Screening for HBV

Opportunistic testing of asymptomatic people at risk of HBV infection should be undertaken in primary practice, particularly for people born in intermediate and high-prevalence countries.

Screening of people from those groups is important as chronic HBV infection acquired at birth or in early childhood usually remains asymptomatic until late in life when liver failure or liver cancer can develop in up to 40% of cases.2

Guidelines from the American Association for the Study of Liver Diseases (AASLD), the World Health Organization (WHO), and the British Association for Sexual Health and HIV (BASHH) recommend screening for HBV infection in priority populations (Table 1).1,3,4

Table 1: Populations at high risk for HBV infection who should be screened

  • MSM
  • People in custodial facilities or who have ever been in custodial facilities
  • PWID
  • People born in intermediate and high risk countries
  • Sex workers
  • Individuals with elevated ALT or AST of unknown aetiology
  • Sexual assault victims
  • People undergoing dialysis
  • Pregnant women
  • Heterosexuals with multiple sex partners
  • PLHIV, HCV or both
  • Persons needing immunosuppressive therapyΔ
  • Needlestick victims
  • HCPs who perform exposure prone procedures
  • Transgender people
  • Travellers to intermediate and high risk countries

Table is not all inclusive. For a full list, please review the 2018 AASLD Guidelines.

Δchemotherapy, immunosuppression related to organ transplantation, and immunosuppression for rheumatological or gastroenterologic disorders.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; HCV, hepatitis C virus; MSM, men who have sex with men; PWID, people who inject drugs; PLHIV, people living with HIV.

Informed consent should be gained prior to testing and consideration should be given to the individual’s cultural beliefs and practices, health literacy, behaviour and language. Support and information about the testing process should be provided to:

  • minimise the impact of a positive diagnosis on the individual and their families,
  • change high risk health-related behaviour, and
  • reduce anxiety

Screening tests for HBV5

Initial testing should include:

Hepatitis B surface antigen (HBsAg). The presence of HBsAg signifies HBV infection and usually becomes detectable during weeks 4–10. Chronic HBV infection is defined by the persistence of HBsAg for more than 6 months.

Antibody to surface antigen (anti-HBs). Anti-HBs is a protective antibody that develops with the resolution of acute infection or following successful vaccination against HBV.

Antibody to core antigen (anti-HBc). Anti-HBc immunoglobulin G (IgG) remains positive for life following exposure to HBV; however, unlike anti-HBs, anti-HBc is not a protective antibody, and this test may occasionally give a false-positive result.

Interpretation of the above test results allows for the categorisation of most people by their HBV status as either a) susceptible to infection; b) immune through vaccination, c) immune through resolved infection; or d) chronically infected with HBV. This avoids missed diagnoses, unnecessary vaccination, recalling people or requesting additional tests.

Table 2: HBV test results and their interpretation5

HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface antigen; IgM anti-HBc, immunoglobulin M antibody to the hepatitis B core antigen; HBV, hepatitis B virus.

Table 3. What if the results are inconclusive?5

Tests Results
HBSAg Negative
anti-HBc Positive
anti-HBs Negative

HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface antigen

In isolated cases, test results can be inconclusive (see Table 3). In such cases, interpretation possibilities include:

Distant resolved HBV infection – the most common interpretation, particularly in people born in HBV-endemic areas.

False positive result – more common in people with a low risk of past HBV infection.

Resolving acute HBV infection – in the period between HBsAg loss and development of detectable anti-HBs.

Passive transfer of maternal anti-HBc – in children up to 3 years of age.

Occult HBV infection – where HBV DNA is detectable in the absence of HBsAg; this can be determined by detecting HBV DNA in serum.

In the event of inconclusive test results, confirmation via repeat serology testing should be considered.

Asymptomatic at-risk individuals who are not immune to HBV should be targeted for vaccination. People from high risk groups should be tested for active or resolved infection prior to vaccination, as vaccination is not beneficial for persons already exposed to HBV.

Those who are chronically infected with HBV need to be identified to receive appropriate management.4 Furthermore, household contacts and sexual partners of HBV-positive individuals require notification and screening.

The presence of acute or chronic HBV should be notified to the public health authorities (the route of which depends on the country).4

Conveying a confirmed HBV test result

Conveying a test result needs to be conducted in a culturally appropriate and safe manner with a gender and dialect-appropriate interpreter for people with low English proficiency.

It is important that the results are given promptly, where privacy is assured, and the individual’s concerns be addressed through the provision of clear information, access to counselling and psychosocial support.

The following table summaries points to consider when conveying a confirmed acute or chronic HBV infection.

Table 4. Points to discuss when conveying a HBV test result5

Result

Discuss

Additional points to convey

Acute

HBsAg +ve

anti-HBc +ve

anti-HBs -ve

Likelihood of clearing infection or going on to chronicity.

Medical management, referrals

Immediate needs and support.

Modes of transmission and risk reduction.

