The Good The Bad and the Ugly...

[Force]

Good news my Doctor decided to end treatment today after 36 weeks not the duration of 48 as planned. I was SVR after 4 weeks.

Not sure when I should return back to work though I am presently on a  Medical leave till Feb and things were not good between me and my employer  upon leaving. I have a feeling they might be writing me a cheque when I return saying bye bye.

Does anyone know who I contact regarding my rights when under going treatments and trying to deal with work issues?

I also did consult with a lawyer and documented every action they took against me.

[Trish77]

Nice stats...looking good, jerry.  Hoping for the best.  How's your sides so far?

Trish

[orleans]

way ahead--11/05 VL 216,000
1/08 VL 53,600
pretx base 8/8/08 VL 289,000 first shot 8/9/08
8/22/08(2 week) UND <10 IU/ml
9/19/09  (week 6) UND< 2 IU/ml (NGI)
11/6/08 (week 12) UND<10 IU/ml
jerry

[Trish77]

Particularly after reading all the posts above, if you go short course treatment, make sure your PCR's are very high sensitivity.  I'd also see if you can get earlier PCR's as well, as in Week 1, Week 2, etc. til you see that UND if you're at all considering shortened 24 week treatment.  When you go UND will tell you quite a bit.  That's my thinking on it.

Good luck, jerry.

Trish

[orleans]

I have a Dr appoint Wed. morn and plan on discussing this with him. Any more thoughts? jerry

[orleans]

Why the bitter rancor friend? SOC has been constantly adjusted as knowledge has increased. Why would one expose oneself to the dangerous post treatment effects of these drugs if not needed? It appears the concensus if shifting away from 48 weeks for SOME G1s, world wide. I say THANK THE LORD!  I am considering modifying my treatment because of my RVR and low baseline VL. Only a fool, considering the lastest info would not. Force, most all of us are rooting for you, you go dude. I respect anyone willing to think out of the box a little, both those that are willing to suffer "extreme tx, ie. double dosers etc. as well as someone like kittyface who tried Alinia as a mono tx. (17% of G4s that did mono Alinia SVRed!, as well as 68% of the RIBA less arm) jerry

[geterdone]

And one other thing that reeks about this post is your doctors irresponsibility to cut your 48 protocol short unless there is some imminent danger to your health and with out mounds of documentation and the most sensitive PCR <2 and way out of whack blood work during your treatment duration so far and your lack of fact findings of those assessments here on the board, of course unless you have whined and cried so much to him that he just threw up his hands and said ok, treatment failure why should I waste my time leaves me to believe that your just tired of feeling bad, well get over it and finish what you have started and then life will get better, got it!

Geterdone

[Trish77]

"One thing I will also mention I workout faithfully every other day and this past month sometime twice daily I will contribute part of my success to this. It has kept me positive and in a good frame of mind which encourages healing the body and a speedy recovery."

I'm glad this worked for you .... however, I have to say that while exercising the body is good, not everybody can do this while on treatment.  It's whatever keeps you in a positive frame of mind.  There have also been studies done that show that staying "positive" doesn't impact the outcome, only how you handle the treatment itself.  I think it's important to make the distinction. Getting through the treatment DOES impact the outcome and it's important to keep your attitude in a good place to give yourself the best shot at getting through treatment.  I wouldn't want anyone who struggles with depression while going through treatment to think that they are somehow killing themselves physically.  

I don't mean at all to minimize what you've accomplished, I think it's great.  I just wanted to say that for those who may not have been able to achieve the same kind of thing while on treatment.  

Trish

[Trish77]

"'m curious as a small employer – why would you stay on medical leave until February if you're not sick? Isn't that ripping off the system?"

If you're assuming he's currently  not sick because he's done treatment now, it does take awhile to recover from treatment and from the experiences I've read here, that varies from person to person.  I'm still experiencing a large amount of fatigue nearly two weeks off of treatment and, surprisingly, more brain fog and lack of concentration now than before...which could also simply be due to my own circumstances and a certain amount of disorientation in general!

