Biopsy Results

[klonny55]

I have my biopsy and ultrasound results:

Biopsy:
Portal/periportal inflammation is grade 3/4
Lobular inflammation is grade 2/4
Fibrosis is stage 2-3/4
Very mild steatosis is present
Iron stain is negative

The ultrasound report found no hepatic masses, no spleen enlargement, no gallstones, no evidence of cirrhosis. It does say:

"CBD mildly dilated proximally tapers to normal caliber at the level of the pancreatic head. No intrahepatic biliary ductal dilation No ductal calculi in the visualized portion of the duct. Consider MRCP/ERCP for further evaluation if the LFTs are abnormal.

Small amount of gallbladder sludge. No cholelithiasis or evidence of acute cholecystitis."

So I am taking this as mostly good news. I do have a couple of questions if anyone out there can help it would be very much appreciated. I have my follow up with the hep doc in 2 weeks and of course will discuss all this then but am curious about a couple of things:

What is the significance of the portal/periportal inflammation? It seems grade 3/4 is high. Does this relate to how fast the scarring is progressing?

What does the part about the common bile duct in the quotes above mean?

I am now confronted with the decision about treatment. My doc is saying they are not treating genotype 2s (like me) until the Sofosbuvir/Ribavirin combo is available. I will have to decide whether to agree or get a second opinion and consider the SOC treatment available now.
There is also a trial I found that seems as if I would be eligible for. It's the only one for genotype 2s (among others) I could find. It's in Boston which is 2 1/2 hours from me. It is a phase 2 study and I do not know what the second drug is, GS-5816, it isn't ledipasvir is it?

This how it is described:

A Phase 2, Multicenter, Randomized, Open-label Study to Investigate the Safety and Efficacy of Sofosbuvir+ GS-5816 for 12 Weeks in Treatment-naive Subjects With Chronic HCV Infection

http://clinicaltrials.gov/ct2/show/NCT01858766?term=genotype+2&recr=Open&state1=NA%3AUS%3AMA&rank=2

Anyone know anything about this?

Thanks!

[rivll]

Very encouraging Klonny.
I think the sofosbuvir/ribavirin is your ticket and I am happy you can wait for it.
Also glad you are in such competent hands.
All the best to you,
Riv

[klonny55]

Thanks, I looked into the phase 2 trial of sofosbuvir and GS-5816 and it is closed anyway. There are no other trials out there for genotype 2s that I can find so I will put that aside and re-evaluate my options in 6 months.

[Advocate1955]

This sounds like a reasonable plan given your particular set of circumstances:  G2, Sof/Rib 12 wk course likely available around Dec/Jan, and moderate liver damage (F2-3).  I agree with others, given your specific situation, I would not jump into a phase 2 trial, and I would wait for the new treatment, but if there are any delays in approval, I would start SOC for G2 in early 2014.
Keep us posted.
Advocate1955

[klonny55]

So I had my follow up with the hepatologist last week and he said that he was pleased and surprised with the result of my biopsy (stage 2-3). He had expected more damage to my liver given my history (at least 30 years since infection and drinking history) I asked the where will I be in one year without treatment question and he said probably in the same place you are now. I asked about non-linear/accelerated progression of fibrosis and was told yes this can be true for some but from his experience he would not expect to see that in my case and at any rate he assured me I would not have to wait a year for treatment. I was told that I always have the option of doing the SOC of interferon and ribavirin if I wanted and/or the something went wrong with the FDA approval of sofosbuvir and that being a genotype 2 put me in a good place for treatment. He said to come back in 6 months and meanwhile no drinking (I'm not) and to relax and enjoy life. This is coming from the Dartmouth Hitchcock/Mayo clinic Dartmouth College teaching hospital where I was told they see two new HCV patients a day.

I'm going to take the advice and do just that, relax, ride my bike and enjoy the summer.

[christinatas]

i hope you look before you cross the road all day tomorrow.lol...

[klonny55]

Yes I agree, waiting is probably the best plan. Everything I read is suggesting an approval at the end of this year. I know it's not a guarantee but nothing in life comes with a guarantee. I could get hit by a bus tomorrow and that would make all this moot wouldn't it. I have no symptoms at this point and am busy getting fit as possible by riding my bike and losing weight, no co-morbidities except for high blood pressure which is coming down without medication as I lose weight (124/80 at the docs yesterday) I feel like I am in good shape for waiting a few months.

