non rvr

hi all. as some of you know ive startedtreatment 8wks ago and am 3a, i done a viral test at 4 wks and got results when i meet doc 2day. i started with a vl of jus over 5.9m. my 4wk vl was jus over 1.1m. im on 180 peg and 800riba per day and i way 90kg, i have asked doc wat happens next as its not the vl he was looking 4 and said he`ll decide wat course of action 2 take hen he gets my 12wk vl. he said he might add a futher 16wks to my 26wks but depending on my vl.
if he`s not happy with vl he`l stop treatment.
i have tried 2 get him 2 entertain the opion off upping my riba but he`s not budging.
so if any 1 out there had same experiance or any1 can tell me what they think my chances of svr are.
thanx santa

[FlGuy]

Unfortunately, the dose of riba probably has something to do with it.

[santaclaus]

i was thinking that myself, i have no sides, i feel just like i did before i started and ive tried to get more riba but he keeps telling me im at the max amount 4 my geno type. RRRRRRRRRrrrrrrrrrrrrrrrrrrrrrrrrrrr.
jus wondering if there could be any way my strain could become immune to treatment?

[jmjm530]

You had less than a one log-drop at week 4 which isn't good, especially for a genotype 3. As FlGuy suggests, it may have something to do with the riba since you are not on a weight-based dose which you should be, at least according to the treatment protocols that the better liver specialists seem to be following these days. If you don't feel your medical team is at the top of their game and/or doing the best they can for you -- then the option exists to get another opinion right away. If you do, you want to see a hepatologist (liver specialist) as opposed to a GI. My guess is that your current doctor is not a hepatologist, but nothing surprises me these days.

-- Jim

[jmjm530]

but he keeps telling me im at the max amount 4 my geno type.
--------------
That's a good clue that this guy is a bit  behind the clock.

[epiphiny]

I'm a Geno3a, 77kgs and I'm on 1200 Riba per day.  This is my 2nd TX, I am UND.

On my first TX I was only on 800 Riba per day and just as you are describing now I had NO sides and NO Viral Response.

I agree with everyone else here -  it would seem that your Doc is working off the old protocols for G3 rather than the newer weight based dosing protocols.

You could arm yourself with some studies to present to your Doc, there are plenty around.  Or you could spend the time finding a new specialist...

Given that the idea is to get to UND as soon as possible you could always up the dose yourself while you look for a new guy.  Depends on how many meds you have in hand...

Of course I am not a doctor, this is just my opinion. You would be much better served to find a new Doctor, even if you have to pay for your first consult.  Get the best guy you can find - the AASLD web site has list of specialists in all areas.

Oh, I've just seen that you are in Ireland, don't know where you would access specialists list there.  You could check out the UK Hep C Forum, there are some good people over there with knowledge of the system on your side of the world.

hepcukforum dot org

Epi :)

[Marcia2202]

I'm a 3a and weighed 58 kg when I started treatment, am now down to 55. I am on 800mg of riba and did not RVR4 either. Even though 800mg IS weight based for me. I find it very curious that they still treat the old way at your hospital in Ireland. The protocol has long changed to weight based for g3's. I would print out some studies from the internet and show to your doctor and push him to up your dose. I believe he is really jeopardizing your chance of SVR.

Good luck to you.

Hugs, Marcia

[santaclaus]

when i said 2 him bout upping ribba he checked the leaflet from inside of the roche box and sais that i was on the max, dont make sence 2 me.
he is head of hepatoligy unit in beaumont hos in dublin, even goes by the name of prof murray???
i might try ringin roche ireland and see if they would be willing to up dose and get onto this fool.
im really upset by this clown, so if any1 has links to sites with oproval so i can be armed wiyh this info for him.

if i was able 2 get my hands on some extra riba would u think it wise 2 up it myself?

thanx all 4 answers

[epiphiny]

Here is a link to the previous discussion you started on this topic, there is some pretty good info in there.

http://www.medhelp.org/posts/show/639343

Also a link that jmjm has already posted for you:

http://www.****.***

I'm sorry I don't have any more time to do more searches for studies for you as I'm at work but the info is out there if you search for it.  

