Biopsy not always accurate

I am new to the forum and I am very happy that this source of information is available. My husband was diagnosed with hepatitis C 2 years ago. He tried to apply for life insurance, and blood test revealed hepatitis C. He is 47 years old. I wanted to tell what happened to us. Maybe this will help somebody else.
Of course, it was a shock when he was diagnosed. He never used drugs or had blood transfusions. We think he was infected 25 years ago in the NAVY-he told me that they immunized long line of recruits with the same air-jet device, and blood was flowing. We immediately went to hepatologist for testing. His labs were pretty much normal, ALT/AST slightly up. He never had any symptoms at all. Hepatologist convinced us to do biopsy. He said it is golden standard of the diagnostics. I was scared to death of this procedure, but we decided to do it, and everything went OK-no problems. The result was great-stage 1, minimal fibrosis, minimal inflammation. We were very happy and decided to postpone treatment and just do monitoring every 6 months. Doctor did not suggest any other tests.
Well, a few months ago he started having disturbing symptoms-severe skin itch, weakness, indigestion, light stools, dark urine. Labs show ALT/AST in 200 range, platelets just slightly below normal (136), bilirubin was 3.0 at one time (it fluctuates lately). These symptoms appear periodically, then go away and labs temporarily normalize. He also lost 15 lb in the last 6 months.
When all of this happened, the doctor finally ordered ultrasound. It showed diffuse increase in liver echogenicity and mildly enlarged spleen. Now they tell me-and I uinderstand it pretty well myself-that it may be advanced fibrosis or cirrhosis. But I have extensive medical education, I saw cirrhotic liver in a lab, and I know that progression from stage 1 to cirrhosis can not happen in 2 years. It is a long process. The biopsy missed correct diagnosis. I doubt that it can be called a golden standard after what happened to my husband, though it does provide some valuable information in some cases.
I would recommend to anybody who is newly diagnosed and gets encouraging biopsy results not to be complacent and to request ultrasound-just to be sure. It is beneficial to combine the results of several tests together and to see the big picture. If he would have ultrasound 2 years ago, it would definitely show enlarged spleen and echogenic changes. Maybe this would raise some susupicion about condition of his liver. I think, it is important to have a test that can assess the entire liver instead of just a tiny piece. The doctor should have known this, but we learned the hard way instead.
Again, I am very happy to meet you all. I read this forum every day, and I learned a lot. Thank you for listening.

Tanya

[hopeforall108]

according to some new studies done recently that pcr s done on biopsy tissues may not always be very accurate either because medics now think that parts of the liver my now not harbour viruses so the can show clear for hcv when another part of the liver might still be infected

[Jenny_Penny]

I'm sorry this happened to your husband. I don't know what the answer is. There is approximately a 30% sampling error on liver biopsies but it is the best we have. People who are not treating should probably have a liver biopsy every three to five years. Serial biopsies give a better indication of what is going on. Also coupling the biopsy with one of the non-invasive blood tests for fibrosis may be a good idea too. I am not as sure that ultrasound would be a benefit. I have cirrhosis and my ultrasound is fairly normal.

I hope your hubby can treat and get rid of the virus and doesn't have to worry about this any more.

[tashka]

Yes, it looks like my husband is one of  this 30%-and it is pretty large number of mistakes. I agree with you that it is better to do several tests instead of just one-be it biopsy or ultrasound. It is great that your ultrasound is normal. I kind of hold some hope that my husband's mildly enlarged spleen is not a sign of portal hypertension. Maybe it was always enlarged-there was no baseline ultrasound. Maybe I am in denial. Nobody suggested any blood tests for fibrosis, and I just recenly learned about Fibroscan, but don't know where and how to get this test.  
Treatment is a complicated matter. He has genotype 1, high viral load.  And there are other factors that make 48 weeks of brutal treatment impossible right now.
If I may ask, do you have any symptoms?

[newleaf09]

The fact that his labs changed so very much in 2 years (from normal to signs of liver failure) makes me wonder if his original biopsy was not too far off.  There is genetic variation, person to person, in how fast fibrosis progresses.  It's just so unpredictable.

