have a MELD score I assume you are being well cared for. When was your B-vitamins checked last? Magnesium? Deficiencies here could make your neuropathy worse. How about any diabetes issues? (can contribute to neuropathy). Review any drugs you may also be taking and check against any sides you are having, ; some lower B-vitamins, for instance, making neuropathy worse.
===========

It looks to me as though you may need to recover, check a few things and you could probably retreat in a year and have a 95% chance of SVRing; thereabouts, based on the Abbvie trial results.

I'm basing that on you waiting to recover, a few possible possible tweaks that could improve outcomes (bolster any deficiencies; Vit B, D, A magnesium, improve insulin issues, if any).

Abbvie has a great treatment which is more effective on 1-B's than 1A's, but your issue now is possible resistance to a PI; ABT-450 (part of the abbvie regimen) a protease inhibitor, so you would have to wait for that resistance to diminish.

I believe you could treat with Gilead's Sovaldi, Ledipasvir (NS5A inhibitor), and RBV as soon as it is approved; this fall.

As mentioned, the fall AASLD will have some data and may also have some presentations for people whom like yourself need treatment advice on where to go from here.

Willy

[hepcandme]

Here's my basic info:

Diagnosed with Hep C in 1992
May have been infected as early as 1974 through blood transfusion but, hard to say?

Genotype 1B (I had thought 1A for a long time)

Cirrhotic - low level edema and ascites, portal hypertension

MELD score 12 in October 2013
Reduced to 10, then 9 and held steady at 8 since last April

Treated off label with Sovaldi/Olysio from April -June
Relapsed at 4 weeks EOT

MELD score now 10
ALT levels doubled (but still not Terrible - 47)
Viral load at close to one million at 4 weeks EOT
Other labs in normal or close to normal range - platelets a bit low

First time treated and now can say I am a null responder  :(

My understanding is that one does not build up a tolerance for Sovaldi but that Olysio is out of the picture for me now

I am very anxious to try again because I just don't feel well - what I call The Uber Fatigue and aches. I wish that I could work out 4 times a week but really have a hard time getting out of bed, insomnia, headaches, constant pain caused by related neuropathy. I just feel pretty awful most of the time and dream of a time when my energy level was more than a lizard sunning on a rock

I am trying to be patient for the new "miracle" drugs but I was treated off label probably because my circumstances were "interesting" to researchers

Cirrhotic, naive treatment patient with fairly good lab numbers

Serious, I would have stayed on the S/O for 24 weeks if that was on offer but I agree with a precious poster that sometimes it feels like a crap shoot - how long to treat, what combo, add Riba or not, what will insurance co agree to fund?

And I have read that people on Riba had some really awful side effects so I don't really want to take it and my reading of the latest trials show no additional benefits

But I don't want to be a baby about this and will take the Riba

But no to Interferon, thank you

[susan400]

I know that as far as in the research areas, the 1A versus 1B may have some baring on response.  I am not a scientist, and I'm really not that great at keeping all the science of Hep C straight in my head.  Usually, when somebody starts discussing the chemistry aspects of the Hep C virus, I start getting brain fog and feel like my head is spinning and really can't make any sense of it.  But, I have treated more times than anybody else I know of.  I'm sincerely hoping that this treatment is it for me & that I SVR.  I get my 2nd viral load (week 8) on Aug. 13.  I met with my doctor last week and we were having the discussion.  Hoping that this is it for me, but the 'what if' conversation.  If for some reason, I fail to clear the important hurdle of undetected through this treatment and on the end of treatment check as well and I relapse...   I have told him and he supports my decision, that I will not turn around and jump right into the Ledi/Soval combo.  Or even the Abbie one that's coming up soon.  I will wait about 3 yrs again.  Right not with as much as I've treated, my body can only take so much.  My doctor does say though, that even though I've never SVR'd, YET, that all of these treatments have helped to temporarily suppress the virus and give my liver a chance to rest.  I've had this for 30 yrs and actually have very little damage.  I don't do any major dietary restrictions, but I do work out about 5-6 days (even have been known to do 21 days in a row) a week.  I do weights like every other day with a day off in between and the other days I do cardio equipment, i.e. treadmill, elliptical, stationary bike.  I pretty much eat whatever I want, except try to avoid fried foods and spicy foods(only because spicy foods kill my gut).  I haven't drank alcohol, or smoked cigarettes for 19 years.  All these things, my doctor says have helped to keep my damage level under control.  Also, I've never had a weight problem and haven't done the yo-yo gain/loose weight thing.  I pretty much have stayed within the same 5 lbs for the past 20 years.  I might go up 5, but then, a month last be back down the same 5.  Never losing like something crazy like 40+ lbs. or like gaining 50+ lbs., nothing extreme like that.  My blood sugars have also, never turned diabetic.  Other than the fact that my immune system obviously s*cks, because otherwise, seems to me, I would have SVR'd by now.  But, at least this time, I have that hope since I finally heard undetected back on week 4 blood draw.   Susan400

