Stopping tx 12-16 weeks

[brown_eyed_grl]

My Hepatologist  feels I could probably stop at 12-16 weeks. I am a geno2 ...had the disease for 33 yrs. If I am UND at 4 weeks this is the plan.

Do you think it's wise to stop that soon? Why do most 2's do the 24 week tx?

Julia

[EarthMan]

The studies have showed results for 16 weeks in lieu of the 24 weeks for your genotype. Providing EVR by week 4, the SVR rates showed really no difference in the studies as well with the 16 weeks. I would take into consideration the degree of liver damage also. Stage 3 or 4 damage might want to go the full 24 weeks. Fatty liver amount should be taken into account as well.

I do not believe that this has caught on here in the States much unless the patients have done their homework and works with their doc to treat in this specific approach. Otherwise the patient just follows what the doctor tells them and I believe this plays a part for geno's 2 treating for 24 full months.  I believe in individualized approach for treatment anyway.

[pigeonca]

If you're taking Pegasys and are UND at week 4, 16 weeks seem to be acceptable.  If Peg-Intron, 12 weeks might be okay.  But to play it safe, go the whole 24.  The odds are slightly better with the full duration of treatment.  OTOH, if your sides are unbearable, shortened tx is definitely an option.  My doctor pulled me off Peg-Intron after only 13 weeks.  I was UND 4 weeks after quitting, and next week will get the results of a 4 month post PCR.  Just got some of the other numbers from that blood test yesterday, and my ALT remains normal, which is an excellent sign.  I'm praying.  But if I could have, I wouuld have completed the 24 week course.

[shastri20032003]

There have been several studies for geno 2 and 3 on treatment duration where some of of these studies lean towards stopping early if you are UND at wek 4 while the other studies recommend going the distance OF 24 Weeks
I am geno  10a=3 and I am on week 20/24.. I was UND at week 4 and could have had the option to stop earlier,but as my sides have been managable I have decided to go the distance
Having said that....even if my sides were less managable than they are now....I would have tried  to finish 24 weeks by Gods grace rather than face  a higher possibility  of a relapse...this is my personal opinion
But I guess it all comes down to how  bad your sides are affecting you
Please find a link below advocates that longer treatment is better for hep C
Longer Hepatitis C Treatment Best?
Cure Rates Are Higher With Longer Treatment Of 6 Months, Research Suggests
(WebMD) Shortening treatment to less than six months does not appear to be a good strategy for patients with the most curable types of hepatitis C virus infection, new research suggests.

Patients with hepatitis C genotypes 2 and 3 who were treated for four months had lower cure rates and higher relapse rates than those treated for six months.

The study, which appears in Thursday's New England Journal of Medicine, shows that longer treatment benefits even those with highly treatable hepatitis C, researcher Mitchell L. Shiffman, MD, tells WebMD.

"I tell patients if they can tolerate treatment and can stay on it for 24 weeks, they have a better chance of achieving the best possible outcome, which is a cure," he says.

Hepatitis C Treatment Strategies
Long-term infection with hepatitis C virus (HCV) is a leading cause of cirrhosis, liver cancer, and liver transplants in the United States. As many as 4 million Americans are infected, but most don't know it, experts say.

About 70 percent of infected Americans carry the genotype 1 form of hepatitis C, which tends to be less responsive to treatment than genotypes 2 and 3.

With aggressive treatment, nearly 80 percent of people with genotypes 2 or 3 achieve complete and sustained viral eradication, or cures, compared with about 40 percent to 45 percent of people carrying genotype 1 virus.

These days, most patients are treated with a long-acting version of the injected drug interferon along with the antiviral drug ribavirin.

The standard course of treatment for patients with the more treatable types of hepatitis C infection is half that of patients with genotype 1 hepatitis C — 24 weeks compared with 48 weeks.

In several recent studies, it was reported that shortening treatment to four months and even three months had no impact on cure rates in hepatitis C genotype 2 or 3 patients.

In an effort to test these findings, Shiffman and colleagues from Virginia Commonwealth University compared outcomes among genotype 2 or 3 patients treated for four months and six months.

They report that 31 percent of patients treated with the shorter course of therapy eventually relapsed, compared with 18% of patients who got the full six months of treatment. Relapse was defined as having detectable levels of virus in the blood at follow-up despite complete viral eradication at the end of treatment.

Overall, 62 percent of patients treated for four months achieved sustained viral responses, compared with 70 percent of patients treated for six months.

Among patients who achieved complete viral responses within a month of starting treatment, 79 percent of those treated for four months achieved complete, sustained responses, compared to 85 percent of the patients treated for six months.

Individualized Hepatitis C Treatment
Shiffman understands the desire of patients and doctors to shorten treatment. The drugs used to treat hepatitis C are very expensive and they can cause severe fatigue, fever, depression, and other hard-to-tolerate side effects.

But he says a better strategy than shortening treatment is lowering drug dosage in patients who have trouble tolerating hepatitis C treatments.

He adds that rapid response to treatment has become as important as viral genotype for predicting response to treatment.

Patients who show no signs of hepatitis C infection within a month of beginning treatment have a 90 percent cure rate, regardless of genotype, he says.

"We are learning that the optimal way to treat hepatitis C is to monitor the virus during treatment, no matter what the genotype, and adjust treatment duration based on response."

T. Jake Liang, MD, of the National Institutes of Health, says this individualized approach to hepatitis C treatment will become more common as more is learned about the virus.

Liang is chief of the liver disease branch of the National Institute of Diabetes and Digestive and idney Diseases.

"As our technology improves we will be more able to identify patients who will benefit from a shorter course of treatment," he tells WebMD. "For now,
though, genotype 2 and 3 patients who can tolerate the treatment should remain on it for a full six months."

Heres the link below

http://www.cbsnews. com/stories/ 2007/07/11/ health/webmd/ main3047056. shtml

Wishin you the best in whatever you decide

[Fact]

Following is the actual clinical review of Schering's application for PEG-Intron to The Center of Biologics Evaluation and Research (CBER), the division of the FDA that regulates these types of drugs. In other words, it is the highest authority's (CBER) review of PEG-Intron, as studied by the very people who most wanted it to be approved (Schering). It reads like an admission, an admission that the drug is neither safe nor effective, but "hey, it's all we've got". It may shock you. It may only confirm what you already know.

§ PEG-Intron is the Same Drug as Interferon Only Worse
§ PEG-Intron is NOT Safe
§ PEG-Intron is NOT Effective

You need only read one paragraph into the study to learn that PEG-Intron is the same drug as Interferon, only modified to stay in your system longer  (Thereby killing you more consistently) ."PEG-lntronTM, peg-interferon alfa-2b, is a covalent conjugate of recombinant interferon alfa-2b with monomethoxy polyethylene glycol product. The biological activity of peg-interferon alfa-2b is derived from its interferon alfa-2b moiety."

compared to interferon alfa-2b treatment.Time to response to treatment and time to relapse were  not superior with peg-interferon alfa-2b treatment compared to interferon alfa-2b treatment. Health-Related Quality of Life Scores were not improved in any of the interferon treatment groups either during or after treatment."

