Introduction

Hepatitis B is an infection of the liver, caused by the hepatitis B virus (HBV). It is the most common cause of hepatitis worldwide, and there are believed to be over 350 million chronic cases. It is endemic in Asia and the Far East (up to 10% have chronic hepatitis B), but rare in the developed world. In the UK, bout 1 in 350 people have hepatitis B.

Spread occurs via infected blood – e.g. via sexual intercourse, vertical transmission from mother to baby, and historically it was also seen in blood transfusions.

The incubation period is between 6-23 weeks.

The serologically important factors, which help it determining immunisation status as well as disease status include:

  • Surface antigen – HBsAg, and surface antibody (anti-HBs)
  • Core antigen – HBcAg, and core antibody (anti-HBc)
  • e antigen – HBeAg

All patients with hepatitis B need assessment and management.

Hepatitis B is preventable by vaccination. In both the UK and Australia, this is now part of the routine vaccination schedule in children. Usually three doses are required to confer immunity.

Most cases in the UK are the result of injecting drug use or sexual exposure.

About 10% of cases of infection will go on to develop chronic hepatitis B. Chronic disease is defined as detectable levels of surface antigen (HBsAg) 6 months after infection.

Epidemiology and Aetiology

  • Major health problem – 350 million chronic cases worldwide
  • Incubation 1 – 4 mths
  • Parenteral transmission – sexual, IV, perinatal
  • 0.5% of UK population are carriers, but this is as much as 10-15% in some countries in the developing world. in some far eastern countries, 1/3 of people are carriers
  • In UK, 1 in 350 have chronic hepatitis B infection
  • In recent years, rates have declined amongst younger populations due to vaccination
  • Risk factors
    • IV drug use
    • Multiple sexual partners
    • Occupational exposure – e.g. healthcare workers
    • Close family or contact who is infected or a carrier
    • Receiving regular blood products
    • Travel to high risk areas
    • Children born to mothers who are carriers or infected
    • Prison inmates
    • In the UK most cases are due to sexual exposure or IV drug use

Presentation

May be asymptomatic, or have minor flu-like symptoms. Symptomatic individuals may present with:

  • Fever
  • Malaise
  • Faitgue
  • Joint pains
  • Urticaria
  • Pale stools / dark urine / jaundice
    • Jaundice occurs in 10% of newly infected children and up to 50% of newly infected adults

Acute Hepatitis B

  • Incubation period 6 weeks – 6 months
  • 1% of patients will develop liver failure
  • 90% will recover
  • 10% will go on to develop chronic hepatitis B infection
  • Jaundice, malaise, abdominal pain, nausea & fever – 1 to 3 months
  • 70% anicteric (not jaundiced)

Maternal transmission is different

  • 90% of newborns born to infected mothers will have chronic hepatitis B infection
  • Up to 25% will have chronic complications. Including:
    • Cirrhosis
    • Hepatocellular carcinoma

Chronic Hepatitis B

10% of cases of infection will go on to develop chronic hepatitis B. The risk of developing chronic disease depends on the age at which the infection is acquired. The risk in neonates from maternal transmission >90%, whilst in adults, it is around 10%, and in children who acquire the infection after birth the risk is even lower. Many patients are “healthy carriers” without any ongoing symptoms.

  • In healthy patients who are non-drinkers, with normal LFTs the disease often has a benign course
  • In those with more severe disease, then there is a risk of liver cirrhosis and hepatocellular carcinoma (HCC)

Diagnosis

  • Derranged LFTs
    • ↑bilirubin
    • ↑ALT / AST
    • ↑ALP
  • Positive HBsAg
    • Present in blood for 1-6 months post exposure
    • If present after 6 months then this is diagnostic for carrier status
  • HBeAg
    • Present from 6 weeks to 3 months after exposure
    • May or may not be present in chronic disease
    • Indicates period of high infectivity – as it shows high levels of viral replication in the blood
    • Indicates worse prognosis
  • Anti-HBs
    • Antibodies to surface antigen
    • Appear 10 months after infection
    • Imply immunity
    • Also seen in previous vaccinated individuals
  • HBV genotyping
  • Quantitative hepatitis B virus DNA
    • Higher viral load is associated with worse prognosis and is correlated to liver damage
  • HIV and Hepatitis C
    • Patients should also be screened for these two diseases

Understanding Hepatitis B testing

There are several antigens and antibodies that are present during, and following Hepatitis B infection. Understanding which of these is present and when can help you identify if a persen has a current or past infection, and their immunity status.