I have cirrhosis and just finished TX.  All of my bloodwork is normal except PT/PTT.  I was quickly diagnosed last fall and lucked right into a trial.  I think I had most of the damage from taking high doses of naproxen sodium (aleve) for back problem.  Before I stopped drinking and taking the naproxen, I had poor clotting, huge bruises I could not account for and just before the naproxen finally got out of my system I spent 3 days itching like crazy.

Look up every non-food substance that goes into your husband's mouth for potential liver damage among the less common side effects.  Look up everything that touches his skin or ends up being breathed in.  No alcohol.  Get him walking a little.  If his failure symptoms subside he will hopefully be permitted to treat.  Good luck.

[tashka]

The only thing I can think about is this past year he had many infections-boils, sore thought, bronchitis-and took multiple courses of antibiotics. He absolutely doesn't drink and never did. He feels OK, works, exercises, has a lot of energy. His albumin, total protein, alkaline phosphatase, GGT are all normal. ALT/AST/bilirubin fluctuate. He has no edema and no bruising/bleeding problems.
Thank you for your response and advice.

[Jenny_Penny]

First, sorry I got your name wrong. To answer some of your questions about my particular story.....I was diagnosed with cirrhosis in 1991 and treatment never worked on me. So you can see that people can live a very long time with stable cirrhosis. My symptoms are some fatigue but actually more like a lack of stamina. I'm not tired and I don't want to sleep more than is normal but I don't have the energy to do many things that my friends and colleagues can do. I also have had over the last 10 years a lot of joint and muscle pain. My spleen has been enlarged since my first ultrasound in the early 90's. My platelets are a bit low. But again, I am here enjoying my life and I hope your husband does as well as I have been doing.

With all due respect, if your husband's doctor feels he should treat now, I hope you can make that happen. With a possibly rapid progression, I'd hate to see him try and wait.

[tashka]

It is very encouraging to know that you are doing so well-I would say incredibly well. Even without successful treatment! Thank you so much for responding. Nothing is written in stone, and we might reconsider treatment decision. But right now we want to try some alternatives and just see what happens. We did nothing at all during this 2 years, because there were no symptoms whatsoever. Thank you for your concern. Right now all of his symptoms are gone, and we will have labs done in July.

[Jenny_Penny]

Alternatives do not work. In fact they can mask symptoms so the patient thinks they are better. If your husband is progressing as fast as it appears, he needs to treat now if his doctor approves.

[Bill1954]

Tashka, one of the problems with waiting at stage 4 is that as platelets decrease, so do the chances of treatment. With platelets at 136,000 he can treat now; but if they fall below 70,000 some doctors will begin excluding him from treatment. IFN can suppress platelet production as well as the liver disease itself, and there currently isn’t any intervention for this.

No one is trying to make decisions for you both, but beware that the clock is ticking.

I had late stage 3 per biopsy in January 2005 with splenomegaly; I treated aggressively two times since then and finally achieved SVR. I was told by my doctors that I had most likely progressed into early cirrhosis since, but avoided transplant by treating the disease.

Good luck to you both,

Bill

[FlGuy]

Did he have a second biopsy? It wasn't clear to me.  You might also consider that it may not have been the biopsy, it may have been the pathologist.  The slides should be available to you.  Have they been re-analyzd by someone else?  

In agreeing with Bill I'm wondering about "are other factors that make 48 weeks of brutal treatment impossible right now".  There are some factors that trump others. And, have all other possibilities other than advanced liver damage been ruled out?

Many people advance to cirrhosis without the disturbing symptoms that you listed.

[tashka]

No he did not have second biopsy. They just watch him now-what will happen to his labs.
His doctor is puzzled and says that with such great biopsy he should not have these symptoms.
I don't see the point of doing yet another biopsy. If this is advanced liver disease, this will be apparent from his symptoms.
I didn't see slides, but I have a description and it looks great. Minimal inflammation confined to just a few portal tracts. No necrosis. Fibrosis is also minimal and confined to just a few portal tracts. Liver architecture intact. Adequate sample size-3.5 cm. I don't think this can be confused with advanced liver damage. Nobody reanalyzed the slides.
I understand that many people progress to cirrhosis without disturbing symptoms-or any symptoms at all. But can hepatitis C patient show the symptoms that he has and NOT have advanced liver disease? That is what I wonder about. What can be other possibilities that you think should be ruled out? His doctor wants to consult some other hepatologists that he knows. I want to be on top of all this.
Thank you very much for responding.