After reading 43 pages of evidence, in Schering's own words, that PEG-Intron is not effective and not safe.


Dr. Russell Blaylock, a board-certified neurosurgeon and author of the books Health and Nutrition Secrets That Can Save your Life and Natural Strategies for Cancer Patients, contributed this outstanding article about interferons, which are used widely for the treatment of multiple sclerosis (MS), hepatitis, cancer and more. If you, or someone you know, are taking these drugs, this article will help you decide if the benefits outweigh the many risks.

By Russell L. Blaylock, M.D.
http://www.russellblaylockmd.com/

How Interferon Ruins Your Brain:

The mechanism of this injury to the brain appears to involve the brain's special immune cell called the microglia. Normally, these cells remain dormant in the brain. That is, they are sleeping. Microglia cells can be activated by numerous factors, including mercury, aluminum, iron, overvaccination, and brain trauma, strokes, infections (viruses, bacteria, rickettsia) and cytokines such as interferons.

Once activated, microglia can move about the brain secreting very toxic compounds, which include two excitotoxins (glutamate and quinolinic acid). These excitotoxins dramatically increase free radical generation in the brain as well as oxidation of lipids (called lipid peroxidation). These radicals damage synaptic connections, interfere with neurotransmitters and can even kill neurons. In addition, these activated microglia generate other toxic compounds such as prostaglandins (PGE2), which increase brain inflammation.

If the microglia activation is short lived, the damage to the brain is minimal and recovery takes place. Yet, should the activation continue, which would occur with high-dose and long-term use of interferons, the damage could be substantial and irreversible.

[CockSparrow]

Hello abyss

[CockSparrow]

brown_eyed_grl
Being a G2 RVR doing the short course will give you an excellent chance of SVR. However doing 24 weeks gives you a slightly higher chance of SVR. If you were LVL the short course is worth considering, otherwise do the full 24 weeks. Relapse sux.
Me I’d do 24 weeks just to make sure you kill the all little buggers.

Shastri
G2s and G3s should not be lumped together. G2s have a higher SVR rates than G3s. G3s also have higher relapse rates, even though they have similar RVR rates.
The Studies don’t break things down enough.
G2 LVL RVRs have over 90% SVR in both the short course and the Full course.
CS

[shastri20032003]

G2s have a higher SVR rate and lower relapse rates than G3s..Accepted but I was not zeroing in on that, My point was that irrespective of being a G2 or G3, we should try to go the distance and finsh 24 weeks,sides permitting. By doing this there is a higher chance of SVR and lower probability of relapse,even though it might be marginal
Take care

[antman]

hey how are your shrunken testicles? did you think by changing your screen name we  wouldn't know it was you? your just a walking commercial for that quack blalock. nice try pal.

[jmjm530]

Depending on which study you look at, there's either no difference, or around 6-8% difference in SVR rates for those geno 2's and 3's who are non-detectible by week 4. But even in the studies that show a difference, your odds are still excellent -- around 80% if I remember correctly -- if you do the shorter course. Where I take issue with Shiffman's analysis of "tolerating" treatment is doesn't appear to factor in the potential damage additional weeks of interferon can do in the long term, which of course there are no studies. If it were me, I'd do short term unless I had stage 3 or 4 liver damage, and then do the full course.

-- Jim

[brown_eyed_grl]

I dont know what stage my liver is in. Last bx was in '98. My team didnt feel it was necessary to do another one b/c of my chances to achieve SVR.

Jim, why would you chose to stop tx at 12-16 weeks? Wouldnt you be concerned you might relapse?

[jmjm530]

Shas: G2s have a higher SVR rate and lower relapse rates than G3s..
------------------------------------------------------------------------------------------------
My understanding is that SVR and relapse rates for geno 2's and 3's are identical. Or perhaps you're referring to the relapse rates in the shorter course studies that I don't have handy? In any event, could you post a study(s) to support your position. Thanks.

-- Jim

-- Jim

[desrt]

Don't have time to find the study right now, but will try to find it later. The first study I read about g2/g3 short course put g2 SVR almost identical with 12 weeks (+or- 5%) while g3 dropped from 80-85% down to 67%. This was a study from over a year ago, I think.

[brown_eyed_grl]

Thank you so much for that info. I think I may do the full 24 weeks. Better to air on the safe side.

Julia

[jmjm530]

Probably for the same reason your doctor is suggesting you stop.

As mentioned above, depending on the study you look at, the odds are either identical (short vs longer course) or around 6-8% difference. In any case, your odds are still excellent -- around 80% -- even by the studies that do show a difference. (Please double-check all figures against orginal study data as this is by memory). So, the reason I'd stop is to spare myself the potential longer term effects of the interferon after weighing the risks and rewards of each approach. Again, assuming I was not a stage 3 or 4. That said, good arguments based on the same data can be made for the longer course, and Shiffman has made one. No right or wrong here, just different takes. As to concern of relapse, that's always a concern, but no guarantees that 24 weeks won't result in relapse either. I suggest you take your time and think it over. If you end up disagreeing with your doctor's recommendation for the shorter course, I'm sure he'll let you continue on to 24-weeks if that's what you want. And if he doesn't, I'm sure you can find a good doctor who will.

-- Jim

[brown_eyed_grl]

Does LVL mean low viral load? My VL was 1.42 aat start of tx. The Dr's still seem to think I can stop early. I mean they know best ...right?

Julia

[nygirl7]

If you aren't having too many big problems...go all the way to week 24.  Make sure you get any stragglers left behind. Believe me - we've seen too many Geno 2's relapse, you don't want to come back and have to 48?

It's just not worth it to me since 16 is so close to only 24.

And one small study does not REALLY undo all the years of studies that have been done that suggest 24 weeks is OPTIMUM treatment for geno 2.

(Of course if you have minimal liver damage and not overweight and don't have fatty liver you could go for it.  I personally just don't really think it's worth it).

But then again I'm the first wierdo that I found around that begged to go for 72 weeks - so take me with a grain of salt.  I just don't want to have to do this again if I don't ever have to, you know?

Regardless - we wish you ALL of the best B.E.G.

[jmjm530]

Ironically the same logic being used for the shorter-course treatments is identical to the logic being used for extended treatments. That logic is to treat the INDIVIDUALLY (not as a group), and more specificially to treat the individual's patient's viral repsonse. Lots written on this lately over at Clinical Options and Berg has published a nice article on individualized treatment that unfortunately we've only had snippets of due to the fact that it's written in German.