Who to tell and how.

Testing of sexual partners, family members, household contacts.

Health maintenance strategies (e.g. ↓ alcohol, weight loss, smoking cessation, IDU harm reduction).

Strategies for managing HBV which are flexible and appropriate to the person’s needs.

Adequate time to answer questions.

Appropriate use of interpreters and translated resources.

Chronic

HBsAg +ve

anti-HBc +ve

anti-HBs -ve

Need for ongoing, potentially lifelong monitoring.

Treatment options, medical management, referrals.

Adapted from: ASHM. Hepatitis B and primary care providers. 2014

HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface antigen; IDU, intravenous drug use

Prevention of HBV

HBV vaccination is inexpensive, safe and effective. The currently available HBV vaccines consist of recombinant HBsAg produced in yeast and have been available for more than two decades. A series of 3 intramuscular injections may achieve Seroprotective antibody to hepatitis B surface antigen (anti-HBs) levels >10 million IU/mL in approximately 95% of vaccinated individuals.6

WHO recommends universal HBV vaccination for all infants, and that the first dose should be given as soon as possible after birth. This strategy has resulted in a dramatic decrease in the prevalence of chronic HBV among young children in regions of the world where universal infant vaccination programmes have been implemented.6,7

People from high-risk groups should be tested for active or resolved infection prior to vaccination, as vaccination is not beneficial for persons already exposed to HBV. Immunization should also be considered for all adults at risk of HBV infection (Table 5).8

Table 5. Groups at risk of exposure to HBV infection who should be considered for vaccination8

History of current or recent injection drug use
International travelers to countries with high or intermediate levels of endemic HBV infection (HBsAg prevalence ≥2%)
Chronic liver disease (including, but not limited to, HCV, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an ALT or AST level greater than twice the upper limit of normal)
HIV infection
At risk for infection through sexual exposure (e.g., sex partners of HBsAg-positive persons, sexually active persons not in a long-term mutually monogamous relationship, persons seeking evaluation or treatment for a sexually transmitted infection, MSM)
At risk for infection by percutaneous or mucosal exposure to blood (e.g., household contacts of HBsAg-positive persons, residents and staff of facilities for developmentally disabled persons, healthcare and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids, haemodialysis patients and predialysis, peritoneal dialysis, and home dialysis patients)
Persons with diabetes mellitus <60 years and persons with diabetes mellitus aged at least 60 years at the discretion of the treating clinician9 
Incarcerated persons
Other persons seeking protection from HBV infection (even without acknowledgment of a specific risk factor)

At the time of writing, there is no compelling evidence for recommending a booster dose of HBV vaccine in routine immunisation programmes.6

Hepatitis B immunoglobulin

Hepatitis B immunoglobulin (HBIG) is prepared from pooled plasma, with samples selected on the basis of high levels of anti-HBs. HBIG is recommended in infants born to HBsAg-positive mothers and to non-immune people exposed to blood of people with chronic HBV infection.5

For unvaccinated adults, HBIG should be given within 72 hours of exposure, because efficacy diminishes with time from 48 hours after exposure. The HBV vaccine can be given at the same time as HBIG or within 7 days of exposure.5

What if my patient is not immune after vaccination?

If adequate anti-HBs levels (≥10 mIU/mL) are not reached after the third dose:5

  • If unknown, test to exclude HBV infection (HBsAg and anti-HBc).
  • HBsAg negative non-responders should be offered further doses – given as either a fourth double dose or a further 3 doses at monthly intervals, with further testing for response at least 4 weeks after the last dose.
  • Persistent non-responders should be informed that they are not protected and should minimise exposures. They should also be told about the need for HBV immunoglobulin within 72 hours of parenteral exposure to HBV.

Assessment of people with chronic HBV

Because chronic HBV is a dynamic disease, persons who are not receiving treatment should be assessed regularly to determine whether an indication for treatment has developed.3

The need for treatment is generally based on the combination of three criteria:10

  • assessment of serum HBV DNA
  • serum alanine transferase (ALT) levels, and
  • severity of liver disease (based on assessment of fibrosis).

Clinical history11

Initial evaluation includes a comprehensive history. Aspects that deserve close attention include ethnic background, family history of HBV and/or hepatocellular carcinoma (HCC). Cofactors for liver disease should also be considered, including alcohol consumption, smoking and co-infection  with hepatitis C virus (HCV), hepatitis D virus (HDV), and HIV.

Physical examination

A physical examination can uncover peripheral signs of chronic liver disease, including:5

  • hepatic encephalopathy,
  • splenomegaly,
  • ascites, and
  • peripheral oedema.

Approximately 10-20% of patients with chronic HBV develop extrahepatic manifestations involving multiple organ systems. Examples include:5

  • polyarteritis nodosa,
  • colitis,
  • glomerulonephritis,
  • neuropathy,
  • vasculitic skin rashes, and
  • palpable purpura.