[Willy50]

Um no, actually I am throwing the idea out for considering adding RBV even if it is only for 4 or 6 weeks, if one is cirrhotic, a past TX failure, other negatives that may impact on SVR rates. Consider even a little instead of none at all.

If your doctor is proposing riba I would guess it is merited, and dosing can always be reduced, and so far be it from me to recommend reduction.

The original post was about sub-genotype response, and I was addressing that issue that the OP may have needed a bit more of a boost. IF the OP was a null responder to Sovaldi and Olysio it is even questionable if riba would have tipped the scales, but yes, maybe riba with 24 weeks; one may have gauged that by response rates and/or week of viral clearance

~W

[zarmar]

I respond to reasoning positively, as well.  I will have a go with my Dr.  

The consulting Hepatologist I saw at Mount Sinai before Tx began and with whom I correspond with from time to time was pushing Ribi given my profile.  I don't know if  can crunch timing at this point, but if I could see her before the 8/15 ax drops on the 12 wk course, wonder if she could authorize Ribi for 4 wks?  

Thanks ever so much - I am a fish way out of my depth trying to address this new Tx world.

[Livelife777]

Willy your right.   It really is a crapshoot, and I believe the experts in the field don't have the right answers.   Your reasoning and sound advice makes perfect sense to me.  
...Kim

[Willy50]

My take on it.....
there is no data on this, or very little.
I currently have a past treatment failure friend who is on Sov/Oly without riba, so I think it is common, but I question if it is wise, given that many are cirrhotics which will have increased hurdles if failure occurs.

My friend is RBV intolerant, but he has suffered through RBV before, and it would probably provide roughly the difference between treating for 12 weeks versus the added benefit of several percent of treating for 24 weeks. (just a few % points)

I guess I wonder if it would make sense to do 4 weeks of riba, then stop or continue with the riba based on a 4 week PCR and other factors, like anemia?

Even if one stopped, there would essentially be a taper as the half life decreased, and I believe it would be effective in speeding the viral reduction at a super critical time, raising the efficacy without making for serious side effects. I don't think it would seriously affect most cirrhotics, but could provide a small bump in efficacy/cure rate. It's purely speculative, and I've no clue about lymphoma issues, nor am I recommending RBV as an add on at the end of TX.

I'm just not aware of any "rule" that says all drugs must be used the exact number of days as all other drugs. We commonly see RBV dose reductions done with negligible reduction in SVR rates, so if anything, there IS data that shows this may be effective. The magic line for genotypes, past failures, cirrhotics may not yet be known; maybe 6 or 8 weeks would be better.

My point is that 4-6 weeks of riba on the front end might be as effective and WAY cheaper than adding another 4, 6, 12 weeks of DAA treatment.

willy

[zarmar]

Thank you for this discussion.  I am a 1a newbie to Tx, but not to HCV as I have advanced, compensated cirrhosis after 40 years with the disease.  My S/O 12 week course ends on 8/15. I am not a good candidate for RIBI given my comorbidities with lymphoma.  My concern is that my hepatologist won't know until the next week if I am SVR at EOT - I was UND at wk 8.  The 16 wk course mentioned in this post sounds like a good option for me rather than leaving S/O perhaps too early for my stage, and wait for S/L or other to be approved in a few months.  My pharmacy told me this week they are not aware of any compassionate care prescriptions being submitted for S/L at this point.  Is this a good argument for me to make to my Dr. to request a 4-wk add-on of S/O so there is not the interruption and a better shot at SVR?  I have the impression from a conversation with the pharmacist a few days ago that it is up to Dr.  Thanks all for your expertise on this.