-- Jim

[brown_eyed_grl]

I definitely hear you NYgirl. Youve been thru so much and have so much experience, so I know what youre saying comes from the heart. I do not EVER want to go thru this again . If you remember when I first came around, I was a mess. SO now Im txing and moving one one week at a time. To stop early could be a huge mistake. No way I wanna do this again. 48 weeks? I DONT THINK SO!!

Julia

[Bill1954]

Hi Julia;

This just came through my inbox, and I thought I’d pass it along; it just posted today. From the site:

http://www.hivandhepatitis.com/hep_c/news/2007/072007_b.html

“In conclusion, the authors wrote, "Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen."
However, the results suggest that a 16-week course of therapy may be adequate for a carefully selected subgroup of patients”.

See the web page for full commentary by Liz Hyleman.

I’ll withhold personal comment; I honestly haven’t been following GT-2 or GT-3 treatment protocol, so my thoughts aren’t up-to-speed or even relevant. I’m just passing this on. Take good care, and good luck with your decisions.

Bill

[ladybug52]

How long to treat, when to treat or whether to treat is an individual decision. If you ask here, all you are going to get is personal opinions.

"Believe me - we've seen too many Geno 2's relapse, you don't want to come back and have to 48?

I really don't know where Nygirl gets her data as I have not seen any geno type 2's who dosed correctly, were und early and yet relapsed. Perhaps she will post the large number she is referring to.
I am not SVR but was und early on and quit at 16 weeks. What you do with your life is your business, good luck.
Bug

[shastri20032003]

Hi jim,please find the link below supporting G2s having a higher SVR rate and lower relapse rate than G3s....

http://www.hivandhepatitis.com/2006icr/ddw/docs/052306_b.html

And here are the results
Results

1829 G2/3 patients were enrolled and randomized to WBD (24 wks n=317, 48 wks n=602) or FD (24 wks n=322, 48 weeks n=588).
SVR rates were similar in the WBD and FD groups (62 vs 60%, respectively) and were higher in the 24-week group (68 vs. 65%) than the 48 weeks (60 vs. 58%, respectively) due to a higher dropout rate after 24 weeks of therapy with missing data in that group (SVR not known, treated as NR).
G2 had a higher SVR and lower relapse rate than G3 (72 vs. 63% with 24 weeks of WBD therapy and 5 vs. 10%, respectively).
G3 patients had higher SVR with WBD (57 vs. 52% in 24 week group) but this difference was not statistically significantly.
Relapse rates were highest in G3 high viral load patients treated for 24 weeks (16%).
Multivariate analyses revealed G2, less advanced fibrosis, and 24 weeks of therapy as significant predictors of SVR. Safety and rates of drug discontinuation were similar between the groups.

Based on these findings the authors conclude, “Compared to Genotype 1 patients, WBD ribavirin and 48 weeks of therapy offers less advantage to FD in combination with PEG-IFN alfa-2b, in patients with HCV genotype 2 and 3.”

“Compared to G2 patients, SVR rates are lower and relapse rates are higher for G3 patients. G3 patients may benefit from higher ribavirin dosing

Take care

[pigeonca]

When we compare studies, we need to remember not only to separate out geno 2 from geno 3, but also to distinguish between those who are UND at 4 weeks and those who aren't.  Not all studies make that differentiation, which can be confusinng.

[CockSparrow]

The logic behind individualising Tx appeals to me. If you meet the right criteria then shorten Tx.
In you dont fit the criteria do 24 weeks. If you dont want to do this again do 24 weeks.
In some G2/3 cases 48 weeks is whats needed.

The risk of relapse is slightly higher with the short course. If your VL is measured in copies/ml then yes you are LVL <2,000,000/ml. However some studies suggest that 1.000,000 is the LVL cut off point. If it is in IUs you are HVL, in which case do the full course.
Jims point is valid though you still have an excellent chance of SVR with the shorter course. However as Shartri states the relapse rate is slightly higher. This risk is worth it if you were prepared to have another run at Tx then the SVR rate for relapsers of the short course is excellent.

Shastri - We dont really disagree. Its just that with G2s the risk of relapse is not that much greater with the short couse so long as you RVR, are LVL and your liver damage is <F3. In your case being 3k i would do 24 weeks. In fact if you were HVL I personally would want to do 48 weeks with WBR.
The relapse rates are lower. Be a little skeptical though the G3 studies are mostly for 3a.

Jim - G3s definately have higher relapse rates than G2s. If G3s dont RVR their SVR rate is <50%.
I have seen this as low as 38%. These rates are for both PegINFs.
G2s who dont RVR still have a 70% or so SVR rate.
G3s who dont RVR are NOT easy to treat. Tx has failed me twice and I am 3a.

pigeonca - We also need to consider HVL v LVL and degree of liver damage, otherwise spot on.
CS

[CockSparrow]

Messed my reply to you up a bit. so i'll do it again.
We dont really disagree. Its just that with G2s the risk of relapse is not that much greater with the short couse so long as you RVR, are LVL and your liver damage is <F3.
The relapse rates are lower with 24 weeks especially for G3s.
As you are 3k be a little skeptical of the studies though as the G3 studies are mostly for 3a.

[shastri20032003]

quote" The logic behind individualising Tx appeals to me. If you meet the right criteria then shorten Tx. "unquote
Noted your point. But all said and done.....this is just a personal opinion......sides permitting,its better to do a few more weeks and finish SOC than have these lingering doubts in our mind after we finish on a shortened treatment .
Its after all a treatment for a chronic life threatening disease that we are undergoing and if we can complete it,why not?
By the way...just saw your profille....you are from the wonderful beautiful Gold Coast.....the pic in my profile is in the gold coast zoo....
Give my regards to Shane Warne!
Take care

[CockSparrow]

Once again we dont disagree. But if i were F1 LVL and RVRed you would have to at least consider it.
Non RVR is when it is ruled out and consideration of longer Tx is required.
Unlikly i'll be seeing Warney. When were you down this way.
CS

[jmjm530]

This study suggests only a 4% difference between short and longer course (Peg Intron 14 weeks vs Peg Intron 24 weeks)  if 80% of the meds were taken 80% of the time. The SVR rates are 91% and 94% for the shorter and longer course respectively.  
http://www.hivandhepatitis.com/2007icr/easl/docs/042007_b.html
The authors did not find the 4% difference not significant enough to advise the longer course..."...Based on their findings, the study authors concluded, �With a 5% significance level, 14 weeks treatment with pegylated interferon alpha-2b and ribavirin is non-inferior to 24 weeks treatment in patients with genotype 2 or 3 and RVR.�"

Again, I did not find any difference here between geno 2 and geno 3 replapse rates.
If anyone has a study to back up that assertion please post so we can put in it context. My understanding is still that geno 2's and 3's have around 80% chance of SVR with geno 1's around 50%.

