If 12 wk UND --> 72 wk tx ?!

Below are my VL test results, personal profile,  and my biopsy results.
Based on my 8th VL test results, my doctor said he assumes that my 12 wk VL test will be UND and if so,  he wants me to treat for 72 weeks !  I asked my doctor my chances of SVR and he said 60% if UND at week 12.  He said that my chances of SVR do not increase by extending tx to 72 wk, rather he told me that tx for 72 wk decreases the relapse rate (and that affects the SVR chances).
I thought if I reached UND at week 12, that would be good enough for 48 weeks of tx and I certainly did not expect to hear that my tx plan is now for 72 wk !  I was happy that it looked like I was responding to tx, but am very surprised to hear that I now have to do extended tx.                                                                         I am still trying to take this all in - and would appreciate any thoughts or personal views on this.
Thanks GingerB.

VL tests were done by  LabCorp Quantasure Plus  which goes down to a sensitivity of  10 IU:
Pre tx VL  = 2.8 mil IU = 6.453 log.    
2 wk post tx VL = 136,000 IU = 5.134 log.  
4 wk post tx VL = 10,900 IU = 4.037 log.
8 wk post tx VL =  270 IU   = 2.43 log

8th wk hgb = 10.0 (hgb pre tx = 14.5)
I am Female, Caucasian,  56 years of age.  
5 feet 5 inches tall,  weight 119 lbs (currently down to 115 lbs).
Genotype 1a.  Grade 2  Stage 2
Started tx Jan 8, 2008:  Pegasys 180 mcg weekly and 1000 mg ribavirin daily.
2/07  Liver biopsy with iron stain:  measuring 2.1 x o.1 x 0.1 cm
  The hepatic parenchyma is preserved without architectural distortion.
  Mild portal inflammation is present with increased lymphocytes,
  scattered eosinophiles and few neutrophiles.  A rare hyperplastic
  Kupffer cell is identified within the portal tract.  Interface hepatitis
  is focally present.  There is mild lobular inflammation with foci of
  macovesicular steatosis.  Stainable iron is not identified.  Trichome
  stain shows mild portal and periportal fibrosis.  Bridging fibrosis in
  not identified.  Clinical correlation is suggested.
  Final Diagnosis:  Chronic Hepatitis, Grade 2, Stage 2.

[charm27]

If your UND by weeek 12 I never heard of anyone txing past 48 weeks.  Im sorry I dont understand that.?

If you are stull detectable after week 12 thats a different story.

[Bobby1952]

" He said that my chances of SVR do not increase by extending tx to 72 wk, rather he told me that tx for 72 wk decreases the relapse rate (and that affects the SVR chances). "
---------------------------------------------------------------------------------------------------------------------
I don't understand the above statement. " Aren't both statements the same thing??
If tx for 72 weeks decreases the relapse rate then wouldn't that increase your chance of SVR.?
  Either way if you are UND by 12 weeks you should treat for 48 weeks.  

Bobby

[jmjm530]

As I mentioned in the other thread, you might ask your doctor to spell out his reasoning, i.e. with trial data, etc, or anything else he may be factoring in.

There is one study-- Berg I think -- that suggests 72 weeks increases the SVR rate in geno 1's if not UND at week 4. (This is a different Berg study that suggests exending if not UND at week 12). You might want to search out that trial and order the full-text version. If I come across it, I'll post but not sure if I can get to it soon.

But that one Berg? trial aside, most seem to treat for only 48 weeks if UND by week 12, and given that you don't have significant liver damage, I'd carefully weigh extending 72 weeks. If it were me, to help me weigh that -- in addition to digging up the Berg study and perhaps some others -- I'd collect all my medical records and arrange for one or preferably two additional consultaions with some top hepatologists who can carefully review your entire history and help guide you. You have plenty of time since you're only at week 9?, but I'd start making the appointments as soon as your week 12 labs are in. This is a very important decision and you want the most brain and study power behind it.

-- Jim

[R Glass]

Jim, if it is not too much trouble, could you post the link to that thread. I vaguely remember it. It’s not that I am lazy, I did my shot earlier and you know how it is. I was undetected at 4 weeks and was told if I were to stop tx at week 16 (2 more weeks), I would have an 80% chance at SVR. If I complete the 24 weeks, I was told he could almost guarantee SVR. I am having a problem understanding how 8 weeks would make a 20% difference.