I really think you would be better finding another Doc who is up with new protocols.  All the printed material (such as the insert your Doctor quoted from) are still based on old studies, it takes time for the new info to make it to print and filter down.

Go for it, Santa, it's your health, your life, YOU have to fight for it!

Epi.

[copyman]

i would go off label and add aliana to the combo drugs along with upping the riba. If your doc was up to date with the latest protocol he would increase the riba ASAP !!! Tell him you want to be treated as individual not as a "outdated" protocol. If he will not do it then find a new doc. In the meantime I would up the riba on your own to at least 1000mg. Best of luck

[Facta_non_verba]

I agree with everyone else about the weight-based ribavirin. The problem with upping your dose is that you will likely become anemic. Here in the States some docs don't offer rescue drugs like they should, but some countries have "health care for all," but they come with a "well almost" clause. Does Ireland's system offer drugs like Procrit and Neupogen?

I could picture a scenario where your doc doesn't know that you've upped your ribavirin dose, you become anemic and he stops your treatment. Gotta think about that. On the other hand, if you don't become undetectable by a certain time, you'll have to stop anyway because it's unlikely your doc will off extended treatment.

Jeff
Facta non Verba

[copyman]

i can picture a scenario where you up your riba and become undetectable and even if you become anemic you can always lower it. Or worse yet stay with what you are taking never become Unde and stop TX at 12 weeks.

[comeagain]

here is a link about both extending and upper riba for geno 2/3  its a bit tricky to understand the tabbels though, it seems if you get to UND the relaps rate is much smaller if both extending to 48weeks  and upper the riba to 1200 you shall lock at the relaps % once you undetectable its a small study you can show it to your doc if his able to read it right.

http://www.natap.org/2007/DDW/DDW_01.htm
ca

[epiphiny]

You're a treasure, ca, that's the study santa needs!

[cathy77]

I am geno 3a a relapser, i did the 24 weeks on weight based high dose and 1000 riba a day, I had a 2 log drop at 4weeks and became udetectable 12weeks but was struggling along with being diagnosed with Sjorgrens syndrome which was unbearable but managed to get the end undetectable, 1 month later relapsed. my weight was 67 kilo's

[fretboard]

Here's a link, I hope it works, sciencedaily.  There should be information on the package insert.  Also, check out www.AASLD.org

http://www.sciencedaily.com/releases/2007/10/071001160641.htm

I hope this helps...

[epiphiny]

Another excellent study, thanks!

[jankar]

I think you need to work with your doctors rather than working alone - you need professional back up if things become difficult. Another doctor, or take along the research and do not move until current dr gets some advice from another specialist.

I am 1 b, 75 kg and take 1200 riba per day. 6 weeks into treatment - unsure of my results to date but had a good EVR.

[CockSparrow]

Merry Christmas Santa. -Sorry! Can’t help myself.

Well you have had a 0.73 log drop. Which aint that good.
Unlike most of the others I don’t think it’s the Riba dose that produced such a poor 4 week result.
Although, It could well impact your ability to EVR.
Its your poor response to Interferon that’s the problem, OK the Riba dose isn’t helping. But your main problem is that IFN isn’t working that well.

“Santa - any1 can tell me what they think my chances of svr are”
Without Increasing the IFN and Riba dose and extending to 48 weeks if you respond to the higher doses - Not Good.
In saying that there is always a G3 that breaks the rules. Here hoping you are 1 of them.

G3s are supposed to be easy to treat.
Like me, You seam to be trying to prove that aint necessarily always the case.
If you are not careful you will be joining me in the G3 NR club.

No offence but for now I am going to reject your application.

So what can you do about it.
Here is what ML Shiffman Thomas Berg have to say.
Ask why you cant do it this way. Get your Dr to disagree with Shiffman and Berg rather than you.