-- Jim

[shastri20032003]

RVR and F1LVL...granted ....would consider it but being the way I am...overcautious...thats where it would stop for me at least!
You are from the land of Warney and Pointing is good enough for me......
Was in your side of town around October"05 with the kids,just after the Indy car race,stayed at the Genesis apartments and the kids had a rocking 10 day holiday there
Plan to come there again hopefully...its too good a place not to!
Take care

[shastri20032003]

Hi Jim. I think you overlooked my reply to you.Heres the link again which compares relapse rates between geno 2 and geno 3
http://www.hivandhepatitis.com/2006icr/ddw/docs/052306_b.html
Take care

[jmjm530]

Thanks for posting the study which did show slightly better relapse rates for geno 2's vs geno 3's, but also showed better SVR rates for geno 3's on 24-week WBD, although they deemed the difference statistically insignificant. Probably more can be gleaned from the actual full-text study vs the commentary. As mentioned, the study I posted above, does not differentiate between the two groups and the usual figures for SVR are 80% for both groups.  What should be noted here  is that the overall SVR rates were only around 60% or both groups as opposed to 80% which may mean this is not a representative patient population, possibly having more with advanced liver disease.

-- Jim

[susan400]

Can you PLEASE stop publishing this same survey over and over and over again.  We got it.  You think that your opinion and your favority survey is the whole truth and that we should never again try with Peg-Intron.  I don't happen to agree.    Can we please move on to you publishing something else now?

Susan

[CockSparrow]

I made the mistake of ignore a lot of WIN-R stuff because the drop out rate was too high, However it aslo has good info on the differences. Should have taken more notice of the WBR stuff as well.

The following link gives some good graphs on the differnces between G2 & G3 SVR rates.
http://www.cmeconsultantsinc.com/bulletins/bulletin2.asp

I cant find the stuff on Accelerate Study that separates G2s&3s.
I really have to tidy up my filing system.
However The main difference is in the Non RVR SVR rate.
Both genotypes have similare RVR rates.
G3 HVL has quite a high relapse rate (16-23%).

I didnt embed the link for this one so i'll post it.
2nd Annual Canadian Association for the Study of the Liver Winter Meeting: Updates in Hepatology

March 31 to April 2, 2006,
Toronto, Ontario

ABSTRACTS

IS IT TIME TO SEPARATE THE MANAGEMENT OF
GENOTYPE 2 AND GENOTYPE 3 IN CHRONIC HEPATITIS C?

Jeff Powis1, Kevork Peltekian2, Sam Lee3, Morris Sherman1, Vince Bain4, Curtis Cooper5, Mel Krajden6, Rob Balshaw7, Jenny Heathcote1, Eric Yoshida8

1. University of Toronto, Toronto, Ontario;
2. Dalhousie University, Halifax, Nova Scotia;
3. University of Calgary, Calgary;
4. University of Alberta, Edmonton, Alberta;
5. University of Ottawa, Ottawa, Ontario;
6. British Columbia Centre for Disease Control;
7. Syreon;
8. University of British Columbia, Vancouver, British Columbia

BACKGROUND: Chronic Hepatitis C (HCV) infections with genotype 2/3
(G2/3) are associated with favourable sustained virologic response (SVR) rates, however, G3 may respond less well.
We examined predictors of lack of SVR among G2/3 patients.

METHODS: Posthoc analysis of a non-randomized, open-label, phase III-B trial evaluating 180 mcg PegIFN alfa-2a (40KD PEGASYS) and 800 mg/d RBV (COPEGUS) for 24-48 weeks. Analysis included all treatment-naïve patients with G2/3 who received ≥14 weeks of therapy. Predictors measured prior to initiation of anti-viral therapy were considered: genotype, METAVIR score, log initial viral load, BMI, age and gender. Univariate predictors with p<0.15 were entered into a multiple logistic regression (MLR) model. Subgroup analysis was completed for G2 and G3.

RESULTS: In total 173 patients were analyzed of which 105 (60.7%) were G3 and 68 (39.3%) were G2. No patients treated for <14 weeks stopped therapy due to lack of a week 12 virologic response. Significant MLR predictors of lack of SVR were cirrhosis (F4) (p=0.007), and genotype (p=0.008). Cirrhosis was a predictor of SVR specifically among G3 with SVR rates of 18.2% compared to 87.5% among those with cirrhosis and G2 (p=0.037).

CONCLUSIONS: 1) Cirrhosis and G3 were significantly associated with lack of SVR. 2) The association between cirrhosis and lack of SVR is specific to genotype 3 infections.

Can J Gastroenterol Vol 20 No 3 March 2006

[mikesimon]

Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3.
Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Solá R, Shafran SD, Barange K, Lin A, Soman A, Zeuzem S; ACCELERATE Investigators.

Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. ***@****

BACKGROUND: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin. METHODS: We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment. RESULTS: The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02). CONCLUSIONS: Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Socie

[mikesimon]

I did notice that but I must admit I do not know how ribavirin dose affects Genotypes 2 & 3. Being a type 1 I am not up to date on 2's and 3's and when I was following this thing more  closely 800 mg was standard for 1 & 2's. I will defer to you in this issue. I just got the article in my email yesterday so I posted it hoping it would have some value. Be well, Mike

[jmjm530]

Sparrow, Forgive the quick read, but it's been one of those days. What the study seems to be saying is that genotype 3's have a higher relapse rate than other genotypes if cirrhosis (stage 4) is present. This appears to be consistent with the Win-R study, which proably had their share of stage 4's. That said, I don't think this contradicts the shorter course option for genotypes 3's (or 2's) without significant liver damage. Frankly, I think (and have stated) that the full 24 weeks makes sense for either genotype if they have significant liver damage, because more at stake. Thanks for the discussion.

Mike, note the study posted is for fixed (800 mg) riba as opposed to weight-based. Other studies, posted previously, have shown about the same rate of SVR (or 4% less with compliance) in the shorter course. My understanding is that most current liverheads now treat genotype 2's and 3's weight base. Since some good hepo's were involved, no doubt the study was started before or used data before weight-base dosing of geno 2's and 3's became more common.

-- Jim

-- Jim

[jmjm530]

The newer shorter course studies mostlyused weight-base dosing and did not have comparable results with fixed (800 mg) dosing. But as usual, lots of caveats, including pre-tx viral load, etc. Very hard to ever compare apples to apples in these studies or at least Macintosh apples to Macintosh apples.

All the best,

-- Jim

[CockSparrow]

jim - I disagree about the comparing apples bit. There is a trend that is becomming apparent.
G3s with enough of the caveats you mention need WBR. If G3s dont RVR they should do 48 weeks.
If they start Tx with HVL then they should also do 48 weeks. To not do so produces quite high relapse rates. This trend is not as apparant in G2s but still applies to an extent.