As for ripping off the system, that goes two ways, doesn't it.  If an employer gave an employee a hard time simply BECAUSE he felt it necessary to go on medical leave and then expected to be fired when coming back simply BECAUSE he went on medical leave and for no other reason, that's the employer ripping off the employee and the system isn't it.  If your employer was doing this to you, would you feel an obligation to come back to work earlier than your medical leave requires if you expect to be fired for no other reason than you went on a medical leave in the first place because you truly needed to?  It's a bit of a catch-22, when someone else's lack of ethics requires you to consider responding in a way that would normally be considered unethical.  Neither is right in the strictest sense of the word ... but does raise some interesting questions.  

Trish

[geterdone]

Ok, here is the Ugly

It seems to me that you’re building false hope and trying to skate the 48 protocol because of your ego and you really can’t handle the treatment because it is starting to inhibit your exercise regimen now and you’re starting to give into your weakness. Being UND at week 4 does not always guarantee SVR even at the end of treatment and even more so if you have skipped a week of the ribavirin early on because of the anemia caused by it in which it really hit your ego because it has and is interfering with your life style. The question put forth about work is another rouse in that how can I still have 3 months off with out being caught and what laws can protect me if it should come to light in which the little force has not since starting treatment. I don’t know all the particulars of your treatment situation and have not seen any vl or blood numbers to go by, what were your starting vl numbers and pcr numbers. At 36 weeks I am sure you have had several. Good Luck in what ever you decide but you should try to stay the course for the 48 week or you may find yourself doing this treatment again.

geterdone

[fretboard]

About your job issues, you would contact the labor commission in the state that you're in.  In CA this is them, good luck.

http://www.dir.ca.gov/DLSE/DLSE.html

[portann]

"Ask me no questions and I'll tell you no lies."

[Marc1955]

I'm curious as a small employer – why would you stay on medical leave until February if you're not sick? Isn't that ripping off the system?

[CockSparrow]

Found this interesting from
Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon  -2a (40 kd)/ribavirin therapy
(HEPATOLOGY 2006;43:954-960.)

Our multiple logistic regression model demonstrates that HCV RNA level is the only independent and significant baseline predictor of RVR.
Patients with higher baseline HCV RNA levels were less likely to achieve an RVR, although those with a RVR (9.2% of those with baseline HCV RNA >600,000 IU/mL) were as likely to achieve a SVR as patients with low baseline viral loads.

One other analysis has reported higher overall SVR rates in patients with subtype 1b than subtype 1a infection (53% vs. 45%, respectively, P= .0039) in patients treated for 48 weeks with peginterferon a-2a (40 kd) plus ribavirin.8

Our logistic regression model showed patients  with subtype 1b infection responded particularly well to combination therapy if the HCV RNA level was below a threshold of 600,000 IU/mL.
The corresponding threshold in patients infected with subtype 1a infection was lower (Less than 200,000 IU/mL). With the exception that all Asian patients had subtype 1b infection, there were no statistically significant differences between patients infected with subtypes 1a and 1b.
This suggests that HCV genotype 1b is more sensitive to combination therapy.
Further study is required to elucidate the mechanisms that underlie this phenomenon.

CS

[Force]

"If you strike me down, I will become more powerful, than you can possibly imagine." -Obi-Wan Kenobi, Ep. IV
-------------------------------------------------------------------------------------------------------------------------------

I don't remember Jim saying that....

LOL it's a quote from star wars

[CockSparrow]

Jensen and colleagues [16] aimed to explore the prognostic factors for an RVR (HCV RNA =600,000 IU/mL) achieved SVR rates lower as compared with those with a low viral load of less than 600,000 IU/mL (74% versus 93%). Stage of fibrosis also influenced SVR rates in patients defined as ‘‘super-responders’’
(SVR rates were 90% with stage F0–F2 versus 79% with stage F3–F4).

Note how SVR odds decline with Increasing fibrosis. Even for RVRs. There is an Abstract from AASLD from the Canadian POWER study group that shows the same thing.