[Willy50]

Some people are familiar w/ Dr. Paul Kwo. Here is an article somewhat germane to this discussion;

http://hepatitiscnewdrugs.blogspot.com/2014/05/reconsidering-whether-to-treat-genotype.html

"Therefore, in genotype 1b patients, I recommend sofosbuvir plus simeprevir, and in patients with genotype 1a, I recommend sofosbuvir plus simeprevir with ribavirin"

===================
I would suggest that your issues now in treating are your possible resistance to PI's for a period of time, your cirrhosis, your past null response, and to some degree your geno-subtype (1B or 1B; I don't know which you are), and other considerations; if you have other co-morbidities which make using riba an issue, potential for decompensation, etc.

Before considering the Gilead sovaldi ledipasvir combo I would want to see how it scores against past TX failures, past null response, with cirrhosis and for your genotype and sub-genotype.

The issue of resistance; you may have to wait up to 1-2 years..... for the resistance to PI's to revert back to wild type, but there may be more current info on this. It's the last info that I thought I understood.

If you treat in the next year, I think you will see 12 weeks with RBV minimum, regardless of whether it is Gilead or Abbvie. (I am inferring you are a G-1A)

willy

[nan535]

Thank you both for your kind words.  I am happy to know you both have supportive partners to help you through this very difficult period in your lives. I can only imagine how hard it is for someone doing it alone. This is one of the reasons I post here. I see how much he needs someone to be his advocate and it makes me wonder what happens to those who don't have anyone there to support the.  So if I can be of help to someone by sharing our experience,  that's great.

I am praying one day in the not too distant future Hep C will be noted only in the history books.

Nan

[Willy50]

Hi, I'm sorry that I was not up to speed on your particulars. I just looked and it appears you just failed Sovaldi and Olysio. And you are cirrhotic.

What this means to me is that you can try either of the soon to be approved  drug treatments; either from Gilead or Abbvie.
Both should be available by late fall winter.

It is all in the rear view mirror at this point, but I do not quite understand why you did not use riba in your last TX. It is neither here nor there now, but you almost certainly have it in your future. I like the idea that your doctor was proactive enough to get you on off label Sov/Oly, but I do question why the doctor skipped riba.

We may soon see the kind of stats for cirrhotics with and without riba on the two drugs, but maybe not. Sometimes the records remain a mish mash of anecdotal. It is the actual trials which provide the kind of spreadsheets of results that are most meaningful.

I would not be in a neck break to retreat. Make sure you pick the right drug treatment best suited to your staging, genotype, subgenotype, response, il-28 genotype, etc.

I would also make sure all your levels of everything were up Vit D, all B vitamins, A, your iron is where it should be, and I would even work on tiny things like BMI or getting as fit as one can. Use every small thing you may need to get you over the final hurdle.

I would not be overly alarmed about resistance to Sovaldi, but the protease inhibitor (olysio) may result in some resistance for a spell. It seems to me that the gilead treatment took one relapser and almost immediately re-treated them, and the second go-around they cleared and SVR'ed. DO keep in mind that you may have some potential resistance issues so you may need to used everything at your disposal this next attempt.

I will repeat, I do not quite understand why your doctor did not use riba this last attempt and I do not quite agree with their statement about no difference between genotype 1A and 1-B response. Please make sure and double check the doctors recommendations against various responses on this forum before your next TX. (It costs nothing to get confirmatory opinions)

Also, do pay attention to the next Liver conference; AASLD this fall. There should be relevant information to your case,  (once again, even if it is only confirmatory. )

And am I to understand.... you are a null responder to Sovaldi/Olysio? How about other past treatments? If you have treated in the past and also been a null responder I would really question..... there would have to be a good reason that riba was skipped this past time, IMHO.

Maybe I am just walking into a discussion or circumstance I know nothing about and am missing something?

best,
Willy