Treatment and Testing for Hepatitis B

Screening tests for hepatitis B

HBsAg tests whether someone is currently infected with HBV
Anti-HBc indicates current/past infection
Anti-HBs indicates immunity >10 and HBsAg is negative.
HBeAg indicates a high level of infectivity

Initially a positive HBsAg test simply reveals the presence of HBV in the blood. In order to consider an individual to have CHB, a further confirmatory test six months later is required.

HBsAg, Anti-HBs and Anti-HBc testing should be offered to household and sexual contacts of people with HBV and vaccination should be offered via GP to those who are susceptible to the virus. This is free of charge on the immunisation schedule to people under 18, sexual partners, household contacts, and other groups.

All infants of HBsAg positive mothers should have HBIG and hepatitis B vaccine at birth (within 12hrs is recommended). Then Dtap-IPV hepatitis B/HIB at six weeks, three and five months and tested for immunity at nine months.

Refer to the Immunisation Handbook.

Monitoring tests for hepatitis B

HBsAg hepatitis B surface antigen
HBeAg hepatitis B e antigen
LFT Liver function tests (All LFT’s including AST)
AFP alpha-fetoprotein tests
FBC Full Blood Count
HBV DNA Hepatitis B Viral Load (when required)

Treatment 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?

All patients with chronic HBV once commenced on Anti-Viral treatment will need it lifelong, unless otherwise advised and further assessed under a Specialist.

Chronic HBV patients also need regular lifelong monitoring for any possible hepatocellular carcinoma and/or progression to cirrhosis.

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.

Anti-viral Medications

Entecavir is an oral tablet used in adults who have active virus and liver damage. Entecavir is funded as a first-line therapy for patients with chronic hepatitis B. Almost all patients achieve viral suppression (undetectable HBV DNA) and biochemical response (ALT below the upper limit of normal). Entecavir resistance is rare at less than one percent after six years.

Tenofovir is also an oral tablet. It has replaced Adefovir in New Zealand as the first-line therapy for Lamivudine-resistant hepatitis B infection. It is the preferred treatment during pregnancy and breastfeeding and dramatically reduced the risk of vertical transmission.

No resistance to Tenofovir has been observed after five years of therapy. Renal function (creatinine, calcium, and phosphorus) should be assessed before commencement of Tenofovir and periodically while on treatment.

Pegylated Interferon (Pegasys) boosts the body’s immune system and changes the virus’ ability to multiply. It is a synthetic version of a protein naturally produced by the body (interferon). In select individuals it may be recommended as treatment. Pegasys is injected under the skin once a week for 48 weeks. The goal of therapy is to put the virus into an inactive state. The virus may be cured in a very small proportion of people treated.

The hepatitis B virus cannot usually be cured and in most cases, anti-viral therapy needs to be lifelong. In select cases therapy may be discontinued but only under close supervision by a specialist. Pegylated Interferon (Pegasys) is not widely used in NZ due to effective Anti-Viral treatment available.

Seroconversion of hepatitis B surface antigen

HBsAg seroconversion when a patient has cleared the Hepatitis B Virus (HBV) from their blood. (HBsAg is negative or not detected).

About one percent of people with hepatitis B will spontaneously lose HBsAg per year. Following seroconversion from HBsAg + to HBsAg - the HBV infection is usually no longer active and they are immune from further infection, but can still be at risk of HCC.

HBV reactivation can occur with potent immunosuppressive therapy and may need cover with prophylactic antiviral treatment.

People who seroconvert >50 years old may still be at risk of hepatocellular carcinoma (HCC), although this risk is reduced compared to being HBsAg positive. The Hepatitis Foundation will monitor these people indefinitely.

Patients with close family history for HCC and/or cirrhosis will require 6 monthly liver ultrasound scans in addition to these 6 monthly bloods indefinitely. Cirrhotic Patients should be monitored under Secondary Care Gastroenterology indefinitely and be registered with HFNZ.

Download Management of Hep B for Health Professionals Booklet