An unexpected result? qHBsAg and severity of fibrosis

[StephenCastlecrag]

The following research shows how difficult it is understand the complexity of Hepatitis B disease.

Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naïve, e antigen-positive patients

    Michelle Martinot-Peignouxa, Corresponding author contact information, E-mail the corresponding author,
    Roberto Carvalho-Filhoa,
    Martine Lapalusa,
    Ana Carolina Ferreira Netto-Cardosoa,
    Olivier Ladaa,
    Richard Batrlab,
    Friedemann Krausec,
    Tarik Asselaha,
    Patrick Marcellina

    a Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), INSERM U-773 and Service d’Hépatologie Hôpital Beaujon APHP, Université Paris-Diderot, 92110 Clichy, France
    b Roche Diagnostics Ltd., Forrenstrasse, 6343 Rotkreuz, Switzerland
    c Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany

    http://dx.doi.org/10.1016/j.jhep.2013.01.028, How to Cite or Link Using DOI

    Permissions & Reprints

Abstract
Background & aims

Little is currently known about the association between serum HBsAg or HBV DNA levels and the severity of liver disease in chronic hepatitis B (CHB) patients. Therefore, we investigated these relationships in a large cohort of unselected, well-characterized, treatment-naïve CHB patients.
Methods

CHB patients were assessed at the Hôpital Beaujon in Paris, France, between 2000 and 2008. Serum samples and liver biopsies were obtained on the same day. HBsAg, HBV DNA, and HBV genotype were investigated using commercial diagnostic assays and liver histology was scored using the METAVIR system.
Results

406 patients were included in this cross-sectional study. Serum HBsAg and HBV DNA levels in hepatitis B e antigen-positive (HBeAg[+]) patients showed strong correlation (r=0.44, p<0.0001), as did serum HBsAg levels and fibrosis severity (r=0.43, p<0.0001). HBeAg(+) patients with moderate to severe fibrosis exhibited significantly lower serum HBsAg and HBV DNA levels compared with patients with no or mild fibrosis. Modeling analysis suggested a serum HBsAg cutoff of 3.85 log IU.mL−1 would provide a theoretical sensitivity of 100% (95% CI: 0–100), theoretical specificity of 86% (95% CI: 50–100), and a negative predictive value of 100% (95% CI: 67–100) in HBeAg(+) patients infected with HBV genotype B or C.
Conclusions

We found an association between low serum HBsAg levels and moderate to severe fibrosis in HBeAg(+) CHB patients. Furthermore, we describe a serum HBsAg cutoff for the prediction of fibrosis severity in CHB patients infected with HBV genotype B or C.

[StephenCastlecrag]

I have no access to the full paper and therefore can only give you my guesses. It was a retrospective study, I guess most of the patients in the cohort have genotype B and C, which makes sense because they are most likely to be Asians, infected at birth and maybe in the immune clearance phase when they presented at the hospital.
In Europe, most indigenous patients have genotypes A and D, and are infected as adults. I believe most of them would go straight to the immune clearance phase which tends to be shorter for them.

Whatever the explanations, I think the key point, as Stef2011 said, is don't rely on a single bio-marker and its reading at a single point in time to base a diagnosis or prognosis. A history and/or comprehensive set of tests are more accurate.

[CoWriter]

"i think this is can be explined by the immune attack on hbv, when still hbeag positive hbsag is very high usually, probably some are able to lower it by a strong immune attack which also makes more damage to the liver "

But if that is true then it would happen to all genotypes, not just two.  

Would you happen to know which genotypes were included in the study (besides B and C)?

Interesting post, thank you.

Co

[rosy888]

"hbeag negative patients are very different, most have bcp/precore (which is not correlated to chronic or inactive carrier), low hbsag, higher firbosis already than hbeag pos"

why they generally have low hbsag? similar to generally having low DNA count?

also, can mutated virus be measured when checking virus DNA? are anti-virus drug effective on mutated virus?

[stef2011]

in general very low hbsag less than 500-1000iu/ml on hbeag neg is less fibrosis, no replication, slow hbsag clearance, less hcc risk

[stef2011]

hbeag negative patients are very different, most have bcp/precore (which is not correlated to chronic or inactive carrier), low hbsag, higher firbosis already than hbeag pos

[smile_boy]

But they Didn't talk about HbeAg Negative patients.. :(

[OrientS]

it is a complicated issue!

the very difficult disease that you can not  foresee what will happen is hepatitis B.

i am naive-treatment on entecavir .5 mg since September '12 ..
i hope during few coming months we will hear about the big discovery either in west of the earth or in the east of the world that some person found a chemical compound that can kill hbsag in 5 days without any side effects .. and we will give him a Noble Prize ..

[StephenCastlecrag]

That is my initial thinking too. It should be able to be confirmed by knowing the ALT and age. In truly immune tolerant patients, the hbvdna should be high and may be so will be the qHBsAg.

[stef2011]

i think this is can be explined by the immune attack on hbv, when still hbeag positive hbsag is very high usually, probably some are able to lower it by a strong immune attack which also makes more damage to the liver

this study shows that all tests are necessary too to have a clear picture, not just hbvdna, ast-alt and a baseline biopsy like they do in US and some other countries