Also of interest are these investigators’ observations that frequency of relapse rates could be determined according to the assays applied to determine HCV RNA. In the case of a negative real-time PCR HCV RNA at week 4, the relapse rate was 10% as compared with relapse rates of 30% in patients still positive with the sensitive assay at week 4.

Jim always going on about having sensitive PCR tests makes sense when you see stats like that.
Close enough just aint good enough.

Between February 2001 and November 2003, the Dynamically Individualized Treatment of Hepatitis C Infection and Correlates of Viral/Host dynamics (DITTO-HCV) study group evaluated a dynamically individualized treatment schedule according to the early virologic response (compared with a standard-of-care peg-IFNa plus ribavirin combination therapy for 48 weeks) [18]. Patients categorized as having an RVR (definition: total log10 decline of HCV RNA during the first 4 weeks >Log2 and a second phase decline Log0.09 per day) were randomized to 24 or 48 weeks of treatment.
SVR rates in HCV type 1–infected patients with an RVR who were treated for only 24 weeks were substantial (65%) but were lower than in those treated for 48 weeks (83%).
No significant difference, however, was observed when patients with a low viral load (ie, <800,000 IU/mL) were considered, in whom SVR rates were nearly identical regardless of whether they were treated for 24 or 48 weeks (82% versus 83%) [18].

Would it be possible to shorten treatment duration further?
In a prospective, multicenter, randomized controlled study from Germany,HCVtype 1–infected patients received an individualized treatment duration from18 to 48 weeks tailored according to early viral kinetics. Patients with a low viral load (<800,000 IU/mL and RVR defined as <5.3 IU/mL by means of TMA assay) achieved an SVR of 95% after the 18-week treatment duration, and these findings were similar to the comparable control group treated for 48 weeks (94% SVR rate) [19].

Who says G1s are difficult to treat. G1 RVRs seem damn easy to me.
I never imagined anyone would be game enough to shorten G1 Tx to 18 Weeks.
Notice how sensitive the PCR test was though.

Definition of a new hepatitis C virus RNA cutoff to predict sustained virologic response
The determination of viral load has turned out to be of such importance to predict SVR that a more refined definition of the cutoff level indicating  low versus high viral load is desired so as to tailor treatment duration more accurately.

In the past, patients have been classified as having a ‘‘high’’ or ‘‘low’’ viral load using a cutoff of 2 x 10^6 copies/mL (2,000,000 copies/mL) (corresponding to 600,000–800,000 IU/mL, depending on the assay).

Note: The 2,000,000 copy/mL cutoff was found using one of HRs PCR tests.
So in a way IUs are all HRs fault.

I never knew that 600-800,000 IU/mL were actually the same thing using different PCR tests.
Interesting dontcha think

This was defined in the era of conventional IFNs, however. Several retrospective studies have now been undertaken with the aim of determining the most effective cutoff to differentiate between high and low viral loads based on the probability of an SVR with peg-IFNa plus ribavirin therapy [20–22].

Using the logistic regression model taking into account discrete (eg, gender, race, cirrhosis status) and continuous (eg, age, weight, baseline viral load, pre-treatment ALT quotient) variables, HCV RNA turned out to be a strong independent predictor of SVR, but this effect was not linear, indicating that at greater than a cutoff of 5.6 log10 IU/mL, the contribution of viral load in predicting an SVR was minimal.
Thus, a baseline HCV RNA level of approximately 400,000 IU/mL was found to be optimal for use as a cutoff for the probability of achieving an SVR in patients who had type 1 HCV treated for 48 weeks.

Less than the limit of 400,000 IU/mL, there is a nearly linear correlation between the amount of HCV RNA and the chance to establish an SVR, whereas HCV RNA levels greater than 400,000 IU/mL showed no significant effect on the SVR rates [20].

The reason for the finding that a viral load greater than 400,000 IU/mL had no significant effect on SVR is far from clear. One might speculate, however, that at greater than this level, the chance to achieve complete HCV RNA elimination from serum is reduced and many patients have minimal residual hepatitis C viremia.
Nevertheless, it still remains to be seen whether the now established cutoff based on the standard PCR test holds true when the real-time PCR assays are used to measure HCV RNA levels.