Optimizing the Current Therapy for Chronic Hepatitis C Virus: Peginterferon and Ribavirin Dosing and the Utility of Growth Factors.
Clin Liver Dis 12 (2008) 487–505

Mitchell L. Shiffman, MD

This article focuses on how altering the doses of peginterferon and ribavirin can affect the three milestones leading to SVR, namely, virologic response, breakthrough, and relapse.

Patterns of virologic response
The term early virologic response refers to a 2-log decline in HCV RNA from the pretreatment baseline or being HCV RNA undetectable within 12 weeks after the initiation of treatment.
Approximately 80% of patients who have genotype 1 and virtually all patients who have genotypes 2 and 3 achieve an EVR. Patients without an EVR rarely if ever achieve an SVR

Patients who have genotypes 2 and 3 who do not become HCV RNA undetectable after week 4 have an SVR of only 49% [4], and a recent retrospective analysis has suggested that prolonging treatment in these patients could also reduce relapse

Effect of interferon dosing on virologic response
It has long been recognized that the ability of interferon to reduce HCV RNA in serum is a dose-dependent process.
Studies conducted at the author’s center longer than a decade ago demonstrated that increasing the dosage of standard interferon from 3 to 5 to 10 mU and then to 20 mU three times weekly every 3 months in those patients who remained HCV RNA positive led to a stepwise increase in the overall percentage of patients becoming HCV RNA undetectable.
Up to 80% of patients treated with this approach eventually became HCV RNA undetectable.

High daily dosages of consensus interferon (9–15 mg/d) and higher dosages of peginterferon, up to a peginterferon alfa-2a dose of 360 mg/wk and a peginterferon alfa-2b dose of 3.0 mg/kg/wk, respectively, have been shown to lead to a virologic response in approximately 15% to 20% of patients who previously failed to become HCV RNA undetectable after treatment with standard doses of interferon or peginterferon
The major limitation to using higher doses of interferon or peginterferon is the adverse events of these agents, which increase with increasing dose and cause patients to discontinue treatment.

The current recommended starting doses for the two peginterferons were derived by balancing response and discontinuation rates to achieve the highest overall rates of SVR. Because most patients respond to the current starting dosages of peginterferon (180 mg/wk for peginterferon alfa-2a and 1.5 mg/kg/wk for peginterferon alfa-2b), it is not appropriate to initiate treatment with higher doses of these medications.

In contrast, it is quite rationale to consider escalating the dose of peginterferon or switching to high doses of daily interferon in patients with a suboptimal response who could tolerate such a treatment strategy.

It is therefore reasonable to consider escalating the interferon dose in patients with a partial virologic response as soon as this response pattern is recognized.
This typically occurs between treatment weeks 12 and 24 (Fig. 4). If patients do not have a further decline in HCV RNA and become virus RNA undetectable with 3 additional months of high-dose interferon therapy, it is highly unlikely that a virologic response is going to occur and treatment thereafter should be discontinued.
If such patients do not achieve an EVR or become HCV RNA undetectable within 12 to 24 weeks of treatment, however, this approach should also be abandoned. In either situation, a higher dose of peginterferon or high doses of daily consensus interferon can be used.

Effect of ribavirin dosing on virologic response
Ribavirin is an essential ingredient in the treatment of chronic HCV and affects all three of the milestones required to achieve an SVR (see Table 1).
Ribavirin is a weak antiviral agent and does not cause a reduction in serum HCV RNA when used alone [28]. When combined with interferon, however, it more than doubles the virologic response rate

Ribavirin enhances virologic response by accelerating the decline in HCV RNA over that observed with interferon alone [30]. Although the combination of peginterferon and ribavirin does not increase the percentage of patients who achieve an RVR, it more than doubles (from 18% to 38%) the percentage of patients who become HCV RNA undetectable by treatment week 12

The starting dose of ribavirin may also play a role in enhancing virologic response. In several randomized controlled clinical studies a 3% to 9% higher virologic response rate was consistently observed when the starting ribavirin dosage was increased by 200 to 400 mg/d.

