Hepatitis B

• dsDNA virus
  • Components – Antigens
    • HBsAg: Outer surface coat encases virus
    • HBcAg: Inner nucleocapsid core encases genome
    • HBeAg: Circulating peptide encoded by core gene
• Initially acute, may progress to chronic hepatitis
• More likely to get chronic hep B if infected at age < 5 , adult infection risk < 5%
• Transmission
  • Vertical – mother to child
  • Parenteral – shared injection equipment
  • Horizontal – sexual or household contact
• Hepatitis B Virus present in blood and body secretions
  • Saliva
  • Tears
  • Vaginal secretions, semen
  • Breast Milk
• Timing
  • Incubation: 60 to 90 days on average

Risk Factors

• HIV Infection
• Intravenous Drug Abuse
• Sexually Transmitted Disease
• Hemodialysis patients
• Healthcare workers
• Travel from endemic areas – (e.g., China, parts of Africa, Alaska, Pacific islands)

Epidemiology of Hepatitis B

• Overall Infection: Approximately 30% of the world’s population, or about two billion people, have been infected at some point.
• Chronic Infection: In 2015, around 257 million people were living with chronic HB infection, with a global prevalence estimated at 3.5%.
• Mortality: HB causes approximately 887,000 deaths annually, mainly due to cirrhosis and liver cancer. This represents the largest share of the 1.34 million annual deaths from hepatitis viruses A–E.

Prevalence by Region

• High Prevalence Areas (>8% chronic infection): Includes East, Southeast, and Central Asia, sub-Saharan Africa, Pacific Island countries, parts of the Middle East, South America, and Eastern Europe.
• Moderate Prevalence Areas (2-7% chronic infection): Encompasses 43% of the global population.
• Diagnosis Rates: Only 17% of those infected in the Western Pacific Region have been diagnosed as of 2016, indicating a significant hidden burden of disease.

Impact of Vaccination

• Reduction in Prevalence: In the WHO Western Pacific Region, the prevalence among 5-year-olds decreased from 9.2% pre-immunization to 0.93% in 2017.
• Chronic Infections: Despite reductions in prevalence, many of those infected remain chronically infected for life.

Epidemiology in Australia

• Chronic HB Infection: Cases continue to rise due to migration.
• Liver Cancer: Liver cancer, often linked to HB, is the second fastest-growing cancer in Australia, with incidence rates increasing significantly from 1982 to 2017.

Risk Among Travelers and Overseas Workers

• Infection Rates for Overseas Workers: High monthly incidence rates in the 1980s and early 1990s, particularly in Africa, Latin America, and Asia.
• Traveler Activity Risks: Surveys from 2000 to 2004 show that a significant portion of Australian adult travelers engage in activities that pose a risk of exposure to HB.

Global Control Efforts

• UN 2030 Agenda for Sustainable Development: Includes goals for combating hepatitis.
• Global Health Sector Strategy on Viral Hepatitis: Set targets to reduce new chronic HB infections by 30% by 2020 and achieve a 0.1% prevalence among children aged at least 5 years by 2030.

Immunizations

• In Australia, routine adolescent immunisation commenced in 1997 and universal infant vaccination commenced in May 2000. 
• Therefore those who were 34 years old or younger in 2020 and who grew up in Australia can generally be assumed to have been vaccinated
• Most people living with chronic hepatitis B in Australia were born overseas, particularly in the Asia Pacific region, Europe, Africa and the Middle East

Clinical

• Asymptomatic infection is common
• Acute hepatitis
  • lethargy
  • nausea, fever, anorexia, jaundice, pale stools, dark urine
• Incubation approx 45 – 180 days
• Chronic hepatitis – if infection > 6 months – 10%
• Complications
  • Cirrhosis – annual risk 12%
  • Hepatocellular carcinoma