Interest Article and So are the sections on lengthening Tx

CS

[CockSparrow]

Below is an excellent article from Clinics of Liver Disease on Tailored Treatment for G1s.
I have only copied the bits on Shortening Tx.
You may also want to check out this study.
Early Identification of HCV G1 Patients Responding to 24 Weeks Peginterferon a-2a (40 kd)/Ribavirin Therapy
(HEPATOLOGY 2006;43:954-960.) *

Tailored Treatment for Hepatitis C
Clin Liver Dis 12 (2008) 507–528
Thomas Berg, MD

Summary of the current concepts of tailoring treatment duration in patients who have hepatitis C virus type 1

Patients who have an RVR and low baseline viremia may be potential candidates for shortening treatment duration from 48 to 24 weeks.
Around 10% to 15% of all HCV type 1–infected patients reach these criteria. The optimal cutoff to define low viremia (400,000, 600,000, or 800,000 IU/mL) in this setting is still unclear.

As long as HCV RNA is undetectable by sensitive real-time PCR assays or TMA tests at week 4, however, levels of less than 600,000 IU/mL seem to be appropriate (more conservative physicians may even choose 400,000 IU/mL).

Because hepatitis C viremia may fluctuate in the natural course of the disease, however, it is desirable to have at least two measurements of HCV RNA before starting therapy to confirm low-level replication over time. To exclude to the best possible level the presence of minimal residual viremia at week 4, which clearly increases the likelihood of experiencing a relapse, the most sensitive HCV RNA assays should be used when shortening treatment duration is considered. Furthermore,

Principles of tailored treatment in hepatitis C virus type 1
Treatment response in patients who have chronic HCV infection is quite heterogeneous and depends on host factors (ie, age, gender, alanine aminotransferase [ALT] levels, stage of fibrosis, insulin resistance) and viral factors, such as serum concentration of HCV RNA at the time of initiation of antiviral therapy, including HCV genotypes [2–7].

Thus, virologic factors and host factors must be considered if one tries to get sound information on the individual likelihood of response. 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.

Viral kinetic studies have further expanded our knowledge of the mechanisms of IFNa action and have shown that the likelihood of achieving sustained virologic response (SVR) clearly depends on the speed of the response [8–10]. It is well established that the rate of SVR is inversely correlated with the time on treatment that is necessary to clear HCV RNA from serum.

Individual prognosis with respect to the long-term treatment outcome can therefore be best predicted by early viral kinetics, because all baseline factors finally alter the speed of response (Fig. 1). Indeed, if one includes viral kinetic parameters in multivariate models to predict SVR, most the baseline factors lose their predictive power.

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

Importance of the sensitivity of the hepatitis C virus RNA test Undetectable hepatitis C viremia on treatment, even when evaluated by standard qualitative HCV RNA tests (detection limit of 50 IU/mL) does not, per se, indicate that the virus was completely eliminated from the serum.

There is now emerging evidence that by applying more sensitive assays (eg, transcription-mediated amplification [TMA] or real-time polymerase chain reaction [PCR] assays with a detection limit!10 IU/mL), a significant proportion of patients who were shown to have undetectable HCV RNA levels by standard assay are still viremic (Figs. 3 and 4) [11,12].

This implies that many patients considered so far to have had a relapse might, in fact, have been nonresponders with a minimal replication level (minimal residual viremia) (see Fig. 2B).

Quite importantly, the detection of minimal residual HCV RNA levels at week 12 must be taken as a serious predictor for a possible later relapse event. Morishima and colleagues [12] provided evidence that all patients in whom a minimal residual viremia could be detected at week 12 and still confirmed at week 20 had a relapse.
The application of extremely sensitive HCV RNA tests to design individualized therapeutic strategies is therefore indispensable.

