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should I do a biopsy?
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should I do a biopsy?

Dear All,

I am a 30yr old male and had HBV positive for more then 15 yrs (HBV E negrative). I had some liver function and DNA test recently.

On July 12:
DNA: 7411     reference: <357 IU/ml
ALT:   49        reference: 0-41 U/L
AST:  29         reference: 0-40 U/L

I then changed a to a Hepatologist:
On Sep. 11:
DNA:  575        reference: <100 IU/ml
ALT:   65          reference: 0-65 U/L
AST:   23          reference: 0-50 U/L
Genotype:     C
Ultrasonic: everything looked fine

The Hepatologist suggested a liver biopsy, and I declined at that time asking for waiting on next test:

Then On Nov. 27:
ALT:  64           reference: 0-65  U/L
AST: 30            reference: 0-50 U/L
I am still waiting on the DNA test results, and will have an appointment with my doctor in 2 weeks.

My question is:  is my ALT elevated since the test in July, the absolute value is higher, but the second lab seems have higher reference value 0-65 versus 0-40, I am wondering if they are using a different test method or something. Since my value is within the reference range now, am I getting better? My genotype C result concerns me the most,  should I do a biopsy if the doctor recommend again? I dont really want to do it if not necessary since I thought I am getting better.  If I do start antiviral treatment, with the DNA at low level, will the treatment be effective???

Thanks for your help and information, I am really concerned here. Thanks!!
20 Comments Post a Comment
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Avatar_m_tn
I would wait for the result of the DNA test before deciding whether to have a biopsy or not.

The change in "reference range" is not necessary a change in the testing method. Reference Range for ALT is determined by statistics: they measure the ALT of a big sample of the general population, and a reference range is usually defined as the set of values 95 percent of the normal population falls within (that is, 95% prediction interval).
Research indicates the reference range for ALT should be:
0-30 for male, and 0-19 for female.

You are correct, if your DNA is < 2,000 iu/ml, treatment is not recommended in all guidelines. For persistently elevated ALT, you may like to see whether you have fatty liver.  
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Avatar_m_tn
You can do fibroscan before deciding about the biopsy. Sometimes it is even better for fibrosis monitoring.
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Avatar_m_tn
Dear StephenCastlecrag,

thanks for your comment. I just got the DNA result today, it's 730IU/ml, so I think overall, my condition seems pretty stable, the results are almost identical to 3 months ago.

I am also suspecting fatty liver, but my ulstrasonic results three months ago was good. I didnt exercise regularly though. Maybe I should start work out regularly and see what happen after another three months?

For the ALT reference value, is there any difference with testing equipment and/or reagents? It's just alittle confusing, since even if they sample a large population, the normal range should be similar for a certain region, right? I generally do see 40 as ALT upper limit, but and it's the first time I saw 0-65 as the reference range, this hospital is a hepatology special clinic, so I dont know if that makes any difference.

again, thanks for the reply!
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Avatar_m_tn
Dear Rome70,

Thanks for the suggestion. Unfortunately, fibroscan is somehow not available in the U.S.  My doctor said biopsy is safe, but I would like to do it only when it's necessary since this procedure should not be done in a regular base.
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Avatar_m_tn
I've seen ALT 65 U/L from some labs, so it is common, though 40-45 U/L is much more common
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Avatar_m_tn
Yes, your dna is stable and because it is  less than 2,000 iu/ml, there is no need to treat according to all guidelines.
In the past, the sample to determine the reference range came from the general population and it included people with or without liver diseases. So in an area where you have a high prevalence of Hepatitis B or obesity, the upper normal limit (ULN) would be pushed up. So, scientists believe the reference range should only be determined from a sample selected from a healthy population. As far as I know, the reference range is independent of testing equipment/reagents. However, ALT can change between day and evening. People with fatty liver can have elevated ALT.
Biopsy is usually done once to establish a baseline record and to determine whether treatment should be initiated.
I don't know why Fibroscan is not yet publicly available in the US, it is certainly well known and well regarded by liver specialists.
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Avatar_m_tn
I do not get this guidelance from EASL. It seems with low viral load below 2000 iu/ml long term chance of getting cirrosis (cirrhosis) is low because it will take decades with such low viral load to severely damage liver. But what about risk of getting HCC without cirrosis (cirrhosis)?

