Newbie - very worried by biopsy results

[boink_LA]

Just got my latest biopsy result and to be honest I'm kind of freaking out a little. Just taking the time to read through how much encouragement people give to others on this forum is very helpful.

My last biospy in 2005 was stage 1 grade 1. I did 14wks of Pegasys then but was non-responder. I'm 48 y.o. male, also HIV+ (stable and undetectable) and otherwise very healthy, eat well and exercise regularly. I've been feeling perfectly fine...at least I was until now :(

Now it looks like possible cirrhosis. I'm really stunned that it has progressed so fast:

SUMMARY
-Fragmented and nodular liver biopsy with at least focal bridging fibrosis
-Chronic hepatitis C with minimal activity (grade 1 of 4)
Comment: Although the degree of fragmentation here precludes accurate staging, the presence of nodular regeneration, focal bridging fibrosis and fragmentation raises concern for underlying cirrhosis.

I'll be starting Infergen+RIbaviran as soon as dr gets insurance approval.
How reversible is this likely to be - if I respond? And what else can I do to take care of myself? (I dont drink alcohol at all).

[Upbeat]

you might want to look into the new pi's comming out.  If you were a non responer before,  the odds of you responding now with a worse biopsy reading is not good.  Like I said check out the new pi's

[Bill1954]

I’d personally put quite a bit of weight into the fact that the samples were fragmented; I understand that staging is difficult in this situation. The only definitive thing I read into that is that you at *least* have focal bridging fibrosis.

If frank cirrhosis is present, it’d very likely be apparent in biochemical markers such as INR, platelets, albumin, things of that nature. While possible, it seems hard to imagine that fibrosis would advance that quickly; even with the HIV comorbidity.

I’m personally unaware of any advantages that diet might afford other than the obvious; well-balanced meals perhaps following a structure such as the American Heart Association… something like that. Heavy with veggies, plenty of fiber….

Welcome to the discussion group, by the way. It sounds like you’re a survivor right off the get go; nice to hear you have the HIV well managed.

I don’t blame you for wanting to get something started treatment wise right away… you are familiar with the HCV protease inhibitors and their current development timelines? If you haven’t discussed this with your doctor, it might be good to do so prior to initiating Infergen therapy… that stuff has a rep for being pretty demanding.

Good luck; before you get worked up into too much of a lather over that report, I’d have a qualified doctor review your recent labs; CBC and Comprehensive Metabolic Panel and see if it even corroborates cirrhosis.

Best to you—

Bill

[copyman]

bill is right. if you have cirrhosis then your blood test should have some abnormilities. If I was you I would do some or all of the following:

Have the biopsy slides read by another pathologist

Consult with a Hepatologist (liver specilist) to put a plan together. Personally I would wait for the new PI's coming out in about a year maybe less.

get a blood test called a Fibrosure. This test is not accurate for middle stages of Fibrosis but is fairly accurate for cirrhosis.

If close to boston, nyc, miami or cal then make an appointment with a doctor that has a FibroScan machine to assess liver damage using this non-invasive test.

Best of luck

[newleaf09]

To expand on Bill's comment: the liver produces albumin and clotting factors.  If there is extensive liver damage, albumin may be low and clotting time would be too long (INR compares clotting times of PT & PTT).  Bilirubin may be high because the liver is not functioning well enough to excrete it into bile as it should.  Glucose, triglycerides and cholesterol are also made in the liver and its malfunction will make those low as well.  AFP is frequently out of range with cirrhosis.  Liver is also involved in platelet production, so they'd be low with cirrhosis.  Look at your bloodwork numbers and see if the numbers agree with the biopsy staging.  

It's possible to have more severely damaged areas in the liver that just happen to be the spot they sampled, with other areas functioning fairly well.  Look at the bloodwork.

[boink_LA]

Thanks for the responses. My doctor did mention that the blood test results seemed to indicate a problem as well, and specifically mentioned the platelet test. I don't have a copy of the bloodwork but could certainly get it.

My doctor is a well-respected liver specialist (Saab) at UCLA here in LA, so it's not that I feel that I'm not getting good care or don't have a qualified doctor now.

I'm aware of the protease inhibitors currently undergoing trials but can not get them now (all current trials are closed) and don't think this is something that can wait for a year...or more. The doctor advised not waiting as well.

But I just can't believe it. I'm suddenly filled with fear every day. That's the worst part right now.