[zazza]

Isn't it the Sanchez-Tapias study which looks at extended tx if not UND by week 4?

"Longer Treatment Duration with Peginterferon Alfa-2a (40KD) (Pegasys) and Ribavirin (Copegus) in Naive Patients with Chronic Hepatitis C and Detectable HCV RNA by Week 4 of Therapy: Final Results of the Randomized, Multicenter Teravic-4 Study"; AASLD abstract, Hepatology 2004; 40 (Suppl 1): 218A:

"Data from viral kinetic and pilot studies suggest that treatment for
longer than 48 weeks may increase sustained virological response
(SVR) rates in patients who do not have a rapid decrease in HCV
RNA after the start of treatment. The TeraViC-4 study is focused
on such patients. Those without a rapid virological response (non-
RVR) at week 4 (ie patients with detectable serum HCV RNA, >50
IU/mL by PCR) to Pegasys plus Copegus were randomized to a
total duration of 48 or 72 weeks of treatment.

Methods:
Treatment-naive patients with detectable HCV RNA and elevated
ALT levels received Pegasys 180 mcg/wk and Copegus 800 mg/d for
4 weeks in this phase 3, randomized, parallel group, multicenter
Spanish study conducted under the ICH Harmonised Tripartite
Guideline for Good Clinical Practice. At week 4, nonRVR was
assessed by qualitative PCR assay (COBAS AMPLICOR HCV
Test v2.0 detection limit 50 IU/ml). Patients with nonRVR (ie those
with detectable HCV RNA) were randomized 1:1 to continue
treatment to complete a total of 48 (group A) or 72 weeks (group
B) of Pegasys/Copegus combination therapy. SVR was defined as
undetectable HCV RNA (<50 IU/mL) at the end of a 24-week
treatment-free follow-up period.

Results (Table):
A total of 517 patients were enrolled and treated, 327 of whom had
detectable HCV RNA after 4 weeks of treatment. The SVR rate
was significantly higher in patients treated for a total of 72 vs 48
weeks, including those with genotype 1 and high baseline viral
loads. The type and incidence of adverse events were generally
similar in groups A and B. In particular, the incidence of neutropenia
and thrombocytopenia was similar in the two groups. The
proportion of patients withdrawn for adverse events or laboratory
abnormalities was similar between the two groups. The potential
benefit of therapy can be stimated by HCV RNA determination at
week 12 in those patients treated during 48 weeks, and at week 24
in those treated during 72 weeks.

Conclusions:
Extending the treatment duration from 48 to 72 weeks with Pegasus
plus Copegus in patients who do not have an RVR by week 4
significantly reduces relapse rates and significantly increases SVR
rates. Most patients without an RVR were infected with HCV
genotype 1 and/or had high baseline HCV RNA levels. Importantly,
extended treatment does not increase the incidence of
adverse events."

The Berg study comments:

"Sanchez-Tapias et al recently presented data from a study that also analyzed the effect of a prolonged treatment period using PEG-IFN-alfa-2a plus ribavirin in patients without early virologic response at week 4 (HCV-RNA positive by qualitative PCR). They showed that SVR rates were significantly higher in the 72-week group as compared with the 48-week group (45% vs 32%) and that the 72-week treated patients expressed significantly lower relapse rates (13% relapse vs 48% in the 48-week group). These data are basically in accordance with the results of our present study and confirm the concept of extending treatment duration in slow virologic responders. However, from our data it can be deduced that the week-12 response might be a better time point from which to select patients for the evaluation of treatment duration because SVR rates were not significantly different in patients who already were HCV-RNA negative at week 4 and those becoming HCV-RNA negative at week 12."

"Extended treatment duration for hepatitis C virus type 1: Comparing 48 versus 72 weeks of Peginterferon-Alfa-2a Plus Ribavirin"; Gastroenterology 2006; 130: 1086-1097.

[GingerB]

I found a relatively recent study (below) that recommends 72wks for 12wk UND. It is a study in Italy by Mangia, Minerva, Bacca et al (2007) presented at the Barcelona conference.

I have no scientific background, but it seems to me that some of the p (probability) levels are high. I thought the p level should be < 0.05 for the results to be considered valid? But I I am really not familiar with intrepreting all this infor.  Also the sample is very low for some of the categories.