Thanks for all the insights, I especially think Medic's idea of the question to the doc about where I might be in a year without treatment is spot-on, thanks for that! Hopefully the discussion will help others in a similar situation as mine. With all the drugs in development the decision to treat or wait is a particularly dynamic and changing one right now.

[klonny55]

Thanks so much for the excellent response to my question. There are two arms in this study:

Experimental: SOF(400mg)+GS5816(25mg) once daily for 12 weeks Drug: SOF in combination with GS-5816

Experimental: SOF(400 mg)+GS-5816(100 mg) once daily for 12 weeks Drug: SOF in combination with GS-5816

The difference being the dosage of GS-5816, 25mg vs 100mg If I'm reading it right this is one pill once a day. No mention of a placebo. I understand what you are saying about phase 2 trials. One question I would ask would be if I do not respond or relapse does that limit future options. I am at the very beginning of considering all this since the biopsy results came in less than 24 hours ago. I will consider my options very carefully!

[pooh55811]

Here is the post from the other site and the list of questions:


Questions to Ask about Trials:

Anyone interested in participating in a clinical study should know as much as possible about the study and feel comfortable asking the research team questions about the study, the related procedures, and any expenses. The following questions might be helpful during such a discussion. Answers to some of these questions are provided in the informed consent document. Many of these questions are specific to clinical trials, but some also apply to observational studies.

What is being studied?

Why do researchers believe the intervention being tested might be effective? Why might it not be effective? Has it been tested before?

What are the possible interventions that I might receive during the trial?

How will it be determined which interventions I receive (for example, by chance)?

Who will know which intervention I receive during the trial? Will I know? Will members of the research team know?

How do the possible risks, side effects, and benefits of this trial compare with those of my current treatment?

What will I have to do?

What tests and procedures are involved?

How often will I have to visit the hospital or clinic?

Will hospitalization be required?

How long will the study last?

Who will pay for my participation?

Will I be reimbursed for other expenses?

What type of long-term follow-up care is part of this trial?

If I benefit from the intervention, will I be allowed to continue receiving it after the trial ends?

Will results of the study be provided to me?

Who will oversee my medical care while I am in the trial?

What are my options if I am injured during the study?

[pooh55811]

"Maybe a strategy would be to wait until the December 8 FDA review date for sofosbuvir, see how that goes and make a call then. "
------------------------------------

I would not want to delay treatment for years if I was at Stage 2-3 fibrosis but, in your situation, since you cannot start Tx until October at the earliest anyway, I think your strategy is a plausible strategy. If the Sofosbuvir is not approved or there are some delays, then you can always fall back on the Inf and Riba.

I don't know much about the trial you mentioned. However, as far as a Phase 2 trial, I would be hesitant to jump into a Phase 2 trial when hopefully the Sofosbuvir Tx will be approved and you could do that Tx next year. With trials, you do not know which arm you will be in. You sure do not want to get into a Placebo arm if you are Stage 2-3. Also, from what I have read, it is usually better, if one is going to be in a trial, to get into a Phase 3 trial. It is further along. Also, know your options, such as the availability of a rescue arm if the arm you get into is not working.

I did find some information on GS_5816.

http://www.natap.org/2013/EASL/EASL_34.htm

I also found another discussion about this trial (I think it is the same one you are talking about). One person lists a bunch of questions anyone entering a trial should ask and I will post them in a second post.

http://www.mdjunction.com/forums/hepatitis-c-discussions/general-support/10645422-gs7977-and-gs5816-trial

[klonny55]

The wild card is the trial that I found and mentioned in my earlier post. Does anyone know anything about GS-5816?

[klonny55]

Yes from what I understand the treatment time for the current interferon/ribavirin treatment is 24 weeks and the new sofosbuvir/ribavirin is 12  weeks. So if I were to start the 24 week treatment the beginning of October (the soonest possible with the six month no drinking waiting period) I would be done around the beginning of April. If I started the 12 week treatment the first of the year it would also be around April 1 that I would finish. Add to that that the SVR rate for the interferon treatment is about 70-80% for my genotype and in the phase three trials the SVR rate for the sofosbuvir/ribavirin treatment is about 95% for genotype 2s You can see why they are saying to wait.

