Hepatitis B

Background

Hepatitis B virus (HBV) is a DNA virus of the Hepadnaviridae family, causing both acute and chronic liver disease. HBV is spread by direct contact with infected blood or body fluids. The pathogenesis of HBV is driven by its ability to infect hepatocytes and trigger immune-mediated liver damage.

Epidemiology

In England an average of 350 cases of acute HBV per year were reported annually. Around 200,000 people are thought to be living with chronic HBV infection, an estimated prevalence of 0.45%
The majority of cases (>95%) occur in individuals who acquired the infection overseas in endemic regions before arriving in the UK (high risk areas include Africa, Asia, the Middle East, parts of South America and eastern Europe)

Transmission

Transmission routes include:

• Perinatal (vertical) transmission
• Sexual transmission
• Parenteral transmission via needle sharing, needlestick injuries or other contact with infected blood

Clinical features
HBV has an incubation period of 40 to 160 days (approximately 6 weeks to 6 months), with an average of 90 days from exposure to symptom onset.

In infants and younger children, it is generally asymptomatic but often results in chronic infection. Note the risk for chronic infection varies according to the age at infection and is greatest among young children. Approximately 90% of infected infants (up to 1 year of age) and 30% of children aged between 1–5 years will remain chronically infected with HBV. By contrast, approximately 95% of infected adults recover completely from acute HBV infection and do not become chronically infected.

Acute hepatitis features:

• fever
• malaise
• nausea
• right upper quadrant pain
• jaundice
• dark urine
• and pale stools.

Investigations
Liver transaminase (ALT and AST) levels are markedly elevated in acute infection and may fluctuate in chronic cases.

Complications of hepatitis B infection

• chronic hepatitis (5-10%)
• fulminant liver failure (1%)
• hepatocellular carcinoma
• glomerulonephritis
• polyarteritis nodosa
• cryoglobulinaemia

Immunisation

Immunisation against hepatitis B

• Contains HBsAg adsorbed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology
• The standard vaccination schedule consists of three doses, with a single booster dose recommended five years after the primary series
• High risk groups who should be vaccinated include: healthcare workers, intravenous drug users, sex workers, close family contacts of an individual with hepatitis B, individuals receiving blood transfusions regularly, chronic kidney disease patients who may soon require renal replacement therapy, prisoners, chronic liver disease patients
• Approximately 10-15% of adults fail to respond or respond inadequately to three vaccine doses. Risk factors for poor response include age >40 years, obesity, smoking, excessive alcohol use, and immunosuppression
• Anti-HBs testing is recommended only for occupationally exposed individuals (e.g., healthcare workers) and patients with chronic kidney disease. Anti-HBs levels should be checked 1-4 months after primary immunisation

The table below shows how to interpret anti-HBs levels:


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Interpreting Hepatitis B Serology

Understanding hepatitis B serology is crucial for medical exams. Key points to remember:

• Hepatitis B surface antigen (HBsAg) is the first marker to appear in infection. It normally indicates current infection but does not differentiate between acute and chronic infection.
• If HBsAg persists for >6 months, this suggests chronic infection (infective carrier state).
• Anti-HBs (antibody to HBsAg) indicates immunity from past infection or vaccination but is absent in chronic infection
• Hepatitis B core antigen (HBcAg) is not routinely measured in clinical practice, but its antibody (anti-HBc) is measured. Both IgM and IgG antibodies may be tested
• Anti-HBc IgM appears early in acute infection and usually disappears within 6 months.
• Anti-HBc IgG may take up to a month to appear following infection so may not be present if testing early. Persists for life and indicates past or chronic infection
• Hepatitis B envelope antigen (HBeAg) is a marker of high infectivity and active viral replication
• Anti-HBe (antibody to HBeAg) suggests transition to a lower-infectivity state and may indicate a shift from active disease to an inactive carrier state.

Management of hepatitis B

• Notify the Health Protection Unit (HPU) promptly to facilitate appropriate surveillance and contact tracing.
• Advice patient to avoid alcohol & how to minimise the risk of transmission to partners and contacts.
• All patients should be referred to a gastroenterologist or hepatologist
• Symptoms of pain, nausea and itch should be managed with appropriate drug treatment. Paracetamol, ibuprofen and codeine are appropriate to prescribe for pain. Metoclopramide or cyclizine may be used for nausea. Chlorphenamine is often used for itch.

Once under specialist care drug treatment options include:

• Pegylated interferon-alpha used to be the only treatment available. It reduces viral replication in up to 30% of chronic carriers. A better response is predicted by being female, < 50 years old, low HBV DNA levels, non-Asian, HIV negative, high degree of inflammation on liver biopsy
• While NICE still recommends pegylated interferon as first-line therapy, newer antiviral agents (e.g., tenofovir, entecavir) are increasingly preferred for long-term viral suppression, similar to the treatment approach in HIV management