[FlGuy]

I don't have any alternate theories for you, it's certainly not my realm. As you seem to achnowledge it doesn't seem to matter where his liver was it more a matter of where it is now.  Assuming it's advanced and is stage 3 or 4 then I'd assume that the position that "there are other factors that make 48 weeks of brutal treatment impossible right now" may change as well.  As you point out, treatment is complicated and brutal. Not to make light of the situation but treatment is tougher for sick people.  And, you cannot assume that it's just a matter of 48 weeks of treatment and then 'done'.  Bill 1954 when through two treatments of 72 (I think) and 96 weeks.  I did it twice too. So, if continued investigation reveals more damage than currently known, there are decisions to make. Good luck.

[tashka]

Thank you for being truthful and upfront about treatment. I uderstand that our situation is difficult and really there are no good solutions and no easy decisions. I know how difficult and dangerous treatment is, and I am sure that with his genotype and viral load he will probably need more than 48 weeks.  He will be closely followed up, we will consider all our options, and decide. We will watch his platelets and other labs. Maybe we will do some non-invasive test to assess his level of fibrosis.
Thank you again.

[nygirl7]

Please find a doctor who will consider another biopsy right away.  Either through error or just a terrible chance at a very virulent virus strain if he is indeed stage 3/4 it's time to take matters into your own hands and get proactive.  Like the guys said above treatment doesn't always work out the way you'd imagine it is going to and you need to have time to come up with plan B if he does not succeed.

Are you going to a very top heptologist? I would get a second opinion at LEAST from the best doctors you can find (I had to pay cash for it but it saved my life in the end).

The docs should have originally done both biopsy and ultrasound - perhaps if they did what is pretty standard you'd have a better idea now if the slides were read incorrectly somehow or if his information got switched with someone else or if indeed in two years he has progressed that far. If the later is the case.......you need to get him into aggressive treatment NOW.

Good luck, I"m sorry for your horrible set of circumstances.

[newleaf09]

His labs exhibit classic symptoms of early cirrhosis c (compensated) moving towards late stage (decompensated).  The itching and dark urine are caused by the inability to clear bilirubin through normal channels.

It no longer matters about the slides from the original biopsy (you can't turn back time anyway).  Personally, I don't think a second biopsy is even required with such clear physical symptoms and labs indicative of cirrhosis.

There is a thin line between compensated (early) and decompensated (late stage liver disease).  If at all possible, he really needs to treat and soon before he starts to decompenaste.  Crossing over to decompensated (variceal bleeding is the worst of that but it's all bad) may mean he is too sick to treat and looking at numerous hospitalizations just to manage the complications of advanced cirrhosis.  There is really no turning back once he decompensates.  He could get on the transplant list but if virus is still in his blood it will reinfect the new liver and shorten his life.

I don't mean to be frightening, but I have cirrhosis and these were all serious considerations that I went through before deciding to treat.  I don't think it's safe to watch and wait.

[willing]

it's hard to say whether (a) the initial slides were misread (b) the sample collected was not representative (though size seems adequate) or (c) there was unusually rapid progression. However, as newleaf points out the most important aspect seems to be confirming a diagnosis of advanced fibrosis, if that is in fact the case and considering treatment. To confirm, some of the following may be worthwhile  :  a serum-based test (fibrospect/fibrosure) which would at least rule out the F1 on the off chance observed symptoms are due to another causet; a fibroscan, though if you're in the US there are only 4 research centers with equipment (Boston and Florida are two); explicit measurement of portal vein diameter and spleen size from the US; checking for varices and other signs of cirrhosis via endoscopy. As far as tx options, the currently recruiting R7128 trial (id  NCT00869661 on clinicaltrials.gov) is likely one of your best options. Severity of fibrosis does not appear to be an exclusion criterion, it's a very promising drug candidate and unfortunately the phase III  trials for tx-naive of the two major PIs are no longer recruiting.

Until all the results come in it would be premature to be alarmed. On the other hand, of the options above (c) seems the most likely and if progression has been that quick tx sooner rather later seems advisable.

Best wishes.