At the most simple level:

  • HBsAg negative – do not have current HBV
  • HBsAg positive – have acute or chronic HBV and require further tests. If positive for >6 months are considered to have chronic HBV

Clinical StatusPositive Serological Markers
Immunity following previous natural exposureAnti-HBc (may be negative if infection was a long time ago)
Anti-HBs
Previously VaccinatedAnti-HBs
Acute InfectionHBs-Ag
Anti-HBc
HBV-DNA
HBe-Ag (may be negative depending on timing)
Chronic InfectionHBs-Ag – HBsAg present 6 months after exposure is diagnostic for chronic infection
Anti-HBc
HBV-DNA
(all above still positive 6 months after diagnosis)

Pathology

In chronic disease, viral DNA may become incorporated into host DNA. HbsAg is present on the surface of infected hepatocytes, and this causes T cells to induce apoptosis in these cells. The pathogenesis is different to that of HAV (Hepatitis A Virus) , where the apoptosis is not induced by the immune system, but by the infected cell itself – thus HAV does not have the ability to cause chronic disease.

Complications

  • Acute liver failure rare – 0.1 to 0.5%
  • Chronic Hepatitis B is specified as viraemia at 6 months after initial diagnosis/sympotms
    • Occurs in about 10% of adult infection, and 90% of vertical transmission cases
    • Chronic disease can be divided into e-antigen positive and e-antigen negative
    • E-antigen positive disease is associated with higher viral replication, and therefore higher risks of infectivity
    • Chronic infection benign in the majority of patients – especially in non-drinks with normal liver function
    • Chronic infection depends on age of initial infection:
    • 90% of people who get the disease in vertical transmission (i.e. from their mum) will develop chronic disease
    • 5-10% of adults who contract hepatitis B will develop chronic disease
    • 30% of people with chronic infection will get cirrhosis
    • In chronic HBV 40% men and 15% women die from liver failure
  • Cirrhosis
    • HIV and HepC infection increase the likelihood of cirrhosis
  • Hepatocellular carcinoma
    • Can develop without cirrhosis

Management

If acutely unwell – will need hospital admission. Otherwise can be managed in primary care, with non-urgent referral to gastroenterologist or infectious diseases specialist upon confirmation of diagnosis (positive HBsAg).

Symptomatic management is often all that is required in the acute phase. Itching due to jaundice may be difficult to manage.

It is important to check for other commonly associated infections, including HepC and HIV.

  • 10% of patients with HIV will also be infected with HBV
  • Liver complications are more common in those with co-infection with HIV. However, conversely, HBV is not thought to affect HIV disease progression.

If not already done, ensure diagnosis is confirmed with serological testing, and FBC and Lots are performed.

  • Antiviral therapy – only for selected patients with chronic infection – requires specialist input – usually those patients with HBeAg positive disease and liver disease
    • Interferon is often first line
      • 48 week course
      • Many side effects
    • Lamivudine
    • Entecavir
    • Tenofovir (adefovir)
    • Variable success rates
  • The aim of treatment is to reduce the risk of complications. Therefore patients who already have cirrhosis are likely not to benefit. Other factors when deciding who to treat include:
    • HBe-antigen status
    • Elevated Transaminase
    • HBV DNA levels
    • Not cirrhotic
  • Prevented by vaccination
  • Lifestyle advice
    • Counsel about the diagnosis and the course of the disease, including advise not to donate blood and the route of transmission
    • Advise alcohol abstinence – especially if LFTs are abnormal
    • Safe sex advice
      • Advise partners become vaccinated, and to avoid sexual contact (including oral sex) until vaccination is complete, or until the patient becomes non-infectious

Reducing transmission

Vertical transmission

To babies of infected mothers:

  • Give HBIG within 24 hours of birth
  • Give full course of vaccination
  • These two can be given simultaneously (at different sites)
  • This reduces vertical transmission by 90%

Intimate contacts

  • Contact tracing may be required
    • This can be difficult in chronic infection
  • Infectious period is from 2 weeks before jaundice, until HBsAg negative serology
  • HBIG can be given to contacts after a single exposure (e.g. sexual contact or needle stick) – should be given as soon as possible (most effective in first 48 hours) but can be given up to a week after exposure

Prognosis

  • 80% of patients will have full recovery
  • 10% develop chronic hepatitis
    • Associated with cirrhosis and liver carcinoma
    • Risk of cirrhosis is 10-20% without antivirals
    • Once cirrhosis has developed, there is a high risk of culminant liver failure
    • 5-year survival in decompensated cirrhosis is 15%
  • 10% go on to be “carriers”

References

  • Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Hepatitis B - patient.info

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