[willing]

sorry about the fear, please be encouraged by the fact that there are many here with cirrhosis of whom several have gone to SVR. It will take up a chunk of your time and energy. Having a good Dr. is key. If he suspects cirrhosis he probably won't want to do another bx, but there are other reliable indicators. Fibroscan machines are hard to come by on the west coast, but the Fibrosure is easy. Also an ultra sound can detect abnormalities in blood flow - make sure to ask for measurements of portal vein and spleen diameter as these are good diagnostics. You'll want to get copies of all your blood tests and get familiar with monitoring changes in  key cirrhosis indicators (platelets/bilirubin/INR/albumin) as well as those affected by tx (Hgb, neutrophils, etc) Progression from stage 1 to 4 in 5 years is very unusual. Starting ASAP seems a good strategy. Make sure to ask about adding NTZ/ALINIA to your tx. It's an existing approved drug that can make a hefty contribution to your success odds :  here's a recent report from EASL

http://www.kenes.com/easl2010/Posters/Abstract130.htm

that got a 56% SVR rate in a  mixed patient group

[HectorSF]

Hi welcome.

Usually the diagnosis of cirrhosis is relatively easy… But it appears that the sample of your liver wasn’t large enough to accurately stage your liver disease “the degree of fragmentation here precludes accurate staging”.

You could always have another biopsy done that hopefully would get a better sample. But since you plan on treating again anyway, it really isn’t a necessity to find out how advanced your liver disease is. What is, is. You can’t go back to a time when your liver was healthier. If you achieve SVR your liver disease will stop progressing and over time your liver will repair itself to some degree so it won’t be a possible life threatening issue for you.

You are doing the right thing. Try retreating. If you are again a non-responder you will know somewhere between 8 and 12 weeks by observing your viral load. Remember that the new meds will be coming to market next year.
“Retreatment of previous peginterferon/ribavirin (pegIFN/RBV) nonresponders with telaprevir for 12 weeks plus pegIFN/RBV for 24-48 weeks conferred sustained virologic response (SVR) rates in more than one half of patients”. This is much better than the odds with the current treatments.

"Consensus interferon plus ribavirin can produce a sustained virological response (SVR) in a minority of chronic hepatitis C patients who did not achieve SVR with a prior course of interferon-based therapy, especially among patients those who initially responded but then relapsed, according to a study in the June 2009 issue of Hepatology.
Investigators with the DIRECT study looked at 487 participant who did not achieve SVR with previous treatment using pegylated interferon plus ribavirin, some who initially responded but then relapsed during or after completion of therapy and other who never experienced a substantial decrease in HCV viral load during treatment.
Participants were assigned to receive consensus interferon (245 patients at 9 mcg/daily and 242 at 15 mcg/daily) or else no further treatment. Consensus interferon is a manufactured product that contains common sequences from multiple other types of interferon.
Results
Overall, about 7% of patients in the 9 mcg consensus interferon group and 11% in the 15 mcg group achieved SVR.

Sustained response rates were higher among participants who were prior relapsers rather than never-responders.

Response was also more likely among participants with lower baseline fibrosis scores.

Previous relapsers who experienced at least a 2 log drop in HCV RNA during their prior course of treatment and who did not have cirrhosis had the highest SVR rate, at 32%.

"The present study demonstrated that some patients with chronic hepatitis C who have failed to respond to treatment with [pegylated interferon] and ribavirin can be successfully retreated with daily [consensus interferon] and ribavirin," the study authors concluded. "The greatest SVR rate during retreatment in the present study was observed in [cirrhosis stage] F0-F3 patients who had a partial virologic response during their prior course of treatment."
7/17/09

Remember to stay away from alcohol and any drugs that may harm your liver. NSAIDs, aspirin, etc.

Your managing your HIV and you will be able to manage HCV by applying yourself as you have done before.

Good luck with your retreatment!
HectorSF

[willing]

I know this decision leaves you between a rock and hard place, but I would think twice before planning on adding one  of the 1st gen PIs (telaprevir or boceprevir). As a non-responder your odds with re-tx on  plain ifn aren't great (though you may be able to arrest/slow progression). As Hector points out these odds can be improved with a PI, but they are still not that great:

"The rates of sustained virologic response among patients with no previous response were 39% in the T12PR24 group, 38% in the T24PR48 group, and 11% in the T24P24 group, and the rates among patients with a previous relapse were 69% in the T12PR24 group, 76% in the T24PR48 group, and 42% in the T24P24 group. In the PR48 group, the rates were 9% among patients with previous nonresponse and 20% among patients with a previous relapse."
from the recently published NEJM summary of the PROVE3 data
http://www.ncbi.nlm.nih.gov/pubmed/20375406

So, as a NR, with the PI you're looking at 40% odds and  9% without. The trouble is that a failed tx with the PI will increase your resistance profile, making the drug less effective if you need it for another try.