Acc to studies undetectable DNA reduces chance of getting HCC by 73%. So why monitor if it is less than 2000 iu/ml?  You need to make it undetectable then add at least three cups of coffee per day, blueberry and visit your doctor for monitoring you liver while waiting for replicor or myrcludex to get final cure.

http://www.hbvadvocate.org/news/HBJ8.7.htm



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Avatar_m_tn
Good points. I am not an expert, so these are just my personal opinions. Liver cancer can occur with or without HBV, and if you have HepB, it can occur with or without cirrhosis. So why is HBV a risk factor HCC and why HBV + cirrhosis  is a very significant risk factor for HCC?
HBV is a risk factor for HCC because the virus can incorporate itself into the liver cell DNA. I believe this incorporation takes place when an infected liver cell divides. So a high viral load, reflecting a high pool of cccDNA is available for incorporation, predisposes to HCC. But the risk of incorporation is greatly increased if we also have increased infected liver cells divisions. Also, generally, increased cell divisions increases risk of cancer because of dna mutations during cell division. Cell divisions are increased by chronic inflammation and lead to fibrosis and cirrhosis. So, I think you do not need a zero viral load to reduce the risk, you just need a low viral load that does not cause inflammation (as indicated by normal ALT). So I believe undetectable DNA reduces chance of getting HCC mainly because it reduces inflammation.
Research also indicates the HBV X-protein may be associated with HCC, and that cirrhosis separately promotes HCC because of the dis rupture of the liver architecture.
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Avatar_m_tn
Another report just released indicates that aspirin decreases the risk of HCC and liver disease.

http://www.examiner.com/article/aspirin-may-reduce-risk-of-liver-cancer-heart-attack-and-embolic-stroke
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Avatar_m_tn

HCC risk is mainly pushed by fibrosis degree than virus hbvdna, according to latest studies fibroscan higher than 8kpa and hbsag higher than 1000iu/ml on hbeag neg increase chances for hcc

simvastatin, vitamin e (the natural one, not the synthetic), fish oil omega 3, cofee, metformin (a diabetes 2 drug).normal sugars/no insuline resistance/no fatty liver are also all good to prevent hcc.it looks like hcc is pretty linked to oxidative stress and sugar/lipid unbalance in the liver which is triggered by our immune system failing to clear hbv (so it is linked indirectly to hbv)

the 2 highest risk for hcc are diabetes, diabetes+hbv, diabetes+hbv+fatty liver+insuline resistance.....and at last hbvdna level, infact having hbvdna und does not prevent hcc just reduce chances

i mean do not focus on virus only but on sugar/lipids/fatty liver, insuline resistance, oxidative stress first (in a word healthy life style) and only secondly to hbvdna, hbsag, ast/alt.simvastatin, metformin, fish oil can cut risk of 30-50% so check these parameters and try to keep them in check naturally if possible
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Avatar_m_tn
Stef, can the 48 week course of interferon also improve liver histology? By how much according to Metavir grade?
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Avatar_m_tn
hi, djxpress,

do you know what made the difference? I think what StephenCastlecrag mentioned makes sense, but the thing is the two hospitals I did my tests are in the same region, for healthy population, I assume the ALT range should be the same given that same equipment and assay were used.
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Avatar_m_tn
Hi stef2011,

thanks alot for the reply. For my situation, do you think I should start anti-virus treatment? As I remember, entacavir had very slight chance of HCC as well, right? I just dont know what to do if the biopsy verified that I do have some fibrosis going on.
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Avatar_m_tn
Hi StephenCastlecrag,

I am also very disappointed on the lack of fibroscan in the U.S. We are definitely behind other developed countries on HBV patient treatment. Honesty, I am just scared about the biopsy since I wont know what to do if the results are not good. Starting anti-virus treatment? but my DNA is very low already, how can that help?  Do nothing? my liver is being damaged....
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Avatar_m_tn
It is now known that fibrosis/cirrhosis can be reversed when the underlying Hepatitis B is treated, so it is nothing to be afraid of. Personally, I don't think your doctor will insist on a biopsy, as your dna is < 2,000 iu/ml. There are other non-invasive assays for fibrosis, such as FibroSure. Ask your doctor.
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Avatar_m_tn
i am also in the U.S. with no fibroscan.
my doctored ordererd an MRI to check for liver cancer.
you should do MRI or CT scan before doing biopsy.
ultrasound is also good but does not give you as much detail.
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Avatar_m_tn
MRI and CT with contrast liquid make kidneys damage, although healthy kidneys can recover it is not a no damage test 100% so it is best to use a good ultrasound machine which can detect nodules as little as 1mm and go for ct scans/mri only if there is a nodule which can be maligne

i am monitored in one of the best research center and we use US even if i was cirrotic (not anymore), if Us has so much snesibility and is repeted every 4months it is very difficult to miss changes.

of course mri/ct is superior but not 100% free of damage.....also do check that doctors are not prescribing the most expensive test just to rip you off extra money
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Avatar_m_tn
There is a big difference between imaging for fibrosis and imaging for cancer. MRI is of course excellent for detecting liver cancer, far more accurate than ultrasound. The only downside is that it is expensive. Knowledge of fibrosis and degree of necrosis and inflammation are mostly used to determine whether treatment is needed.
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Avatar_m_tn
Forgot to say, fibroscan cannot detect cancer or any leison at all. It just measure the stiffness of the liver.
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Avatar_m_tn
Finally talked to my doctor today. He suggested me to do nothing for now since the viral load and ALT look stable. Asked to check up every three months, and so ultrasonic every six months. No need for biopsy for now. I actually feel pretty released now, will keep exercising and eating right... Good luck everyone.
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