Cont.

[CockSparrow]

Tailored Treatment for Hepatitis C
Thomas Berg, MD

Treatment guidelines recommend that patients infected with HCV genotype 2 or 3 infection can be treated for 24 weeks with the combination of  peg-IFNa plus ribavirin at a dosage of 800 mg/d
If one is aware of the influence of viral and host factors with respect to the possible consequences of therapeutic response, it indeed seems rather illogical to treat all patients with the same fixed therapeutic regimen.

The rational background of any individualized therapy is based on the concept that rapid responders need less therapy as compared with those patients who are slow responders.

the article by Shiffman discussed how to identify the optimal doses in an individual-based strategy to influence the efficacy of the response. Perhaps even more important to solve the problem is to try to influence the therapeutic response by modifying treatment duration, thereby differentiating between slow and rapid virologic responders.

For instance, relapse rates were nearly three times higher in type 3–infected patients with a high viral load (gtr 600,000 IU/mL) as compared with those with low viremia (23% versus 8%) after a 24-week course of peg-IFNa-2b at a dose of 1.5 mg plus weight-based ribavirin (800–1400 mg).

Also in type 2 and 3 infection, viral kinetics (ie, time to HCV RNA negative status) are of increasing importance to optimize antiviral treatment individually.
Compared with type 1 infection, viral decline is more rapid in type 2 and 3 infection. Because most patients achieve an RVR at treatment week 4, this explains, analogous to the situation in type 1 infection, why most patients are sufficiently treated with a 24-week treatment course.

Extending treatment duration in those who are slow to respond
There are data from randomized prospective trials that show prolonging the duration of treatment increases SVR rates in genotype 1–infected patients who are slow to respond.
This raises the question of whether intensification of the therapeutic regimen could increase SVR rates in genotype 2– or 3–infected patients who do not achieve an RVR.

There are no data from prospective trials available on this topic. This question has been addressed through a retrospective analysis of data [36] from the trial by Hadziyannis and colleagues.
In patients who did not have RVRs, end-of-treatment response rates ranged from 65% to 76% across the four treatment groups.
Consistent with results observed in genotype 1-infected patients, relapse rates decreased in inverse proportion to the intensity of treatment and were lowest in those treated for 48 weeks with peg-IFNa- 2a plus ribavirin at a dosage of 1000/1200 mg/d (4%) and highest in those treated for 24 weeks with ribavirin at a dosage of 800 mg/d (26%).
Although these results must be confirmed in a prospective study, they suggest that intensification of therapy may be effective in increasing SVR rates in genotype 2– or 3–infected patients who do not achieve an RVR at week 4.

Summary: tailored treatment for hepatitis C virus type 2 and 3
It is no longer appropriate to generalize that patients who have HCV genotype 1 and 4 are ‘‘difficult to cure’’ because of viral kinetic evidence to the contrary.
Conversely, it is no longer appropriate to think of all patients who have HCV genotype 2 or 3 as ‘‘easy to cure.’’ Although genotype is an important driver of response and is useful in designing the initial treatment plan, it is clear that once treatment is initiated, RVR is the most important and powerful predictor of SVR.
In genotype 2– or 3–infected patients, response-guided therapy using measurement of the virologic response after 4 weeks of combination therapy allows the treatment regimen to be tailored to the individual.

CS

[redrodeo]

How can there be so much confussing information about this. Man.....I am geno3a also 55 yo male. Tried tx two times before was never able to handle the s/e's. And it always came back. This time I started tx Dec last year and finished in May and so am still undet! Go figure. Why this time? For some strange reason my vl before starting was low. In the past it was 3-5mil, this time it was under 100,000. I have no idea why. I wasn't doing anything different in fact I felt less healthy this time. Had been dumped by a girlfriend the year before wasn't over that, was taking pain pills because I hurt my neck.
So don't give up hope. But I think you need more riba and would just do it. If you need some I have some left over.
Red

[meki]

3a --- SVR no RVR --- weight based Riba 1200...