The opposite is also true. If a G3 doesnt have any of the negative predicts then the short course is then an option. The Accelerate study only just hit staistical significance with SVR rates and it didnt usr WBR. Basically G3s should be on WBR, then decisions to shorten Tx or extend make more sense.

The problem I have with the studies on G2/3 is that most of them dont break down the data enough for me. They lump 2/3s together, dont compare HVL, steatosis and cirrhosis etc.

What i am saying is that G3 is both an easy to treat genotype, yet at the same time can be quite difficult. When G3s dont RVR the SVR rate is not that good with 24 weeks.
CS

[jmjm530]

CS: The problem I have with the studies on G2/3 is that most of them dont break down the data enough for me. They lump 2/3s together, dont compare HVL, steatosis and cirrhosis etc.
---------------------
In part, this is what I meant about apples to apples. Different studies seem to present different things. One mentions high pre-tx viral load, another might not. One uses WBR another does not. And then another may include more cirrhotics, etc.

My guess is that at least some (certainly not all) of these questions would be answered if you go to the full-text studies as opposed to the abstracts that most of us see posted here.

On a personal note, I always got hold of the full-text studies -- either found, purchased on line, wrote the researcher, or went to a medical library -- in the case of any study that I was going to base a treatment decision on in any meaningful way. I was not a genotype 2 or 3, so never ordered any of those studies, but I certainly hope any geno 2 or 3 using study data to help formulate a treatment strategy will not base any decisions on anything but the full-text studies. And of course, then run the studies by their treating doctor.

CS: If (a geno 3) start(s) Tx with HVL then they should also do 48 weeks. To not do so produces quite high relapse rates.

Is this irrespective of RVR? If so, could you please post the study.

[CockSparrow]

This is an ongoing study in Aust called GET-C that is studying this very issue. I havnt been able to find any meaning info on it yet about results.
The CME link contact a deal of info on this.
http://www.cmeconsultantsinc.com/bulletins/bulletin2.asp.
CS

[meki]

Very good discussion you guys.

[jmjm530]

I asked, because at least with geno 1's, RVR seems to trump any number of negative pre-tx negative factors such as age, level of fibrosis, sex, etc. -- at least according to some.

I ran into this issue (RVR trump issue) myself when treating over 2.5 years ago.  As a geno 1 who had significant liver damage (so my initial pathologist said) and was approaching 60, a couple of doctors I consultes with wanted me to extend beyond 48 weeks, to 72 or even longer. At this time -- when extended studies were coming out as well as RVR studies -- two other doctors I consulted with said that 48 weeks was enough and one used the term "RVR trumps (most) all" when I brought up my negative pre-tx factors. Finally, at the 11th hour (week 47)  after a lot of hair pulling trying to find a study that combined RVR ( I was non-detect at week 6) with my other factors (the study did not exist) --  I decided to extend six weeks to 54 weeks, using a combination of modified Drusano (48 plus 6): Israel/Palestinian type negotiations with my NP and Doc (who both disagreed with each other re extending); and an appeal to the voodoo gods. Anyway, I'm SVR, so I guess that means I made the right decision. LOL.

-- Jim

[CockSparrow]

Should have also mentioned that accelerate studies mention the relapse rate for G3 HVL along with  a few others. They show a relapse rate of 16-23% irrespective of RVR breakdown  Put this on top of the reevaluation of studies 4&5 in the pegasys insert that show 48 weeks was necessary for those who didnt RVR.
This reevaluation annoys the cr@p out of me because roche had this info since Pegasys was approved but didnt find it so 24 weeks became SOC. To me it was obvious that 48 weeks would benifit some 2&3s simply because of the relapse rates.This is the same logic as Roche only recommending 24 weeks for G1 LVL who RVR. If HVL and RVR Roche recommend 48 weeks.
I do a bit of join the dots, and is based on problem solving techniques and available data.

Then US INS Cos will pay for 48 weeks if G3 and HVL >600,000 IU. So they must have a reason for doing it seeing as it aint cheap.
The following comes from the CIGNA HEALTHCARE COVERAGE POSITION
patients with genotype 3 who have steatosis and initial high viral loads (HCV RNA >600,000 IU/mL) receive therapy for 48 weeks
CS

[CockSparrow]

Clear at 6 weeks is not RVR and with G1s HVL trumps RVR same with G3s. AT least the relapse rate is quite high with G3 RVR and HVL..
I'll start a thread on it when i find a couple of docos i've got burried in my messed up filing system.

I think the genotypes have a lot more in common during Tx than is generally believed.
If your negotiations went along the Israel/Palistinan route I am amazed you even finished Tx.
SVR wins every time though.
CS

[CockSparrow]

Jim the link below summarises the study below. Not the same source but close enough.
http://www.hcvadvocate.org/hcsp/articles/current_standards_2006.html

The Zeuzum study gives a better picture of the difference between G2s & G3s than my previous post on the differences. It adds to it nicely though.

Although current treatment recommendations are similar for genotype-2 and genotype-3 infection, differences in outcomes have become apparent between patients infected with these different HCV genotypes.
Using data from a trial of 24 weeks of therapy with PEG-IFN a-2b +weight-based RBV (800–1400 mg/d), Zeuzem et al30 showed that the SVR rate was higher in patients infected with genotype-2 HCV (93%) than in those with genotype-3 infection (79%). A high baseline viral load (>600,000 IU/mL) was associated with an increased rate of relapse compared with a low baseline viral load (²600,000 IU/mL) in patients with HCV genotype-3 infection (23% vs 8%) but not in those infected with HCV genotype 2 (9% vs 5%). Higher levels of steatosis in HCV genotype 3–infected patients with a higher viral load were associated with a lower rate of response in this subpopulation.

Quantifying the viral load at baseline and early in therapy can help physicians individualize the duration of treatment in patients with genotype-2/3 infection.27 Shorter duration of therapy (12 to 16 weeks) may be adequate in patients with genotype-2 or genotype-3 infection who become HCV RNA negative by Week 4. At present however, clinicians vary in terms of their comfort levels with the adoption of this as a uniform guideline, preferring instead to utilize the data in favor of truncating therapy only if the patient is having a toxic reaction to treatment. In patients who remain HCV RNA positive at Week 4, responses are less likely with genotype-3 infection than with genotype-2 infection, but with either genotype a duration of 24 weeks of treatment is recommended in the absence of rapid virologic response.29  In patients with genotype-3 infection, the baseline viral load may be important because of the data showing that a high baseline viral load increases the chance of relapse, regardless of early viral clearance.30 In patients infected with genotype-3 HCV and with a high viral load, treatment should not be shortened to less than 24 weeks.
The efficacy of still longer treatment in this subgroup has yet to be determined.

