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Hepatitis B: prevalence and pathophysiology

Despite its growing prevalence, hepatitis B is often undiagnosed. This article discusses its spread, life cycle and prevention, and groups at high risk of infection

In this article…

  • Epidemiology of chronic hepatitis B
  • Life cycle of hepatitis B
  • How the virus is diagnosed

 

Author

Kathryn Oakes is viral hepatitis clinical nurse specialists team lead at King’s College Hospital, London.

 

Abstract

Oakes K (2014) Chronic hepatitis B, part 1: hepatitis B: prevalence and pathophysiology. Nursing Times; 110: 7, 12-16.

Chronic hepatitis B is a growing worldwide public health issue. Its prevalence and the mode of transmission of the virus varies greatly between parts of the world. Prevalence is rising in the UK due to an increase in migration from areas with a high prevalence of chronic hepatitis B.

This article, the first of a two-part series, discusses the prevalence and pathophysiology of chronic hepatitis B, as well as recommendations for screening high-risk groups and immunisation against the disease. Part two discusses the management of the virus.

  • This article has been double-blind peer reviewed
  • Figures and tables can be seen in the attached print-friendly PDF file of the complete article in the ‘Files’ section of this page

 

5 key points

  1. Hepatitis B virus infection is a growing problem worldwide and in the UK
  2. HBV is mainly transmitted through sexual contact or drug use in western countries and through vertical or horizontal transmission in developing countries
  3. The age at which HBV is contracted affects prognosis
  4. Chronic hepatitis B is often asymptomatic and can go undiagnosed, so high-risk groups should be tested routinely for HBV
  5. HBV infection is preventable with a safe and effective vaccine

 

Hepatitis B virus (HBV) is an immense global public health problem, with more than two billion people worldwide living with it (Long et al, 2008). Current estimates suggest that around 350 million of these have developed chronic hepatitis B (CHB) virus infection (Tillmann et al, 2012). This can lead to cirrhosis, liver failure and hepatocellular carcinoma (HCC), resulting in one million deaths worldwide annually (Thursz et al, 2006).

Epidemiology

Worldwide prevalence

The prevalence of CHB and the age at which infection occurs varies dramatically between different parts of the world. There is a high prevalence (8‑15%) in South East Asia, Africa, the Pacific islands, and the Amazon Basin and pockets of the Middle East and North and South America; the prevalence is generally low (less than 2%) in western populations (Table 1).

UK prevalence

In recent years, the number of people with CHB in the UK has risen sharply from 180,000 (Foundation for Liver Research, 2004) to 326,000 (Hepatitis B Foundation, 2007), due to people migrating to the UK from areas with a high CHB prevalence. Health Protection Agency reports (2011) show an antenatal HBV prevalence of 0.42% across England.

People infected with CHB often have no symptoms so many remain undiagnosed, both worldwide and in the UK.

Transmission

HBV is a bloodborne virus that can be found in low concentrations in semen, vaginal fluids, saliva, tears, sweat, urine and breast milk. The virus is 100 times more infectious than HIV and can live outside the body for seven days.

In areas of high prevalence, HBV is generally transmitted from mother to child (perinatal or vertical transmission) during childbirth rather than via the placenta. Transmission from child to child (horizontal transmission) is also common. The tradition of scarification may also be a significant source of transmission in African countries (Kim et al, 2011).

In countries with a low HBV prevalence, the condition tends to affect mainly young adults and is usually transmitted through injecting drug use or unprotected sexual contact (Liaw et al, 2010).

Pathophysiology

Hepatitis B life cycle

The life cycle of HBV is complex but, essentially, it acts as a stealth virus by evading the immune system (Chisari et al, 2010).

During the first stage of infection, the HBV virion (virus particle) attaches to a liver cell (hepatocyte) then penetrates the hepatocyte’s cytoplasm (Locarnini et al, 2010). The HBV virion is uncoated (Fig 1), which means that nucleocapsids can move into the hepatocyte’s nucleus and convert the DNA to covalently closed circular DNA (cccDNA) - a double-stranded DNA structure (Valsamakis, 2007). The cccDNA is very stable and can stay in the host nucleus for many months in chronic disease (Jeulin et al, 2013).The virus makes copies of itself in a process that lacks “proof reading ability”, which allows the virus to mutate (Horvat, 2011). The newly formed HBV virions are released into the bloodstream, from where they invade other hepatocytes and repeat the replication process.

It is thought that HBV causes inflammation and progressive fibrosis in the infected liver by triggering the immune system to attack the hepatocytes (Nebbia et al, 2012).