Investigations

• Hep B surface antigen (HBsAg)
  • indicates that the virus is actively replicating in the liver.
  • first serum marker to be detected following initial infection.
  • Whilst it is the first antigen to appear
  • there is a window period of up to 200 days (average 75 days) between the first exposure to HBV and the detection of HBsAg in the serum
  • patient is infectious until the patient becomes HBsAg negative;
• Antibody to Hep B surface antigen (anti-HBs)
  • host in response to HBsAg
  • either previous, cleared infection or vaccination against hepatitis B virus
• Hep B envelope antigen (HBeAg)
  • present in both acute and chronic infection
  • indicates active viral replication
  • typically have higher levels of HBV DNA and are more infectious and higher risk of transmissibility
  • However, not all people with chronic Hepatitis B are HBeAg positive
  • used to distinguish between active chronic infection and inactive chronic infection.
• Antibody to Hep B envelope antigen (anti-HBe)
  • marks a transition from active disease to an inactive ‘carrier’ state.
  • Anti-HBe remains in serum for life and indicates acquired, natural immunity (i.e. immunity from a previous infection only).
• Ant-HBc
  • indicates recent infection within the last six months.
  • Over time, IgM is gradually replaced by anti-HBc IgG; therefore, anti-HBc is seen in patients with resolved infection and those with chronic infection
  • Anti-HBc IgM – HBc IgM acutely rises and fall
  • Anti-HBc IgG  
• HBV DNA
  • A high HBV-DNA viral load is associated with an increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC).
  • can remain infectious for many years, particularly if they are HBV DNA positive.
  • In patients with active chronic infection, a higher HBV-DNA viral load is expected
• Check
  • anti HDV
  • HAV
  • HIV
  • HepC
• Transaminases
  • Acute hepatitis B infection – Elevated
  • Chronic hepatitis B infection (active) – Elevated
  • Chronic hepatitis B infection (carrier) – Normal
  • Immunity (following acute infection) – Elevated or normal
  • Immunity (following vaccination) – Normal
• IgM core is raised in recent infection, becomes negative in chronic infection
• AFP
• Liver USS
• fibroscan

	HBsAg	anti-HBs	HBeAg	anti-HBe	Anti-HBc IgM	Anti-HBc IgG	HBV DNA
Acute infection	+	–	+	–	+	–	+
Chronic infection (active)	+	–	+	–	–	+	+ (High)
Chronic infection (inactive, carrier)	+	–	–	+	–	+	+ (Low)
Immunity (following acute infection)	–	+	–	+	–	+	–
Immunity (following vaccination)	–	+	–	–	–	–	–

Management

from Australian Family Physician Vol. 42, No. 6, june 2013

• Follow acute infection until HbSag negative
• Assess and prevent other causes of liver disease
• Clearance provides livelong immunity

Establish the Phase of Chronic Hepatitis B:

• Work-Up Post-Diagnosis:
  • Determine the phase using HBV DNA levels, ALT, and HBeAg/anti-HBe status.
  • The phase indicates the likelihood of progressive liver damage and helps decide on further investigations (e.g., liver biopsy) and consideration of antiviral treatment.

Referral for Treatment:

• Criteria for Referral:
  • Determine a patient’s phase of CHB infection to assess the need for treatment.
  • Refer patients with active viral replication (elevated HBV viral load) and active liver damage (elevated ALT, inflammation on biopsy, fibrosis on biopsy or non-invasive testing like FibroScan®).
    • FibroScan®:
      • Use non-invasive methods like FibroScan® to establish the degree of hepatic fibrosis.
      • Since November 2011, liver biopsy is no longer mandatory for eligibility for Pharmaceutical Benefits Scheme-funded HBV treatment.
  • Refer patients with active liver disease or suspected cirrhosis for specialist assessment and consideration of therapy.
• Special Cases:
  • Pregnant women may require therapy to prevent vertical transmission.
  • Co-infected patients (HIV, HCV, HDV) require specialized treatment approaches.
  • Patients undergoing immunosuppressive therapy should be considered for pre-emptive treatment to prevent CHB flare during therapy.
• Success of Treatment:
  • Goals of Therapy:
    • Short-term: Suppress HBV viral load and reduce liver inflammation (ALT level).
    • Key indicators for monitoring response.
  • Effectiveness:
    • Antiviral therapy is effective in reducing the risk of progressive liver damage, cirrhosis, and liver cancer.
    • Four years of treatment can reduce the risk of liver cancer by more than half.
    • Reversal of cirrhosis is increasingly recognized.
    • First-line oral antiviral therapies (entecavir and tenofovir) are potent, well-tolerated, and have a low incidence of resistance.

