EASL 2012 Guideline

[StephenCastlecrag]

The following is an extract from the 2012  EASL Clinical Practice Guidelines: Management of chronichepatitis B virus infection.
The full guideline is available at:
http://www.easl.eu/assets/application/files/ef520780b91cf4f_file.pdf
Please note: 1 IU/ml = 5-6 genome copies/ml

Indications for treatment
The indications for treatment are generally the same for both
HBeAg-positive and HBeAg-negative CHB. This is based mainly
on the combination of three criteria:
 -Serum HBV DNA levels.
 -Serum ALT levels.
 -Severity of liver disease.
Patients should be considered for treatment when they have
HBV DNA levels above 2000 IU/ml, serum ALT levels above the
upper limit of normal (ULN) and severity of liver disease assessed
by liver biopsy (or non-invasive markers once validated in HBVinfected
patients) showing moderate to severe active necroinflammation
and/or at least moderate fibrosis using a standardised
scoring system (A1). In patients who fulfil the above criteria for
HBV DNA and histological severity of liver disease, treatment
may be initiated even if ALT levels are normal (A1). Indications
for treatment may also take into account age, health status, family
history of HCC or cirrhosis and extrahepatic manifestations.
The need for liver biopsy and treatment should be considered
separately in the following subgroups of patients:
 -Immunotolerant patients: HBeAg-positive patients under
30 years of age with persistently normal ALT levels and a
high HBV DNA level, without any evidence of liver disease
and without a family history of HCC or cirrhosis, do not
require immediate liver biopsy or therapy. Follow-up at
least every 3–6 months is mandatory (B1). Consider liver
biopsy or even therapy in such patients over 30 years of
age and/or with a family history of HCC or cirrhosis.
 -HBeAg-negative patients with persistently normal ALT
levels (ALT determinations at least every 3 months for at
least 1 year) and HBV DNA levels above 2000 but below
20,000 IU/ml, without any evidence of liver disease, do
not require immediate liver biopsy or therapy (B1). Close
follow-up with ALT determinations every 3 months and
HBV DNA every 6–12 months for at least 3 years is mandatory
(C1). After 3 years, they should be followed for life
like all inactive chronic HBV carriers. Evaluation of the
severity of fibrosis by a non-invasive method, such as
Fibroscan, might be useful in such cases (C2).
 -Patients with obviously active CHB: HBeAg-positive and
HBeAg-negative patients with ALT above 2 times ULN
and serum HBV DNA above 20,000 IU/ml may start treatment
even without a liver biopsy (B1). In such patients,
liver biopsy may provide additional useful information,
but it does not usually change the decision for treatment.
A non-invasive method for the estimation of the extent of
fibrosis and most importantly to confirm or rule out cirrhosis
is extremely useful in patients who start treatment
without liver biopsy (B1).
 -Patients with compensated cirrhosis and detectable HBV
DNA must be considered for treatment even if ALT levels
are normal (B1).
 -Patients with decompensated cirrhosis and detectable
HBV DNA require urgent antiviral treatment with NA(s).
Significant clinical improvement can be associated with
control of viral replication [60–62]. However, antiviral
therapy may not be sufficient to rescue some patients with
very advanced liver disease who should be considered for
liver transplantation at the same time (A1).

[StephenCastlecrag]

You are spot on. I think EASL guideline is more stringent than AASLD, APASL and US as far as threshold levels of hbvdna for treatment are concerned. Yes, a truly inactive hbver is one that has hbvdna < 2,000 iu/ml AND HBsAg < 2,000 iu/ml (or 1,000 depending) AND normal ALT. No doubt these will be refined in years to come.

[veteranB]

"Previous studies have indicated that a lower HBsAg level is associated with better clinical outcomes, including a higher likelihood of HBsAg loss and lower risk of HBeAg-negative hepatitis. In a recent study comparing the prognosis between inactive HBV carriers (viral load <2000 IU/mL) and non-HBV plus non-HCV controls, the 10-year cumulative incidence rates of HCC were 0.6% and 0.2%, respectively. In our study, the 10-year cumulative incidence rate of HCC in patients with HBV DNA level <2000 IU/mL plus HBsAg level <1000 IU/mL was 0.2%, which was similar to the controls. These data suggested that, in addition to HBV DNA level <2000 IU/mL, HBsAg level <1000 IU/mL can be considered to define low-risk patients who are infected with HBV genotype B or C. "

But we don't have this test available here that measures the actual quantity. We have to drive over to Mexico to get it done. Or give 700ml of blood each time to get it to one company. And you are OK with that as a medical student? :). So how can I feel positive? That is like showing a starving man food but not giving it to him.

From what I have read here surface antigen quantity is in itself another issue. But how many of us actually know ours. I don't. So does the guy that did almost a year of pegasys on here up state he does not know his values. Because we don't have such an important test readily available for patient use.

[veteranB]

do those books also explain how many and for how long those people with HBV DNA above 200,000 have lived or will live they think?

That is why HBV is called a silent killer, because when you start to feel the effects of it, one may need a transplant. Living with more virus could never be better.

[djxpress]

Here's some more positive info from another paper titled "High Levels of Hepatitis B Surface Antigen Increase Risk of Hepatocellular Carcinoma in Patients With Low HBV Load" :

Previous studies have indicated that a lower HBsAg level is associated with better clinical outcomes, including a higher likelihood of HBsAg loss and lower risk of HBeAg-negative hepatitis. In a recent study comparing the prognosis between inactive HBV carriers (viral load <2000 IU/mL) and non-HBV plus non-HCV controls, the 10-year cumulative incidence rates of HCC were 0.6% and 0.2%, respectively. In our study, the 10-year cumulative incidence rate of HCC in patients with HBV DNA level <2000 IU/mL plus HBsAg level <1000 IU/mL was 0.2%, which was similar to the controls. These data suggested that, in addition to HBV DNA level <2000 IU/mL, HBsAg level <1000 IU/mL can be considered to define low-risk patients who are infected with HBV genotype B or C.

[djxpress]

Actually, per 2012 EASL guidelines, the threshold to treat has declined.

I have books printed in the early 2000s that claim anything "under 200,000" copies was minimal and not worth treating.  

[veteranB]

I think  it is do to declining economics in western countries that they have decided to raise acceptable HBV DNA levels. Especially for those EU countries that have to provide free health care.

At the same time if you read carefully this bulletin it is open to interpretation either hight DNA or significant liver disease for the period of over 3 months. But Replicating HBV DNA is bad and it equals more infection which leads to > significant liver disease. No matter how you look at statistically.

So some younger doctors may follow this guideline. Tell the unaware patient without liver disease not to worry about his DNA levels because they are less then 20,000. And the patient forgets about it for several years. And during this type may develop significant fibrosis or HCC.

Not everybody is going to dig into their disease to find out what to do, not everyone will go back to the doctor for follow up because we naturally trust our doctors, that sometimes do make mistakes.

Our goal as patients should be 0 HBV DNA in blood, with the hope that our immune system can do it on its own. Because we also have to worry about the surface antigen quantity as well apparently. That also seems to influence the disease progression.

p.s. but thank you for the post, it is good to know the EASL position for this year. It would also be nice to know what are their views are like  on how we the patients can get the drugs we need approved faster.