Natural history

The incubation period for HBV is 30-180 days. The age at which a person is infected with the virus determines the disease outcome; 90% of those who acquire HBV perinatally or in early childhood will develop CHB, as their immune system cannot destroy and clear infected hepatocytes (Lee et al, 2010).

In adults, 90% of infections are acute and only 5-10% develop into CHB (Shi et al, 2009). Acute liver failure occurs in 1% of acute HBV infections (Liang, 2009). Very rarely (in 1-2% of cases), people with CHB may lose the HBV surface antigen, which is considered to be a definitive recovery. However, the virus can reactivate if they become immunosuppressed (Larrubia, 2011).

The four stages of CHB

The lifetime risk of developing cirrhosis with CHB is 15-40%, with a 2-5% risk of HCC in those with cirrhosis (Nebbia et al, 2012). Many factors affect the rate of disease progression in CHB (Table 2).

It is understood that CHB has four distinct phases with different durations and outcomes (Fig 2). Stages are linked to the degree of HBV replication and the way in which the immune system responds.

  • Immune-tolerant phase: this stage lasts for 10-30 years in perinatally acquired HBV but is absent or has a shorter duration for those infected as children or adults. The hepatitis B viral protein, HBeAg, a marker of active viral replication, is present with high levels of HBV DNA and a normal level of alanine aminotransferase (ALT), a liver enzyme. There is minimal liver damage as the immune system tolerates the virus.
  • Immune clearance phase (immuno-active): those who acquire HBV in late childhood, adolescence or adulthood often present in this phase. When immunotolerability is lost, the immune system attacks infected hepatocytes, resulting in elevated ALT levels and fluctuating HBV DNA levels, and causing liver fibrosis. Seroconversion - loss of HBeAg and formation of the antibody to HBeAg (HBeAb) - takes place in 50% of children and adults within five years of entering this phase, and 70% of children and adults by 10 years, resulting in transition to the third phase.
  • Inactive carrier phase (immune control): this is an inactive phase of HBeAg negative HBV with low or undetectable HBV DNA levels, a normal ALT and no damage to the liver. Occasional surface antigen loss occurs. Patients in this phase form the largest group with HBV.
  • Reactivation phase: this phase can be spontaneous or can be triggered by immunosuppression. Patients can revert to HBeAg positivity but most are HBeAg negative with detectable DNA levels, high ALT and moderate to severe necro-inflammation with variable amounts of fibrosis on liver biopsy (Chen, 2010; Fattovitch et al, 2008; McMahon, 2004).

The management of HBV will be discussed in the second part of the series.

HBV genotypes

There are 10 HBV geographically distributed genotypes (A-J): B and C in Asia; A, E and D in Africa; and A and D in Western Europe and North America (Kao, 2011).

Genotypes A and B have a more favourable response to treatment with pegylated interferon than other types. Genotypes C and D are associated with more serious disease and HCC (Bonino et al, 2010).

Signs and symptoms of chronic HBV

People with CHB often do not have symptoms, so those with the disease may have no way of knowing that they are infected. However, some complain of fatigue, aches and pains, fever, loss of appetite, nausea and abdominal pain.

The majority of acute HBV infections are also asymptomatic but around 30% of adults will present with jaundice, fatigue, poor appetite, weight loss, nausea and vomiting, abdominal pain, pyrexia, dark urine and light stools (Aspinall et al, 2011).

Diagnosis

HBV is diagnosed with a blood test to detect hepatitis B surface antigen (HBsAg). The different HBV serological markers (Table 3) may be used collectively to determine a person’s HBV status. These are shown in Table 4.

HBV testing

Since 2000, all pregnant women have been tested for HBV. The National Institute for Health and Care Excellence (2012) has published a new guideline to promote HBV and hepatitis C virus testing. The guideline recommends that the at-risk groups listed in Box 1 are tested for HBV, and given counselling before and afterwards.

All those who test positive for HBV surface antigen should be referred to a specialist centre within six weeks. Pregnant women should be assessed by a specialist within six weeks of receiving the screening test result so treatment can be offered in the third trimester if necessary (NICE, 2013).

Vaccination

HBV is preventable through vaccination; this is generally a course of three injections given over six months, although accelerated courses are available. NICE (2012) and The Green Book (HM Government, 2009) both recommend that high-risk groups are vaccinated against HBV.

Conclusion

HBV infection can be prevented through vaccination, but CHB remains an international issue and an increasing problem in the UK due to a lack of awareness and the asymptomatic nature of the disease.

The future financial implications of CHB to the health service could potentially be huge if action is not taken.

NICE (2012) has produced guidance to promote and offer testing to people at increased risk of HBV infection. The guidance, which has been universally welcomed, includes raising awareness measures and educational and training programmes. 

 

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