Arrange Regular Monitoring:

• Frequency:
  • Regular monitoring is essential for all CHB patients.
  • The frequency varies based on the phase of infection, extent of liver damage, treatment status, and other complicating factors (e.g., co-infections, immunosuppression).
  • Minimum recommended interval: yearly.
• Monitoring Components:
  • Clinical review
    • liver function tests (LFTs)
    • HBV DNA viral load (annual HBV DNA testing funded by Medicare for all HBsAg positive patients).
  • Additional tests as indicated:
    • HBeAg/anti-HBe status in phases 1 and 2 hepatocellular carcinoma (HCC) surveillance in eligible patients.
      • abdominal ultrasound
      • alpha-fetoprotein
    • Tests can be included in a chronic disease management plan (sample template available at www.ashm.org.au).

Check for Other Infections:

• Hepatitis A:
  • Test for immunity to hepatitis A.
  • Offer vaccination if the patient is susceptible, as infection can cause a life-threatening flare of liver disease in CHB patients.
• Hepatitis C, Hepatitis D (HDV), and HIV:
  • Screen all patients diagnosed with CHB for these infections.
  • Check hepatitis D status in patients diagnosed with hepatitis B who were born in hepatitis D virus (HDV) endemic regions (including Mongolia, Moldova, West and Central Africa).
  • Referral to a specialist should be considered for co-infections as they can complicate assessment, monitoring, management, and treatment.

Identify, Screen, and Vaccinate Contacts:

• Family Members, Household Contacts, and Sexual Partners:
  • Screen using serological tests for hepatitis B.
  • Vaccinate if susceptible; hepatitis B vaccine for contacts of a person with CHB is often provided free of charge.

Contact Tracing

• Notifiable condition.
• Acute Hepatitis B:
  • Trace back 6 months before the onset of symptoms.
• Chronic Hepatitis B in Australia:
  • Most diagnoses are from perinatal acquisition.
  • Contact tracing differs from acute hepatitis B cases.
  • Refer to Australian contact tracing guidelines.
• Infectious Period:
  • Infectious for 2 weeks before symptom onset and until the patient becomes HBsAg negative.
  • Lifelong infectious if chronic infection.
• Testing and Vaccination:
  • Test sexual and household contacts and family members.
  • Offer vaccination to susceptible contacts.
  • Further assessment for those with current infection.
• Transmission:
  • HBV is a blood-borne virus and sexually transmissible infection.
  • Casual household contact (e.g., sharing cutlery) does not pose a risk for hepatitis B transmission.
• Hepatitis B Immunoglobulin (HBIG):
  • Used as post-exposure prophylaxis in high-risk situations (e.g., sexual, injecting, or occupational exposure).
  • Administered as a birth dose to reduce transmission risk from an HBsAg-positive person to their child.

Prevention

• No sexual contact during acute illness unless partner immune
  • Infectious for 2 weeks before onset of symptoms and until the patient becomes HBsAg negative
• Contact tracing 6 months before acute onset
  • Test – sexual contact, household contacts, close family members and vaccinate if not immune
• Consider treating contact with immunoglobulin if high risk exposure
• Notify health department
• Consider STI testing, advise condom use
• If pregnant- specialist review.
  • Infant will need vaccination and immunoglobulin at birth
  • Mother may need anti-virals.