Experiences with shortening treatment duration in hepatitis C virus type 1 infection

Treatment guidelines recommend that patients infected with HCV genotype 1 should be treated for 48 weeks with the combination of peg-IFN plus ribavirin [13,14]. The recommendation of this fixed treatment duration is based on the outcome of a large randomized international trial published in 2004 by Hadziyannis and colleagues [6], in which patients were randomized to treatment for 24 or 48 weeks with peg-IFNa-2a plus ribavirin at a dosage of 800 or 1000/1200 mg/d. SVR rates ranged from 29% to 52% across the four treatment groups, and the highest SVR rates were achieved with a 48-week treatment regimen plus ribavirin at a dosage of 1000/1200 mg/d.

Extension of treatment duration up to 48 weeks increased the SVR rate, especially in patients who had high baseline viremia (R800,000 IU/mL) from 26% to 47%, whereas increasing treatment duration from 24 to 48 weeks in patients who had low viremia (!800,000 IU/mL) yielded only a moderate effect on SVR rates (52% versus 65%).

These data indicate that a subgroup of patients defined by pretreatment HCV RNA levels of
less than 800,000 IU/mL can achieve long-term response rates up to 52% even after a treatment period of 24 weeks.

Based on these findings, Zeuzem and colleagues [15] performed a study to examine whether patients who have HCV genotype 1 and low baseline HCV RNA levels (defined as!600,000 IU/mL) may require just 24 weeks of treatment with peg-IFNa plus ribavirin. Two hundred thirty-five treatment-naïve patients infected with HCV genotype 1 were treated for 24 weeks with peg-IFNa-2b at a dosage of 1.5 mg/kg/wk and weight-based ribavirin (800–1400 mg/d).A comparable group of patients who had type 1 infection and low baseline viremia who had been treated for 48 weeks within the Manns’ trial [3] served as a historical control.

The end-of-treatment virologic response rates were comparable between both studies (ie, 80% versus 74%). SVR rates were significantly different (50% versus 71%), however, because of higher relapse rates observed in patients treated for only 24 weeks (37% versus 4%).

Thus, baseline factors alone, like HCV RNA levels, do not really help to get sound information concerning tailoring of treatment duration. These investigators then re-evaluated their findings and found that a subgroup of patients expressing a rapid virologic response (RVR) already at week 4 (defined as HCV RNA levels <29 IU/mL by real-time PCR) had an 89% chance to achieve an SVR even after only 24 weeks of combination therapy, which was comparable to the SVR rates observed in patients with an RVR treated for 48 weeks (85% in historical control group with RVRs).

Continued

[alijee]

Congratulation dear force you have done the tx very bravely. now you are virus free. i will pray for your svr. Thanking you very much for keeping touch with this site and please encourage the people who are still on tx. you are our pioneer.

[orleans]

March 6th, 2007

PEGASYS(R) Gets European Approval for a Shorter Treatment Duration for Some Genotype 1 and 4 Hepatitis C Patients who Show a Rapid Response to Therapy
http://www.prnewswire.co.uk

- Shorter, Simplified Treatment Option May Encourage More Patients to Seek Treatment

Some hepatitis C patients with difficult-to-treat HCV genotype 1 who respond quickly to treatment with a combination of PEGASYS(R) (pegylated interferon alfa-2a (40KD)) plus COPEGUS(R) (ribavirin) can benefit from a shorter and simplified course of therapy, following Thursday's Commission decision. With the new approval, a subset of patients with genotypes 1 and 4 HCV who achieve rapid viral response can now receive a shortened, 24-week duration of treatment with Roche's PEGASYS plus COPEGUS. This is half the normal treatment duration.

Shorter, Simplified Treatment Shows Excellent Chance for a Cure
The EU approval is based on data from two pivotal clinical trials for PEGASYS plus COPEGUS.(1,2) Results from these trials show that among patients who achieved a rapid viral response (undetectable viral load at week 4) in the first month of treatment up to 93 per cent of patients with genotype 1 HCV with a low pre-treatment viral load and 83 per cent of patients with genotype 4 were cured following only 24 weeks of therapy - a similar cure rate to that seen following 48 weeks of therapy.(3)

"This is excellent news for patients with hepatitis C," said Dr Peter Ferenci, Professor of the Department of Internal Medicine IV, Gastroenterology and Hepatology, at the University of Vienna, Austria. "This means that patients can find out within one month of starting therapy if they have an excellent chance of being cured and can benefit from a shortened treatment duration. This is likely to encourage patients to seek treatment and motivate them to stay on therapy."