My take from this is:   participants who became UND at 12 wks and continued tx to 72 wks had SVR rates 32 of 50 participants (64%).  And 5 of 15 participants (33%) for those that went 48wks. While it is promising that 64% of 72 wk went onto SVR, it is discouraging that only 33% of the 48 wk treatment group went SVR. Is this study saying that being UND at wk 12, I have only a 33% of SVR (assuming 48 wks of tx)? That's worse than the 50-50 chance I thought I had when I started.

"Prolonged Therapy with Pegylated Interferon/Ribavirin May Improve Odds of Sustained HCV Clearance "


Recent studies have provided increasing evidence that among chronic hepatitis C patients treated with pegylated interferon plus ribavirin, rapid virological response (RVR) at week 4 is a good predictor of sustained virological response (SVR) 24 weeks after completion of therapy. Further, mathematic models suggest that in patients with genotype 1 HCV, the SVR rate directly correlates with the duration of treatment after HCV RNA becomes undetectable.

As reported at the 42nd Annual Meeting of the European Association for the Study of the Liver last month in Barcelona, Italian researchers conducted a study to evaluate SVR in relationship to RVR among 663 genotype 1 patients who received pegylated interferon plus ribavirin for either the standard 48-week course (n = 221) or individualized treatment durations of 24, 48, or 72 weeks (n = 442). In the individualized treatment group, those without RVR were treated for 48 or 72 weeks based on whether HCV RNA was undetectable at week 8 or week 12.


Results


236 patients (54%) in the individualized duration arm and 121 patients (55%) in the standard duration group had undetectable HCV RNA at week 8.
At week 12, HCV RNA became undetectable for the first time in 50 patients in the individualized duration arm and 15 in the standard duration group.
Proportions of non-responders at week 12 in the 2 arms were 155 (34%) and 85 (38%), respectively.
Among patients who were HCV RNA negative at week 8, 111 of 318 (35%) in the individualized duration arm and 45 of 163 (28%) in the standard duration group achieved SVR (P = 0.12).
When patients who became negative for the first time at week 12 were analyzed separately, the corresponding SVR rates were 32 of 50 (64%) and 5 of 15 (33%) (P = 0.07).
In the latter subgroup, the only factor significantly associated with SVR was longer treatment duration (P = 0.0001; OR 1.68).
Relapse rates did not differ significantly in the 2 treatment arms (5% vs 4%).
Dropout rates were 15.3% in the individualized duration arm and 13.1% in the standard duration arm.
Conclusion

The investigators concluded that, “Results of this randomized controlled trial confirm that prolonging treatment [beyond] 48 weeks allows better SVR even in the subgroup of patients who clear HCV RNA at week 12 from the start of treatment.”

IRCCS Italy; Ospedale Canosa, Canosa, Italy; Ospedale Casarano, Canosa, Italy; Ospedale Venosa, Venosa, Italy; Universita di Palermo, Palermo, Italy; Policlinico Umberto i Dell’Universita, Rome, Italy; Hospital Sandro Pertini, Rome, Italy; Ospedali Riuniti Foggia, Foggia, Italy; Ospedale Brindisi, Brindisi, Italy.

05/11/07

Reference
A Mangia, N Minerva, D Bacca, and others. In pts who clear HCV RNA at week 12, SVR is higher after 72 than after 48 weeks tx: results of a randomized controlled trial (RCT). 42nd Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain. April 11-15, 2007.

[Cory255]

I've not yet googled the Sanchez-Tapias study.  

[nygirl7]

http://www.natap.org/2004/EASL/easl_06.htm

[Bali05]

if  you are UND by wk12 you achieved EVR.
Standard is stil 48wks as far as I know.

What test does your doctor use to determine UND status ?
from 270
to drop to zero you need another 2.43 log drop
to drop to 42 standard RT PCR<43 you need another 0.81 log drop

[nygirl7]

B-

This post is quite old I was just responding to Cory's mention of not having read Sanchez-Tapias yet.

[Bali05]

thanks , you are right i did not see that

[Diane12855]

I just got my 12 weeks blood draw last Friday. I previously dropped from 6 mil. to 2,000 by 4 weeks. I don't like what I'm reading here. All I have ever heard was that if I was UND by 12 weeks, I'd do 48 weeks. I REALLY want SVR, but I really don't want to have to go 72 weeks.

Sorry... just rambling....

[Cory255]

I'm really surprised it's not referened more often.  It's saved in my favorites folder now.  Thanks.

[rmv930]

tested neg after 5 shot dr thinks i have a very good chance for svr