HBV DNA = 2498, Normal ALT/AST - Should I keep monitoring or get a biopsy?

[itac]

Hi guys, Merry Christmas!

Some background: I'm soon 29 years old, chronic hbver with genotype D and negative hbeag. Never been on any treatment.

Since I got diagnosed back in May last last year, these were my measurements:

ALT/AST always normal.

HBV DNA:
05.04.15 - 1311 ui/ml
08.05.15 - 865 ui/ml
11.05.15 - 1317 ui/ml
02.05.16 - 1316 ui/ml
05.06.16 - 1390 ui/ml
11.12.16 - 2498 ui/ml

HBSAG quant
10.01.15 - 2217 ui/ml
08.30.16 - 312 ui/ml
12.16.16 - 2453 ui/ml

My liver ultrasound I did couple of times didn't reveal any problem other than mild fatty liver - Since I'm not fat or eating unhealthy foods, and it's not known that hep b causes fatty liver, the doctor ordered hep c and test for wilsons disease that can cause fatty liver - but both came back negative - so in my case for the fatty liver he said it might be genetic and I should just exercise and keep a healthy diet.

Fibroscan:
06.18.15 - V (m/s) Median 1,13 (IQR 0,05). E (kPa) Median 3,8 (IQR 0,4 IQR/med 11%)
12.24.15 - V (m/s) Median 1,17 (IQR 0,07). E (kPa) Median 4,1 (IQR 0,5 IQR/med 12%)
05.05.16 - CAP (dB/m) Median 189 (IQR 37). E (kPa) Median 3.9 (IQR 0.4 IQR/med 10%)

A side question, looking at these FibroScan results I see that my E (kPa) which is the stiffness is around 4 kPa which I understand is F0-F1 in terms of the fibrosis score. But I couldn't understand what the V value is? I see it got changed in 2016 to CAP, but it's a different measurement unit - Are V and CAP the same? I found online that CAP means it's the fatty liver levels - From what I understand 189 dB/m is considered pretty low in terms of how fat the liver is - but I couldn't find the reference value for it to know what's considered normal and what not, etc. Could you please advise what's the difference between V value and CAP value? And what's the reference range value for each? Also, is there something in the FibroScan test that can ***** the liver inflammation? e.g. A0-A4? I just don't see it on any of the reports, just the values I posted above - is the liver inflammation deducted based on the combination of these other values (V/CAP/E) or is just missing from these Fibroscan tests results?

And now to the the main question - Since there is currently a tendency of the HBV DNA levels to go up, and I'm hbeag-negative - and the levels just break the cutover barrier for treatment in the US for hbe negative which is HBV DNA 2000 ui/ml and mine is about HBV DNA 2498 ui/ml, but the other condition to start treatment is to have elevated ALT/AST levels, which I don't have, so my gi (Gastroenterologist‎) doctor presented me two options:

1.) Continue monitoring the HBV DNA levels, and see if it keeps going up - or perhaps it's just a fluctuation and it will go under 2000 UI/ML again after some time (that's his personal recommendation).
2.) Get a liver biopsy, if there is inflammation , then start treatment.

Personally, I rather avoid a biopsy if possible and/or delay it as much of possible - but I'm aware of the limitations of the accuracy of the elevated AST/ALT levels - the doctor then told me I can get maybe another Fibroscan to see what's the liver inflammation , but given my side question above about liver inflammation not showing in the Fibroscan result, can the liver inflammation be even assessed by the Fibroscan? Or are there other non-invasive ways to tell the liver inflammation? Perhaps liver MRI or a fibro blood test (that I do recall have the A0-A4 values, and from the past I remember it was A0). Or maybe I should go to get a second opinion with another gi/ Gastroenterologist‎ or even better a Hepatologist? What would you do if you were me?

Thanks!

[StephenCastlecrag]

I tend to agree with your doctor to monitor. As you know, the limit of hbvdna = 2,000 iu/ml is not something that is theoretical, it is just a convenient number chosen by researchers in order to classify patients into various groups. These groups are then followed for many years. It just so happened that for patients with hbvdna < 2,000 iu/ml and normal ALT, most of them(but not all of them) after several years, would show inactive disease and minimal progression of fibrosis. But it is generally true that the lower the hbvdna the better the prognosis. Since your Fibroscan score is low, I think you can afford to wait and observe.
I am not aware that Fibroscan can detect inflammation. ALT itself is an indicator of inflammation.The "V" to me seems to indicate Velocity in metre/sec?
You don't need to be fat to have fatty liver, you can also check your cholesterol levels. Drink more coffee, eat more oily fish (or take Omega Oil supplement) may help.

Cheers for the festive season.

[itac]

Thanks for your reply. So I guess the velocity per meters/second is another way for measuring either the stiffness or fatness, but nothing to do with the liver inflammation. I'm surprised the doctor thought that you can measure liver inflammation with FibroScan. Makes you wonder what else he might get wrong.

If biopsy is the gold standard and most accurate to check for liver inflammation I.e 90%?, then what is the next most accurate non-invasive test for it? You said the blood test for ALT, but how accurate is that, 60% or less/more? What about fibrotest (fibrosure) blood test that gives you the a0-a4 level? Or perhaps there is something else? A new technology? I saw there are some new FibroScan variations/liver mri and others but is there anything good out here that is reliable/accurate and doesn't steal your money?

Thanks again and Happy holidays!

[studyforhope]

Inflammation adds to the liver stiffness caused by fibrosis.  As such highly inflamed livers give unreliable information about fibrosis.

But at a rather low level of inflammation, as reflected in normal alt, a small inflammatory component will not influence liver stiffness to a significant degree.

Fibrosure is a reasonably accurate blood test to estimate inflammation and fibrosis, but it is of limited accuracy.

A liver biopsy can best assess actual liver inflammation,  since inflammation is mainly histological defined by the presence of inflammatory infiltrates in various areas of liver tissue. But since Alt gives a rough estimate of liver cell necrosis,  it is very unlikely that a biopsy will find major inflammatory signs in your case.

The progression of fibrosis is individually quite different, even at the same  level of inflammation, thus it is best measured as such, serially with fibroscan or similar elastography techniques.

Hbv dna is a major driver of inflammation and fibrosis, since virions are the best immune stimulators. That is the reason why the dna limits for interventions have come down with time, to better prevent fibrosis and cancer development.

This is not a precise science,  no exact numbers are available and it is up to a doctors skill and the luck of a patient to find a fairly optimal path to proceed with treatment. As antivirals will have lesser side effects, the decision to treat will be made at even lesser threats since the guiding principle is a balance between perceived liver damage accumulation and side effects of the treatment

[itac]

Appreciate your response studyforhope, thanks.

[mike9111]

What  interesting to me is your hbsag quantitative. I didn't expect it to be fluctuating from 2000 to 300 then back to 2000. Was it all measured in the same lab?

[itac]

No, first lab was in Berlin, second lab in Frankfurt and third one in California. As far as I'm aware all 3 are using the same type of machine Abbot. I'm surprised myself how it could go on almost log 1 reduction in Frankurt just to go up again. Maybe Frankfurt got it wrong... I hope quest do it right in the US. Also my dna went up to ~2450 so it's almost like these values are now correlated. Guess I can forget about spontenoues seroconversion anytime near ;-(