Maybe a strategy would be to wait until the December 8 FDA review date for sofosbuvir, see how that goes and make a call then.

[medic54]

Yes your inflammation is acute (active/continuing) and at fibrosis stage 2 3/4.... but consider: 'averages' of 5 to 9 years between fibrotic stage advance and a 0.28/ fibrotic stage/ yr regression if SVR is achieved. Add the side effects (sometimes permanent) of interferon, the very likelihood of Sofo within a year (or sooner) and that (correct me if I'm wrong) but you'd be looking at half the treatment time on Sofo. Tough call, and a second opinion should always be sought when major medical decisions are in question...but I gotta think that until something negative comes out on Sofo, your doc has made the right call. You might want to press both your doc and a second with this question: 'At my estimated progression rate, if Sofo doesn't make it to market, where will I be this time next year and how much more will that decrease my SVR odds with interferon?' I did read a study which determined the peginteferon/rib SVR odds of success decreased by 5% from grade 2 to 3 but then that was one study and probibley 2.5 to 3.5. Good Luck.

[christinatas]

i know exactly what you mean cause i was worried to death til  i got mine back but i didnt ask dr what was more important where i had already taken treatment class my doc makes everyone attend before class.but i still forgot to ask this question.

[klonny55]

I am assuming that it means I am somewhere in between stage 2 and 3. I don't think one is exactly more important than the other in terms of stage and grade, both are important. The fibrosis stage is the condition your liver is in at the time of biopsy and the grade is the amount of activity occurring that results in the fibrosis. My inflammation grade is 3 in the portal area which is described as moderate from what I can tell. The most important thing is that I don't have cirrhosis which means that when I get rid of the virus my liver will repair itself. This is why the treat now or wait issue is so important. I am being told that I will have to wait to treat until 6 months post drinking which would be the end of September 2013. If I decide to wait for the new treatment it would be after that date anyway.

[christinatas]

so i am confused does this mean you are STAGE 2 OR 3?
FOR ALL READING---what is more important the grade or the stage?is the grade the amount of inflammation?
i think i would wait or do you have to by your doc's standards to make sure you are NOT  drinking anymore?

[ppmguy]

            the dilation of the cbd(common bile duct) is generally from a blockage caused by calculi (gall stones).  when your doc says to wait until next LFT, that is because blockages will cause billirubin to rise significantly. if normal then there is no block.  i have the same problem and a few others i chatted with, also. the mrcp/ercp will give your doc a better idea of whats up.  
          the gilead tx for geno 2 will be here maybe by years end.  no one really knows for sure.  yourfibrosis is 2-3 so you can wait a few months if your dr agrees.
              btw,  my CBD is dilated and nothing was found on mrcp/ercp.
                        best to you          barry
  

[klonny55]

The only values out of range were my ALT and AST. The first was 234/111 in March then 141/59 in April. I have not had them done since April. Everything else is well within normal limits. My doc says the ALT/AST have probably gone down more since I am now 12 weeks without a drink.

Does stage 2-3 fibrosis mean that I am 1/2 way between the two in progression or that there were some areas of 2 and some areas of 3? Or is that the same thing anyway. I have probably had the virus for 30 or more years. Can I assume that if I am at stage 2-3 now with a history of drinking that I can wait 6 months or so for the new treatment to be available? The idea of 12 weeks without interferon is much nicer than 24 with....

Sorry for all the questions

[BoceprevirGal]

  Yes, the inflammation does cause the scarring.  I dont know about the other stuff,
   I had a stage 2 biopsy, with grade 3 infammation, and went ahead and Treated,  but I was a genotype 1a.  I had a 4 wk "lead in" with Interferon and Ribavirin, before my 3rd med was introduced, which was for Victrelis ( only used for geno 1) and I did clear my virus, after the 4 weeks of just the Interferon and Ribavirin, and went on to do 24 more wks, witht hose 3 meds, and I did clear the virus.
    Do you have a copy of your labs, and if so, is anything in the "abnormal range" column?  If so, let us know which labs were out of whack~
   If I were you I would most definitely participate in that Trial~  good luck.