I didn't go UND until way late in the 24 week phase.

Had lousy sides - but I AM SVR.

Had significant damage - was seriously ill for 3 years prior to figuring out it was HCV.... Looked for everything ELSE but HCV

I think I'm a rare case.

Developed Fibromyalgia and Neuropathy after all was said and done. But worth it --- I'm human half the time - before I was a dying zombie ALL the time.

It is not impossible to get SVR if not RVR.

But I do think you're on too low of a dose of Riba --- dependent on your weight.

Much luck to ya!

Meki

[zazza]

I would read very carefully what **** Sparrow has posted above. I agree with him that the main problem is your poor response to interferon.

[santaclaus]

thanx all for replys, but as of now i dont no wat 2 do as my head is up my backside.
i jus think im goin 2 carry on the way i am now and stick it out till the end.
but 1 thing is 4 sure if i have 2 retreat im defo going 2 look 4 a doc who is willing 2 treat aggresively.

cocksparrow, you are prob right bout the injection not working either as 4 the 1st 3wks when i injected i got a light head buzz 4 bout 30 seconds but every shot after i feel nothing. i have never had side or fatige, i work as a steel fabricator and am still able 2 do my 40hrs pus i do some work on some wkends and cope with life jus as i did before i started tx.

thanx again all 4 replys very much appreciate.
ps im checking my list again 2 check whos bein naughty or nice, so u better be nice, ho ho ho ;)

[epiphiny]

Oh santa!  I reckon you should fight the good fight NOW rather than maybe go 24 weeks to no end only to find that you have to treat again for 48, on top of what you've already done...

As you so eloquently put it maybe you should take your head out of your backside and aggressively hunt for for a new doc, and up the riba in the meantime.

Whaddya think about that?

Epi :)

PS:  I hope this doesn't mean I'm on the naughty list!

[jankar]

Hiya - I am with epiphiny - sort it now when there are problems that you can isolate - who wants to go again?

[konyha]

I am Geno 1a and at end of week 9 I had a mere 1.453 VL drop.
Forum members pointed out the weight-based RIBA  and that the 800 mg RIBA I was taking was not even the correct dose according to the product insert!

I had no sides. Some folks have more bearable sides than others, sure...but the absence of symptoms is sometimes a symptom. My doc made it clear that unless I had a 2 LOG VL drop I would not continue treatment. I had no reservations about taking the most efficacious dose of both meds I could in hope for the drop I needed to continue tx.

My next script of Peg and RIBA arrived a few days in advance so I increased the RIBA from 800 to1400mg and took did two shots of PEG on 10/30 and had the VL labs on 11/06. The result of the 11/06 lab was VL drop of 2.011 from baseline.  Of course, my hgb dropped, but that's another story.

On 11/13 the doctor adjusted the RIBA from 800 to 1000 and he gave me a bottle of 200 MG pills.  

I foolishly took the RIBA at 1400 longer than I should and realized I need to cut back since now I am really feeling the effects.....

Hang in there and fight.

[Kristina538]

I'm a 3a also - 52kg.   One specialist advised 800 Riba but my treating Specialist put me on 1000mg (fibrosis and a previous relapse wanted him to give it the best chance).      There are often minimum sx's in the first 4 weeks, but as the meds build up it gets tougher so I really hope you can sort something while you're still feeling okay.

Suggest (if you can) you e-mail your specialist (and copy and paste some links from this thread) - they cannot ignore something in writing.  Good luck.

[epiphiny]

Hey, so glad to hear how you are doing, had been wondering what happened!  Congrats on getting your 2 log drop and for taking the plunge and taking control of your treatment, way to go!!  Look forward to hearing more success stories from you!

Epi :)