New Recommendations for Treatment
A shorter, 24-week course with PEGASYS plus COPEGUS is now an option for the following patients:(4)

Genotype 1 HCV with a low pre-treatment viral load (defined as <800,000 IU/mL) and an undetectable viral load at weeks 4 and 24;
Genotype 4 HCV regardless of pre-treatment viral load and an undetectable viral load at weeks 4 and 24.
"This licence change reflects Roche's commitment to finding better treatment solutions for patients with HCV by improving treatment with existing therapies and developing new medicines to treat hepatitis C," said Claire Steers, PEGASYS Lifecycle Leader at Roche in Basel, Switzerland. "Roche is committed to finding solutions for a broad range of hepatitis C patients by continuing to simplify treatment with PEGASYS."

[portann]

"If you strike me down, I will become more powerful, than you can possibly imagine." -Obi-Wan Kenobi, Ep. IV
-------------------------------------------------------------------------------------------------------------------------------

I don't remember Jim saying that....

[Force]

Hi Jim you were exactly right!

The recommended treatment for patients with hepatitis C virus (HCV) genotype 1 infection is the combination of a pegylated interferon plus ribavirin 1000 or 1200 mg/day for 48 weeks.[1,2] The ability to identify genotype 1 patients that might respond to a reduced length of treatment would limit the burden of therapy in this common but more difficult-to-treat patient population. Recent data from an uncontrolled study suggest that HCV genotype 1 patients with a low baseline viral load who have undetectable HCV RNA after 4 weeks of treatment with the combination of a pegylated interferon plus ribavirin may require just 24 weeks of treatment to achieve a sustained virological response (SVR).[3]

I had treatments for 36 weeks he is pretty confident the virus is gone.

One thing I will also mention I workout faithfully every other day and this past month sometime twice daily I will contribute part of my success to this. It has kept me positive and in a good frame of mind which encourages healing the body and a speedy recovery.

My true test will be 6 months from now with my next blood test but from the energy I have now compared to the last 4 years I know I beat it!

Thank you everyone for being so supportive. I still will continue be an active participant on this site and if I had one wish it would be to wipe this disease clean form everyone it so plays on your mine daily.

"If you strike me down, I will become more powerful, than you can possibly imagine." -Obi-Wan Kenobi, Ep. IV

The Force be with you!

[orleans]

ALRIGHTY THEN!! A hot topic in the halls heh? I am so glad to her this as I am dealing with this issue. For me it is the difference of having 10 weeks left(heaven!) or 34 weeks (need I say?).  Low baseline VL was once considered 800,000, now 400,000 is the mostly agreed on number. The European protocol for 24 week G1 treatment is RVR plus 600,000or less baseline VL. G4 RVRs are also being stopped at 24 weeks and low VL is not needed for them. ANYONE ELSE hearing anything 'bout this? jerry

[zazza]

Was your baseline viral load below 400'000 IU/ml?

[portann]

I saw my nurse today for my 24 week checkup and was surprised that she brought up what a hot topic reducing to 24 weeks for RVR's was in the corridors of last week's AASLD conference in San Franciso. For her to bring it up out of the blue - I'm not even an RVR :(  - probably says something about the spreading acceptance.

Force, I thought you owned a fitness club or was that someone else in the forum? Sorry I can't help you with your employment questions but sincere congratulations on winding up treatment.

Jim, my nurse loves Dr. Schiffman, says how cute and wonderful he is. She went out of her way to attend one of his talks in SF. Was he your doctor?

[jmjm530]

Sounds like they were following a short-course protocol for geno 1's who RVR. If I remember correctly a low pre-tx viral load was also part of the study this protocol may be based on. Maybe Force will fill in the blanks.

-- Jim