Treatment and Testing for Hepatitis B

Dr Chris Moyes, Medical Director HFNZ

Recommended medications for most patients in NZ are either entecavir 0.5mg daily or tenofovir disoproxil 245mg daily, both of which can be prescribed by family practitioners.

Both are extremely effective at suppressing HBV and reduce liver damage and HCC risk with very few side effects and no interaction with other medications, but need to be continued long-term. 

Tenofovir disoproxil is considered to be safest for pregnancy and is the first choice for women of reproductive age. It can aggravate renal failure and very occasionally causes renal tubular problems so creatinine, calcium, and phosphorus levels should be monitored, along with periodic liver function and viral load (HBV DNA quantification).

Who should be treated?

International guidelines vary but all agree that:

• patients with persistently raised ALT levels and HBV DNA above 20,000 IU/mL should be treated.

• patients under 30 yrs who are HBeAg positive with high HBV DNA (often many millions of units) but normal ALT (immune tolerance stage) do not usually need treatment.

This leaves a ‘grey’ area consisting of many patients where recommendations vary, but at HFNZ we have chosen to use a risk-based approach as endorsed by the Asia Pacific Association for the Study of the Liver2. 

REACH-B is a score that predicts risk of HCC (on the free MDCalc App). At present we refer for possible treatment, all patients with a risk above 2% in ten years (this includes many patients with normal ALT, especially those over the age 40).

Treatment reduces subsequent HCC by around ¾ but does not eliminate risk.

However, many experts now consider that earlier treatment may further reduce long-term risks of HCC by reducing integration of HBV into the liver cell genome, and recommend offering anti-virals to any patients over thirty years of age with an HBV DNA > 2000 or HBeAg positive3.  

This is included in current BPAC guidelines, and is suitable for primary care management. Secondary care referral can be restricted to those with evidence of severe fibrosis/cirrhosis or co-morbidities. 

How long should treatment last?

Patients with HBeAg positive active hepatitis can often successfully stop anti-virals after seroconversion to HBeAg negative and acquisition of anti-HBe but need careful monitoring.

HBeAg negative patients who are initially can sometimes stop treatment after several years of normal liver function and undetectable HBV DNA, but the risk of relapse is high and may increases the chances of complications, so we recommend continuing indefinitely unless HBsAg becomes negative.

Detection of Hepatocellular Carcinoma

Patients with chronic HBV infection are at much increased risk of HCC, increasing with age, male gender, and especially with cirrhosis (these patients should be under secondary care). Preclinical detection of HCC is essential for any prospect of cure. 

We include AFP in our six-monthly blood tests, but this detects less than half of tumours at a very early stage (Barcelona 0/A who have high cure rates)4-6. Six-monthly ultrasounds are more sensitive, at around 58%6, but are not logistically practical for all of the 20,000 patients we supervise, and a pragmatic approach is to confine this to patients with REACH-B score 10 yr risk of >5 per cent or family history of HCC.

We are currently piloting the use of a more sensitive marker (protein induced by vitamin K absence or antagonist II; PIVKA II) in combination with AFP and a weighting for age and gender (GAAD) which is reported to be 73 per cent sensitive for early stage HCC6, and this may become the standard of care.