One of the lessons from HIV is that serial anti-viral monotherapy is not a good idea. The FDA is holding a hearing later this month to consider widening access to direct acting antivirals (DAAs). Your case seems a prime example of someone who should have access to one of the polymerase inhibitors still in Phase IIb testing (eg r7128) at the time they start tx with a protease inhibitors (telaprevir or boceprevir). Bringing that hearing to your Dr's attention and seeing if he would be willing to submit a request on your behalf might be a good idea.
Good luck.

[HectorSF]

I agree with willing, you should try to find a retreatment that will give you the best odds of eliminating the virus.

I my own case I am probably running out of time, as I have started to signs of decompensated cirrhosis over the past 9 months or so. I hope to try one more retreatment before I no longer have the option retreatment. If I can hold on for another year I figure I'll have a chance to retreat with Telprevir+pegint+riba. To me the 40% vs.9% looks good."Beauty is in the eye of the beholder". ;-)

boink_LA, since you haven't indicated that you have experienced any signs of decompensation, even if your liver disease is stage 4 (assuming the worst), your liver appears to be well-compensated and could remain that way for many years. This will give you the opportunity to try multiple HCV treatments if you need to do so, before having to use the fallback option of a liver transplant.

Good luck boink_LA. Let us know what happens.

Cheers.
HectorSF

[willing]

sorry to hear about the rough going. You've helped so many here, it would be good to try to return the favor.  All I can think of is contacting can-do about a consultation with his Dr. As I understood it, he specialized in working with cirrhosis in applying the latest round of Boce  testing. At a minimum he might be able to supply an informed opinion about access.
All the best.

[Lonestar823]

There are a few of us here who have treated successfully with Infergen.  I am one of those. There are six other members who no longer post who have also achieved SVR.  They would be Tallahassee, Trigger, Captain , Deb, Flyboy and Joe Mc.   Maybe there are others but I don't know of them.  Two members using Infergen have posted recently.  One is in week 30 and undetected since week 4 and managing okay. The other also EVRd but stopped due to side effects at week 12.  There are many posts of members who quit due to side effects.  

Infergen can be  a viable option for others who have been able to tolerate the other treatments without clearing. Even under the best of circumstances though, those people choosing to follow the infergen path should recognize the real possibility that they may be facing the most difficult mental and physical fight of their life, but not always.

There aren't a lot positive posts here or anywhere that I am aware of regarding Infergen, so I feel it's important to post the successes.  It kicked the butt out of my virus, vl 17,600,000 to start, 1350 at twelve weeks,  but, yeah, it was a battle.  One I'd do all over again if I had to.  

My very best to you,

LS

[HectorSF]

I've got one of the best doctors in the country. Norah Terrault at UCSF's Liver Center, a liver specialist who is recognized internationally for the treatment of viral hepatitis and liver transplantation. Her research includes the study of viral hepatitis and its progression and treatment, especially in liver transplant patients. She leads HCV clinical trials at UCSF.
You can Google her and find videos of her teaching other docs about the latest development in Hep treatment.
"Update in Treatments for HCV" First Aired: 3/12/2009
http://www.uctv.tv/search-details.aspx?showID=15736

She's been helping me manage my symptoms with different meds. Lactulose and rifaximin for HE, diuretics for edema and ascites, Nadolol for portal hypertension.

I treated with peginter and riba under her guidance and she knows I'm a fighter (after about 6 weeks of 12 weeks as a null responder I was bedridden and pretty much a zombie) so there is no issues about getting on the transplant list.

She is looking after me on a regular basis know. I can email and receive answers within a day. Vs in the past when I was seen 2x per year when I was stable.

I am waiting to see how things go in the next month or so. Hoping I can stabilize again.
I will let you know how things develop.

I appreciate your concern very much.
Thanks for writing and your comments and suggestions. I will keep can-do-man in mind.

Cheers!
HectorSF