Laboratory investigations

The tests listed in Table 6 allow clinicians to assess the phase of disease, determine the need for treatment, and determine the degree of underlying liver disease.

Table 6. Tests used in the initial assessment of patients with chronic HBV3-5,10

Test

Importance

HBeAg, anti-HBe and HBV DNA

Important to quantify replication, identify the phase of infection, prognostication, and for consideration of treatment.

HAV, HCV, HDV, and HIV serology

Provide information on co-infection and potential need for vaccination, if susceptible to HAV.

LFT, FBC, PT, INR, AFP and abdominal hepatic ultrasound

Allow for the assessment of liver disease: necroinflammatory activity, synthetic function, thrombocytopenia (potential cirrhosis) , portal hypertension and HCC.

anti-HBe, antibodies to envelope antigen; AFP, alpha fetoprotein; FBC, full blood count; HAV, hepatitis A virus; HBeAg, hepatitis B envelope antigen; HBV, hepatitis B virus; HCC. Hepatocellular carcinoma; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; INR, international normalisation ratio; LFT, liver function test; PT, prothrombin time.

Where laboratory markers reveal inconclusive results, a liver biopsy or a non-invasive test should be performed to assess fibrosis and inflammation. Indications for treatment, as outlined by the European Association for the Study of the Liver (EASL), are listed in Table 7.10

Table 7. Indications for treatment10

*Defined by HBV DNA >2,000 IU/ml, ALT >ULN and/or at least moderate liver necroinflammation or fibrosis;
Defined by persistently normal ALT and high HBV DNA levels;
Even if typical treatment indications are not fulfilled.
HBeAg, hepatitis B envelope-antigen; HBV, hepatitis B virus, ALT, alanine aminotransferase; ULN, upper limit of normal; HCC, hepatocellular carcinoma.

Monitoring

In patients who are not candidates for treatment, monitoring involves periodical assessments of serum ALT, HBV DNA and non-invasive  markers for liver fibrosis. The frequency of monitoring is determined by age, family history, the phase of HBV infection, degree of activity and other factors such as co-morbidities (Table 8).10

Table 8. Monitoring of patients currently not treated10

HBeAg, hepatitis B envelope-antigen; HBV, hepatitis B virus, ULN, upper limit of normal.

The identification and monitoring of patients with or at risk of chronic HBV infection is encapsulated in Figure 1.

In summary, screening people at risk for HBV infection provides an opportunity to diagnose, intervene, and prevent illness and death.

The primary care provider is usually the first point of contact for a person at risk of HBV and therefore plays a central role in this process, together with the ongoing provision of information, support and referral as necessary. In all cases, effective communication between primary care providers, specialists and referral centres is required for optimal management of patients with or at risk of HBV infection.12

Figure 1. Identification and monitoring of patients with chronic HBV infection10

HBeAg, hepatitis B envelope-antigen; HBV, hepatitis B virus, ALT, alanine aminotransferase; anti-HBe, antibodies to envelope antigen; HCC. Hepatocellular carcinoma.

For more information on testing for HBV, visit: the European Association for the Study of the Liver (EASL) at: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines

Hepatitis B

HBV

A comprehensive summary of currently available knowledge on HBV is provided here – information that reiterates the key role of primary care clinicians in screening, diagnosis and management of people living with HBV.

The burden of HBV

HBV

An introduction to key HBV resources on site, from epidemiology to practical information for primary care providers, identifying those at risk and potential candidates for treatment.

Treatment and management

HBV

Discussing who to treat and when to treat, therapy recommendations and continual monitoring. 

Expert insights

HBV

Experts insights on case-based and evidence-based updates on managing patients living with chronic HBV.

References

  1. WHO guidelines on hepatitis B and C testing. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
  2. Gastroenterological Society of Australia. Australia and New Zealand chronic hepatitis B (CHB) recommendations. 2nd edition 2009/10.
  3. Terrault NA, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560-99.
  4. BASHH National Guidelines for the Management for Viral Hepatitides. 2017 interim update. Available at: https://www.bashh.org/guidelines (accessed November 2018).
  5. Australasian Society for HIV Medicine (ASHM). B positive. All you wanted to know about hepatitis B. A guide for primary care providers. Available at: (accessed November 2018).
  6. WHO. Hepatitis B vaccines. Wkly Epidemiol Rec. 2009;84:405–20
  7. WHO. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. March 2015. Available at: https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/ (accessed Jan 2019).
  8. Schillie S, et al. Recommendations of the Advisory Committee on Immunization Practices for use of a hepatitis B vaccine with a novel adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
  9. Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60:1709-11.
  10. EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. Available at: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines (accessed November 2018).
  11. Bell SJ and Nguyen T. The management of hepatitis B. Australian Prescriber 2009;32:99-104.
  12. ASHM. HIV, viral hepatitis and STIs: a guide for primary care. 2008;122.

LID/IHQ/18-12//1048c(1) Date of preparation: August 2019