29. Mangia A, Santoro R, Minerva N, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005;352:2609-2617.
30. Zeuzem S, Hultcrantz R, Bourliere M, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004;40:993-999.

[jmjm530]

Thanks again for the article and I do appreciate you pointing out the differences between geno's 2 and 3.

But as the article states, in general tx recommendations are similar and the shorter course is feasible for some (including myself) for those with little or no liver damage (my opinion on the liver damage)  if you factor in the potential damage from more exposure to the treatment drugs which the study critiques never seem to focus on. Maybe if more of these researchers treated themselves?

Again, some studies show no difference between long and short, and the studies with a difference can be whittled down to 4% in the subgroup with 80% compliance.  Of course, all other study requirements should be met including WBR, non-detec at week 4, etc.

Just want to come back to your comment again about 48 weeks for geno 3's regardless of RVR. Still havent' seen anything to support this -- or even any study guidelines -- or perhaps this is simply your opinion, but if so, should be clarified as such.

I think where we both agree is that incorporating these studies into tx guidelines requires more than a simple reading of a study abstract, but rather reading as many studies as possible in full-text and then do one's best to match one's own stats with those of the study participants. This is not always possible and that's where judgment, art, luck (maybe even some voodoo :) ) come in to fill in the blanks left by science.  (I point out again that meeting at my docs office at week 47 where he and this NP,  disagreed over my tx length and basically the three of us picked a number out of a hat -- 48 plus 6 (week I was non-detect) -- even though it was an educated pick.

All the best,

-- Jim

[jmjm530]

To clarify my last paragraph -- what I meant by "not always possible" was not accessing the studies (that just requires some legwork and maybe a little cash) but what is not always possible is to match up stats. So unless you buy in 100% to the RVR trumps all -- and some are getting close to that -- then your individual stats may simply not match up to those of the study participants. Age, pre-tx weight, fatty liver, race, etc, -- just being a few examples. Or what if you're non-detectible at week 6 (as opposed to 4). Are you still an RVR? That was my case, and my docs told me I was. OK :)

-- Jim

[jmjm530]

Probably should have mentioned "test sensitivity". Different studies use different test sensitivities to determine "RVR". So, for example, if study "A" defines RVR as non-detectible at week 4 to 10 IU/ml, a commonly used Bdna test to 600 IU/.ml would not be a very good match up. Another reason to always try and get the most sensitive test available -- two examples being  Heptimax by Quest (sensitivity 5 IU/ml) or a similar test by LabCorp. Of course, testing very sensitive brings its own set of match up problems such as when you find out that at week 4 you had 23 IU/ml and the study you want to match up with uses a sensitivity of 50 IU/ml. So by study standards you're non-detectible, but do you really match up? How many of the study participants would have been non-detectible at 5 IU/ml versus under 50? Of course, no data on this :)

-- Jim

[CockSparrow]

Not a criticism but your making the same mistakes as the studies. I know the studies suggest that the shorter course is feasible for G2s&3s, but only if you have all the right positive predictors. Most of the short course studies don’t factor these in enough hence the differing results/conclusions. I definitely agree that if the study used WBR so do you when deciding whether to shorten Tx. Not using WBRiba is the one of the reasons why Accelerate had lower svr rates for the shorter course, in. my opinion.

G3 is an interesting geno in that it is both easy to cure yet difficult to treat for some. Whenever G2s&3s are grouped together the 2s raise the svr rate and 3s lower it. So you need to know the % of each geno in the study. This doesn’t paint the complete picture either as it’s a subgroup or two of the G3s that mainly lowers the combined svr rate. (HVL steatosis and F3/4 etc).

My view is that its more than following and meeting the criteria of just one study. You need to link together several different ones. To do this properly more than the abstract is required. The decision point for this should be made before Tx begins as making Tx decisions on Tx is not easy.

For G2s RVR may trump all other predictors, but even then I think that is a bit iffy. With G3s RVR only wins if you are NOT HVL. The relapse rate is still too high even with RVR. Cirrhosis beets RVR every time for all genos anyway. If you have enough negative predictors I’d be reluctant to buy 100% to RVR trumps all, even if it does look good for svr.

As for “Just want to come back to your comment again about 48 weeks for geno 3's regardless of RVR. Still havent' seen anything to support this -- or even any study guidelines -- or perhaps this is simply your opinion, but if so, should be clarified as such.“

It a little more than just my opinion.
“In patients infected with genotype-3 HCV and with a high viral load, treatment should not be shortened to less than 24 weeks.
The efficacy of still longer treatment in this subgroup has yet to be determined.”
The last paragraph from the Zeuzum study above implies that 48 weeks needs to be studied. Its not the only study that states this either.

I have already stated that in Aust a study called Get-C (P04134) which started taking participants in Dec 2005 is studying this. It only stopped enrolments earlier this year. It has some International enrolments as well. It aimed to enrol 625 participants.
The study Guidelines in part state that “The aim of this study is to compare rates of Hepatitis C viral clearance between individuals with genotype 3 infection and high viral load receiving 24 weeks and those receiving 48 weeks of therapy.”

With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from 600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.

There is enough info above to make any G3 HVL consider 48 weeks.
That and the fact that I enquired about it with my Liver Doc when on Tx and didn’t get knocked back.
Pity I was still detectable at 24 weeks.

You will have to tell me how you came up with 54 weeks. You didn’t have a lot to back you up. All the extended Tx studies are for those that are still detectable at 12 weeks. You well and truly EVRed and therefore had 70 80% chance at cure, with 48 weeks.
CS

[CockSparrow]

Forgot to mention in the Get-C study everyone will receive WB Riba (800-1200mg) and 1.5ug PegIntron.

[CockSparrow]

I agree i wouldnt accept RVR if the test was >10IU. The lower the better. 600IU would have too high a chance of relapse if used as decision tool for shortening Tx.
One other thing UND at 6 weeks in not RVR for any geno. Just a very early EVR.
CS

[CockSparrow]

Somehow these two paras got messed up, so i'll post again
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from 600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.
CS

[CockSparrow]

Must be something in this para that it doesnt like. Try again
Once again, The following comes from the CIGNA HEALTHCARE COVERAGE POSITION
patients with genotype 3 who have steatosis and initial high viral loads (HCV RNA >600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.

[CockSparrow]

Must be this para it hates.
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from <50% to 76%. Add this to High relapse rates and the logic is sound.

[drofi]

Here is a download link for the full text  NEJM paper about the Accelerate study:
http://hepatitis-rm.de/downloads/Studie2007.pdf

drofi

[CockSparrow]

You are not wrong about the full text articles.
This clearly shows the diffences and similarites between G2s and 3s
Enjoyed this chat.
CS

[CockSparrow]

Thanx, wondered how i was going to lay my hands on it.
A little strange that the stats are slightly different than the ones publised in abstarct form.
CS

[jmjm530]

Drofi, Thanks for the post.

