Lack of Association between ALT Elevation and Significant Fibrosis in HBV

[4est]

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.
METHODS:
From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis.
RESULTS:
211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥7 or fibrosis score ≥3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2×upper limit of normal (ULN) and >×2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease.
CONCLUSION:
An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold

http://www.ncbi.nlm.nih.gov/pubmed/22389715

[stef2011]

hbvdna alone has no meaning, you need hbsag quant in iu/ml, ast/alt and fibroscan to define hbv status

[Nopatronas]

Hi my HBV DNA Quantative came positive and is 41,500 IU/mL it says HBV DNA Titter.

[stef2011]

it was already known high alt, but not too high and for long time, has no correlation with liver damage.it is also well known that cirrhosis regression is also not correlated to alt, and infact my case has abnormal alt (if we take 30 as normal) and ultra fast regression of cirrohosis

but it was also known that low normal alt, epecially in asians, with high hbvdna can make liver damage

since all the results on heptech i tend to thin that oxidative stress made by  immune system and hbv can make much more damage to the liver and activate proinflammatory macrophages and make liver damage with normal alt

we also know that liver damage is not directly correlated with dying of liver cells but to the fact that macrophages that repair liver at a certain point start to fail and inflammatory macrophages with stellate cells start the liver damage

[StephenCastlecrag]

I am just annoyed that they can come up with such a conclusion. It seems to me they base their analysis on a single reading of the patient's ALT at the time of biopsy, wouldn't it make sense to investigate whether persistent high level of ALT is associated with fibrosis?
May be they mean if you measure your ALT, if it is high, you cannot then say you have significant liver damage. But that is rather useless. I once read that when you have cirrhosis, your ALT will not be high because you have less healthy number of liver cells to be damaged.

[4est]

levels of ALT are not associated with "significant" liver disease - I agree with you in interpretation "high ALT does not necessary mean high liver damage" how about normal ALT - it is this corelated with no liver disease ?
I can agree that high ALT does not necessary mean high liver damage in case of fibrosis, we can discuss high ALT from medicine, alcohol, food ...

they somehow relate the liver injury by AST  and platelet.
AST ? ... hmm this is strange

[StephenCastlecrag]

Parts of the paper allured to this, yet it also states that levels of ALT are not associated with "significant" liver disease - that to me seems to say, high ALT does not necessary mean high liver damage. This is contrary to what we  used to believe in.  So what markers indicate liver injury?

[4est]

I agree that this is a complex paper, but is a ppaper that made a warning that therapy (antiviral therapy) should be made using some other ALT thresholds.

[StephenCastlecrag]

This is a difficult paper to fully understand. What is the role of ALT in the management of chronic HepB?