CS, yes it's all in the details and hopefully anyone following this will see how important it is to get access to a full-text study (as opposed to abstract) when treatment decisions are going to be in part based on the study.  Even looking at the same study in its entirety it's easy to see how different overall conclusions can be made and phrased. A couple of the charts really break things down to help match ups, and the overall conclusions are well hedged depending on individual factors such as pre-tx viral load (where <400,000 actually shows higher VL for the low dose group) plus the ribavirin issue is discussed, but IMO not convincingly although the authors do say more study needed. Still, the trend among the better hepatologists I'm familiar with is to treat geno 2's and 3's with weight base.

I won't do a line-by-line on your previous post other than to say we're in agreement more than not. But I will answer two of your questions/comments re my own treatment.

CS: Clear at 6 weeks is not RVR
---------------------------------------------
It depends on your definition of RVR and what tests you took. For example, if RVR is defined by a study as <50 IU/ml, and you are 25 at wk 4 (using a test with sensitivity of 5) then you are not non-detectible (clear) at week 4 but you are RVR. Or are you? And how many of the "RVRs" per study would have been truly non-dectible with a test sensitive to 5?

My case was even less clear because I was tested weekly from week 1 and was below 50 at week 3 (RVR right?) BUT above 50 at week 4 (when the study would test), even higher at week 5, but under 5 (non-detectible) at week 6. So tell me, was I RVR or not :) Well, no clear guidelines but the consensus of my docs is that I was, also factoring in a week of stopping riba around week 2-3 due to anemia from high doses or riba (2000 mg/day).

CS: You will have to tell me how hou came up with 54 weeks.
-----------------------------------------------------------------------------------

Yes, given my RVR (or even EVR), 48 weeks by most studies should have done it, but at that time (and I'm sure my doc still thinks this way) some very good docs were pushing for more time for those with significant liver damage. My doc felt that given my age (58) and histology, I needed more time than the studies suggested. Being who he was (a guy who does many of the major studies) and the fact that he probably treats more patients than a lot of these studies combined represent, I did factor in his opinion heavily even though two other equally well-versed docs said 48 weeks would be enough.

As stated before the actual number (my doc probably would hv been happier with 60 or even 72 weeks) came from a variation of the Drusano model formula.

Drusano says add 36 weeks (or 24 for I think 70% chance of SVR) to the date you were non-detectible. My doc felt that  48 weeks is more appropriate (at a minimum) to those older and with more fibrosis than represented by the Drusano group. His NP btw felt 48 weeks was fine, in fact given my RVR (and also the fact that my seven day drop was just about two logs) she probably would have let me off treatment in 36 weeks had I pushed for it. She clearly believes and has stated that from her observations, early response is the single most important factor in determining SVR.

Thanks for the discussion.

All the best,

-- Jim

[jmjm530]

One last thing and hopefully I'll stick to it :) In regard to my six week extension. Besides my docs opinion -- and his anecdotal accounts of significant relapse per cents in his practice in older patients -- I was unable to find a study which I could break down into a subset of older patients with Fibrosis who were RVR. Just couldn't find it which is often the case. This therefore left enough doubt in my mind (with of course my docs position) to err on the side of extending a little. It was a difficult decision and somewhat of a compromise, and looking back it still seems reasonable although my hunch is I would have SVR'd with 48 weeks, no problem.

-- Jim

[jmjm530]

Line 4 should have read in part "significant  fibrosis), not "fibrosis"

[jmjm530]

Last paragraph a little unclear. Left out that the Drusano model predicts around 80% SVR if you add 36 weeks. The 70% figure was if you add 24 weeks. This is all by memory and may be off a little, so please check from the source if interested. Also, when I said my NP would let me off in 36 weeks, I wasn not referring to Drusano, but to 36 weeks of total treatment.

[PSP-n-Me]

Hi there - Nice to see you :)

The Clinic I go has a totally differnt approach to the "36 week rule"  they now use, as standard practice, RVR 24 weeks for 1's - if not clear by 12 weeks then it's 72 weeks for 1's and 48 for 2's

But, that said - there is certain critieria for shortened treatment of 1's - you have to have low VL (under 600K) low liver damage (no higher than a stage 1 - they do not consider grade anymore)

I think the times, they are a changing *dip*

[PSP-n-Me]

ooops - I just noticed I spelled *criteria* wrong shhhhhh don't tell hehehehe

[zazza]

Notice that it is called the Drusano MODEL. It is a mathematical model, not supported by studies, and, in my opinion, letting it influence your decision of the length of your tx is dangerous.

Studies I have read make me support the criteria PSP-n-Me's clinic has regarding geno 1:

RVR (UND by week 4), low VL, low liver damage - possible to consider 24 weeks tx
EVR (UND by week 12) - 48 weeks tx
Detectable by week 12, UND by week 24 - 72 weeks

There has, to my knowledge, been no studies to back up treatments of any length between 48 and 72 weeks.

[jmjm530]

That is correct, the Drusano model is a mathematical model built on accumulated data. Be clear that I did not suggest anyone used it to determine treatment length -- I mentioned studies for that -- but simply reported that my doctor -- a leading hepatologist -- as well as my NP, referenced it in my treatment and we ended up using a modified version (my doc thought it didn't apply to me because of age and histology) in my individual case. I have also read here that a couple of other very well-known hepatologists have also used Drusano as a GUIDE to determine treatment length. To say it is "dangerous" in influencing your opinion IMO is an overstatment, unless you mean using it as the sole influence. Unfortunately no science yet in predicting optimum tx length and we have to use as many tools at our disposal -- studies, anecdotal data in the field, and models like Drusano -- to come up with something that makes sense for a given individual. The fact that there haven't been any studies to back up tx lengths between 48 and 72 weeks doesn't mean that someone in conjunction with their doc, can decide that treating within that frame isn't reasonable. When we treat successfully for 72 weeks, I would imagine in most cases that doesn't mean that the virus is still going strong at 71 weeks.

-- Jim

-- Jim

[zazza]

The slow responder who decides to go past the 48 week mark but treats for less than 72 weeks and then relapses, will always have the question unanswered, what if I had done the full course?

[zazza]

To me the danger with the Drusano model is that it is very tempting for the slow responders to just add 36 weeks to the week they become UND. And it is precisely the slow responders who need to calculate their treatment length in "a more exponential way".

Quote from "Extended Treatment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon-Alfa-2a Plus Ribavirin" by Berg et al, concerning the Drusano model:

"However, group B late responders who first became HCV-RNA negative at week 24 (ie, who also had undetectable HCV-RNA levels during the last 36 weeks of the total 72-week treatment period) still had relapse rates of 40%, a finding that clearly contradicts the proposed Drusano and Preston model. Obviously, the HCV-RNA negative phase required to prevent a relapse must be calculated in a more exponential way and seems to be dependent on how early a patient becomes HCV-RNA negative during treatment."

Of course you are correct that having treated long enough one can become virus free at any week, not just at week 48 or 72. But when is "long enough" for a particular patient? We need guidelines to go by, and at present the consensus among hepatologists seems to be leaning more and more towards: Detectable at week 12, UND at week 24, go the full 72 week course.

[jmjm530]

Zazza: We need guidelines to go by, and at present the consensus among hepatologists seems to be leaning more and more towards: Detectable at week 12, UND at week 24, go the full 72 week course.
------------------------------------------------------------
Yes, and that particular study trumps Drusano IMO, as I've stated many times before. However, the way my doc and NP applied Drusano was different, as I was non-detectible before week 12.

Can't really comment too much more on Berg, since I assume the study you quote is the one published in German? Hopefully, you or someone else will offer us a translation at some point, so we know what we're discussing. If it's an English article you're quoting, please supply the link.

But going back to my case again -- the only reference I made to Drusano -- that particular study wasn't published as best I know. And even if it was, I wouldn't have qualified for 72 weeks since I was non-detectible at week 6. So what my doc did was the opposite of your reasonable concern. He didn't use Drusano to shorten my treatment, but he used a variation of Drusano to urge me to treat longer. And the reason this variation of Drusano was used was because there were no studies that matched up to my stats such as "detectable at week 12, UND at week 24...etc. Again, I was RVR but I also was told to hve significant fibrosis plus advanced age.  This is where the limitations of the studies are -- no clear match ups -- and this is where the "art" or judgment calls come into play that IMO justify treatment periods between the study guidelines of let's say 48 and 72 weeks, as in my case and in others.

All the best,

-- Jim

[jmjm530]

BTW hope I'm not coming off argumentative on this, but this isn't just an intellectual discussion for me (not that it is for you) because I litterally lived these studies and decisions by reading all pertinent studies and discussing with at least six hepatologists (3 in personal consultation). Where I came out -- and I'm sure I'm not alone here -- is that the study data are just jumping off guidelines -- be it the formal studies or mathematical models like Drusano -- but often things then have to be tweaked, analyzed and in a sense guessed (educated hopefully) over for the final decision. Or, you can do what probably the majority of patients do and that is do exactly what your doctor says :)

-- Jim

[zazza]

The Berg study I quoted is the full text study in English from 2006 on extended treatment. If you want to, I can send it to you. (Friole also has it, if you prefer contact with her.) Let me know at my screenname underscorejonesathotmaildotcom.

For your information, I will quote here what more is said in this Berg study about the Drusano model:

"Drusano and Preston recently presented a mathematical model to predict whether patients may achieve SVR or suffer from relapse. It was concluded that type 1-infected patients require the continuous abscence of detectable HCV RNA in serum for 36 weeks to attain 90% probabilities of an SVR (ie, relapse rate of 10%). We agree only to some extent with this predictive model, realizing that our week-12 rapid virologic responders who were HCV-RNA negative for at least 36 weeks also had low relapse rates (< or = 15%). However, group B late responders..."

[zazza]

Yes, Jim, I am also living the studies. As you know, I started out with a 70% hope of being an RVR because of my low baseline viral load, only to have to realize that I was a slow responder, detectable at week 12 with a test of the sensitivity of 15 IU/ml. (So was I an EVR or not, being < 50 IU/ml at week 12?) So I, as you, have had my fair deal of struggling with studies and decisions about treatment duration. I have consulted 4 different hepatologists, all with different opinions, and in the end this forum (with the special help of Friole, Nygirl and you) and a family member educated in statistics helped me sort out my thoughts and emotions so that I could make my own treatment decision which has since been approved by my doctor.

I understand the way you and your doctor used the Drusano model, and this seems reasonable to me. I think this is very important for you to point out when you post about this model. I know of my own experience how very tempting any mention of Drusano is to a slow responder. It is IMO important for you to be very clear on how it was used in your case - to add tx duration to the 48 week course, not to shorten the 72 week course.

You certainly do not come off as argumentative. Discussions with people such as you are one of the refreshing elements on this board, which makes our understanding of the fight against this virus increase.

[jmjm530]

While it's almost impossible to qualify everything we say here (like your initial charcterization of Drusano IMO) , I thought I was very "clear" (almost tedious) re Drusano (modified Drusano actually) and how it was applied by my doctor in my individual case which was to INCREASE tx time, not decrease it -- and indeed it seems to be supported by Berg (your post above) for EVRs, which I was (actually RVR). I also have posted numerous times the studies re 72-weeks for geno 1's who were detectible at 12 but non-detectible at 24. Again, these studies (studies in general) don't always match up -- they all have achilles  heels, just different ones --  and therefore all tools should be on the table to work with, including Drusano. BTW thanks for offering up the article, but I thought it was the one in German, and given your last quote from the study, it doesn't appear that I have any disagreements with it.

As to your question -- were you an EVR given your 15 IU/ml where -- on one hand it would appear which study you're using. If the study used 10 IU/ml (or less) as a cut-off than you certainly weren't. But I think your question was more where to place yourself if the study used a cut off of let's say 50 IU/ml. The situation here is obviously more cloudy and in lieu of similar studies using more sensitive tests, one might conclude that the subset of those detectible by sensitive TMA (but not detectible by PCR) at week 12, most probably will have higher relapse rates than those non-detectible by TMA, at least given the same tx time. It's possible those figures are broken down somewhere, but maybe not. Again, one limitation of studies, which is matching up a large study group to one individuals's stats.

All the best,

-- Jim

[drofi]

Some comments:
The randomisation in the Berg-study was unusual: The patients were adjusted to the groups before start of therapy, not depending from PCR results of week 12. In addition, the dosis of ribavirin was low. Today Berg would use a different study design, I am sure.

The steps 24-48-72 are very simple and do not reflect the individual situation, as mentioned by Jim. But who should pay for e.g. 96 weeks and who could stand two years of treatment without a brake? My idea for people with slow response and more bad factors of prognosis would be to go 72 weeks of SOC and ADD 24 weeks of a low dose interferon monotherapy. The body has to change physiology from external IFN to own production from one day to another after 72 weeks. Does this give the few persisting viral copies the chance to strong up? A low dose therapy with mono IFN could add some “pressure” on the dragon without being too bad for the patient and the wallet.
Just an idea and not proven in studies, or is there any experience with it?
Writing this, the next question comes up: What about interferon resistance, does it exist? Would it be an argument not to continue with IFN and wait for better drugs after relaps?
Hmm.

drofi